Draft Risk Profile Pathogens and Filth in Spices

Transcript

1 Draft Risk Profile: Pathogens and Filth in Spices Center for Food Safety and Applied Nutrition Food and Drug Administration U.S. Department of Health and Human Services 2013

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3 MAJOR CONTRIBUTORS Risk Profile Team Leader and Project Manager completion) Jane Van Doren, FDA (April 2010 – April 2010) Sherri Dennis, FDA (January 2010 – (July 2009 – January 2010) FDA Mary Brandt, (February 2009 - July 2009) Marianna D. Solomotis, FDA Risk Profile Team Members Laura Gieraltowski, CDC FDA Vikas Gill, Thomas S. Hammack, FDA Daria Kleinmeier, FDA Martin Muckenfuss, FDA Karen P. Neil, CDC Obianuju Nsofor, FDA Lori Papadakis, FDA Mickey Parish, FDA Jane Van Doren, FDA Ann Westerman, FDA Robin Woo, FDA * George C. Ziobro, FDA Risk Management/Advisor Team Nega Beru, FDA (Spice Risk Management Team Leader) Vincent Bunning, FDA Sherri Dennis, FDA Kathy Gombas, FDA Lane Highbarger, FDA Henry Kim, FDA John Sheehan, FDA Jennifer Thomas, FDA Donald Zink, FDA (Senior Science Advisor) * Retired / Former Employee FDA Draft Risk Profile | i

4 ACKNOWLEDGEMENTS The file: Pathogens and Filth in Spices benefited from contributions, conversations and FDA Draft Risk Pro listed below . We thank information provided by many individuals, organizations, and government officials and acknowledge each one for their contributions. American Spice Trade Association , American Dehydrat ed Onion and Garlic Association, and the Indian Government (Indian Spices Board) for organizing and hosting site visits to spice production and processing facilities and to the employees of the companies visited, for providing information about spices, the spice supply chain, and common practices used in the spice industry. The spice and food industry for sharing and discussing industry guidance, best practices and common challenges through submission to the Federal Register in response to FDA’s call for data and information to support this risk assessment, presentation at sc ientific meetings, and discussions in meetings with FDA and the American Spice Trade Association for submitting microbiological sampling data to the Federal Register. Food and Drug Administration scientists for sharing their data, expertise and information, especially R é gis Lindsay Halik, Pouillot and Robert Blodgett (modeling and statistics); Susanne Keller, Elizabeth Grasso, n Fogg , Mercedes Loftis, and Brenda Aloi , Yinqing Ma , Marilyn Balmer , Linda Fabbri , Kristin Kamas , Norma Office of Regulatory Affair (special laboratory experiments and field s scientists & field personnel assignments); Tracy DuVernoy, Erica R. Pomeroy, and Capt. Suzan Gordon (U.S. outbreaks); Michael DiNovi, Alison Edwards , Ewa Carlton and Karin Hoelzer (consumption); Nicole Nolan (RFR ); Rosemary Gary and Martin J. Stutsman (U.S. regulations); Christine Keys, David Melka, Errol Strain, and Mark Allard (PFGE and NGS); John W. Larkin and Nathan Anderson (pathogen reduction treatment); Patrick McDermott , Maureen ra (antimicrobial susceptibility); Marjorie Davidson (retail establishment and Davidson and Claudine Kabe consumer guidance); Stephanie Briguglio and Mary Same (intern) (literature searches and document preparation), and Amy Miller and Lawrence D’Hoosteleare (filth adulteration). Centers for Disease Control and Prevention (CDC) and state public health departments for their data, expertise and information regarding U.S. outbreaks, especially Shauna L. Mettee, Hannah Gould, and Ian Williams (CDC); Jeffrey Higa (California Department o f Public Health); and Robert Ireland and Daniela Quilliam (Rhode Island Department of Public Health). International scientists Christine L. Little (while at Health Protection Agency, United Kingdom), Gilles Delmas (Institut de Veille Sanitaire, France), Andrea Altieri (European Food Safety Authority), Jordi Serratosa (European Food Safety Authority), and Tobin Robinson (European Food Safety Authority) for providing additional information about published reports of international outbreaks and spice contam ination. Versar, Inc. (David Bottimore, Kathy Coon, and Stephanie Sarraino) for organizing the External Peer Review of the draft report. Larry R. Beuchat (University of Georgia), Linda J. Harris (University of California, Davis), Margaret Hardin (IEH Lab oratories and Consulting Group), Jeffrey Lee Kornacki (Kornacki Microbiology Solutions), and Christine L. Little (independent contractor) for their peer review of the draft report. FDA Draft Risk Profile | ii

5 TABLE OF CONTENTS ... i Major Contributors ii Acknowledgements ... ... iii Table of Con tents List of Tables ... v List of Figures ... vii ... viii Abbreviations and Acronyms Executive Summary ... 1 ... 7 1. Introduction 1.1 Risk Profile objectives and Scope ... 7 -2010 ... 9 2. Foodborne Illness Outbreaks from Microbial Contaminants in Spices, 1973 2.1 Summary of Outbreaks, 1973-2010 ... 9 2.2 Outbreaks in the United States ... 16 2.3 Selected Non -U.S. Outbreaks ... 18 2.4 Public Health Burden ... 19 Spice ingredients used in non- ... 20 2.5 Related Outbreaks – spice capacities 2.6 General Observations Regarding Foodborne Illness Outbreaks Attributed to Microbial ... 20 Contaminants in Spices 3. Types of Pathogen and Filth Contamination Found in Spices ... 22 3.1 Microbial Pathogens Found in Spices ... 22 3.1.1 Types of Microbial Pathogens Found in Spices ... 22 3.1.2 Serotypes Identified in Spices ... 24 Salmonella 3.2 Filth Adulterants Found in Spices ... 28 4. Prevalence and Concentration of Salmonella and Filth in Spices ... 30 4.1 Salmonella ... 31 ... 31 4.1.1 Salmonella Prevalence and Concentration in Spice: From Farm to Table Overview 4.1.2 Primary Production ... 37 37 ... 4.1.3 Distribution and Storage ... 52 4.1.4 Secondary Processing and Food Manufacturing ... 57 4.1.5 Retail/End User Salmonella – 4.1.6 Frequency of Food Recalls in the United States Associated with Contaminated Spices ... 57 4.1.7 International Reports of Food Safety Hazards Associated with Salmonella – Contaminated Spices - ... 58 RASFF 4.2 Filth ... 58 4.2.1. Filth Adulteration Prevalence of Spice: From Farm to Table Overview ... 59 4.2.2. Primary Production ... 59 4.2.3. Distribution and Storage ... 59 ... 61 4.2.4. Secondary Processing and Multi -Component Food Manufacturing 4.2.5. Retail/End User 62 ... 4.3 Prevalence of Both Salmonella and Filth Adulteration of Spices ... 62 5. Characterization of Contaminants ... 64 5.1 Salmonella ... 64 5.1.1 General Characteristics of Salmonella ... 64 ... 5.1.2 Antimicrobial Properties of Some Spices 65 5.1.3 Survivability in Spices 65 ... 5.1.4 Potential for Growth in Moistened Spices and Spice -Containing Foods ... 67 5.1.5 Characteristics of the Non -Typhoidal Salmone llosis ... 69 5.2 Filth ... 72 6. Overview of Spice Farm -to-Table Continuum and Potential Sources of Pathogen and Filth ... 74 Contamination FDA Draft Risk Profile | iii

6 Table of Contents | ... 75 6.1 Primary Production ... 78 6.2 Distribution and Storage 79 ... 6.3 Secondary Processing and Multi -Component Food Manufacturing 6.4 Retail/End User ... 81 ... 7. Spice Production and Consumption 82 82 ... 7.1 U.S. Spice Supply ... 82 7.1.1 U.S. Production ... 7.1.2 U.S. Imports 85 88 ... 7.2 Spice Consumption in the United States 88 7.2.1 Consumer Population ... 88 ... 7.2.2 Consumption Mass and Frequency ... 8. Current Mitigation and Control Options 91 8.1 U.S. Regulatory Standards and Programs 91 ... ... 91 8.1.1 Federal Food, Drug, and Cosmetic Act 91 8.1.2 Public Health Service Act ... 91 8.1.3 U.S. Regulatory Mechanisms ... 103 ... 8.2 Industry Programs Pathogen Reduction ... 103 8.2.1 8.2.2 Industry Guidance from Trade Organizations on Practices Impacting Food Safety of Spices 121 ... 8.2.3 Recalls 124 ... ... 124 8.3 Codex Alimentarius and FAO/WHO ... 126 9. General Conclusions and Potential Future Mitigation and Control Options 9.1 General Conclusions ... 126 9.2 Potential Future Mitigation and Control Options 128 ... 9.2.1 Primary Production 128 ... 9.2.2 Distribution and Storage ... 129 ... 131 9.2.3 Primary and Secondary Processing ... 132 9.2.4 Retail/End user 9.2.5 General ... 134 10. Data Gaps and Research Needs ... 136 10.1 Data Gaps 136 ... 10.1.1 Foodborne Outbreaks ... 136 10.1.2 Prevalence and Concentration of Pathogens and Filth in Spices ... 136 10.1.3 Characteristics of Contaminants ... 137 10.2.4 Mitigation and Control Options ... 137 ... 137 10.2.5 Consumption 10.2 Research Needs 138 ... 10.2.1 Foodborne Outbreaks ... 138 10.2.2 Prevalence and Concentration of Pathogens and Filth in Spices ... 138 10.2.3 Characteristics of Contaminants ... 139 10.2.4 Mitigation and Control Options ... 139 10.2.5 Consumption ... 140 10.2.6 General 141 ... 11. References ... 142 Appendix A: Spice List ... 172 Appendix B: Worldwide Spice Production ... 184 Appendix C: FDA 2010 Study of Concentrations and Distribution of Salmonella in Shipments of Capiscum and Sesame Seed Offered for Entry to the United States. 192 ... FDA Draft Risk Profile | iv

7 LIST OF TABLES tbreaks taking place during 1973 -2010 associated with Table 2.1. Summary of enteric illness ou consumption of microbial contaminants in dried spices and seasonings or foods containing ... 10 these contaminated ingredients Table 3.1. Microbial pathogens detected in spices, 1985 -2012: Review of the scientific literature and a the CDC PulseNet and FDA FACTS databases 23 ... a species and serotypes found in spices in the United States, 2001 -2010. ... Table 3.2. Salmonella 24 Table 3.3. Spices for which filth Food Defect Action Level(s) has/have been established in the United ... States 28 Table 3.4. Types of filth adulterants found in spices: Surveillance sampling of spice shipments offered FY2009. ... 29 for U.S. entry, FY2007- Table 4.1. Summary of scientific surveillance studies measuring the prevalence of Salmonella in spices, 2000-2012 ... 33 Table 4.2. Concentration of Salmonella in spices and spice -containing foods implicated in salmonellosis illness outbreaks ... 36 Table 4.3. Observed prevalence of –contaminated shipments of imported spice and other Salmonella -regulated food shipments offered for entry to the United States, FY2007- FY2009. imported FDA 39 ... Table 4.4. Comparison of observed prevalence of Salmonella -contaminated shipments of some whole and ground/crack ed imported spice offered for entry to the United States, FY2007 -FY2009. ... 41 Salmonella -contaminated imported spice shipments offered for Table 4.5. Observed prevalence of entry to the United States as a function of export country, FY2007 -FY2009 ... 42 a ble 4.6. Salmonella serotype frequency and percentage among isolates Ta in surveillance samples of spice from shipments of imported spice offered for entry to the United States, FY2007 -FY2009. ... 43 enterica isolates from FDA Table 4.7. Antimicrobial Resistance of Salmonella enterica subspecies surveillance sampling of spices from shipments of imported spice offered for entry to the United States, FY2007- ... 47 FY2009. Table 4.8. Screening and enumeration test results for Salmonella in sampled shipments of imported ... December 2010 49 capsicum or sesame seed offered for entry to the United States August- contamination in spice lots from some ASTA member Table 4.9. Observed prevalence of Salmonella -July 31, companies to which no pathogen reduction treatment had been applied, August 1, 2007 2009 ... 53 Table 4.10. Observed prevalence of Salmonella contamination of spice lots from some ASTA member -July 31, companies to which a pathogen reduction treatment had been applied, August 1, 2007 ... 54 2009 Escherichia Table 4.11. Frequency and prevalence of generic contamination in spice lots in some coli ASTA member companies to which a pathogen reduction treatment had been applied, August 1, 2007-July 31, 2009 ... 56 Table 4.12. Prevalence of filth adulteration in shipments of imported spice or other FDA -regulated foods offered for entry to the United States, FY2007 -FY2009 ... 60 Table 4.13. Hairs found in shipments of imported spice offered for entry to the United States, FY2007 - ... FY2009 61 ation of relationship between presence of filth and Salmonella Table 4.14. Examin adulteration of shipments of imported spice offered for entry, FY2000 -FY2009 (except) FY2002 ... 63 Table 4.15. Examination of relationship between presence of filth and Salmonella adulteration of shipments of imported foods offered for entry, FY2000- ... 63 FY2009 (except) FY2002 Table 5.1. Estimated percentage of salmonellosis cases associated with different health endpoints and typical duration of illness. ... 71 Table 6.1. Evaluation of risks for filth contamination at different stages during the production of spices ... 78 Table 7.1. U.S. production of spices in 2010: Dehydrated onion, dehydrated (and fresh) garlic, capsicum, mustard seed, and sesame seed. ... 82 86 Table 7.2. Spice imports in 2010 by weight. ... FDA Draft Risk Profile | v

8 List of Tables | ... 87 Table 7.3. Spice imports by value, 2000-2010. a 90 Table 7.4. Estimated per capita spice consumption base d on food availability, 2010 . ... Table 8.1. Classification of inspections of firms that manufacture, pack or re -pack spices, FY2007- ... FY2012 92 -pack low Table 8.2. Classification of domestic inspections of firms that manufacture, pack or re moisture foods, average annual rates FY2007 ... 93 -FY2012 Table 8.3. Sixteen most frequent citations reported on FDA Form 483 issued during domestic spice December 2011 95 firm inspections, August- ... Table 8.4. Import Alerts involving DWPE that are primarily/exclusively associated with spices and address issues of pathogen and/or filth adultera ... 98 tion. ... 98 Table 8.5. Number of firms listed on Import Alert 99 -19 for DWPE in October 2010 and June 2013 a Table 8.6. Countries with the largest number of firms listed on Import Alert 99 -19 for DWPE of spices Salmonella due to “presence of 99 ” ... Table 8.7. Primary entries reported to the FDA Reportable Food Registry September 8, 2009 - 101 September 7, 2012 ... ... 104 Table 8.8. Accepted reconditioning proposals for spices, 2007 – 2012 (December) ... 108 Table 8.9. Decimal reductions of microbial populations in spices from heat treatments ... 112 Table 8.10. Decimal reductions from gamma radiation for microbial populations of various spices ... Table 8.11. Decimal reductions of APC counts in spices treated with ethylene oxide 117 Salmonella Table 8.12. Estimates of the number of illnesses resulting from a population consuming raw Salmonella - contaminated lot as a function of mean lot spice from a single 40,000 lb. (18144 kg) concentration and serving size, -distributed within the assuming the contamination is Poisson lot ... 121 ... Table A1. Spice list by botanical name 172 Table A2. Spice list by common name 175 ... Table A3. Spice list by part of plant used ... 178 ... 181 Table A4. Common use of spice in foods ... 184 Table B1. Worldwide Spice Production 2009 184 ... Table B2. Anise, badian, fennel, coriander Table B3. Chillies and peppers, dry 185 ... Table B4. Cinnamon (canella) ... 185 Table B5. Cloves ... 186 Table B6. Garlic ... 186 Table B7. Ginger ... 187 ... 187 Table B8. Mustard Seed Ta ... 188 ble B9. Nutmeg, mace and cardamoms Table B10. Onions, dried ... 188 Table B11. Pepper ( Piper spp.) ... 189 Table B12. Poppy Seed ... 189 Table B13. Spices, nes ... 190 Table B14. Sesame Seed 190 ... Table B15. Vanilla ... 191 Table C1. Description of sampled and Salmonella -contaminated shipments offered for U.S. entry ... 196 197 Table C2. Model parameters and descriptors ... FDA Draft Risk Profile | vi

9 LIST OF FIGURES - Salmonella Figure 4.1. Complementary cumulative distribution functions (p × (1 CDF(λ)) for models of contamination among shipments of imported capsicum offered for entry to the United States compared with observations. ... 51 Figure 4.2. Complementary cumulative distribution functions (p× (1 CDF(λ)) for models of Salmonella - contamination among shipments of imported sesame seeds offered for entry to the United States compared with observations. ... 52 Figure 5.1. Survival of Salmonella at 25 ° C and high (97%) RH. ... 66 Figure 5.3. Survival of at 25 ° C and ambient (≤40) RH. ... 66 Salmonella Salmonella at 35 ° C and high (97%) RH. ... 66 Figure 5.2. Survival of 66 ... Figure 5.4. Survival of Salmonella at 35 ° C and ambient (≤40) RH. Figure 5.5. Appearance of ground black pepper at different water activities (a 69 ). ... w Figure 5.6. WHO/FAO dose Salmonella . ... 70 -response model for Figure 5.7. Age dependence of hospitalization and fatality rates for foodborne salmonellosis in the United States, 2010. ... 72 Figure 6.1. Typical stages in spice farm -to-finished product continuum for spices including transport and processing options and con trol points ... 74 ... 75 Figure 6.2. Possible pathways for spice from spice manufacturer to consumer. Figure 7.1. Relative contributions of domestic and imported dehydrated onion to the total annual U.S. supply, 1970 to 2010. ... 83 Figure 7.2. Relative contributions of domestic and imported garlic to the total annual U.S. supply, 1960 to 2010. ... 83 Figure 7.3. Relative contributions of domestic and imported capsicum (including paprika) to the total annual U.S. supply, 1966 to 2010. ... 84 Figure 7.4. Relative contributions of domestic and imported mustard seed to the total annual U.S. supply, 1966 to 2010. ... 85 Figure 7.5. Annual per capita spice consumption in the U.S excluding dehydrated onion and garlic, 89 1966-2010. ... FDA Draft Risk Profile | vii

10 Abbreviations and Acronyms | RONYMS ABBREVIATIONS AND AC Definition Acronym aerobic plate count APC Animal and Plant Health Inspection Service APHIS Agricultural Research Service ARS ASTA Spice Trade Association American water activity a w CC controlled condensation CDC Centers for Disease Control CDPH California Department of Public Health CF coliforms CFR Code of Federal Regulations Center for Food Safety and Applied Nutrition CFSAN CFU colony forming units CGMPs Current Good Manufacturing Practices CI confidence interval CO carbon dioxide 2 COA certificate of analysis Codex Codex Alimentarius CORE Coordinated Outbreak Response and Evaluation Network Food Defect Action Levels DALs DWPE Detention Without Physical Examination Enterobacteriaceae EB Escherichia coli EC European Food Safety Authority EFSA Export Inspection Council of India EIC ethylene oxide EO EPA U.S. Environmental Protection Agency ERS Economic Research Service Emergency Response Unit ERU “Field Accomplishments and Compliance Tracking System,” an FDA database that FACTS includes sampling data FAO Food and Agriculture Organization FAS Foreign Agricultural Service fecal coliform FC Food Commodity Intake Database FCID FD&C Act Federal Food , Drug , and Cosmetic Act FDA U.S. Food and Drug Administration FDB Food and Drug Branch FDOSS Foodborne Disease Outbreak Surveillance System Federal Insecticide, Fungicide, and Rodenticide Act FIFRA FDA Draft Risk Profile | viii

11 Abbreviations and Acronyms | Definition Acronym Food Safety Inspection Service FSIS FDA Food Safety Modernization Act FSMA Good Agricultural and Collection Practices GACP Good Agricultural Practices GAPs GC/FID gas chromatography with flame ionization detection detection GC/MS gas chromatography with mass spectrometry gas chromatography with olfactometry GC/O Global Foodborne Infection Network GFN GMA Grocery Manufacturers Association GMPs Good Manufacturing Practices GRAS Generally Recognized as Safe water H O 2 Hazard Analysis and Critical Control HACCP Points IBD Inflammatory Bowel Disease ICMSF International Commission on Microbiological Specification for Foods ISO International Organization for Standardization JIFSAN Joint Institute for Food Safety and Applied Nutrition kGy kilo gray MPN most probable number Nitrogen N 2 NACMCF National Advisory Committee on Microbiological Criteria for Foods NAI no action indicated National Center for Biotechnology Information NCBI NCDEX National Commodity and Derivatives Exchange NEC Not Elsewhere Classified NGS Next Generation Sequencing NHANES National Health and Nutrition Examination Surveys NIH National Institute of Health OAI official action indicated PHF Potentially Hazardous Food Control Area PSCA Primary Salmonella FSPCA Food Safety Preventive Controls Alliance RASFF Rapid Alert System for Food and Feed RFR Reportable Food Registry RH Relative Humidity RR Relative Risk SRA Sequence Read Archive SSA Seasoning and Spice Association UNCTAD United Nations Conference on Trade and Development U.S.C. United State s Code USDA United States Department of Agriculture U.S. Pharmacopeia USP FDA Draft Risk Profile | ix

12 Abbreviations and Acronyms | Acronym Definition VAI voluntary action indicated World Health Organization WHO World Trade Organization WTO WWEIA What We Eat in America yeast and mold YM FDA Draft Risk Profile | x

13 EXECUTIVE SUMMARY Overview the effectiveness of current control measures to reduce or In light of new evidence calling into question prevent illness from consumption of spices in the United States, the United States Food and Drug ed a risk profile on pathogens and filth in spices. Administration (FDA) develop The objectives of the risk profile were to (1) describe the nature and extent of the public health risk posed by consumption of spices in the United States by identifying the most commonly occurring microbial hazards and filth in spice (2) describe and evaluate current mitigation and control options designed to reduce the public health risk posed by consumption of contaminated spices in the United States (3) identify potential additional mitigation and control options and (4) identify critical data gaps and research needs. The draft risk profile for pathogens and filth in spices provides information for FDA to use in the development of plans to reduce or prevent illness from spices contaminated by microbial pathogens and/or filth. Scope For the purpose of this risk profile, the term “spice” means “any [dried] aromatic vegetable substances in the whole, broken, or ground form, except for those substances which have been traditionally regarded as foods, whose significant function in food is seasoning rather than nutritional, and from which no portion of any volatile oil or other flavori ng principle has been removed” and includes additional dried plants listed a s spices by the E nvironmental Protection Agency , the American Spice Trade Association , and the S easoning and Spice Association , such as dehydrated onion and garlic vegetables used as , as well as other dehydrated seasoning. The specific microbial hazards and filth elements in spices considered in this risk profile include pathogens and filth adulterants detected in spices, implicated in outbreaks, reported as the reason for recalls, and reported in submissions to t he Reportable Food Registry . This report primarily focuses on Salmonella , among the pathogens detected in spices, because it is the only spice- associated pathogen linked with human illness, food recalls, or Reportable Food Registry reports in the United States. Research Methods Research for the report included a comprehensive review of the refereed scientific literature and available government/agency reports, and analyses of relevant FDA and CDC data. Data and information from stakeholders were formally requested in a Federal Register Notice dev eloped by FDA. Submissions to the docket provided critical information on industry guidance and spice sampling and testing by the spice industry. Site visits to spice farms and spice processing and packing facilities, facilitated by spice industry trade or -hand k nowledge ganizations and the government of India, provided the Risk Profile Team with first of current practices. In order to fill some critical data gaps, FDA field assignments and laboratory research were also undertaken. Types of Pathogens and F ilth Adulteration Found in Spices Microbial pathogens that have been found in spices include Salmonella , Bacillus spp. (including Bacillus , and cereus ), Clostridium perfringens , Cronobacter spp., Shigella . Filth Staphylococcus aureus adulterants found in spices include insects (live and dead whole insects and insect parts), excrement (animal, bird, and insect), hair (human, rodent, bat, cow, sheep, dog, cat and others), and other materials ( parts, bird barbs, decomposed rs, stones, twigs, staples, wood slivers, plastic, synthe bird barbules, bird feathe tic fibers, and rubber bands). Foodborne Illness Outbreaks from Microbial Contaminants in Spices During the period 1973- 2010, fourteen reported illness outbreaks were attributed to consumption o f pathogen Canada, Denmark, France, Germany, -contaminated spice. Countries reporting outbreaks included New Zealand, Norway, Serbia, United Kingdom , and the United States. Together, these outbreaks resulted in 1946 reported human illnesses, 128 ho spitalizatio ns and two deaths. Infants and children were the primary enterica subspecies population segments impacted by five of the spice- associated outbreaks. Salmonella FDA Draft Risk Profile | 1

14 Executive Summary | was identified as the causative agent in ten outbreaks accounting for . enterica 87% of reported illnesses % of reported illnesses. Bacillus spp. was identified as the causative agent in four outbreaks, accounting for 13 Consumption of ready -to-eat foods prepared with spices applied after the final food manufacturing pathogen for 70% of the illnesses. Pathogen growth in spiced food is suspected to have played reduction step accou nted a role in some outbreaks, but it was not likely a contributing factor in three of the larger Salmonella outbreaks, whic h involved low -moisture foods. Root causes of spice contamination included contributions -to-table continuum. from both early and late stages of the farm of Salmonella Prevalence and Concentration and Filth in Spices thogens in spices at Limited data were available from the refereed scientific literature on the prevalence of pa most -to-table continuum. The majority of data available were from shipments of imported points in the farm spice offered for entry to the United States (FDA sampling data), lots of spice in spice industry facilities (spice industry sampling data), and retail settings outside the United States (data collected primarily by public health government agencies or academic researchers). Most spices consumed in the United States are Analysis of FDA sampling and testing data for shipments of imported spice offered for entry to the imported. United States during the three year period FY2007 -FY2009 revealed an average shipment prevalence for of 6.6% (750 g Salmonella 7.6%). The average prevalence of Salmonella in sampled sample size; 95% CI 5.7- spice shipments during this period was 1.9 times ( 2.3%) the average prevalence determined for 95% CI 1.6- -regulated foods sampled during that time ( - shipments of all other FDA where screening tests examined 375 shipments only considering er imported FDA -regulated foods that were sampled with 1500 g). When of oth Salmonella the same FDA Category II food sampling protocol as that used for spices, it was found that the times (95% CI 3.4 -5.8%) that of other FDA -regulated impo rted foods shipment prevalence for spices was 4.4 during FY2007- FY2009. A wide diversity of spice types and forms was found to contain Salmonella among shipments of imported spice offered for entry to the United States during FY2007 -FY2009; differences in prevalence rates were Salmonella observed for som serotypes were isolated from spices e spice types/forms. More than 80 different in contaminated shipments during the three 6.8% of isolates exhibited antim icrobial -resistant -year period; Some shipments reported to have been subjected being properties. to a pathogen reduction treatment before offered for United States (U.S.) entry were found contaminated. Contaminated shipments identified during FY2007-FY2009 were exported by many different countries; some differences in shipme nt Salmonella preval ence were identified. FDA undertook a short- -Dec 2010 to collect enumeration data for term targeted study during Aug contaminated shipments of imported capsicum and sesame seed. The mean Salmonella concentration -4 estimates varied widely among contaminated shipments, with ranges of 6 x 10 to 0.09 MPN/g -spice (6 MPN -4 per 10,000 g to 9 MPN per 100 g) for shipments of imported capsicum and 6 x10 to 0.04 MPN/g -spice (6 MPN per 10,000 g to 4 MPN per 100 g) for shipments of imported sesame seeds offered for entry to the -Poisson model of within United States. A gamma - and between -shipment contamination provided the best fit to observations among six parametric models considered. Contaminated spice shipments of capsicum or sesame seed were typically large , constituting millio ns or tens of millions servings. Approximately one - in size e (20% for fifth of the contaminated shipments of capsicum or sesame seed was packaged for retail sal data are available for other capsicum and 22% for sesame seed). No comparable prevalence or enumeration imported spices or for domestically produced spices. The American Spice Trade Association (ASTA) provided sampling and testing data collec ted in spice secondary processing/packing facilities of member companies over a two -year period during 2007 -2009. Analysis and interpretation of these data complicated by an absence of information charac terizing were sample size examined. The spice industr y data provide d evidence that the prevalence of Salmonella in spice lots that had undergone a pathogen reduction treatment was smaller tha n that for untreated spice lots. These sampled treated spice lots in these industry data also provided evidence that the prevalence of Salmonella FDA Draft Risk Profile | 2

15 Executive Summary | smaller than the average shipments of imported spices offered for import was prevalence found for sampled to the United States during FY2007 -FY2009 (FDA surveillance sampling). Salmonella We were unable to identify any reports characterizing the prevalence or concentration in spices of at retail (in food/grocery stores, food service, restaurants, or in ho mes) in the United States. Studies outside -zero upper limits) to 10% with ranging the United States reported prevalence values from 0% (with non of Salmonella varying confidence intervals. Concentrations reported in retail spice samples outside the United -spice States ranged from <0.1 to 0.2 MPN/g (0.086 MPN/g for black pepper and capsicum spice in Japan and 0.2 MPN/g for sesame seeds and mixtures of seeds in the United Kingdom) for surveillance 0.1- from < determined in traceback investigations of spice -associated foodborne Salmonella samples. Concentrations of -spice. outbreaks ranged from <0.03 -11 MPN/g Recent p valence estimates for filth adulteration of spices were only available for shipments of imported re spice offered for entry to the United States. domestically produced spices. Analysis No data were available for surveillance sampling data for FY2007-FY showed that the average prevalence of filth 2009 of FDA of imported spice was 12% (95% CI 10- 15%), which was 1.8 times (95% CI 1.4- of shipments adulteration the average of all other imported FDA -regulated food shipments examined during 2.2%) the value found for that period. Prevalence of filth adulteration of imported shipments of ground/cracked and whole spice were The prevalence of filth adulteration of similar. imported shipments of imported black pepper was smaller than that for several other types/categories of spice shipments. The most common types of filth adulterants lent insects, and animal hair. Nearly all of the insects found in spice were insect fragments, whole/equiva samples were stored product pests, indicating inadequate p . The presence of acking or storage conditions rodent hair (without a root) in spices generally is generally indicative of contamination by rodent feces. Direct evidence of animal fecal and/or insect fecal contamination was found in a small number of the samples. The presence of these is indicative of insanitary conditions and failures in the application of filth adulterants Current Good Manufacturing Practices (CGMPs) . Data on the prevalence of filth adulteration of spice at retail last gathered in the 1980’s in the United States were by FDA and were used to set the maximum of natural or unavoidable defects in foods to concentrations achievable by CGM Ps. concentrations Characterization of Contaminants A variety of animal hosts may introduce Salmonella into a spice production site. Salmonella can survive in the natural environment (outside of an a nimal host) for extended periods and can persist in some food production areas for years. can also survive for extended periods (exceeding 1 year) in low Salmonella mo isture foods including spices. The magnitude of the Salmonella population reduction rate in spice depends on the water activity of the spice (or equivalently, the humidity of the spice environment) and temperature, when the water activity/humidity is elevated. When Salmonella -co ntaminated spices are stored in an environment that meets spice industry standards for low water activity/humidity, the reduction in population of Salmonella in spice with time may be minimal (s hown for ground black pepper). FDA research has also demonstra can grow efficiently in wet ground black pepper (no additional ted that Salmonella nutrients improperly processed, packaged or stored. ), such as might occur if spice is needed -to-Table Continuum and Potential Sources of Pathogen an d Filth Contamination Overview of Spice Farm used in the production of spices around the globe. A wide diversity of farm sizes and agricultural practices is Many spices are produced on very small farms where farm animals are used to plow, crops are harvested by -cropping is also common. Spice from small farms is spices are dried in open air. Multi typically hand, and aggr egated with that of other farms. These collections of spice are later sold to exchanges or to spice processing/packing companies. Producers may store whole spice for ye ars before selling to a buyer. Larger farms, such as those used to produce dehydrated onion and garlic in the United States, may be owned by or contracted with a single major/large spice company that dictates/controls growing, harvest , drying, and storage practices. Spice companies may also contract with groups of farmers in a single region to educate and (WHO), Codex better control growing, harvest , drying, and storage practices . World Health Organization Alimentarius (Codex), and industry standards and guidance designed to minimize/prevent introduction of FDA Draft Risk Profile | 3

16 Executive Summary | pathogens or filth to the source plant or dried spice, such as those related to irrigation water, restriction of animals in the growing area, and farm worker hygiene, can be challenging to implement at many primary production sites. The distribution of spice from primary producer to consumer can be very complex, involving multiple locations, multiple processing and/or packing steps and long periods. Inappropriate packing and storage of Salmonella or filth into spice. spice during any one of these steps may lead to the introduction of Application of additional mechanical and electromagnetic cleaning processes as well as grinding/cracking, blending, and packing typically take place in secondary spice processing facilities. To prevent creation of niches, spice processors may use dry sanitation and cleaning processes in process areas handling spice that has been subjected to a pathogen reductio n treatment. S ome level of spice dust is unavoidable so equipment and facility design play critical role s in limiting the need for wet cleaning in the spice processing areas and preventing cross -contamination of treated spi ces with untreated spice dust. Re placement of equipment or re- design of facilities can be particularly challenging for small spice firms and use of common equipment for multiple types of spice is common. Pathogen reduction treatments are not uniformly applied to all types of spices or all lots of spice of a given type at the secondary processing stage. The efficacy of the most commonly applied pathogen reduction , which treatment methods (steam, irradiation, and ethylene oxide) is dependent on a variety of conditions can alter redu ctions b y orders of magnitude. No studies have systematically examined efficacy of these processes for reductions of Salmonella in spices but data available suggest that each of these methods has the potential to achieve substantial decimal reduction s in spices un der appropriate ly controlled conditions. exist in seasoning and Similar food safety concerns, described above for secondary spice processing facilities, food manufacturing facilities as well as in wholesalers that pack and re -pack spices. In addition, sp ice is sometimes added to foods after the final food manufacturing pathogen reduction step has been applied, if such as step is part of the food preparation process. ce to foods after the In institutional food services, restaurants, and households, application of untreated spi final lethality (cooking) step and the potential for pathogen growth in foods to which Salmonella - contaminated spice has been added are of primary concern. In addition, the potential for contamination of spice by pests in the food pre paration and storage environments or cross -contamination of spice from surfaces or utensils used to prepare other contaminated foods are also of concern. Preventive controls to minimize most of these outcomes include application of the principles described in the state regulations, the FDA Food Code , and consumer guidance. At this time, spice sold in retail settings (to households) do not generally carry an indication of whether the spice had been treated for reduction of pathogens. Spice Production and Co nsumption Most of the U.S. spice supply is imported with the exception of dehydrated onion. U.S. farms also produce Consumer survey data in large fractions of the U.S. supply of dehydrated garlic, capsicum, and mustard seed. the Mintel survey reveal that a large majority of U.S. households, estimated to be 86%, use fresh or dried herbs, spices and seasonings. Spice use in the United States, as measured by food availability, has been increasing by appro ximately 0.5 lbs./decade since 1966. In 2010, the estimated per capita annual spice consumption was 3.64 lbs. (1653 g), excluding dehydrated garlic. Estimates from the FDA/CDC National Health and Nutriti on Examination Surveys (NHANES) indicate a typical co nsumption range of 0.3 -1.7 g -spice per eating occasion for three eating occasions per day. Estimates of the variability and frequency of spice consumption are not available. Current Mitigation and Control Options Current U.S. regulatory mechanisms available to mitigate and control adulteration of spice with Salmonella or include CGMPs, inspections of and environmental sampling in spice manufacturing/packing facilities, filth FDA Draft Risk Profile | 4

17 Executive Summary | en lists and country product sampling, refusals and reconditioning, import alerts (with or without gre agreements) , and some provisions of the FDA Food Safety Modernization Act. -FY2012 was Rates of compliance with CGMPS among spice firms in the United States for the period FY2007 other FD A- regulated low moisture foods. Insufficient approximately the same as that found for firms handling . FDA data were available to evaluate compliance with CGMPS in spice facilities outside the United States -pack spices in 2010 revealed that a sig inspections of 59 domestic firms that manufacture/pack/re nificant Salmonella -processing) facility environment. Lack of effective pest fraction (10%) had in the (primarily post o environmental sampling management was the most frequently cited observation in these inspections. N from FDA were available to determine the prevalence of Salmonella in internationa l spice facility data environments. During the period FY2007- 906 imported spice shipments (including s esame seeds) were refused FY2010, Salmonella and/or filth. Among entry to the United States based on the presence or potential for presence of these shipments, 749 shipments of spice were refused entry because of the presence or potential presence of Salmonella and 238 shipments were refused because of the presence or potential presence of filth. During the period 2007- 2012, CFSAN accepted 50 out of 155 reconditioning proposal s for spices, 37of which addressed contamination with Salmonella . Salmonella or filth and four of these are specific to Five U.S. import alerts address adulteration of spice by spice. I mport Alert 99 -19 lists firms and specific foods for which evidence has indicated the likelihood of Salmonella contamination; a majority of firms and foods listed are spices (71% in 2010 and 67% in 2010, excluding sesame seeds cited as a seed rather than a spice). Import Alert 28 -02 for Indian Black Pepper includes an agreement that leverages in -country regulatory or entry to the United States. authority to improve the food safety of shipments of the imported spice offered f This combination of incentives appears to be effective in reducing the prevalence of Salmonella or filth or entry to the United States. Expansion of this contamination in shipments of Indian black pepper offered f further improvements in type of mechanism to other spices and/or to other countries should lead to contamination rates. The FDA Food Safety Modernization Act provides important new tools to mitigate and control contamination and post treatment cross contamination of spices with Salmonella , including authority to mandate recall s and increase in the frequency of foreign and domestic inspections (implemented), and prevention standards and (proposed rules issued in January 2013 (78 Federal Register 3646) and July 2013 (78 import safety mandates Federal Register 45730), respectively ). The spice and food trade organizations have developed detailed guidance to prevent and control adulteration of spice with pathogens or filth in finished spice or food products. These guidance documents reflect current of scientific knowledge including the ability Salmonella to survive in low -moisture foods such as spices, the enhanced heat resistance of some Salmonella and lessons learned from past contamination and strains, Clean, Safe Spices: Guidance from the American Spice Trade Association , published in 2011, outbreak events. highlights the application of Good Agricultural Practices (GAPs) for growing and harvesting spices, supply -evaluation programs, Good Manufacturing Practices (GMPs), validated microbial chain approval and re reduct ion processes, ASTA Cleanliness Specifications, post -treatment sampling and testing program, environmental sampling and testing program, and the development of Hazard Analysis and Critical Control Point (HACCP) plans. The Grocery Manufacturers Association Control of Salmonella in Low -Moisture Foods guidance and associated journal articles highlight additional preventive controls including stringent control of hygienic practices in the Primary Salmonella Control Area (PSCA) and moisture control. The extent t o which the recommendations in these guidance documents are applied by the spice and food industry is unknown. Guidance from Codex and Food and Agriculture Organization (FAO)/WHO provide science -based ng, establishment design and hygiene requirements, general principles for hygienic production and harvesti FDA Draft Risk Profile | 5

18 Executive Summary | -product specifications that can be applied to personnel hygiene, establishment hygienic processing, and end The spice -specific Code of Hygienic Practice for Spices and Dried Aromatic Plants does not spice. reflect current knowledge in hygienic practices and is being revised by the Codex Committee on Food Hygiene (at the time this report was written). General Conclusions and Potential Future Mitigation and Control Options Failures identified in the farm -to-table food safety system potentially leading to adulteration of consumed spice generally arose from poor/inconsistent application of appropriate preventive controls failing to , such as limit animal access to the spice source plant during harvest or drying phases, failing to limit insect and rodent access to spice during storage, or failing to subject all spice to an effective pathogen reduction treatment (or other lethality step) . Based on our research, we concluded that knowledge and technology are available to significantly reduce the risk of illness from consumption of contaminat ed spices in the United States. We developed a list of potential future mitigations and control options for consideration based on the in this report . The list includes mitigation and control options that scientific data, information , and analysis FDA, the spice industry, government agencies, food manufacturers/preparers , and the consumer may of , other pathoge ns, and filth in spices and to consider to reduce the prevalence and concentration Salmonella reduce the public health burden resulting from consumption of contaminated spices or foods c ontaining contaminated spices. Mitigation and control options identified include capacity building, guidance, enforcement and regulat We emphasize capacity ory strategies, communication, education, and training. building through the creation of partnerships with stakeholders to facilitate improvements in spice safety and reduce the risk of illness from consumption of pathogen -contaminate d spices. These include enhanced communication between FDA and the spice industry and within the spice and food manufacturing industry itself, combined with training across the spice supply chain to ensure understanding of appropriate preventive controls and how to implement them. Data Gaps and Research Needs The development of the risk profile revealed many gaps in information and data regarding the adulteration of spices by pathogens and filth and the potential for this contamination to impact public he alth. We identified these gaps and the research needed to fill them, particularly focusing on research that could improve our ability to assess the public health risk posed by consumption of spices in the United States, to better characterize system failur es that lead to spice contamination, and to explore additional potential future mitigations. FDA Draft Risk Profile | 6

19 1. INTRODUCTION The FDA Draft Risk Profile on Pathogens and Filth in Spices was initiated by the Center for Food Safety and Salmonella 2009 outbreak of Applied Nutrition in response to a large 2008- illness associated with the consumption of microbiologically contaminated ground white p epper in the United States . Subsequently, the Salmonella United States had a larger outbreak of illness, this time associated with consumption of products co within ntaining black and red pepper. This second outbreak, as well as other reports in the literature and score the importance of researching food safety issues associated with spices. FDA served to under The Draft Risk Profile on Pathogens and Filth in Spices was primarily developed to provide information for the Food and Drug Administration (FDA) ris k managers and others to use in regulatory decision -making . The information may also be useful to stakeholders and interested parties such as spice producers and importers, spice and food manufacturers, retail foods establishments, and consumers. 1.1 RISK PROFILE OBJECTIVES A ND SCOPE The Spice Risk Profile has four main objectives: 1. Describe the nature and extent of the public health risk posed by consumption of spices in the United States by identifying the most commonly occurring microbial hazards and fil th in spice. 2. Describe and evaluate current mitigation and control options designed to reduce the public health risk posed by consumption of contaminated spices in the United States. Identify potential additional mitigation or control options designed to re duce the public health risk 3. posed by the consumption of contaminated spices in the United States. Identify data gaps and research needs. 4. For the purpose of this risk profile, the term “spice” means “any [dried] aromatic vegetable substances in the whole, broken, or ground form, except for those substances which have been traditionally regarded as foods, whose significant function in food is seasoning rather than nutritional, and from which no portion of any volatile oil or other flavoring principle has bee n removed” (Title 21 Code of Federal Regulations (CFR) , section 101.22) (FDA, 2012p) and includes spices listed at 21 CFR 182.10 and 21 CFR 184 (FDA, 2012f; FDA, 2012g ) and additional dried plants listed as spices by the Environmental Protection Agency (E PA), the American Spice Trade Association (ASTA) (ASTA, 2012) and the Seasoning and Spice Association (SSA) (SSA, 2012), such as dehydrated onion and garlic , as well as other dehydrated vegetables used as seasoning. The specific microbial hazards and fil th elements in spices considered in this risk profile include pathogens and filth adulterants detected in spices, implicated in outbreaks, reported as the reason for recalls, and reported in submissions to the Reportable Food Registry (RFR). Emphasis is pl aced on the pathogen(s) with the strongest evidence for illness related to consumption of contaminated spices (e.g., outbreaks) and for which the potential for exposure in the United States has been established (i.e., outbreaks, recalls, RF submissions to the R, and surveillance sampling). The risk profile also addresses specific questions posed by risk managers, which include the following: 1. What is known about the frequency and concentration s of pathogen and/or filth contamination of spices throughout the food supply chain (e.g., on the farm, at primary processing/manufacturing, at intermediary processing (where spices are used as ingredients in multi -component products), at distribution (including importation), at retail sale/use, and at the consumer’s ho me)? 2. What is known about differences in production and contamination of imported and domestic spices? 3. What is known about the effectiveness and practicality of currently available and potential future ses associated with contaminated spices (e.g., mitigations and control options to prevent human illnes FDA Draft Risk Profile | 7

20 Int roduction| 1 practices and/or technologies to reduce or prevent contamination, surveillance, inspection, import strategies, or guidance)? 4. What are the highest priority research needs related to prevention or reduction of c ontamination of spices with pathogens or filth? Completion of the risk profile involved decisions about cutoff dates for data inclusion. Within the constraints of data access, collection, analysis, and review, we provide a review of current data that add ress the risk management objectives and questions posed. For the review of outbreaks and analysis of FDA and industry sampling data, the availability of data and the complexity of the analyses involved determined upper year cutoffs for these studies. FDA Draft Risk Profile | 8

21 2. AL FOODBORNE ILLNESS OUTBREAKS FROM MICROBI ES, 1973 -2010 CONTAMINANTS IN SPIC We undertook a comprehensive literature search and reviewed the Centers for Disease Control and Prevention’s Foodborne Disease Outbreak Surveillance System (CDC’s FDOSS) to identify and describe all the foodborne illness outbreaks that have been reported and attributed to consumption of pathogen - contaminated spices throughout the world durin g the ye ars 1973 through 2010. The original report of this study was published in (Van Doren et al. , 2013b). The risk profile include s additional Food Microbiology search criteria, added in response to suggestions by external peer reviewers, but no additional outb reaks beyond those reported in the original report have been identified. The specific objectives of this study were to (1) characterize the public health burden arising from consumption of spices contaminated with microbial pathogens, (2) identify the typ es of microorganisms implicated in foodborne illness outbreaks caused by consumption of contaminated spice, (3) identify and -associated illness outbreaks, and characterize the types of spices and countries of origin implicated in spice (4) identify the lea ding causes of microbial contamination of spices assoc iated with foodborne outbreaks. associated outbreak as the occurrence of two or more similar illnesses resulting from We define a spice- ingestion of a food containing a common spice(s) as an ingredient. Only outbreaks with laboratory detection of the suspected causative agent in the spice/spice blend and either culture-confirmed detection of the causative agent in clinical samples or analytical epidemiological evidence providing a statistically significant associated between consumption of the food vehicle and being a case in the outbreak were included. These inclusion criteria were selected to ensure that the outbreaks identified had compelling evidence that a contaminated spice ingredient was the cause of the reported illnesses. The review included outbreaks taking place during the years 1973-2010. The period of review began in 1973 because it was the year CDC’s Foodborne Disease Outbreak Surveillance System (FDOSS) was initiated and the period ended with 2010 . because it was the most recent year for which data from FDOSS was available whe n this report was written To identify and learn about foodborne illness outbreaks associated with consumption of spices, we reviewed the refereed scientific literature and available government/agency reports using MEDLINE and Google Scholar to search the -language literature using different combinations of the following keywords: English Bacillus , outbreak, foodborne, spice, seasoning, herb, pathogen, , Clostridium , Cronobacter , Campylobacter Escherichia coli , E. coli, O157, O104, Mycobacterium bovis, Mycob acterium tuberculosis , norovirus, Salmonella , sakazakii , Shigella , and Staphylococcus aureus . We also queried the CDC’s FDOSS to identify outbreaks -2010 where a spice was reported as the implicated food (CDC, 2012a). We reported to CDC during 1973 reviewed paper citations and references contained in the articles identified in our search and contacted p on reports in the public health agencies in France, New Zealand and the United Kingdom to follow u Through these contacts, we learned of one addit ional outbreak , which literature. ly has not been previous reported in the literature. For the two most recent illness outbreaks in the United States, additional information was gathered from investigations by FDA and CDC . 2.1 SUMMARY OF OUTBR EAKS, 1973- 2010 The associated illness outbreaks occurring between 1973 and 2010 (Table review identified fourteen spice- 2.1). Four of these outbreaks were identified in a previous review of salmonellosis outbreaks associated with consumption of spices and fresh herbs (Zweife l and Stephan, 2012). Together, these outbreaks resulted in 1946 reported human illnesses, 128 hospitalizations (7% of cases) and two deaths (0.1%). Countries reporting outbreaks were Canada (1 outbreak ), Denmark (1), France (1), Germany (2), New Zealand (1), (3), and the United States (3). Norway (1), Serbia (1), United Kingdom FDA Draft Risk Profile | 9

22 Foodborne Illness Outbreaks from Microbial Contaminants in Spices, 1973- 2010 | 2 -2010 associated with consumption of microbial contaminants in Table 2.1. Summary of enteric illness outbreaks taking place during 1973 dried spices and seasonings or fo ods containing these contaminated ingredients Other - pathogens Hospital Country: Spice Linked to Total b isolated Pathogen Outbreak Reference(s) Comments Date izations c Outbreak Cases a (Spice) during (Deaths) investigation Microbiological link between spice and illness established. Outbreak identified in Mar 1974 after laboratory surveillance detected increased human cases of Weltevreden illness; 2 samples of S. ., Laidley et al Dec 1973 black pepper positive for S . Black pepper Salmonella Canada 1 1974; WHO, – May 17 None reported ) Weltevreden had been previously Piper nigrum ( (India) Weltevreden (Not reported) 1974 1974 identified in Aug 1973. One case attributed to consumption of white . Weltevreden isolated pepper; S from opened container of white pepper with same trademark as S . Weltevreden positive black pepper samples. Microbiological link between spice and illness established. S. Senftenberg, The Brazilian black pepper was S. Lexington, first shipped to the Federal S. Abaetuba Republic of Germany; only a from samples fraction of the original shipment of implicated Nov 1981 was later shipped to Norway. It is black pepper. Gustavsen and Black pepper Salmonella Norway >25% not known whether the pepper was - Aug 126 ( Breen, 1984 Piper nigrum ) Oranienburg (Brazil) (at least 1) processed or repackaged in 1982 Sendai, S. Germany before shipment to S. Glostrup Norway. from other samples of in 12 Salmonella Enumeration of black pepper samples of black pepper found from Brazil. concentrations in the range 0.1 to MPN/g. >2.4 FDA Draft Risk Profile | 10

23 Foodborne Illness Outbreaks from Microbial Contaminants in Spices, 1973- 2010 | 2 Other Country: pathogens - Hospital Total Spice Linked to b izations Date Reference(s) Pathogen Comments Outbreak isolated c Cases Outbreak a during (Deaths) (Spice) investigation Microbiological link between spice and illness established. Paprika Salmonella Capsicum ( Spice mix applied after chip Prevailing Multiple Germany Not reported Lehmacher et - Sep Apr annum temperature dropped to 60°C. ) serotypes: ~1000 Salmonella (South d (on paprika (Not reported) - al ., 1995 1993 Saintpaul, serotypes America) Enumeration of Salmonella in powdered potato Rubislaw, and paprika and paprika- containing chips) Javiana spice mixes found concentrations - in the range 0.04 11 MPN/g. Microbiological link between spice and illness established. , et al. Little Turmeric Bacillus United Outbreak attributed to 2003; Little, (Curcuma longa) subtilis 0 e Kingdom consumption of lamb seekh kebab 2012; Health 1995 2 None reported (on lamb seekh & Bacillus (0) (not known) and B. B. subtilis in a restaurant; Protection kebab) pumilus were detected in the pumilus Agency, 2011 turmeric powder used to make the lamb seekh kebab. Microbiological link between spice Little , et al. and illness established. 2003; Little, United Salmonella Black pepper 1 Kingdom Enteritidis 2012; Health 8 Aug 1996 None reported S . Enteritidis detected in ground ) Piper nigrum ( (0) Protection (not known) PT4 black pepper used in meal Agency, 2011 preparation in a restaurant. Microbiological link between spice and illness established. Pepper None reported Outbreak attributed to Cameron, Bacillus New Zealand (type not 1997 2 None reported (None B consumption of peppered steak; 1998 . subtilis (Malaysia) specified) reported) detected in cooked and subtilis uncooked steak, pepper mix, and 4 peppercorns (>10 CFU/g). FDA Draft Risk Profile | 11

24 Foodborne Illness Outbreaks from Microbial Contaminants in Spices, 1973- 2010 | 2 Other Country: pathogens Hospital - Spice Linked to Total b Reference(s) Pathogen Date Comments isolated izations Outbreak c Outbreak Cases a (Spice) during (Deaths) investigation Microbiological link between spice and illness established. . Braenderup detected in curry S Little, 2012; powder added as garnish to an egg United Curry Powder Health Salmonella 1 dish in a restaurant; dish was kept Aug 2002 Kingdom 20 None reported ( ) blend of spices Protection Braenderup (0) at room temperature before (India) Agency, 2011 S serving; . Braenderup found in samples from both opened and unopened packages of curry powder. Microbiological link between spice and illness established. Identification of implicated vehicle aided by knowledge during Anise seed . Agona S hypothesis generation that Pimpinella ( had been isolated from anise seed Other anisum ) et al ., Koch during routine food safety unspecified (in tea Salmonella Oct 2002 Germany 21 of 39 2005; Rabsch monitoring in 2002. 42 Salmonella containing anise Agona (Turkey) -Jul 2003 (0) ., 2005 et al serotypes seed, fennel All cases of illness in infants <13 seed, and months. caraway) in Salmonella Enumeration of samples of anise seed -containing tea found a concentration of 0.036 MPN/g. FDA Draft Risk Profile | 12

25 Foodborne Illness Outbreaks from Microbial Contaminants in Spices, 1973- 2010 | 2 Other pathogens - Country: Hospital Total Spice Linked to b Comments Reference(s) Outbreak Pathogen izations Date isolated c Outbreak Cases a (Deaths) (Spice) during investigation S . Typhimurium, S . Kentucky, Cronobacter sakazakii from United States Microbiological link between spice unopened (China for and illness established. snack puff dried bags; broccoli . S Seasoning mix & Seasoning mix applied after final Jan 2007 powder; broccoli powder Typhimurium, pathogen reduction step. ., Sotir et al 6 of 56 Salmonella – Dec sources of 69 (coating a snack S . Haifa from 2009 (0) Wandsworth 2007 other puff) finished Isolating S . Typhimurium from ingredients product in the seasoning mix led to identification in seasoning manufacturing . Typhimurium S of a linked mix not facility; . S outbreak. reported) Mbandaka from parsley powder used in the puff snack seasoning mix. United States ( for China Microbiological link between spice dried Wandsworth S. and illness established. broccoli plus “Other Seasoning mix & powder; Jun 2007 pathogens” Salmonella et al Sotir Outbreak identified after sample of ., broccoli powder 2 of 18 18 sources of – Sep listed above for Typhimurium 2009 snack food seasoning mix taken (coating a snack (0) other 2007 . related S during S . Wandsworth outbreak puff) continued ingredients Wandsworth S investigation was positive for . in seasoning outbreak. Typhimurium. mix not reported) Analytical epidemiological evidence B. and laboratory detection of EFSA, 2013; Spice Blend France in the spice blend used in the Bacillus 0 cereus EFSA, 2009a; (Not (in couscous 2007 146 Unknown couscous dish. (0) cereus Delmas, 2013 dish) reported) Outbreak in school/kindergarten. FDA Draft Risk Profile | 13

26 Foodborne Illness Outbreaks from Microbial Contaminants in Spices, 1973- 2010 | 2 Other pathogens - Hospital Country: Total Spice Linked to b Pathogen Reference(s) Comments Outbreak isolated Date izations c Outbreak Cases a (Deaths) during (Spice) investigation Microbiological link between spice and illness established. Fennel seed ( Foeniculum patients reported Parents of case- ) vulgare Mar pouring boiling water over (dry) Serbia (in “baby” tea Salmonella 4 of 14 et al Ilic ., 2010 2007 - Sep baby tea mixture during (Not 14 None reported containing Senftenberg (Not reported) 2008 preparation but did not heat tea reported) fennel seed, infusion to boiling. anise seed, and caraway) 71% of cases of illness in infants <12 months. Microbiological link between spice and illness established. Environmental samples from spice CDPH/FDB/ processing facility tested positive 8 of 60 ; 14 ERU, 2010; for the outbreak stra in. Multiple additional Dec 2008 FDA, 2009a; violations of CGMP noted during White pepper Salmonella United States patients were - Apr Higa, 2011; 87 inspection of spice processing None reported Piper nigrum ( ) (Vietnam) Rissen hospitalized 2009 Hajmeer and facility. before illness Myers, 2011; (1) Identification of implicated vehicle Higa, 2012 aided by knowledge that the outbreak strain had been isolated in 2006 from an FDA import sample of black pepper. Microbiological link between spice and illness established. United States Black pepper Black pepper and red pepper CDC, 2010; (black Piper nigrum ( ) applied to salami products after the Gieraltowski - pepper 52 of 203 and red pepper Jul 2009 – Salmonella f final pathogen reduction step. et al. , 2012; S . Senftenberg Vietnam; red 272 (0) Capsicum ( spp.) Apr 2010 Montevideo DuVernoy, pepper - -style (on Italian . Senftenberg from Isolating S 2012 India & salami) implicated product led to China) S identification of a linked . Senftenberg outbreak. FDA Draft Risk Profile | 14

27 Foodborne Illness Outbreaks from Microbial Contaminants in Spices, 1973- 2010 | 2 Other Hospital - pathogens Country: Spice Linked to Total b Comments isolated Pathogen Reference(s) Date izations Outbreak c Cases Outbreak a during (Spice) (Deaths) investigation Microbiological link between spice Black pepper United States and illness established. ) Piper nigrum black ( ( and red pepper CDC, 2010; - pepper Not reported Outbreak identified during Jul 2009 – S. Salmonella spp.) Vietnam; red ( DuVernoy, Capsicum S. Montevideo 11 (Not reported) Apr 2010 Senftenberg vestigation Montevideo outbreak in (on Italian -style 2012 pepper - after sample of unopened retail salami) India & package of salami was positive for China) continued . Senftenberg. S Microbiological link between spice and illness established. White pepper EFSA, 2013; Denmark Bacillus 0 Contaminated white pepper in ) 2010 Piper nigrum ( 112 Unknown EFSA, 2011a cereus (Unknown) (0) stew. Canteen/workplace catering (in stew) setting. Storage time/temperature abuse suspected as contributing. a parentheses. Country where outbreak occurred following by country of origin of the spice in b serotypes listed are serotypes of Salmonella enterica subspecies enterica . Salmonella c Number of cases of illness listed are the number of documented cases of illness. Several sources indicate that this number significantly underestimates the actual number of illnesses 04; Chalker and Blaser, 1988). See text for further details et al associated with the outbreak (Scallan et al , 2011; Mead . ., 1999; Voetsch et al ., 20 d during the outbreak. Approximately 42% of illnesses Salmonella found in paprika or paprika -powdered potato chips Number of human cases of illness associated with rare serotypes of were associated with the three prevailing S . serotypes e Duration of outbreak not known (Little, 2012; Health Protection Agency, 2011) f a portion 2010). A SNP -based evolutionary analysis of Montevideo isolates suggests that Number of cases of illness listed are number of epidemiologically linked cases of illness (CDC, of the epidemiologically linked cases of illness may not be associated with this outbreak (see text, den Bakker et al. , 2011). FDA Draft Risk Profile | 15

28 Foodborne Illness Outbreaks from Microbial Conta 2010 | 2 minants in Spices, 1973- associated outbreaks and 87% of the illnesses were caused by serotypes of Ten of the fourteen (71%) spice- enterica . Four outbreaks were caused by Bacillus subspecies Salmonella enterica spp., accounting for 13% of ted with two or more different organisms ( multiple serotypes of the illnesses. Four outbreaks were associa or Salmonella species of Bacillus) . Salmonella serotypes associated with human illnesses in these multiple outbreaks included Agona (1 outbreak), Braenderup (1), Enteritidis (1), Javiana (1), Montevideo (1), Oranienburg (1), Rissen (1), Rubislaw (1), Saintpaul (1), Senftenberg (2), Typhimurium (1), Wandsworth (1), and Weltevreden (1) (Table 2.1). Bacillus species identified as causative agents in spice -associated outbreaks included B . cereus (2 outbreaks), B. subtilis (2) and B. pumilus (1). The evidence for the spice- associated B. subtilis and illness outbreaks reported in Table 2.1 included both epidemiological and B. pumilus B. subtilis B. pumilus are seldom reported as foodborne pathogens but microbiological data (Little, 2012). and these organisms may produce a mild toxin after growing to high numbers in a food (Logan, 2011). Spices implicated in the outbreaks were black pepper ( Piper nigrum ; 4 outbreaks), red pepper ( Capsicum spp.; 2 outbr eaks), white pepper ( Piper nigrum ; 2 outbreaks ), unspecified pepper (1 outbreak), curry powder (a blend of spices; 1 outbreak), anise seed ( Pimpinella anisum ; 1 outbreak), fennel seed ( Foeniculum vulgare ; 1 outbreak), turmeric ( Curcuma longa ; 1 outbreak), a spice blend (1 outbreak) and a seasoning blend containing contaminated broccoli powder (1 outbreak); some outbreaks were associated with multiple spices or food vehicles (Table 2.1). Seventy -one percent (10/14) of the outbreaks were associated with spices classified as fruits or seeds of the source plant. The countries/regions of origin of the implicated spices were identified in nine outbreaks and included Brazil (1 outbreak), China (2), India (3), Malaysia (1), South America (1), Turkey ( 1) , and Vietnam (2) (Table 2.1). In every case where it could be determined (9/14 This observation is not unexpected ed. outbreaks), the spices implicated in the outbreaks were import because many of the countries in which outbreaks were identified are not major spice pro ducing countries In at least two of the outbreaks, post- -contamination is suspected to have (FAO, 2013b). import cross Salmonella Rissen in white pepper [ Piper nigrum ] and Salmonella Montevideo in contributed to the outbreak ( Pi per nigrum ] and red pepper ( Capsicum spp.); see discussion in Section 2.2). black pepper [ 2.2 OUTBREAKS IN THE UNITED STATES Three foodborne illness outbreaks attributed to consumption of pathogen -contaminated spices were reported in the United States during the study p eriod. All three outbreaks took place within a 40 month period (Jan 2007- April 2010) and accounted for 457 laboratory -confirmed illnesses, 68 hospitalizations, and one death (Table 2. 1). Age data were available for 404 of the 457 confirmed cases. The age b reakdown for these three outbreaks was: <1 year, 5%; 1 to 4 years, 17%; 5 to 9 years, 14%; 20 to 49 years, 32%; and >50 years, 32%. The distribution of ages affected in these three U.S. outbreaks demonstrates that nearly all ages in the population have be en affected by these outbreaks. In the earliest spice- associated outbreak identified in the United States, 69 cases of Salmonella Wandsworth illness were confirmed from 23 states between January 2007 and December 2007; 96% of ill persons wer e children < 6 years old (Sotir et al ., 2009). Public health investigations performed by state and federal regulatory authorities implicated a seasoning mix consisting of broccoli powder, parsley powder, and other spices used to coat a snack puff after the final food man pathogen reduction step (Sotir et al ., 2009) . ufacturing Salmonella The only ingredient in the seasoning mix to test positive for Wandsworth was the broccoli powder, collected at two U.S. snack food manufacturing facilities and imported from China. It is n ot known whether the broccoli powder had undergone a pathogen reduction treatment before its application to the snack food (Sotir et al. , 2009). None of the environmental samples collected in the two snack food manufacturing facilities tested positive for Salmonella (Sotir et al. , 2009). Product testing also identified Salmonella Salmonella Mban daka from parsley powder (Sotir et al ., Typhimurium from the seasoning mix and 2009). A cluster of 11 human cases of Salmonella Typhimurium illness epidemiologically linked to the snack puffs was subsequently identified; no confirmed human cases of Salmonella Mbanda ka illness were reported ., 2009). (Sotir et al FDA Draft Risk Profile | 16

29 Foodborne Illness Outbreaks from Microbial Conta 2010 | 2 minants in Spices, 1973- associated outbreak in the United States, 87 cases of Salmonella In the second spice- Rissen illness that CDPH/FDB/ERU, 2010; Higa, curred between December 2008 and April 2009 were reported from 5 states ( oc 2011). Human cases of illness resulted from food consumption at restaurants and hospitals and included . Epidemiologic investigations, traceback individuals from age 5 months to 94 years (Higa, 2011) investigations, and product testing implicated white pepper ( Piper nigrum ) ground and packed by a single CDPH/FDB/ERU, 2010; Higa, 2011; Hajmeer and Myers, 2011) company in California ( . Samples of whole and ground white pepper were collected from the California spice processing and packing yzed during the investigation. One unopened bag of imported whole white peppercorns was facility and anal Salmonella Rissen outbreak strain, suggesting contam ination of the spice took place found to contain the before import ( The whole white peppercorns implicated in this outbreak originated CDPH/FDB/ERU, 2010). from Vietnam and had been sold as “steam washed” ( CDPH/FDB/ERU, 2010; Myers and Higa, 2011; Hajmeer and Myers, 2011). Whi le steam treatments are often applied to spices to reduce/eliminate microbial pathogens (ASTA, 2011), “steam washing” is primarily used to clean dirt from spices and may not provide an effective pathogen reduction step (Myers and Higa, 2011; Hajmeer and My ers, 2011). No other pathogen reduction treatment had been applied to the spice (Myers and Higa, 2011) but the suspected imported whole white pepper lot was accompanied by a Certificate of Analysis (COA) that indicted that the lot had tested S almonella before import ( negative for CDPH/FDB/ERU, 2010). The sensitivity of the screening test used for the COA is not known so it is possible that the lot could have contained a low concentration of Salmonella or a highly clustered distribution of Salmonella undetec ted by the screening test (ICMSF, 2002; Bassett et al. , 2010). Environmental sampling data collected in the implicated spice processing and packing facility in California found widespread contamination of the spice processing facility, with ~40% (46/116) of swab samples taken throughout the facility testing positive for Salmonella (CDPH/FDB/ERU, 2010). A ll of the Salmonella isolates Salmonella Rissen outbreak strain (CDPH/FDB/ERU, for which a strain was determined (19/46) matched the . Contamination o 2010) f the grinding room was particularly extensive, with 94% (34/36) of swabs collected Salmonella Rissen and 100% (14/14) of the isolates examined for in the grinding room testing positive for CDPH/FDB/ERU, strain, matching the outbreak strain (Hajmeer and Myers, 2011; FDA , 2009). Inspections ( 2010; FDA, 2009; Hajmeer and Myers, 2011) Current Good of the facility revealed multiple violations of the Manufacturing Practices (CGMP) regulation for foods at 21 CFR 110 (FDA , 2012i; U.S.C., 2007). FDA issued a Salmonella Warning Letter to the firm that stated in part, “The finding of in multiple processing locations within your facility indicates that this pathogenic organism may have become established in a niche ross contamination of the spice processing/packing environment in your facility” (FDA, 2009). With such g -contamination from the facility environment to the spice also played a role in facility, it is possible that cross this outbreak. During the third spice - associated outbreak in the United States, epidemiological investigations identified 272 laboratory -confirmed cases of Salmonella Montevideo illness from 44 states and the District of Columbia during the period July 2009 to April 2010 (CDC, 2010; Gieraltowski et al. , 2012); ill persons ranged in age et al. from <1 to 93 years (CDC, 2010; Gieraltowski , 2012). A next generation sequencing (NGS) analysis of human isolates collected during the time of the outbreak suggested that the total number of cases of illness et al. associated with this outbreak may have been significantly smaller (den Bakker , 2011). However, the NGS analysis only included 20 putative outbreak isolates and relied on comparison with NGS data from es analyzed on a different experimental platform (Lienau et al. known outbreak isolat which may have , 2011) impacted the study conclusions . Epidemiologic and traceback investigations of the Salmonella Montevideo outbreak implicated consumption of ready coated salami) manufactured by a single company in -to-eat salami products (including pepper- Rhode Island ( Gieraltowski et al. , 2012). Traceback and product testing determined that black pepper ( Piper nigrum ) from Vietnam and red pepper ( Capsicum spp.) from India and China used in the salami products , 2012; DuVernoy, 2012). A et al. were contaminated with Salmonella Montevideo (CDC, 2010; Gieraltowski FDA Draft Risk Profile | 17

30 Foodborne Illness Outbreaks from Microbial Conta minants in Spices, 1973- 2010 | 2 Salmonella Senftenberg private laboratory also isolated from an unopened retail sample of the implicated , 2012). PulseNet subsequently identified 11 human cases of product (Gieraltowski Salmonella et al. -field gel electrophoresis pattern (PFGE), and two of the patients reported Senftenberg with the same pulsed purchasing the implicated product (Gieraltowski , 2012). et al. Evidence collected during the outbreak investigation revealed that some of the black pepper used in the et al. manufacture of the salami products was reported to have been treated with steam (Gieral towski , 2012). sterilized” (DuVernoy, 2012). Some of Descriptions of the treatments included “steam washed” and “steam the red pepper lots implicated in the investigation were reported to have been treated with ethylene oxide, and some a fter import into the United States (DuVernoy, 2012). It is not known if the steam or some before ethylene oxide treatments had been validated as an effective reduction step for . Some of the Salmonella treated imported black pepper shipments were accompanied by Certifi cates of Analysis (COAs) reporting negative tests for (DuVernoy, 2012). However, review of the COAs revealed that at least some of Salmonella the tests were conducted on a smaller sample size than FDA typically uses to examine spices at import (i.e., ning one 25 g sample as compared with 30 x 25 g [two -375 g composite samples]) (Andrews and exami Hammack, 2003). Therefore, it is possible that some of the treated imported black pepper contained low s of Salmonella n (ICMSF, 2002; Bassett et al. , 2010) unreached concentration or highly localized contaminatio . As in the Salmonella Wandsworth outbreak associated with snack puffs, investigation of the food by steam manufacturing process revealed that spices were applied to the salami products after the final (meat production/fermentation and drying) pathogen reduction step (CDC, 2010; Gieraltowski , 2012) . Growth et al. Salmonella of - in the salami products is not suspected as contributing to this outbreak because salami is a low moisture, shelf -stable food. While it was not possible to definitively determine where in the supply chain the spices were contaminated, Montevideo Salmonella the weight of evidence suggests that contamination of the black and red pepper with took place after the spice shipments were imported into the United States, that is, from cross -contamination. Experimental evidence supporting this hypothesis includes the NGS study that demonstrated that clinical, product, and environmental isolates associated with the outbreak were most closely related with one Montevideo isolate collected from the east coast of the United States and were distinct from Salmonella et al. , 2011; Allard Montevideo strains from other parts of the world (Lienau , 2012). Other evidence et al. supporting post- import cont amination includes the facts that the spice associated with the outbreak was imported from three different countries that are geographically distinct (CDC, 2010; Gieraltowski et al. , 2012) and that “a common source in the distribution path from production to the Company A facility [salami et al. , 2012). manufacturing facilities] was not identified between the black and red pepper” (Gieraltowski While “unopened” boxes of spice in the salami manufacturer were found to contain the outbreak strain (Gieraltowski et al. , 2012), the spice in these boxes came from U.S. suppliers who had stored, repacked, and in some cases, processed (e.g., ground/cracked) the spice before shipment to the salami manufacturing facility (DuVernoy, 2012). - U.S. OUTBREAKS 2.3 SELECTED NON The largest spice- associated outbreak was identified in Germany in 1993 (Lehmacher ., 1995; Table 2.1) et al Salmonella . The in which an estimated 1000 cases of illness occurred between April and September 1993 ars old, including 14 infants <1 year old majority of illnesses were in children ≤14 ye . A large number of Salmonella serotypes were associated with this outbreak; Salmonella Saintpaul, Javiana, and Rubislaw accounted for 42% of the human illnesses and many other Salmonella serotypes were isolated fro m patients or implicated foods (Lehmacher . 1995). et al Traceback investigations and product testing identified paprika ( Capsicum annum ), used in seasoning for potato chips, as the contaminated food vehicle (Lehmacher et al ., 1995) . Some, if not all, of t he paprika was imported from South America. It was not known where or when the paprika was contaminated or whether a pathogen reduction treatment had been applied to the paprika . Enumeration experiments revealed that the FDA Draft Risk Profile | 18

31 Foodborne Illness Outbreaks from Microbial Conta minants in Spices, 1973- 2010 | 2 s of Salmonella ples of spice and food implicated in the outbreak were small − 2.5 MPN/g concentration in sam (25 MPN per 10 g; paprika), 0.04-11 MPN/g (4 MPN per 100 g to 11 MPN per g; paprika -containing spice otato chips) − and 0.45 MPN/g (5 MPN per 100 g to 45 MPN per 100 g paprika mixes) and 0.05- -powdered p -powdered potato chips for at can survive in the dry environments of paprika and paprika Salmonella that et al. , 1995) . As noted for other outbreaks, the spice mix was least 8 and 12 months, respectively (Lehmacher et al applied after the final . food manufacturing (potato chip) pathogen reduction step (Lehmacher ., 1995) Bacillus Four outbreaks of spp. illness attributed to consumption of foods containing contaminated spice took New Zealand (Cameron, 2013), place in Denmark (EFSA, 2011a; EFSA, 2013), France (EFSA, 2009a; EFSA, 1998) United Kingdom (Little et al ., 2003; Little, 2012; Health Protection Agency, 2011), accounting , and the for 262 illnesses. Three of these outbreaks took place in settings where food services provide meals for la rge numbers of people (a canteen/workplace, a restaurant, and a school/kindergarten) . Growth of the pathogen . in the food was suspected as contributing to at least one of the outbreaks (EFSA, 2011a) Salmonella Two outbreaks were attributed to consumption of tea inf -contaminated usions prepared from ≤13 months of age (Koch et al. spices and served primarily to infants et al. , 2005; Ilic who were , 2005; Rabsch , 2010). Taken together, 52 (93%) of 56 of the individuals who became ill in these two outbreaks were et al. infants (Koch , 2005; Ilic et al. , 2010). In both investigations, contamination of the multicomponent tea et al. was traced to a single contaminated spice ingredient: aniseed ( ) in the Salmonella Agona Pimpinella anisum outbreak in Germany (Koch , 2005; Rabsch et al. , 2005) and fennel seed ( Foeniculum vulgare ) in the et al. , 2010) et al. Salmonella Senftenberg outbreak in Serbia (Ilic . Epidemiological investigations revealed that in some cases, boiling water was not used (Koch et al. et al. , 2010) to , 2005) or was probably not used (Ilic Salmonella prepare the tea infusions. Subsequent growth of surviving cells in the cooled tea infusion may ted to the number of cases of illness observed (Koch et al. , 2005) have also contribu . The outbreak investigations did not reveal where in the supply chain tea contamination took place but both identified weaknesses in supplier control, i.e., the use of unregistered producers (fennel seed; Ilic et al. , 2010) and the reported use of manure as fertilizer in seed production (anise seed, reported by the spice importer; Koch et al. , 2005). 2.4 PUBLIC HEALTH BURDEN Although an estimated 1946 human illnesses were identified in the fourteen outbreaks reported above, the actual health burden is likely much larger due to underreporting and challenges in foodborne disease surveillance and outbreak response . In the United States, the CDC estimates that 1.0 million people in the United Sta tes become ill from Salmonella -contaminated food consumed each year (Scallan et al ., 2011; CDC, 2011) . This estimated value includes a correction for underreporting derived from data obtained from several surveillance/reporting systems (Scallan ., 201 et al 1) . Applying the CDC underreporting multiplier for Salmonella (29.3 Scallan et al ., 2011), the public health burden of the three spice -associated outbreaks in the ; United States is roughly estimated at ~13,400 human illnesses. Many countries do not have the ability to track foodborne illness and for those countries that do track foodborne illness, the reporting structure/information may be insufficient to attribute outbreaks to spices. For example, until recently, European Union member country reports of o utbreaks attributed to spices were reported together with outbreaks attributed to fresh herbs (see for example EFSA, 2009a) and the additional information reported did not always allow distinction between fresh and dry . In the United States, reporting to P ulseNet is limited to selected pathogens, which makes detection of geographically dispersed outbreaks of other pathogens, such as spp., more difficult. Even when a spice is suspected as being the Bacillus contamination source, it cannot or is not always co nfirmed . For example, our research identified seven additional outbreaks attributed to consumption of contaminated spice (4 Salmonella illness outbreaks, 2 Bacillus cereus illness outbreaks, 1 Clostridium perfringens outbreak) (Millet and Staff, 1999; Litt le et al. , 2003; , 2011; EFSA, 2013), but which did not meet our inclusion criteria ealth Protection Agency Little, 2012; H FDA Draft Risk Profile | 19

32 Foodborne Illness Outbreaks from Microbial Conta 2010 | 2 minants in Spices, 1973- . As a (lacking microbiological or epidemiological evidence specified in Section 2: Materials and Methods) -contaminated spice is result, the number of world -wide outbreaks associated with consumption of pathogen likely underreported. Ingredient -related outbreaks are especially challenging to investigate because of the many possible foods that . In addition, could be involved and the potentially complex supply chains associated with each ingredient especially minor ingredients consumers of contaminated food may not be aware of all ingredients in the food, such spices. As a result, it is possible that more spice -associated outbreaks occurred within the United States or in other countries that reported one or more spice outbreaks . According to the CDC, only 43% - associated of reported foodb -10 had a food reported (CDC, 2013a) . orne disease outbreaks in the United States in 2009 -life of spices and the ability of pathogens to persist in spice for long The long shelf periods (demonstrated for ) also create challenges for outbreak identification because illnesses from consumption of Salmonella contaminated spice may be separated by time and space. 2.5 RELATED OUTBREAK S – SPICE INGREDIENTS US ED IN NON- SPICE CAPACITIES At least five outbreaks associated with spice ingredients that are used in non -sp ice capacities took place . Three , 2005) and one outbreaks associated with tahini (Unicomb et al. during the study period Salmonella Salmonella et al ., 2001; Fisher et al ., 2001; Little, 2001; Brockmann, outbreak linked to helva (Andersson 2001; Guérin et a l ., 2001) were identified during the literature review . Both of these products are made predominantly of sesame seeds ( spp.) . Together these outbreaks were responsible for at least 128 Sesamum illnesses in six countries (Unicomb et al . , 2005; Andersson et al ., 2001; Fisher et al ., 2001; Little, 2001; Brockmann 2001; Guérin et al ., 2001) . Some spice seeds, such as fennel ( Foeniculum vulgare ) and mustard . Numerous sprout-associated , are also used to produce sprouts for human consumption ( Brassica spp.) outbre aks have occurred, and many of these outbreaks have been traced to bacterial contamination of the EFSA, 2011b . One B. cereus illness outbreak associated seed ( ) amplified during the sprout production process with sprout consumption took place in the United States in 1973 and was traced to contamination of the seed et al. mixture, which included soy, cress and mustard (Portnoy -scale 2011 outbreak of , 1976). The large Shiga -toxin producing Escherichia coli serotype O104:H4 in Germany and France, while not in t he temporal scope of this review, was also attributed to sprout consumption and traced to contaminated fenugreek seeds ( Trigonella foenum -graecum ), although the bacterium was never isolated from the seeds (EFSA, 2011c) . These outbreaks highlight the fact t hat some spices have multiple applications in food production and can carry a risk of foodborne illness in these other applications . Application of mitigation and control strategies to the production, storage and handling of spices could also reduce the ri sk of illness from these foods. 2.6 GENERAL O BSERVATIONS REGARDING FOODBORNE ILLNESS OUTBREAKS ATTRIBUTED TO MICROB IAL CONTAMINANTS IN S PICES - Our review identified fourteen foodborne illness outbreaks attributed to consumption of pathogen contaminated spic es between 1973 and 2010. that consumption of pathogen - These outbreaks demonstrate contaminated spices can result in human illnesses and that the illnesses that arise can be severe enough to necessitate . The review also demonstrates that outbreaks hospitalization and, occasionally, result in death . Individuals of all attributed to consumption of contaminated spice can involve large numbers of illnesses ages can be affected, including infants and young children, who comprised the majority of cases of illness in five outbreaks and were the apparent target consumer of some of the contaminated foods consumed (Lehmacher et al ., 1995; Koch et al ., 2005; Ilic et al ., 2010; Sotir et al ., 2009; EFSA, 2009a) . Within our review, spp. were the most common bacterial pathogens linked Salmonella enterica subspecies enterica and Bacillus to spice -associated outbreaks . A single spice vehicle can be contaminated with multiple Salmonella serotypes -serotype/species outbreaks. As evidenced by the 1993 paprika or Bacillus species, resulting in multi FDA Draft Risk Profile | 20

33 Foodborne Illness Outbreaks from Microbial Conta minants in Spices, 1973- 2010 | 2 Capsicum annum )- associated outbreak (Lehmacher ., 1995) and documented by other studies (Keller et ( et al et al. can survive in dried spices and other low Salmonella , 2013; Podolak al. , 2010 and references therein) . Enumeration data collected during three outbreak investigations found moisture foods for prolonged periods concentration s of contamination, indicating that low concentration s of contamination in spices can cause low et al. , 1995; Koch human illness (Gustavsen and Breen, 1984; Lehmacher , 2005) . The Salmonella et al. Wandsworth outbreak (Sotir et al ., 2009) illustrated that dried vegetable powders used in seasoning blends . may carry the risk of illness if contaminated -to-eat foods prepared with spices appli ed after the final food manufacturing pathogen Consumption of ready reduction step accounted for at least 70% of the illnesses (CDC, 2010; Sotir , 2009; Lehmacher et al. , et al. 1995). In three out of four outbreaks for which spice process treatment information was recorded, it was , et al. found that no pathogen reduction treatment had been applied to the spice (Rabsch et al. , 2005; Sotir 2009; Myers and Higa, 2011) owth in spiced food was suspected to have played a role in some . Pathogen gr outbreaks but it was probably not a contributing factor in three of the larger Salmonella illness outbreaks, which involved low -moisture foods (CDC, 2010; Sotir et al. , 2009; Lehmacher et al. , 1995) that do not support microbial growth when maintained at a low water activity . The root cause of spice contamination was not determined in most of the outbreaks . In four outbreaks, the outbreak strain was isolated from unopened packages of the spice ingredient in the food manufacturing facility, which supports the hypothesis that contamination of the spice took place at an early stage in the -to-table continuum (e.g., during production, early processing, or packing/storage before farm import) (Laidley et al. , 1974; Gustavsen and Breen, 1984; CDC, 2010) . In two outbreaks, evidence supported possible contributions from cross -contamination in later stages of the farm -to-table continuum (e.g., post- import spice processing or food manufacturing environments ) (Hajmeer and Myers, 2011; Lienau et al. , 2011; Allard et al. , 2012) . Most investigations did not report whether the spice had been subjected to a pathogen reduction treatment before receipt by the spice/food manufacturer/retail user and did not enumerate the pathogen in the spice ingredient and food . Gathering this information in future outbreak investigations, could help . investigators determine which of the possible routes of contamination were involved FDA Draft Risk Profile | 21

34 3. TYPES OF PATHOGEN ION FOUND IN AND FILTH CONTAMINAT S PICES ENS FOUND IN SPICES 3.1 MICROBIAL PATHOG 3.1.1 TYPES OF MICRO BIAL PATHOGENS FOUND IN SPICES In order to determine the types of microbial pathogens found in spices, we reviewed the refereed scientific literature and available government/agency reports using Web of Science, Google Scholar, and PubMed to search the English- language literature using different combinations of the following keywords: microbiological, microbial, quality, survey, outbreak, foodborne, spice, seasoning, herb, pathogen, Bacillus , , bovis Campylobacter , Clostridium , Cronobacter , Escherichia coli , E. coli, O157, 0104, Mycobacte rium bovis, Mycobacterium tuberculosis . We , norovirus, Salmonella , sakazakii , Shigella , and Staphylococcus aureus reviewed paper citations and references contained in the articles identified in our search. The literature review examined publications and reports published between January 1, 1985 and July 1, 2012. PulseNet database for information about the types of spices in which Salmonella We also reviewed the CDC 1 has been detected and evidence that other pathogens had been detected in spices. The review for pepper and pepper -type spices (entries including the words “pepper”, “chili”, or “cayenne” and, for the capsicums, clearly indicated as a dry product) included information on isolates uploaded to PulseNet during the period Sept 2001-February 2010 whil e the review for non -pepper spices included information on isolates uploaded between January 2001 and June 2010. Bacteria isolated from food products tested as part of routine food safety surveillance and compliance programs as well as foodborne outbreak i nvestigations in the United “Field Accomlishments and States are normally submitted to PulseNet. Finally, we also reviewed the FDA 2 ) FACTS Compliance Tracking System” ( database for the years 2006 -2010, to identify spices not captured in . the PulseNet review A diversity of microorganisms has been detected in spices . Table 3.1 lists the microbial pathogens detected in spices as reported in the scientific literature, the CDC PulseNet database or the FDA FACTS database during e. A few studies examined selected spices for E scherichia coli O157:H7 the review periods described abov (Singh et al ., 2007; Beki 2008; Kahraman and Ozmen , 2009); none was found. Investigations of the 2011 Shiga E scherichia coli O104 illness outbreak in Europe that was attributed to contaminated -toxin producing fenugreek seeds (used in sprout production) were unsuccessful in detecting the outbreak strain in seeds from the same source (EFSA, 2011c) . Investigations of the Clostridium botulinum out break in Japan in 1984 involving consumption of fried lotus rhizome solid mustard did not isolate the organism from any of the 11 . The report of identified in kinds of mustard samples examined (Otofuji et al ., 1987) Listeria monocytogenes bay leaves (Vij t al. , 2006) was later clarified as a contaminant in fresh bay leaves rather than dried b ay e leaves (Hogan, 2011) . 1 PulseNet is a national network of public health and food regulatory agency laboratories in the United States coordinated by the CDC . The network consists of state health departments, local health departments, and federal agencies (CDC, USDA/FSIS, FDA). Pu lseNet participants perform standardized molecular subtyping (or “fingerprinting”) of foodborne disease- causing bacteria by pulsed -field gel electrophoresis (PFGE) . PFGE can be used to distinguish strains of organisms such as Salmonella . DNA “fingerprints,” or patterns, are submitted electronically to a dynamic database at the CDC . The PFGE data are stored in the CDC PulseNet database. 2 results of experimental food or environmental sampling tests performed by that includes FACTS is an FDA database FDA . FDA Draft Risk Profile | 22

35 Types of Pathogen and Filth Contamination Found in Spices | 3 Micro Table 3.1. in spices, 1985 -2012: Revie w of the scientific literature and bial pathogens detected a and FDA es PulseNet the CDC FACTS databas b bial Pathogens Spice Reference Micro 2003 1997; Banerjee and Sarkar, ajowan, alfalfa seeds, allspice, anise seed, et al., ias Ar ; c CDC DOH/Victoria/AU, 2010; FSAI, ; asafetida, basil, bay, black pepper, capsicum PulseNet - (hot and sweet), cardamom, cayenne, celery 2004; Gustavsen and Breen, 1984; FDA - d ; Hampikyan et et al., 2009; Hara -Kudo seed, cinnamon, coriander, cumin, curry leaf, FACTS fenugreek leaves and seeds, fingerroot, 2006; Higa, 2011 ; Kaul and Taneja, 1989; al,. fennel, Salmonella spp. garlic, ginger, nigella, London rocket, mace, 05; Kneifel and Berger 1994; Koch et al. 20 mint, mustard seed, nutmeg, oregano, parsley, Moreira et al. 2009; Sagoo et al. 2009; Satchell sage, thyme, sumac, sesame seeds, turmeric, 2007; Shamsuddeen, et al. 1989; Singh et al. 2006 2001; Vij et al. et al. white pepper, spice mixes/seasonings (e.g., 2009; Stewart curry, five spice, garam masala) ajowan, alligator pepper, allspice, asafetida, Antai, 1988; DOH/Victoria/AU, 2010; capsicum (hot basil, bay leaf, black pepper, ; Brown and Jiang, 2003 Banerjee and Sarkar, and sweet), caraway, cardamom, celery seed, 2009; FSAI, 2004; Garcia et al., 2008; Cosano 2001; Hampikyan et al., chervil, chives, cinnamon, cumin, cloves, 2009; Kahraman et al., Bacillus coriander, cumin, dill, fennel seeds, fenugreek, spp. and Ozmen, 2009; Kneifel and Berger, 1994; fennel, garlic, ginger, nutmeg, mace, ) B. cereus (including -Domján 1988; Little Kovács 2003; et al., marjoram, mustard seed, nutmeg, onion, et et al., 2009; Pafumi, 1986; Sagoo Moreira oppy seed, oregano, unspecified pepper, p al., 2009; Witkowska et al., 2011 rosemary, saffron, thyme, turmeric, white pepper, spice mixes/seasonings ajowan, anise seed, bay leaf, black cumin, Aguilera e t al ., 2005; Banerjee and Sarkar, black pepper, capsicum (hot and sweet), 2009; Pafumi, 1986; et al., 2003 ; Cosano Clostridium caraway, chives, cinnamon, clove, coriander, -Romo, 1998; Sagoo Rodriguez et al., 2009; Shamsuddeen, 2009 cumin, ginger, fenugreek, garlic, ginger, mace, perfringens mustard seed, nutmeg, onion, oregano, parsley, saffron, white pepper Ahene et al ., 2011; Baumgartner et al ., 2009; et al spp. Iverson and Forsythe (2004); Jarada t ., anise seed, rosemary Cronobacter ., 2011 et al 2009; Turcovský ajowan, bay leaf Banerjee and Sarkar, 2003 Shigella Banerjee and Sarkar, 2003; Hampikyan et al., asafoetida, black pepper, capsicum, Staphylococcus 2009; Kahraman and et al., 2009; Moreira cardamom, cinnamon, garlic, ginger, aureus Ozmen, 2009; Shamsuddeen, 2009 white pepper. a Literature reviewed period: January 1, 1985 through July 1, 2012 PulseNet database was reviewed between Sept. 2001 and . The CDC -type spices and reviewed between January 2001 and June 2010 for non -pepper spices uploaded to February 2010 for pepper and pepper the CDC PulseNet , supplemented by the FDA Salmonella isolate database reviewed during the period 2006 -2010 for spices not database -2010. captured in the CDC PulseNet database review for the period 2006 b Different forms of the same spice or spice mixture are generally not distinguished, e.g., dried coriander leaves and seeds, o r masala r chicken and masala mix for beef . Capsicum may include both hot and sweet varieties such as cayenne, paprika, chili powder, spice mix fo . A single common name was selected for a spice in this table, which and other dried whole or ground spices made from capsicum peppers may differ from the name in the original reference, e.g., ajowan instead of bishop’s weed or omum. c Salmonella isolates from (a) pepper and pepper -type spices (entries including the words “pepper”, “chili”, or “cayenne” and, for the capsicums, clearly indicated as a dry product) uploaded to the CDC PulseNet database between Sept. 2001 and February 2010 and (b) all other spices uploaded to the CDC PulseNet database between January 2001 and June 2010. d isolates from spices sampled by FDA duri Salmonella ng 2006 -2010, reported in the FDA FACTS database. As discussed in Chapter 2, only and Bacillus spp. have been definitively linked to human illness Salmonella . Furthermore, Salmonella contaminati on of outbreaks resulting from consumption of contaminated spices spices has been the leading cause for spice- associated recalls in the United States (1970 -2003: Vij et al. , 2006; 2008-2009: Ma, 2013) and the leading hazard reported for spices and seasonings in the Reportable Food Registry in first three annual rep orts (Sept. 8, 2009 - Sept 7, 2012) (FDA, 2013a; FDA, 2012a; FDA, 2012b). Therefore, as dictated by the scope of the risk profile, the remainder of the risk profile focuses on Salmonella contamination of spices and also addresses contamination by commonly occurring types of filth. FDA Draft Risk Profile | 23

36 Types of Pathogen and Filth Contamination Found in Spices | 3 SALMONELLA SEROTYPES IDENTIFIED 3.1.2 IN SPICES In order to probe the diversity of serotypes found in spices, we focused on isolates from spices Salmonella PulseNet database and the FDA collected in the United States. FACTS Data was gathered from the CDC base database . Two separate analyses of the CDC PulseNet data were performed to identify bacterial . The first analysis, completed in March 2010, -pepper spices pathogens isolated from pepper and non i solated from black pepper, white pepper, and/or capsicum, limiting the latter to dried evaluated Salmonella chili or cayenne pepper . The second analysis was completed in July 2010, and reviewed bacterial pathogens t were labeled as a “spice” in the CDC PulseNet isolated from all other spices . For this analysis, products tha were included in the spice analysis with the following exceptions: herbs also labeled “fresh”, black database pepper, white pepper, chili/cayenne pepper capsicum, and products outside of the scope of the risk profile (e.g., tahini) . Items not labeled as “spice” but which met the risk profile definition of “spice” were included in the analysis (e.g., paprika and sesame seeds) with the following exceptions: herbs labeled “fresh” or not labeled as dry, ground, powdered or otherwise indicated as low moisture. Additional serotypes were identified from the FDA FACTS database, examining years 2006 -2010, including both surveillance and compliance product sampling. Data the CDC PulseNet and FDA FACTS databases are collected from reports in from a number of labs so they may contain errors unknown to the authors. All FDA data submitted to these databases, regardless of the lab in which the data was collected, were first reviewed by a supervisor for accuracy of analysis. . A wide diversity of Salmonella Table 3.2 lists the serotypes and the spices in which they were found serotypes were isolated from domestic or imported spices in the United States or in spice shipments offered for entry to The serotype of some Salmonella isolates from spices the United States between 2001 an d 2010. was not determined, was pending or was not reported from these databases; these isolates were not included . in Table 3.2 a Salmonella species and serotypes found in spices in the United States, 2001 -2010. Table 3.2 . c b Serotype Spice Abaetetuba basil, black pepper, capsicum, curry leaf black pepper, coriander, curry powder, ginger Aberdeen Adabraka coriander capsicum, cumin, curry powder, garam masala, mint, nutmeg, anise, black pepper, Agona oregano, sesame seed Alachua cumin Altona capsicum Amersfoort sesame seed Amsterdam sesame seed Anatum capsicum, coriander, cumin, fenugreek, sesame seed, spice mix Augustenborg turmeric Bahrenfeld cumin, London rocket Ball black pepper, sage Bangkok curry, turmeric Bardo black pepper capsicum, coriander, cumin, curry powder, fennel, ginger, garam masala, sesame seed, Bareilly turmeric, spice/seasoning mix Barranquilla capsicum, pepper Bergen curry powder, sesame seed, spice mix Bere coriander, masala Bispebjerg oregano, sage Blockley basil Bonn sesame seed capsicum Bovismorbificans FDA Draft Risk Profile | 24

37 Types of Pathogen and Filth Contamination Found in Spices | 3 b c Serotype Spice black pepper, turmeric Braenderup Brandenburg black pepper, thyme capsicum Brazzaville capsicum Bredeney Brindisi sage Brooklyn sage Canada black pepper Caracas basil, cumin coriander Carmel Carrau oregano, sesame seed, paprika Cerro capsicum, sesame seed, turmeric Champaign capsicum, chili powder, fenugreek Chandans oregano masala mix, Chingola spice and seasonings coriander Claibornei Colindale cumin Corvallis cumin Cubana celery, coriander, cumin, sesame seed, garam masala Derby black pepper, capsicum, five spice, sage coriander Djibouti Dublin curry Eastbourne turmeric Elokate black pepper Enteritidis black pepper, capsicum, fenugreek, oregano, spice/seasoning mix sesame seed Everleigh Freetown capsicum, cumin, spice/seasoning mix Fresno sesame seed cumin Gamaba Gaminara anise seed, capsicum, coriander, sesame seed Give capsicum, oregano, sesame seed, turmeric Glostrup Sage, sesame seed Gozo capsicum capsicum Grumpensis Haifa basil Havana anise seed, capsicum, coriander, masala, sesame seed Heidelberg black pepper, sesame seed Hermannswerder sage Hindmarsh capsicum basil, black pepper, capsicum, coriander, fenugreek leaf, turmeric, sesame seed, white Hvittingfoss pepper sesame seed, white pepper Idikan capsicum, spice/seasoning mix Infantis turmeric powder Inpraw Istanbul capsicum Javiana allspice, black pepper, cumin, sage, white pepper Johannesburg ginger capsicum, cumin, mint, fennel, sesame seed, thyme Kentucky Kingabwa capsicum Kottbus black pepper, white pepper Kumasi black pepper Lexington ginger oregano Liverpool FDA Draft Risk Profile | 25

38 Types of Pathogen and Filth Contamination Found in Spices | 3 b c Serotype Spice cumin Livingstone Llandoff sesame seed coriander, fenugreek London Luke garam masala oregano, white pepper Madelia cumin Magwa capsicum Martonos black pepper, capsicum, cumin, curry powder, garlic, fennel seed, parsley, sesame Mbandaka turmeric, spice/seasoning mix seed, black pepper, capsicum, coriander, turmeric, spice/seasoning mix Mgulani sage Miami Mikawasima laurel leaf Milwaukee capsicum Minnesota basil, sesame seed capsicum Molade arnica, black pepper, capsicum, coriander, cumin, mint, oregano, nutmeg, sesame Montevideo seed, thyme, spice/seasoning mix capsicum, cumin, thyme Muenchen spice/seasoning mix Muenster cumin Nchanga allspice, black pepper, capsicum, cardamom, coriander, cumin, curry powder, nutmeg, Newport oregano, sesame seed, turmeric, spice/seasoning mix capsicum Nordrhein capsicum, oregano Nottingham cumin Onarimon Onderstepoort cumin, rosemary Oranienburg coriander, oregano, sage capsicum, Orion anise seed, curry powder Oslo black pepper Othmarschen sage capsicum Panama Paratyphi B turmeric, sage, spice mix Paratyphi B var. L(+) tartrate + black pepper, capsicum, coriander, mint, turmeric, spice mix Pomona turmeric black pepper, capsicum, celery, coriander, turmeric, sesame seed, spice/seasoning Poona mix Potsdam cumin, sesame seed Reading cumin d Richmond capsicum, coriander, fenugreek, masala, rosemary , sesame seed, spice/seasoning mix Rissen pper, capsicum, white pepper black pe Rubislaw black pepper, caraway seed, sesame seed, white pepper, spice/seasoning mix Saintpaul coriander, cumin, ginger, mustard, sesame seed, spice/seasoning mix cumin, sage Salford Sandiego black pepper, capsicum, cardamom, coriander, cumin Saugus capsicum Schleissheim sesame seeds, thyme, turmeric Schwarzengrund capsicum, sesame seed, turmeric, spice/seasoning mix black pepper, capsicum, celery seed, coriander, cumin, curry powder, garam masala Senftenberg nutmeg, sesame seed, thyme Simi sage Singapore capsicum , cumin, white pepper Stanley black pepper, capsicum FDA Draft Risk Profile | 26

39 Types of Pathogen and Filth Contamination Found in Spices | 3 b c Serotype Spice curry powder Stormont Sundsvall capsicum, chili powder masala Tallahassee Teddington annatto seed cumin, laurel leaf, mint, sage Telaviv cumin Telelkebir fenugreek leaf, spice/seasoning mix Telhashomer capsicum, celery, sesame seed, spice/seasoning mix Tennessee capsicum, curry powder, spice/seasoning mix Thompson capsicum Treforest Tucson capsicum basil, black pepper, capsicum, coriander, curry powder, dill weed, fenugreek, five Typhimurium spice, ginger, masala, mint, oregano, rosemary, saffron, sage, sesame seed five spice, garam masala Umbilo Urbana black pepper Vejle black pepper basil, black pepper, turmeric, coriander, spice/seasoning mix Virchow d d broccoli powder Wandsworth Warragul sage anise, basil, bay, black pepper, capsicum, coriander, cumin, curry powder, mace, Weltevreden masala, nigella, onion, sesame seed, turmeric, white pepper, spice/seasoning mix sthampton We capsicum Westminster cumin, sesame seed Wichita spice/seasoning mix sesame seed I 3,15,34:d: - II 40:z4,z24: - oregano anise seed, oregano II 40:z4,z24:z39 cinnamon II 48:d:z6 sesame seed IIIa 48:z4,z24: - capsicum, cumin IIIb 60:r:e,n,x,z15 - fingerroot IV 43:z4,z23: VI 6,14:a:1,5 spice mix a isolates from (a) black pepper, white pepper, and chili/cayenne pepper capsicums uploaded to the CDC PulseNet database Salmonella the CDC PulseNet database between January 2001 and June 2010 between Sept. 2001 and February 2010 (b) all other spices uploaded to -2010 in the FDA FACTS database . Data in the CDC PulseNet a nd FDA and (c) additional isolates from spices sampled by FDA during 2006 FACTS databases are collected from reports from a number of labs so they may contain errors unknown to the authors. b enterica subspecies enterica (I) unless noted otherwise Salmonella c Different forms of the same spice or spice mixture are generally not distinguished, e.g., dried coriander leaves and seeds, or masala spice . Capsicum may include both hot and sweet varieties such as cayenne, paprika, chili powder, and mix for chicken and masala mix for beef . A single common name was selected for a spice, which may differ from other dried whole or ground spices made from capsicum peppers the name in the original reference, e.g., ajowan instead of bishop’s weed or omum. d Broccoli powder was the contaminated ingredient in the seasoning mix implicated in the S. Wandsworth outbreak (Sotir et al ., 2009; see also Chapter 2 and Table 2.1). Investigations of the microbiological quality of spices produced and examined outside of the United States have reported some of the same serotypes reported in Table 3.2 but also have identified additional serotypes . For example, Sagoo et al. (2009) identified four additional serotypes associated with isolated from spices spices (Aequatoria, Edinburg, Friedenau These , and Hato) and isolated 13 of the serotypes listed in Table 3.2. studies demonstrate that a wide variety of spices can become contaminated with a wide variety of Salmonella serotypes . We were unable to identify any data to support the hypothesis tha t spice contamination is limited to a subset of Salmonella serotypes . Frequency data for individual serotypes (e.g., numbers of isolates reported) derived from the CDC PulseNet or FDA FACTS databases are not reported because these data cannot be easily int erpreted, e.g., serotypes associated with a large outbreak are likely to have multiple entries arising from sampling during the outbreak investigation and therefore provide no information on FDA Draft Risk Profile | 27

40 Types of Pathogen and Filth Contamination Found in Spices | 3 inated spice supply containing a particular relative prevalence in the spice supply (percentage of the contam Salmonella prevalence in spices (percentage of the spice supply contaminated with Salmonella ), serotype) . including relative prevalence by serotype and antimicrobial resistance, was estimated for shipments of orted spice offered for entry to the United States during FY2007 -FY2009 a imp nd is discussed in Chapter 4. OUND IN SPICES 3.2 FILTH ADULTERANTS F A finding of filth adulteration of spice can arise from the presence of avoidable defects in spice or excessive ncentrations of natural or unavoidable defects in spice. Avoidable defects in spice are extraneous materials, co defined by FDA as “any foreign matter in a product associated with objectionable conditions or practices in and includes “objectionable matter contributed by insects, rodents, and production, storage, or distribution” birds; decomposed material; and miscellaneous matter such as sand, soil, glass, rust, or other foreign substances” (FDA, 2012g) . Spice adulterated with avoidable filth can result in a food being deemed ection 402(a)(1) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) , which “adulterated” under s ection prohibits “any poisonous or deleterious substance that may render it injurious to health, ” or s which pr of the FD&C Act, ohibits foods “prepared, packed or held under insanitary conditions 402(a)(4) whereby it may have become contaminated with filth, or whereby it may have been rendered injurious to tion depends on the nature health.” The concentration of avoidable filth elements that constitute filth adultera case basis. -by- of the adulterant and is determined on a case egulations at 21 CFR 110.110 (FDA, 2012h) address how FDA establish FDA r maximum concentration s of es natural or unavoidable defects in foods for human use that present no health hazard . FDA established Food of specific elements of filth Defect Action Levels (DALs) which define the maximum “levels” (concentrations) es in the in specific foods (FDA, 2013g) . FDA based DALs on an extensive survey of retail foods including spic 1980s and set values to reflect significant deviation from the best practices of industry and agriculture at that . The spices for which a DAL has been established are given in Table 3.3 time . Not all spices have DALs nor have DALs been established for all possible adulterants in a spice . If no DAL has been established for a filth . Spices for which filth Food Defect Action Level(s) has/have been established in the United Table 3.3 States Ground Spice Whole Allspice x x x Bay (Laurel) Leaves Capsicum x x Paprika x Cinnamon or Cassia x x x Cloves x Condimental seeds x Cumin seed x Curry Powder x Fennel seed x Ginger x Hops x Mace Marjoram x x x Nutmeg x Oregano x x Pepper (black or white) x x Sage x x Sesame seeds x Spices, leafy x x Thyme x FDA Draft Risk Profile | 28

41 Types of Pathogen and Filth Contamination Found in Spices | 3 -by- case basis element in a spice then FDA will review the analytical results of filth in that shipment on a case taking into account the types of filth elements found, concentration of the filth element in the sample, and the Spice with excessive concentration risk to public health to determine whether it violates the FD&C Act. s of or unavoidable defects violate s natural ection 402(a)(3) of the FD&C Act, “consisting in whole or in part of any filthy, putrid, or decomposed substance or is otherwise unfit for food” (FDA, 2012h). In order to determine the types of filth adulterants found in spices, we reviewed FDA sampling data (reported FACTS database) for shipments of imported spice offered for entry to the United States during the the FDA in -FY2009. Table 3.4 lists the various filth adulterants that were isolated from spices three year period FY2007 as part of FDA surveillance sampling of spice s hipments offered for U.S. entry, FY2007 - FY2009 . Almost all of stored product pests, which indicate that the spice was the insects that were found in these shipments were prepared, packed, or held under insanitary conditions whereby it became contaminated . Among the insects Monomorium pharaonsis L. monocytogenes isolated from the spices is (L.), Pharaoh ant, a known carrier of , 2001) (Olsen hair fragments without a hair root is generally indicative et al. . The presence of rodent hair or on of spi (Vazquez, 1977) because when grooming, rodents ingest hair and hair of fecal contaminati ce fragments, which are excreted in their feces. Other adulterants may result from improper cleaning of the animal or insect excreta). spices (e.g. staples, sticks, stones) or improper storage (e.g. bird feathers or barbs, Tab le 3.4. Types of f ilth adulterants found in spices: Surveillance sampling of spice shipments offered for U.S. entry, FY2007 -FY2009. Insect Insect Hair Other Common Name Scientific Name L. Acarus siro mite Human hair Animal grain Ahasverus advena (Waltl) foreign grain beetle Bat Animal Fecal Material (LeConte) Cat Animal Hair Ahasverus rectus coffee bean weevil Cow Insect Excreta Araecerus fasciculatus (De Geer) almond moth Dog Bird Barbs Cadra cautella Cheyletus eruditus Mammalian Bird Barbules (Schrank) mouse/rat rusty grain beetle Cryptolestes ferrugineus Bird Excreta (Stephens) (Schonherr) flat grain beetle other Bird Feathers Cryptolestes pusillus Rancid Dienerella costulata (Reitter) Rabbit Enicmus consimilis Rat Moldy Mannerheim Dirt Rodent Eurytoma tylodermatis Ashmead - convergent lady beetle non Hippodamia convergens striated Fiber, Synthetic (Guerin) Laccifer lacca (Kern) Sheep Paper Lasioderma serricorne (F.) cigarette beetle Striated Plastic Lophocateres pusillus (Klug) Siamese grain beetle Rubber Band Monomorium pharaonis (L.) Pharaoh ant Seed Oryzaephilus mercator (Fauvel) merchant grain beetle Staple Saw - toothed grain Oryzaephilus surinamensis (L.) Stick beetle (Hubner) Indian meal moth Stone Plodia interpunctella (F.) lesser grain borer Rhyzopertha dominica Twig Sitophilus granarius (L.) granary weevil Wood Sliver Stegobium paniceum (L.) drugstore beetle (Herbst) red flour beetle Tribolium castaneum Typhaea stercorea (L.) hairy fungus beetle FDA Draft Risk Profile | 29

42 4. PREVALENCE AND CONCENTRATION SALMONELLA AND OF FILTH IN SPICES We reviewed the scientific literature and available government/agency reports for surveillance studies that reported measurements of prevalence and/or concentration of Salmonella and filth in spices at any point -to-table continuum . We also r esearched Salmonella along the farm s found in spice samples concentration associated with foodborne outbreaks as well as antimicrobial resistance found in Salmonella strains that have been isolated from spices. Our literature review primarily used PubMed, Google, and Goo gle Scholar to search the English -language literature using different combinations of the following keywords: Salmonella , filth, prevalence, level, enumeration, spice, herb, microbiological, quality, bacteriological, quality, evaluation, safety, profile, a ntimicrobial, activity, resistance, property, properties, drug, resistant, resistance. We also reviewed citations and references contained in the articles identified in our internet searches on this topic and other references collected during our work on this report (e.g., foodborne outbreaks, Chapter 2). In addition to the literature search, we analyzed FDA surveillance sampling data for Salmonella and filth in imported spice shipments offered for import over a three year period, FY2007 -FY2009. Full deta ils of the sampling protocols and inclusion criteria are provided in Van Doren et al . (2013a) . FDA undertook a targeted sampling assignment to gather information on typical concentration Salmonella . Under this assignment, s of FDA analyzed samples of capsic um and sesame seeds from shipments offered for import to the United States prevalence and Salmonella . Full details of the study design, Salmonella during a five month period in 2010 for . (2013c) concentration . The 2010 study also al results, and data analysis are provided in Van Doren et examined shipments for the presence of filth and these results are compared with the FY2007 -FY2009 study . Finally, we analyzed FDA surveillance data over a ten year period (FY2000 -FY2009) results in Section 4.2.3 to explore Salmonella and filth in imported spice shipments. the potential correlation between presence of Details of the U.S. study are provided in Section 4.3. FDA requested scientific data and information from the spice industry and other stakeholders through a Federal Register Notice announcing the risk profile project, identifying data gaps, and requesting comments and scientific data and information to help fill the data gaps (FDA, 2010e). In response to this request, the American Spice Trade Association subm itted spice sampling data collected in ASTA member spice processing facilities over a two year period by some of its members (ASTA, 2010; Ruckert, 2010). These data are discussed in Section 4.1.4. The discussion that follows summarizes data available from studies around the world on the prevalence and Salmonella concentration of and/or filth in spices . Comparison of prevalence values in different studies is complicated by the fact that each study may have examined a different amount ly leads of spice, which general a different limit to . For this reason, we report the mass examined whenever reporting prevalence of detection values, e.g., 6.6 % (750 g; 95% CI 5.7 -7.6%) . Where possible, we report the 95% confidence intervals (95% CI) for the prevalence values as shown in the previous example. Different studies may have employed different methods of analysis, which can lead to differences in test sensitivities or selectivities . We assume that methods employed in the reported peer -reviewed and government studies h ave been validated and that results among studies are comparable . Interpretation of differences in prevalence or concentration values across studies should consider context (because the spice examined in each study is different) , which we scussion. provide in our di FDA Draft Risk Profile | 30

43 Prevalence and Concentration of Salmonella and Filth in Spices | 4 SALMONELLA 4.1 4.1.1 SALMONELLA PREVALENCE AND CONCENTRATION IN SPICE: FROM FARM TO TABLE OVERVIEW Limited data are available from the scientific literature on the prevalence of pathogens in spices at different -to-tab le continuum. Information provided by studies published during the period 2000 points in the farm - 2012 is summarized in Table All of the values listed in Table 4.1 are from surveillance studies and m ost 4.1. . It is likely that a majority of spices examined in Australia, samples were collected from retail establishments Belgium, Czech Republic, Federal Republic of Yugoslavia, Germany, Hungary, Ireland, Japan, the Netherlands, Slovakia, Slovenia, and the Uni ted Kingdom in these studies were imported because these countries are not major producers of the spices examined . All spices examined in the U.S. study described in Table 4.1 were served imported . Nineteen studies examined samples exclusively from retail; the ob -prevalence in Salmonella spices in these studies ranged from 0 to 10% (3 -135 g; 95% CI 0- . Two studies examined samples of 40%) Salmonella spices exclusively from spice processing/packing facilities; these reported prevalence values ranging from 0 to 1% (25 -135 g; 95% CI 0 – 10%) . Two studies examined spices exclusively from the point of import, finding prevalence values of 0.5 -6.6% (25-750 g; 95% CI cannot be calculated for one study) . Two studies examined “ ”, which we presume to mean spice that had not been subjected to a non-irradiated spices pathogen reduction treatment, and reported prevalence values ranging from 3 to 10% (25 g; 95% CI 0.3- 30%). A majority of the studies summarized in Table 4.1 reported observed Salmonella prevalence values in the range of zero to one percent, regardless of setting, and many of the reported prevalence values reported are the statistically smaller than the value determined in the U.S. study (Fisher exact test, p < 0.05) . Because screening test protocols used in all of the non- U.S. studies examined a smaller mass of spice than that used in the U.S. study , it is likely that at least some of the observed differences Salmonella between the smaller onducted outside the United States versus tests conducted in the United prevalence values reported in tests c States arise from different limits of detection. The smaller prevalence values reported in the different countries and settings may also reflect real differences in prevalence either arising from a difference in the microbiological quality of the spices examined or differences resulting from the application of one or more processes intended to reduce the microbial load. Pathogen reduction treatments such as ethylene oxide, steam treatme nt or irradiation are commonly applied to spices to reduce the risk of microbial contamination (ASTA, 2011; see Section 8.2.1 a discussion of pathogen reduction treatments). Some insight into this latter hypothesis is provided in Section 4.1.3, where the p revalence of Salmonella contamination in spice shipments offered for import to the United States are compared on the basis of applied processes, and in Section 4.1.4, nt is compared Salmonella in spice lots examined post -pathogen reduction treatme where the prevalence of with the value for spice lots pre -treatment . Salmonella prevalence in retail spice samples in the United States is unknown. Neither FDA nor the spice industry collects enumeration data on a regular basis because the regulatory Salmonella s measured in spices and Salmonella concentration standard is absence of . Table 4.2 summarizes products associated with salmonellosis outbreaks attributed to contaminated spices or determined in surveillance studies. While the outbreaks associated with alfal fa seeds were attributed to consumption of alfalfa sprouts, the enumeration data are included in this table because the concentration s were determined in the dry seeds and alfalfa seeds can be consumed as spices. concentration s ranging from 0. 0007 to 11 MPN/g -spice (7 MPN per 10,000 g to 11 MPN per g) Salmonella have been reported as shown in Table 4.2 . Most of the Salmonella concentration s determined for spices in surveillance and outbreak investigations in other countries reported in Table 4.2 are in th e same range as the values for capsicums and sesame seeds determined in the 2010 U.S. surveillance study (Van Doren, et al ., FDA Draft Risk Profile | 31

44 Prevalence and Concentration of Salmonella and Filth in Spices | 4 - and black pepper 2013c) but the largest values, reported for samples of spice gathered during the paprika - ted in Table 4.2 (Lehmacher et al ., 1995; Gustavsen and Breen, 1984), are at least one attributed outbreaks lis order of magnitude larger than the largest values observed in surveillance studies. It should be noted that the concentration s of Salmonella in spice samples analyzed in surveillance and outbreak investigations may not necessarily reflect actual concentration s in food at the time of consumption. s of Salmonella in shipments of imported capsicum or Surveillance data on the prevalence and concentration sesame seed shipments were gathered by FDA in 2010 . These data were used to develop a descriptive model of contamination prevalence and concentration s between -and within - imported shipments of capsicum or . The study found sesame seed offered for entry to the United States and are discussed in Section 4.1.3 shipment mean concentration Salmonella in contaminated capsicum or sesame seed shipments vary s of widely between shipments and that many contaminated shipments contain low concentration s of contaminating organisms (Van Doren et al ., 2013c). The Salmonella s concentration s reported in spices, Table 4.2, are small but not atypical of concentration However, in contrast reported in other foods associated with foodborne salmonellosis (WHO/FAO, 2002). with many other types of foods, spices are consumed in very small amounts during a single eating occasion Salmonella (Section 7.2.2) so the dose expected from consumption of spice during a single eating occasion is expected to be small er than that for other foods with similar concentration s of contamination but consumed in larger quantities. FDA Draft Risk Profile | 32

45 Prevalence and Concentration of Salmonella and Filth in Spices | 4 Salmonella in spices, 2000 Table 4.1. Summary of scientific surveillance studies measuring the prevalence of -2012 Sample Sample Spices containing Prevalence a d c Reference N Country 95% CI Collection Spices sampled e b Size (g) Salmonella (%) Point caraway, chili, cloves, coriander, cumin, fennel, fenugreek, ginger, DOH/Victoria/AU, f 217 0 Australia Retail mustard, nutmeg, sumac, turmeric, 125 0-1 none 2010 Chinese five spice mix, garam masala, other spice mixes not DOH/Victoria/AU, g 25 0.5; 4.9 Australia Import peppercorn; paprika peppercorn; paprika reported 2010; FSANZ, 2001 25 22 0 0 - 10 not reported none EFSA, 2006a Belgium Processing plant bay, basil, black pepper, cinnamon, Retail 25 Brazil 233 5.6 3.0 - 9.4 clove, cumin, dehydrated green onion, . 2009 black pepper, cumin Moreira, et al oregano, parsley Retail/ Czech not reported EFSA, 2006a Production spice 25 74 3 0.3 - 9 non - irradiated Republic Plants geranium, basil, marjoram, jews mallow, peppermint, spearmint, h 297 0 0-1 25 dill, celery, parsley, cumin, caraway, Retail Egypt none Abou Donia, 2008 anise, fennel, coriander, dill, black pepper, chamomile, karkade, saffron Retail 25 20 0 0 - 10 not reported none EFSA, 2006a Estonia bay, basil, black pepper, capsicum, Federal caraway, cinnamon, clove, coriander, Republic of et al Stankovic Retail 25 101 0 0-3 ., 2006 curry, dill, ginger, mustard, nutmeg, none i Yugoslavia oregano, rosemary, sesame, thyme, white pepper sesame seed Brockmann et al ., 40 10 Germany 2 - Retail sesame seed 25 16 2004 25 Hungary not reported EFSA, 2010a 198 1 0.1 - 4 not reported not reported Hungary not reported 25 267 0.4 EFSA, 2009b 0.009 - 2 not reported not reported FDA Draft Risk Profile | 33

46 Prevalence and Concentration of Salmonella and Filth in Spices | 4 Sample Sample Prevalence Spices containing a c d N Country Collection 95% CI Spices sampled Reference e b Salmonella Size (g) (%) Point allspice, aniseed, asafetida, bay bishop’s weed, black cumin, (tejpat), black pepper, caraway, cardamom, Banerjee and Sakar, 1 0.2-5 India Retail celery seed (ajmud), chili, cinnamon, 25 154 ginger, poppy seed 2003 clove, coriander, cumin, fenugreek, garlic, ginger, mustard, poppy, turmeric capsicum, curcuma (including Primarily Pre - f none 125 25 0 0 - 10 Ireland turmeric), ginger, nutmeg, other spices j Retail and herbs FSAI, 2005 capsicum, curcuma (including chili pepper and chili turmeric), ginger, nutmeg, piper spp. powder, curry, sesame 0.93 0.3 - 2 25 Ireland 647 Primarily Retail (e.g., black and white pepper), other j seeds, turmeric spices and herbs allspice, ajowan, anise, artemisia, capsicum, basil, bay leaves, black pepper, capsicum, caraway, celery, Chinese five spice, cinnamon, clove, coriander, cumin, curry powder, curry ., et al -Kudo Hara black pepper, red Japan Retail 25 leaf, dill weed, fennel, fenugreek, 259 0.8 0.09 -3 er pepp 2006 garlic, garam masala, mandarin, mustard, nutmeg, oregano, paprika, parsley, sage, star anise, turmeric, white pepper, other dried peppers, other spice mixtures l 0 Mexico Retail 3 304 ., 2001 0 - 1 bay, cumin, garlic, pepper, oregano none Garcia et al EFSA, 2010b; EFSA, 1857 3.4 2.6 - 4.3 Netherlands not reported not reported 25 Retail 2011d not reported 30 25 27 10 4 Slovakia non - irradiated spice not reported EFSA, 2007a - EFSA, 2006a; EFSA, Slovenia 25 40 0 - 7 none Retail 0 2006b EFSA, 2007a; EFSA, Retail Slovenia 25 30 0 0 - 9 none 2007b EFSA, 2011e; EFSA, - 25 44 0 0 7 Noted as convenience sample none Slovenia Retail 2012 Beki and Ulukanli, allspice, black pepper, cinnamon, Retail 25 75 0 0 - 4 Turkey none 2008 cumin, red pepper FDA Draft Risk Profile | 34

47 Prevalence and Concentration of Salmonella and Filth in Spices | 4 Sample Sample Spices containing Prevalence a d c Collection N Country Spices sampled 95% CI Reference b e Salmonella Size (g) (%) Point Kahraman and Spice Producers black pepper, capsicum, cumin, 25 170 Turkey 0 - 2 none 0 peppermint, thyme and Retail Ozmen, 2009 allspice, black pepper, et al Hampikyan allspice, black pepper, capsicum, ., 2.9 1.5 - 4.9 420 25 Turkey coriander, cumin, Retail coriander, cumin, ginger, white pepper 2009 ginger, red pepper Ulukanli and Retail 25 65 0 0 - 5 basil, mint, thyme none Turkey Karadag, 2010 United ., 2009; et al Willis m 25 1031 2.3 1 0.74 - Retail alfalfa, poppy, sesame alfalfa, sesame seed Willis et al ., 201 3 Kingdom aniseed, allspice, basil, bay, black United f 1.5 - Retail 135 2833 1.1 0.74 pepper, capsicum, cinnamon, coltsfoot, Kingdom , black pepper, allspice coriander, cumin, dill, fennel, cayenne, chili, fenugreek, garam masala, ginger, cinnamon, coriander, Sagoo, ., 2009, lemongrass, mace, mustard, nutmeg, et al cumin, curry, fennel, oregano, parsley, saffron, sage, Little, 201 2 fenugreek, garam United Manufacturing f tarragon, thyme, turmeric, white 132 1 0.2-5 135 masala, mint, okra, Kingdom and Packing pepper, other piper spp. (e.g., green, m sage, turmeric red, mixed), other spices and spice n mixes United spice mix (not ., 2003 et al Little Retail 25 386 0.3 0.1 - 1 spice mixes (not specified) specified) Kingdom Wide variety of spices and spice mixes including basil, black pepper, capsicum, Wide variety of spices and spice mixes cinnamon, coriander, p 2844 6.6 5.7- United States U.S. Import 750 Table 4.3 7.6 (see Table 4.3) cumin, curry powder, fennel, fenugreek, mustard, oregano, sesame seed, turmeric, white pepper Multiple Spice Producer 25 79 0 0 - 4 ., 2009 saffron none Cosano et al Countries a Country were sample was collected. b Total mass examined by Salmonella screening test. c 95% exact confidence limit (Clopper and Pearson, 1934). FDA Draft Risk Profile | 35

48 Prevalence and Concentration of Salmonella and Filth in Spices | 4 d Spices sampled list combines different forms of the same kind of spice under one name (e.g., ground and who le caraway seeds are listed as caraway) and combines related species under one name (e.g., cayenne, chili, paprika, and “red pepper” are listed as capsicum). See reference for more detailed list. e list reports spice name as no Spices containing ted in the reference. Salmonella f -sample mass) -samples per spice sample; total mass examined is listed (i.e., five times sub S tudies tested five sub . g -specific prevalence values for peppercorns (0.5%) and paprika (4.9%). Spice h Does not include tea samples. i Cur rently the State Union of Serbia and Montenegro. j Majority of samples from importers/distributors, producers/blenders, packers/wholesalers or food manufactures/preparers (establishments using large amount of spice). k Salmonella were from retail; one turmeric sample was collected from import/production/wholesaler and the curry powder sample was collect ed Four of six samples testing positive for from an establishment that uses large amounts of spices for food production. l Typhi Salmonella . Samples examined for the presence of m Only includes seed samples (sesame, poppy, and alfalfa). n Sagoo . (2009) reported spice types from all sample collection points together. et al p 25- g sub Protocol involved two screening tests, each 375 -samples). -g composite sample derived from 15 -samples (total of 30 sub Salmonella in spices and spice- containing foods implicated in salmonellosis illness outbreaks of Table 4.2. Concentration Concentration a b N Type of Sample Spice/Food Reference (MPN/g) Outbreak 0.1 - >2.4 12 Gustavsen and Breen, 1984 Black Pepper Lehmacher 2.5 1 et al ., 1995 Paprika Outbreak c containing spice mixtures Outbreak - 0.04 Paprika 11 - Lehmacher et al ., 1995 9 Aniseed containing tea Outbreak 0.036 4 Koch et al ., 2005 - 5 0.04 - 0.45 Outbreak Lehmacher et al ., 1995 Paprika Flavored Potato Chips Tahini, hummus, and sesame seed - helva Outbreak ., 2005 <0.03 - 0.46 10 Unicomb et al d 30 Sprout 0.0007 - 0.016 Alfalfa seeds - Inami et al ., 2001 Outbreak e Outbreak - Sprout < 1 Alfalfa seeds NA Stewart et al ., 2001 f Surveillance (retail) 0.086 Black Pepper and Red Pepper 2 Hara - Kudo et al ., 2006 g 6 Surveillance (retail) <0.1 - 0.2 Sesame seeds and mixtures of seeds Willis et al ., 2009; Willis, 201 3 h et al Surveillance ., 2001 0.0036 30 Inami Alfalfa seeds Capsicum 0.002 - 0.23 18 Table 4.8; Van Doren et al ., 2013c Surveillance (Import into U.S) ., 2013c 0.002 Sesame seed 0.23 23 Table 4.8; Van Doren et al Surveillance (Import into U.S) - a Samples collected as part of salmonellosis illness outbreak investigations or surveillance. Unless otherwise noted, the outbreak was associated with consumption of the spice or low - moisture food containing the spice . b Number of total samples tested. NA indicates the number of samples examined was not reported. c Enumeration measur ements took place approximately 1 year after the salmonellosis outbreak; samples were produced during the outbreak time perio d. d Values reported are for the dry seed. Values in table were derived from data reported by Inami . (2001) using the excel spreadsheet provided in the FDA Bacteriological Analytical et al Manual (Blodgett, 2010). e Values reported are for the seed but seeds were soaked in water for three hours before beginning the enumeration procedure (S tewart et al ., 2001), which may have led to s ome bacterial growth. f -Kudo et al . (2006) (positive screening test and negative MPN tubes) as described in Van Doren et al . (2013c). Value was derived from the observations reported by Hara g Mixtures of seeds contained sesame, pumpkin, sunflower, linseed, and hemp (Willis, 201 3) . Identity of seeds sampled from Willis (201 3); enumeration values from Willis et al . (2009). h Location of surveillance sampling in the seed supply chain was not reported. FDA Draft Risk Profile | 36

49 Prevalence and Concentration of Salmonella and Filth in Spices | 4 TION 4.1.2 PRIMARY PRODUC tudies examining e were unable to identify any s in/on spice producing plants Salmonella W contamination . As a result we can provide no information on the prevalence of in/on spice producing -harvest pre Salmonella plants at this point of production. . (2009) examined 79 25- g samples of saffron spice collected directly from producers from a Cosano et al , placing a 95% CI on the observed prevalence in these samples variety of countries and found no Salmonella . Kahraman and Ozmen (2009) examined 25- g spice samples from producers and of 0 -4% (25 g, Table 4.1) retailers in Turkey (distribution of samples from the different points in the spice food chain was not specified) and found no Salmonella . It is not possible to evaluate the limit on prevalence specific for p rimary production from the reported data but the combined sample set yielded a from Kahraman and Ozmen (2009) 95% CI of 0- The Food Safety Authority of Ireland ( FSAI, 2005) reported finding one 25- g 2%, Table 4.1. sample of turmeric collected from “import or production or packing premises or wholesaler” positive for Salmonella . None of the batch samples (reported in the “primarily retail” sample set listed in Table 4.1) examined from “primarily pre -retail” settings, which included a majority of samples from “import or Salmonella (FSAI, 2005) . As noted above, production or packing premises or wholesaler” tested positive for the sample size examined in these studies was only 25 g, which limited detection to larger concentrations of Salmonella es . in the spice sampl 4.1.3 DISTRIBUTION A ND STORAGE As described in Chapter 6, the supply chain for spices can be compl ex and span long times . Distribution and storage steps can take place at multiple points in the supply chain. Surveillance data on the prevalence and in spices during distribution and storage is limited to evaluations of these Salmonella co ncentration of quan tities at the point of import. W Salmonella e were not able to identify any surveillance studies of s in spices located in storage facilities or at other points of the distribution chain. prevalence or concentration Prevalence data reported between 2000 and 2012 is available from Australia and the United States, Table 4.1 . In Australia, the prevalence of Salmonella in peppercorns (type not specified) collected at the point of import, was determined to be 0.5% (25 g) while that for paprika was 4.9% (25 g) (DOH/Victoria/AU, 2010) . Without knowledge of the total number of samples examined, it is not possible to determine whether the observed differences these two types of spice are significant or whether the observed prevalence in prevalence for values determined in Australia are statistically different f rom those in the United States. As noted in Table 4.1 the study by the Food Safety Authority of Ireland (FSAI, 2005) included batch and single samples from “import or production or packing premises or wholesaler” as well as from other p oints in the spice supply chain. One 25 -g sample of turmeric collected from “import or production or packing premises or wholesaler” Salmonella in Ireland tested positive for Salmonella (FSAI, 2005). Reports of -positive spice samples in the FDA RFR also provide information Salmonella -positive spice samples found in FDA - on the frequency of store registered facilities, which include facilities that distribute, manufacture, process, pack/re-pack, and Data from the first three years of the RFR are described in Section 4.1.2 . Food recalls associated with spices. Salmonella -positive spice may resu lt from samples collected during distribution or storage and these are described in Section 4.1.6. SALMONELLA IN SHIPMENTS OF IMPO RTED SPICE OFFERED F OR ENTRY TO THE UNITED 4.1.3.1 STATES Data reported in this section were derived from two studies of FDA surveillance sampling data unless otherwise noted: (1) review of results of the annual sampling program for the three years FY2007 -FY2009 and (2) review of sampling results from a targeted sampling assignment in 2010 (August -December) that in shipments of imported capsicum and sesame seed offered for entry Salmonella focused on enumeration of FDA Draft Risk Profile | 37

50 Prevalence and Concentration of Salmonella and Filth in Spices | 4 Food Microbiology (Van Doren to the United States. Full reports of both studies were originally published in et et al. al. ese studies are compared with an earlier study of , 2013c) , 2013a; Van Doren . The data from th et al prevalence in spice shipments offered for import to the United States (Satchell Salmonella ., 1989) and other relevant data. in shipments of imported s pice offered for entry to the United States , Observed prevalence of Salmonella FY2007 -FY2009 - Salmonella prevalence in imported spice shipments offered for entry to the United States during FY2007 7.6%), Table 4.3. This value does not differ statistically from the value FY2009 was 6.6% (750 g; 95% CI 5.7- determined by FDA for examination of a set of 31 imported spice shipments offered for entry to the United et al ., 1989) . These States during the period March 1987- January 1988, 6% (750 g; 95% CI 0.8-20%) (Satchell blished studies to examine the prevalence of two studies are the only pu contamination of spices in Salmonella the United States. During FY2007- FY2009, sampled imported spice shipments offered for entry to the United States were 1.9 times more likely to be found contaminated than sampled shipments of all other FDA -regulated foods offered 3 for U.S. entry combined (relative risk (RR), 95% CI 1.6 -2.3; Fisher exact test for difference, p<0.001) . Interpretation of this value is complicated by the fact that a number of different sampling protocols were -regulated foods other than spices and these differences could lead to used for imported shipments of FDA test sensitivity differences . Comparing only data for shipments that were sampled with the same FDA Category II food sampling protocol used for spices (Andrews and Hammack, 2003), we found an even larger RR for contamination of imported spice shipments as compared with shipments of other imported FDA - RR = 4.4 (95% CI 3.4- . The larger prevalence of regulated foods: 5.8; Fisher exact test for difference, p<0.001) Salmonella in imported shipments of spices as compared with other imported FDA -regulated foods can be surprising to some because the low water activity of spices does not support growth, whereas the Salmonella high water activity o f some other imported FDA -regulated foods will support growth when other conditions for growth are met (e.g., nutrients and pH) (FDA, 2012d) . Further, many spices have inhibitory compounds ., 1999; Ceylan and et al that provide antibacterial activity against Salmonella (Arora and K aur, 1999; Hammer ., 2011; Fung, 2004; Indu et al ., 2009a and 2009b; Tajkarimi et al ., 2010; Hussien et al ., 2006; Du et al discussed in Section 5.1.2) . These compounds can limit growth and survival of Salmonella in (wet/inoculated) spices and foods containing spices or their essential oils under some conditions (Arora and Kaur, 1999; Hammer et al ., 1999; Ceylan and Fung, 2004; Indu et al ., 2006; Du et al ., 2009a and 2009b; Tajkarimi et al ., 2010; Hussien ., 2011) . Clearly, other factors, including the ability of Salmonella to survive in a variety of et al low moisture foods including some, if not all, spices (Podolak et al ., 2010; Lehmacher et al ., 1995; Keller et al ., 2013), are more important in determining the prevalence of Salmonella in imported spice shipments offered for entry to the United States. Impact of spice properties on observed prevalence of in shipments of imported s pice offered Salmonella , FY2007 for entry to the United States -FY2009 - Spices are derived from a variety of plant parts, which may result in differences in exposure to pathogen containing wildlife, insects, and soil during growth, harvest or primary processing. In order to determine hipments contaminated with whether these differences influence the proportion of imported spice s Salmonella , we grouped spice screening test results by plant part, Table 4.3 . Spices derived from plant fruits, such as black pepper , white pepper , and capsicums, or plant seeds, such as cumin, mustard and sesame, were grouped together in the fruit/seed category . Spices derived from plant roots included dried roots, such as turmeric and ginger, as well as dehydrated onion and garlic . Examples of spices included in the leaf category are oregano, basil, and varieties of mint . Exampl es of spices included in the bark/flower category include cinnamon/cassia, cloves, and saffron. Data for shipments in which the plant part was ambiguous were excluded from this part of the analysis, e.g., shipments described as “coriander” but lacking info rmation as to whether it was the seed or leaf . 3 R elative risk is the ratio of prevalence values. FDA Draft Risk Profile | 38

51 Prevalence and Concentration of Salmonella and Filth in Spices | 4 Table 4.3 –contaminated shipments of imported spice and other . Observed prevalence of Salmonella -FY2009. imported FDA- regulated food shipments offered for entry to the United States, FY2007 95% Confidence # Shipment Salmonella a N Interval Prevalence (%) Spice/Food Positive b 2844 All Imported Spices 6.6 - 7.6 187 5.7 b 600 17508 3.4 regulated Foods 3.2 - 3.7 - All other Imported FDA c Categories of Spices d 8.0 6.3 5.1 - 1465 92 Fruit/Seed d 15 202 7.4 Root - 12 4.2 d 6.8 18 160 11 - 17 Leaf d Bark/Flower 66 2 0 - 10 1 subjected to Spices different processes Spices subjected to a Pathogen Reduction e 4 137 3 Treatment 0.8 - 7 e 2707 6.8 183 5.8 - 7.8 Spices Not Treated/Not Known if treated f 5.4 790 Spice Blend 4.0 - 7.3 43 f 7.1 141 1999 - 6.0 - 8.3 Spice Not Blend 131 1658 Ground/cracked Spice 6.6 - 9.3 7.9 Whole Spice 51 884 5.8 4.3 - 7.5 g Specific Spices h Capsicum 492 7.1 5.0 - 9.8 35 - 1 1 0 73 7 Cinnamon/Clove/Nutmeg 16 110 15 Coriander - 23 8.5 138 8.0 11 4.0 - 14 Cumin 17 195 8.7 5.2 - 14 Curry Powder 1 112 2.7 - 8 3 Fennel/Fenugreek/Mustard 10 82 12 6.0 - 21 Oregano/Basil 291 4.5 13 2.4 - 7.5 Pepper, Black 0 1 87 1 - Pepper, White 6 Sesame Seed 177 11 7.0 - 17 20 3 118 7 - 10 8 Turmeric i Seasonings, NEC 4.7 32 685 Spices/Spices and 3.2 - 6.5 284 7.0 20 4.4 - 11 All Other spices a 95% exact confidence limit (Clopper and Pearson, 1934). b All shipments of imported FDA Salmonella -regulated spices or other imported foods that were sampled during the study period. screening tests for spices examined 750 g of spices; screening tests for all other FDA -regulated foods examined 375, 750, or 1500 g of food, depending on the FDA food category (Andrews and Hammack, 2003). c Categorizations derived from product code (FDA, 2012j) and description . When description was insufficient to categorize, the sample was not included . d Categorization of spice shipment based on the part of the plant from which it is derived . e Spice shipment classified as “commercially sterile”, “heat treated” or “irradiated” and those in which the product description identified treatment (e.g., “treated with steam” or “treated with ethylene oxide”) are categorized as “Treated Spices .” All other spices are categorized as “Not Treated/Not Kno wn if treated .” f The category “Spice Blend” includes shipments of spice mixtures while “Spice Not Blend” includes shipments of a single type of spice. g Different forms of spices with the same name, such as dried coriander leaves and seeds, are grouped t ogether. h Capsicum includes paprika as well as hot and other sweet dried capsicum peppers. i Shipments of spices “not elsewhere classified” (NEC) in the product code (FDA, 2012j) are assigned to “Spices, NEC”, “Spices and Seasonings, NEC”, or “Mixed Spic .” es and Seasonings, NEC Prevalence values among the plant part categories ranged from a mean of 2% (750 g; 95% CI 0 -10%) for spices derived from the bark/flower of the plant to 11% (750 g; 95% CI 6.8- 17%) for spices derived from plant leaves and differ ences among some of the categories are significant (chi -square test statistic for . Application of the multiple proportions (8.8) > chi -square critical value (7.8) at the 95% confidence level) Marascuilo procedure establishes that a (statistically) larger proportion of imported shipments of spices in both leaf and fruit/seed spice categories offered for entry to the United States are contaminated with FDA Draft Risk Profile | 39

52 Prevalence and Concentration of Salmonella and Filth in Spices | 4 than imported shipments of bark/flower spices. Because 95% of the bark/flower samples Salmonella examined were either cinnamon/cassia or clove, the difference could arise from reduced test sensitivity for st (Arora and Kaur, 1999; Salmonella these spices (Section 2.2), the antibacterial activity of these spices again ., 2009a; Tajkarimi Ceylan and Fung, 2004; Du ., 2010; Hussien et al ., 2011), or differences in et al et al Salmonella growing/processing conditions, including . Reduced test sensitivity and antibacterial exposure activity Salmonella (Hammer et al ., 1999; Burt, 2004; Du et al against et al ., 2010) were not ., 2009b; Tajkarimi sufficient to significantly limit the prevalence of Salmonella in imported shipments of oregano and allspice in the U.S. study; the shipment prevalence of Salmonella for these two spices was 12% (750 g; 95% CI 5.8-22%). Salmonella frequency and prevalence in shipments of specific types of imported spices was also evaluated, . Values are presented for spices for which there were at least 65 shipments examined during the Table 4.3 year period. In this section of Table 4.3, different spices with the same common name, such as three- . “Capsicum” includes paprika as well as hot and other sweet coriander seed and leaf, were grouped together s. In a few cases, we grouped results for different spices together in order to be able to dried capsicum pepper include these data in Table 4.3 and meet the minimum number of shipments. We included the “spices/spices and seasonings, NEC (not elsewhere classified)” category bec ause “NEC” products codes are commonly assigned to imported spice shipments and this category includes less common spices and spice mixtures. -6%) or the sum Observed prevalence values ranged from 1%, for shipments of white pepper (750 g; 95% CI 0 of shipme nts of cinnamon/cassia, clove and nutmeg (750 g ; 95% CI 0- 7%), to 14% (750 g; 95% CI 8.3- 22%) for coriander . Application of the chi square test for multiple proportions indicates that the prevalence values for the different types of spices are not all the same (test statistic (50.8) > chi -square critical value (21.03) at the 95% confidence level) . However, there are not enough data for each type/category of spice to identify airs of spice types that were which differences are significant; the Marascuilo procedure did not identify any p statistically different. Additional research is needed to distinguish prevalence values among the spice types but these data demonstrate that shipment contamination is common among a wide range of spice Salmonella . types The -specific prevalence values in Table 4.3 can be compared with values determined for these spices in spice other countries . Moreira et al . (2009) found major brands of retail black pepper collected in Botucatu, San Paolo, Brazil between January 2004 and Apr il 2006 to have a statistically larger prevalence (18%, 25 g; 95% CI 1 -30%, p <0.001) than that found in imported black pepper shipments in this report, even though the Brazilian screening test protocol was less sensitive (examined 25 g as compared with 75 0 g). While Brazil is a major global producer of black pepper, only 3 (1%) of the black pepper shipments examined in the U.S. study were imported from Brazil. Willis et al. (2009) found a smaller Salmonella prevalence for sesame seeds at retail in the Unit ed Kingdom (1.7%; 25 g; 95% CI 0.9-2.9%) than that found in the U.S. study (p<0.001) . In this U.K. study, the mass of spice examined in the screening test was smaller than that used in the U.S. study (25 g ., 2009; Van D as compared with 750 g; Willis et al oren , 2013a; Table 4.1), which could have led to the et al. smaller observed prevalence value. Impact of processing on observed prevalence of in shipments of imported s pice offered for Salmonella entry to the United States -FY2009 , FY2007 The frequency and prevalence of Salmonella in shipments of spices that had undergone different processes, including pathogen reduction treatments, blending, or grinding, are compared to those for spices that had not undergone the process in Table 4.3 e shipments which were classified as “commercially sterile”, “heat . Spic treated”, or “irradiated” or for which the industry supplied product description specified that a pathogen reduction process treatment had been applied to the spice (for example, “steam treated” or “treated with ethylene oxide”) were grouped together in Table 4.3 as “Spices subjected to a Pathogen Reduction Treatment.” A more detailed analysis of these data was precluded because some of these classifications do not differentiate among treat ment types and the total number of shipments in this group was small . All other shipments were grouped in “Spices Not Treated/Not known if treated .” We do not know whether the small portion of imported spice shipments number of spice shipments in this category is a true reflection of the pro that have been subjected to such treatments because importers are not required to provide process FDA Draft Risk Profile | 40

53 Prevalence and Concentration of Salmonella and Filth in Spices | 4 treatment information unless the spice shipment has been irradiated and even in this case, the FDA product code builder (FDA, 2012j) allows importers to choose other ways of defining their product. Therefore, it is possible that the “Spices Not Treated/Not known if treated” group includes spice shipments that had U.S. entry undergone a pathogen reduction treatment before . Salmonella prevalence for spice shipments subjected to a pathogen reduction treatment before The observed U.S. entry was approximately one- half that for shipments of spices that were not treated or for which no treatment information was provided but the dif ference is not statistically significant (Fisher Exact Test) . The confounding of treated and untreated spice shipments in the “Not treated/Not known” category could be . What is more important is the fact that shipments of responsible for the similarity of these prevalence values “treated” spices were found to contain Salmonella . Effective pathogen reduction treatments should not leave bacteria in the spice . Sagoo et al any viable Salmonella . (2009) also reported finding “treated” spice samples at retail in the United Kingdom with unsatisfactory microbiological quality but did not note whether . Salmonella contamination of “treated” shipments could reflect insufficient pathogen Salmonella was found . No in -treatment contamination reduction treatment and/or post formation was available on whether the treatment processes applied to the spices had been validated and as is discussed in detail in Section 8.2.1, different treatment processes and treatment conditions can result in very different net reductions in microb ial populations. The prevalence for shipments of blended spices (mixtures) was statistically similar to that for Salmonella non-blended spice shipments . Similarly, shipments of ground/cracked spice were not found to have statistically different prevalence values than shipments containing whole spice . While no differences were apparent when comparing the average prevalence for these different categories of spice shipments across all . For example, larger prevalence types of spices, significant differences did exist for some types of spices values were found for shipments of imported ground/cracked capsicum and coriander shipments as compared with their whole counterparts, Table 4.4, with relative risks of contamination of 11 (750 g; 95% CI, ∞ ) respectively . In contrast, differences in shipment prevalence were not 2- 220) and >10 (750 g; 95% CI , 2- . In , Table 4.4 observed for ground/cracked cumin or black pepper as compared with their whole counterparts . (2009) found that a larger proportion of spice flakes had unsatisfactory the United Kingdom, Sagoo et al microbiological quality than those in their whole form, but did not specify whether this difference was primarily related to Salmonella presence/absence. There are a number of hypotheses that can explain the differences in observed prevalence for ground/cracked versus whole forms of capsicum or coriander ., introduction of Salmonella during the grinding/cracking process or more efficient detection of observed (e.g in these ground spices due to dispers Salmonella ion of originally highly localized contamination); additional research is needed to distinguish among them. Salmonella -contaminated shipments of some whole Table 4.4. Comparison of observed prevalence of and ground/cracked imported spice offered for entry to the United States, FY2007 -FY2009. a a Ground/Cracked Spice Whole Spice Salmonella Relative Risk Salmonella # N (RR) Shipment Spice Shipment # Positive N Positive b Prevalence (%) Prevalence (%) [95% CI] 1 122 0.8 33 366 9.0 11 [2 - 220] Capsicums Coriander 0 43 0.0 16 24 >10 [2 - ∞ ] 68 3] Cumin 5 59 8 6 79 8 0.9 [0.2 - Pepper, Black - 7 156 4 6 135 4 1.0 [0.3 3] a . When description was insufficient to categorize, the sample Categorizations derived from product code (FDA, 2012j) and description was not included . b Relative risk of shipment contamination for ground/cracked spice as compared with whole spice ; 95 % exact confidence limit (Clopper and Pearson, 1934). FDA Draft Risk Profile | 41

54 Prevalence and Concentration of Salmonella and Filth in Spices | 4 Salmonella Impact of source country on observed prevalence of ted s pice offered in shipments of impor -FY2009 for entry to the United States , FY2007 In order to examine whether the “country of origin” impacts the observed prevalence of Salmonella contamination of imported spice shipments offered for entry to the United States , values were determined for spice shipments imported from different countries without regard to spice type. In most cases, the exporting country is the country where the spice was grown, dried and, if applicable, processed but in some cases, the export country of recor d is not the country where the spice was grown. Shipments from 79 different countries were examined during the study period; contaminated shipments e from 37 different countries. Contamination of spice shipments is not limited to only a few source cam countries. Salmonella shipment frequency and prevalence values by country are provided in Table 4.5; only -specific prevalence countries for which at least 65 imported shipments were examined are included. Country 5%) for spice shipments imported from Canada to 14% (750 g; values range from 0.9% (750 g; 95% CI 0- Application of the chi -square test for multiple 95% CI 8.6- 21%) for shipments imported from Mexico. prevalence values among this set of countries are not all Salmonella proportions determined that the et al. , 2013a). More research is needed to understand the differences in statistically similar (Van Doren in spice imported from some countries. prevalence of Salmonella Salmonella -contaminated imported spice shipments offered for . Observed prevalence of Table 4.5 entry to the United States as a function of export country, FY2007 -FY2009 Salmonella a Exporting Country Shipment # Positive 95% Confidence Interval N Prevalence (%) 1 110 0.9 0 - 5 Canada 9 245 4 2 - 7 China India 1057 8.7 7.1 - 11 92 Indonesia 82 2 2 0 - 9 21 Mexico 19 136 14 8.6 - Pakistan 205 3 1 - 6 6 Thailand 111 5 6 2 - 10 Vietnam 7 149 5 2 - 9 b 45 749 6.0 All other countries 4.4 - 8.0 a 95% exact confidence limit (Clopper and Pearson, 1934). a Totals 71 other countries for which fewer than 65 imported shipments were examined per country during FY2007 -FY2009. Willis . (2009) found the Salmonella prevalence for retail samples of seeds sold in the United Kingdom et al was smaller for seeds imported from the European Union member countries than for seeds imported from ments from non-European Union member countries. Making the same comparison, we find that spice ship Salmonella prevalence value than European Union member countries did not have a statistically smaller shipments from non- European Union member countries (p>0.05), but we note that the total number of shipments from these European Union member co untries was small (79). Salmonella serotype diversity i solated from s pices in shipments of imported s pice offered for entry to the United States, FY2007 -FY2009 Salmonella serotypes were identified (or partially identified) for isolates from most of the contaminated spice shipments (180/187). Multiple serotypes were identified in 12% (22) of the contaminated shipments yielding a total of 204 unique isolates. Nearly all of t he isolates characterized were determined to be Salmonella enterica subspecies enterica . Six isolates were characterized as Salmonella enterica subspecies II, IIIa or IIIb, Table 4.6. The serotype Salmonella Rissen was not among the serotypes identified fr om Salmonella isolates examined in this surveillance study despite its association with a large scale outbreak attributed to contaminated imported white pepper that took place during the study period ( CDPH/FDB/ERU, 2010). It was samples associated with the outbreak. isolated from investigative FDA Draft Risk Profile | 42

55 Prevalence and Concentration of Salmonella and Filth in Spices | 4 The data in Table 4.6 establish that shipments of imported spices can be contaminated by a wide diversity of Salmonella serotypes. The most frequently observed serotype during the three year study was Salmonella Welt evreden, which constituted only 6.3% of all isolates characterized. Other studies have also reported a wide diversity of serotypes found in spices (Lehmacher ., 2009; Willis et al ., 2009) . The et al ., 1995; Sagoo et al Salmonella serotypes is also not observation that a single sample of sp ice can be contaminated with multiple . (1995) isolated eleven different serotypes . unusual. In one paprika sample, Lehmacher et al a Table 4.6 . Salmonella serotype frequency and percentage among isolates in surveillance samples of -FY2009. spice from shipments of imported spice offered for entry to the United States, FY2007 # unique % of unique Spice Serotype b b Isolates Isolates anise, bay, capsicum, coriander, curry powder, 13 6.3 seasonings NEC, onion, sesame seed, spices and Weltevreden white pepper capsicum, cumin, curry powder, oregano, sesame 12 5.9 Newport seed, spices NEC capsicum, cumin, curry powder, garlic, sesame 5.4 Mbandaka 11 seed, spices and seasonings NEC anise, black pepper, capsicum, cumin, curry 4.9 Agona 10 powder, oregano capsicum, coriander, cumin, curry powder, fennel, 8 4 Bareilly ginger 3 allspice, capsicum, coriander, mint, spices NEC 6 Montevideo curry powder, sesame seed, spices and seasonings 3 Senftenberg 6 NEC basil, black pepper, coriander, curry powder, five 3 Typhimurium 6 spice mix, 5 Anatum 2 capsicum, cumin, sesame, spices NEC Aberdeen 4 2 ginger, coriander, curry powder Cubana 2 celery, spices and seasonings NEC 4 Give 4 2 capsicum, oregano, sesame seed Hvittingfoss 4 2 basil, coriander, spices NEC, turmeric Mgulani 4 2 capsicum, spices and seasonings NEC capsicum, coriander, mint, spices and seasonings Paratyphi B var. L(+) tartrate + 4 4 NEC Rubislaw 2 black pepper, spices NEC 4 2 capsicum, sesame seed, spices and seasonings NEC Tennessee 4 4 2 basil, spices and seasonings NEC, turmeric Virchow Derby 1 black pepper, five spice mix, sage 3 Enteritidis 3 1 black pepper, spices and seasonings NEC Poona 3 1 celery, coriander, turmeric Sandiego 3 1 cardamom, coriander, cumin 3,10:b: - 2 1 capsicum, sesame seed Bere 2 1 coriander, spices and seasonings NEC Bergen 2 1 curry powder, spices and seasonings NEC 2 Cerro sesame seed, turmeric 1 Havana 1 sesame seed, spices and seasonings NEC 2 1 allspice, black pepper Javiana 2 2 Kentucky cumin, sesame seed 1 London 2 1 coriander, fenugreek Saintpaul 2 1 cumin, mustard Schwarzengrund 1 capsicum, turmeric 2 II 40:z4,z24:z39 2 1 anise, oregano IIIb 2 1 mint, spices NEC Barranquilla 1 0.5 capsicum 1 0.5 sage Brindisi cumin 39:z10:z6 1 0.5 FDA Draft Risk Profile | 43

56 Prevalence and Concentration of Salmonella and Filth in Spices | 4 # unique % of unique Spice Serotype b b Isolates Isolates 1 0.5 spices NEC 43:z4,z23: - 1 0.5 curry powder 47: z4, z23: - 0.5 cinnamon/cassia 48:d:z6 1 1 spices NEC 6, 14 : a : 1, 5 0.5 1 0.5 capsicum 6,7,14:e,n,z15 1 0.5 basil Abaetetuba 1 0.5 coriander Adabraka 1 Altona capsicum 0.5 1 0.5 black pepper Ball 1 0.5 Bangkok spices and seasonings NEC 0.5 sesame seed Bonn 1 1 0.5 black pepper Braenderup Brazzaville 0.5 capsicum 1 Bredeney 1 0.5 capsicum 1 0.5 black pepper Canada 1 0.5 coriander Carmel 1 0.5 oregano Carrau 1 0.5 curry powder Dublin 0.5 turmeric Eastbourne 1 1 0.5 black pepper Elokate Freetown 0.5 spices NEC 1 1 0.5 cumin Gamaba 0.5 coriander Gaminara 1 1 0.5 Glostrup sesame seed Hermannswerder 1 0.5 sage 1 0.5 sesame seed Idikan Lexington ginger 1 0.5 Llandoff 0.5 sesame seed 1 1 0.5 capsicum Martonos 0.5 basil Minnesota 1 1 0.5 Molade capsicum Muenchen 1 0.5 capsicum 1 0.5 spices and seasonings NEC Muenster Nordrhein 1 0.5 capsicum Nottingham 0.5 oregano 1 0.5 Oranienburg oregano 1 Orion 1 0.5 curry powder Othmarschen 1 0.5 spices NEC Paratyphi B 1 0.5 turmeric Potsdam 1 0.5 sesame seed 0.5 Richmond 1 spices and seasonings NEC Simi 0.5 sage 1 1 0.5 capsicum Stanley 0.5 capsicum Sundsvall 1 1 0.5 Telelkebir cumin Telhashomer 1 0.5 fenugreek 1 0.5 five spice mix Umbilo Vejle 1 0.5 black pepper Westminster 0.5 sesame seed 1 0.5 Wichita spices and seasonings NEC 1 IIIa 48:z4,z24: 1 0.5 sesame seed - IIIa 1 0.5 capsicum a subspecies enterica unless otherwise note; partial serotypes included. Where appropriate, serotype names reported Salmonella enterica have been combined in this frequency table e.g., “Sieburg” is listed with Cerro, as compared with the table presented in Van Doren et al. , 2013a. b For each spice shipment sampled, the number of unique isolates identified is the number of different serotypes identified. Th erefore, the number (percent) of isolates is the number (percent) of contaminated spice shipments found with that serotype. FDA Draft Risk Profile | 44

57 Prevalence and Concentration of Salmonella and Filth in Spices | 4 Salmonella isolates from all FDA Similar serotype diversity has been observed among -regulated imported ., 2003; Zhao foods (Zhao . Further, the most common serotypes found in spice shipments et al et al ., 2006) offered for entry to the United States do not appear to differ substantially from those reported for all types of entry and sampled by FDA (Zhao -regulated imported food shipments offered for . 2003, Zhao et al . FDA et al 2006) . For example, Weltevreden and Newport were the two most common serotypes isol ated from imported -FY2009 (U.S. study) and were among spice shipments offered for entry to the United States during FY2007 the top four serotypes isolated in 2000 and 2001 from examined imported shipments of FDA -regulated foods . 2006) ., 2003; Zhao, offered for U.S. entry (Zhao . These data support the hypothesis that the et al et al . serotypes most frequently isolated from imported spices are not specific to or preferentially found in spices and other imported FDA A more detailed comparison of serotype prevalence values for spices -regulated foods is not possible because of the significant differences in sample design between the FDA FY2007 -FY2009 et al. , 2013a) and the studies of Zhao and coworkers (Zhao ., 2003; Zhao et al ., 2006; study (Van Doren et al 2008), where data for spices and targeted samples, such as samples collected as part of an outbreak Zhao, . Inclusion of targeted samples in the analysis of investigation, were included in the summary statistics serotype prevalence will generally bias values to serotypes associated with the triggering event because multiple samples of the same food source are sampled . Salmonella serotypes isolated from spices offered for import to the United States We can also compare the with those isolated from food samples in other countries . Among the 42 serotypes isolated from food samples -2009 in Asia (a major source of spices for the United States collected during 2007 ) and reported to the World (WHO) Global Foodborne Infections Network (WHO/GFN, 2012), half were also isolated Health Organization from spices in the U.S. study (Table 4.6) . The serotype diversity observed for isolates from spices offered for import to the United States and imported FDA -regulated foods in general, differs in character with that generally observed for isolates from animal meats for which a small number of predominant serotypes is common (USDA/FSIS, 2012; FDA, 2012a; FDA, . The much ., 2005) 2012c; Sasaki et al ., 2012; Guo et al ., 2011; Yang et al ., 2010; Kudaka et al ., 2006; Cui et al wider diver sity of Salmonella serotypes found in spices may be a reflection of a much wider diversity of - contamination sources, such as soil, water, rodents, birds, and insects, as compared with that for animal derived meat products. Salmo nella isolated from spices in s Antimicrobial r of imported s pice offered for esistance of hipments -FY2009 entry to the United States, FY2007 Salmonella isolates from imported spice shipments offered for entry to the United Fourteen (6.8%) of the -year study per FY2009 were found to exhibit antimicrobial resistance, iod FY2007- States during the three Table 4.7 . Approximately half (8/14) of the isolates with antimicrobial resistance were found to be resistant . Two isolates ( Salmonella serotypes Agona and Ne wport) were resistant to to three or more antimicrobials . Perhaps most importantly, approximately one -quarter of the resistant strains (4/14) seven antimicrobials -line antimicrobial agents used to treat salmonellosis in some populations (Guerrant et were resistant to first al ., 2001; Thielman and Guerrant, 2004): trimethoprim/sulfamethoxazole (2) and ceftriaxone (2) . None of the -line antimicrobial for salmonellosis (Guerrant ., isolates was resistant to ciprofloxacin, another first et al acid (8/14), which has been found to be an indicator of low 2001), although many were resistant to nalidixic level resistance to fluoroquinolones (Rodriguez et al ., 2005; Threlfall et al ., 2006) and may be a first -Avial step towards the development of resistance to ciprofloxacin (Van Looveren et al ., 2001). Other common antimicrobial resistances exhibited among the resistant isolates were to sulfisoxazole (10/14), tetracycline . No (9/14), chloramphenicol (6/14), streptomycin (5/14), kanamycin (4/14) and ampicillin (3/14) resistance was observed among the isolates to amikacin, amoxicillin/clavulanic acid, or cefoxitin. The isolation of highly resistant Salmonella strains from spices has been reported by others (Zhao et al ., 2006, Zhao, 2008; Brockmann et al ., 2004) including Salmonella Typhimurium DT 104, w hich was involved in the et al 2001 salmonellosis outbreak associated with sesame seed -helva consumption (Fisher ., 2001; Brockmann, 2001; Little, 2001; Guérin, 2001) and is characteristically resistant to ampicillin, FDA Draft Risk Profile | 45

58 Prevalence and Concentration of Salmonella and Filth in Spices | 4 ide and tetracycline (ACSSuT) chloramphenicol, streptomycin, sulfonam . This phenotype was observed in one isolate each of serotype Typhimurium and Agona in the U.S. study, Table 4.7. Salmonella The prevalence of antimicrobial resistant Salmonella strains in imported spices contaminated with doe s not appear to be larger than that found for strains isolated from imported FDA -regulated foods in et al general (Zhao ., 2006; Zhao, 2008) and is smaller than that reported for retail meats in et al ., 2003; Zhao et al et al ., 2012) or in China (Yang the United States (USDA/FSIS, 2012), Japan (chickens; Sasaki . 2010) . As with the serotype diversity, the smaller antimicrobial resistance profile for spices as compared with retail meats is consistent with a much wider diversity of contamination sources. FDA Draft Risk Profile | 46

59 Prevalence and Concentration of Salmonella and Filth in Spices | 4 Table 4.7 . Antimicrobial Resistance of enterica subspecies enterica isolates from FDA surveillance sampling of spices from Salmonella shipments of imported spice offered for entry to the United States, FY2007 -FY2009. tamicin Cefoxitin Amikacin Ampicillin Kanamycin Gen Ceftriaxone Tetracycline Amoxicillin/ Sulfisoxazole Ciprofloxacin Streptomycin Nalidixic Acid Clavulanic Acid Trimethoprim/ Chloramphenicol Sulfamethoxazole Serotype Spice Export Country - s s s s s s s s s s R s s s Thailand spices NEC 43:z4,z23: R s R s R R s s s s R R s R Mexico oregano Agona Trinidad and s s s s s s s s s R s s s Bareilly curry powder s Tobago Syrian Arab R s s s s s s s s R R R s R Bredeney capsicum Republic Derby s s s s s R s s s R s R s s China (Mainland) five spice mix s s s s I s s s Give s R s s s s India capsicum spices and Havana s s s s s R s s s s s s s s India seasonings NEC s s s s s R s s Muenster s R R R s R Pakistan curry mix Newport s s R s s s s R R s R R R R Mexico oregano Siegburg s s s s s s s s s R s s s s India turmeric s Typhimurium s I R s s R s s R R R s R Egypt basil s Typhimurium s s s s s s s s s R R s s Pakistan curry mix Virchow s s s s s s s s s R R R R s India turmeric Virchow s s s s s R s s R R R R s s Egypt basil a -). Resistant (R), Intermediate (I), Susceptible (s), Not Tested ( FDA Draft Risk Profile | 47

60 Prevalence and Concentration of Salmonella and Filth in Spices | 4 concentration shipments of imported capsicum and sesame seed offered for entry to the Salmonella in United States, Aug -Dec 2010 . s of Salmonella In order to determine the typical concentration in spice shipments offered for entry to the United States, FDA u ndertook a special sampling assignment targeting two spices: capsicum and sesame seed . The short term assignment was designed to sample shipments randomly and thereby provide a snapshot of the shipment distribution with respect to Salmonella presence and c oncentration. A full report on this study has been published (Van Doren et al. , 2013c) . A total of 299 capsicum and 233 sesame seed shipments were sampled. Results and discussion relevant to this section of the risk profile are presented below. Full details of the sampling plan and methods used in the study as well as characteristics of the shipments sampled are provided in Appendix C. Screening and MPN test results are presented in Table 4.8 . Between -shipment distributions of Salmonella mean concentratio ns in contaminated shipments examined varied widely among sampled shipments with -4 estimated mean shipment concentration s among contaminated shipments ranging from 6 x 10 to 0.09 -4 (6 MPN per 10,000 g to 9 MPN per 100 g) for capsicum shipments and 6 x 10 MPN/g to 0.04 MPN/g (6 MPN per 10,000 g to 4 MPN per 100 g) for sesame seed shipments . Within -shipment contamination observed was . Our experiments were not capable of discerning the within - not inconsistent with a Poisson distribution shipment contamination distribution among spice -serving sized samples. Observations from this 2010 FDA study were used to develop a model of between - and within -shipment Salmonella contamination of imported capsicum or sesame seed shipments offered for entry to the United States . Six parametric models were examined; four of these are illustrated in Figures 4.1 and 4.2 . The best -fit models of contamination for both shipments of imported capsicum and imported sesame seed were gamma - Poisson distributions (nominal shipment contamination prevalence of 100%), as determined by AIC, i.e., between -shipment mean concentration s of contamination were described by a gamma distribution while within -shipment distribution was described by a Poisson distribution. The assumption of Poisson -distributed within -shipment contamination was explicitly examined in the study for both types of spices and it was found that the data were not inconsistent with the assumption (Van Doren et al. , 2013c). The observations and models developed in the 2010 FDA study predict that most contaminated shipments of capsicum or sesame seeds contain relatively smal l mean concentration s of Salmonella . As a consequence, sampling plan design, particularly selections of an appropriate sample size and validated method of analysis, are critical to ensure efficient surveillance. For the best -fit parametric model descriptio ns of Salmonella contamination found in this study, we estimate that approximately 25 -50% of contaminated capsicum or sesame seed shipments examined would be detected by FDA’s standard 750 g or 1500 g testing protocols. In contrast, sampling protocols exam ining only 25 g of sample would be much less efficient, detecting approximately 5 -10% of contaminated shipments examined . These results and others are shown in Appendix C, Table C3. FDA Draft Risk Profile | 48

61 Prevalence and Concentration of Salmonella and Filth in Spices | 4 Salmonella Table 4.8. Screening and enumeration test r i n sampled shipments of imported capsicum or sesame seed offered for esults for entry to the United States August- December 2010 a Mean Composite Concentration (MPN/g) [95% CI] (MPN Pattern) Mean Shipment Concentration Spice # Shipments Composite 1 Composite 2 Composite 3 Composite 4 a [95% CI] (MPN/g) 0.002 0.0006 - 0.015] 3 [0.00027 (0/NA) (0/NA) (0/NA) [0.00008 - 0.0043] (1/0,0,0,0) 0.0097 0.0020 [0.0026 - 0.036] 1 (0/NA) (0/NA) (0/NA) [0.0006 - 0.0062] (1/2,0,0,0) 0.002 0.002 0.0011 0.015] - 1 [0.00027 - 0.015] [0.00027 (0/NA) (0/NA) [0.0003 - 0.0046] (1/0,0,0,0) (1/0,0,0,0) 0.0054 (1/POS) (1/POS) (1/POS) (0/NA) 1 - 0.0135] [0.0021 Capsicum 0.0080 0.002 0.0048 0.0035 - [0.00027 [0.0011 - 0.021] (0/NA) 1 0.015] [0.0023 - 0.028] 0.0081] [0.0015 - (1/1,0,0,0) (1/0,0,0,0) (1/1,1,0,0) 0.0048 0.0097 0.0048 0.0045 0.021] (0/NA) 1 [0.0011 - 0.021] 0.036] [0.0011 - [0.0026 - [0.0020 - 0.0097] (1/2,0,0,0) (1/1,0,0,0) (1/1,0,0,0) 0.002 0.002 0.002 0.0097 0.0033 - 0.015] - 0.015] [0.00027 0.015] - [0.00027 [0.0026 - 0.036] [0.00027 1 [0.0014 - 0.0076] (1/2,0,0,0) (1/0,0,0,0) (1/0,0,0,0) (1/0,0,0,0) 0.023 0.092 0.23 0.23 0.092 [0.0057 [0.022 - 0.38] 0.94] - - 0.093] [0.057 - 0.94] [0.057 1 [0.045 - 0.19] (1/3,0,0,0) (1/3,3,0,0) (1/3,3,0,0) (1/3,2,0,0) 0.0014 (0/NA) 2 (1/POS) (0/NA) (0/NA) [0.0003 - 0.0056] 0.002 0.0006 0.015] [0.00027 - 7 (0/NA) (0/NA) (0/NA) 0.0043] [0.00008 - (1/0,0,0,0) 0.0048 0.0013 1 (0/NA) Sesame [0.0011 - 0.021] (0/NA) (0/NA) 0.0051] [0.0003 - (1/1,0,0,0) Seed 0.0018 (0/NA) 1 (1/NA) (0/NA) (1/NA) [0.0004 0.0076] - 0.0019 (1/NEG) (1/POS) 1 (0/NA) (0/NA) 0.0061] - [0.0006 FDA Draft Risk Profile | 49

62 Prevalence and Concentration of Salmonella and Filth in Spices | 4 a Mean Composite Concentration (MPN/g) [95% CI] (MPN Pattern) Mean Shipment Spice Concentration # Shipments Composite 4 Composite 1 Composite 2 Composite 3 a [95% CI] (MPN/g) 0.002 0.002 0.0011 [0.00027 [0.00027 - 0.015] 2 (0/NA) - (0/NA) 0.015] [0.0003 0.0046] - (1/0,0,0,0) (1/0,0,0,0) 0.0037 (1/NA) 1 (1/NA) (1/NA) (0/NA) [0.0011 - 0.0126] 0.0054 (1/POS) 2 (0/NA) (1/POS) (1/POS) [0.0021 0.0135] - 0.0043 0.032 0.038 - - [0.013 - 0.078] [0.0096 0.15] [0.001 0.018] 0.0104 b b b (0/NA) 1 (1/3,0,1,0) (1/0,1,0,0) (1/2,0,2,2) [0.0059 - 0.019] c c c : (1/POS) Revised : (1/POS) Revised : (1/POS) Revised 1 (1/POS) (1/POS) (1/POS) (1/POS) > 0.006 0.0048 0.0097 0.0097 0.015 0.0091 0.048] 0.036] [0.0026 - 1 - [0.0046 [0.0011 - [0.0026 - 0.036] 0.021] [0.0048 - 0.017] (1/2,0,0,0) (1/1,0,0,0) (1/2,1,0,0) (1/2,0,0,0) 0.023 0.0097 0.015 0.0097 0.013 1 [0.0026 [0.0026 - - 0.093] 0.036] [0.0046 - 0.048] - [0.0057 0.036] [0.0069 - 0.024] (1/3,0,0,0) (1/2,1,0,0) (1/2,0,0,0) (1/2,0,0,0) 0.093 0.042 0.023 0.042 0.042 [0.0098 [0.0057 [0.0098 - 0.18] 1 - 0.18] 0.093] - [0.022 - 0.39] - [0.020 0.088] (1/3,2,0,0) (1/3,1,0,0) (1/3,1,0,0) (1/3,0,0,0) 0.023 0.23 0.023 0.023 0.036 [0.0057 0.093] - [0.0057 - 0.093] 0.093] [0.0057 [0.057 - 0.94] 1 - 0.074] [0.017 - (1/3,0,0,0) (1/3,3,0,0) (1/3,0,0,0) (1/3,0,0,0) a et al. , (2013c). 95% confidence limits on mean concentration are provided in brackets (Blodgett, 2010). Screening and enumeration test results as reported and described in Van Doren MPN pattern for composite samples, given in parentheses, includes 1/ for the positive screening test followed by the number of tubes at each dilution that tes ted positive, ordered from highest to lowest sample mass used (375g/100g,10g,1g,0.1g); 1/POS for composites in which one or more tubes in the dilution assay tested positive for Salmonella ; 1/NEG for composites -up dilution assay was performed. Estimates for the mean in which none of the dilution assay tubes tested positive; 1/NA or 0/NA for composites in which no follow Salmonella r details. concentration See Van Doren et al . (2013c) fo in the shipment was determined from the full set of test results for that shipment. b Rarity index for dilution assay results is small (<0.05), indicating the pattern is unusual/unexpected . c et al . (2013c) for additional detail We use the binary dilution assay result (POS/NEG) (noted as “Revised”) when developing models of shipment contamination. See Van Doren FDA Draft Risk Profile | 50

63 Prevalence and Concentration of Salmonella and Filth in Spices | 4 0.05 0.04 0.03 Probability 0.02 0.01 0.00 -3.0 -3.5 -2.5 -1.5 -1.0 -2.0 S e n o (MPN/g) l a l a level, l o g l m 10 - CDF(λ)) for m odels of Salmonella Figure 4.1. Complementary cumulative distribution functions (p × (1 contamination among shipments of imported capsicum offered for entry to the United States The series of compared with observations. solid black steps illustrates the observed between -shipment distribution; dashed series of steps describ e the 95% confidence limits for observed values (Kaplan -Meier estimates; Kaplan and Meier, 1958) -Poisson (blue), . Smooth curves illustrate model estimates: gamma . -Poisson (red) lognormal- Poisson (orange), log -logistic -Poisson (green), and Weibull FDA Draft Risk Profile | 51

64 Prevalence and Concentration of Salmonella and Filth in Spices | 4 0.12 0.10 0.08 0.06 Probability 0.04 0.02 0.00 -1.0 -1.5 -2.0 -2.5 -3.0 -3.5 g S o l (MPN/g) o n e l l a level, l a m 10 - CDF(λ)) for m Salmonella Figure 4.2. Complementary cumulative distribution functions (p× (1 odels of contamination among shipments of imported sesame seeds offered for entry to the United States compared with observations. solid black step The series of -shipment s illustrates the observed between distribution; dashed series of steps describe the 95% confidence limits for observed values (Kaplan -Meier estimates; Kaplan and Meier, 1958). Smooth curves illustrate model estimates: gamma -Poisson (blue), lognormal -Poisson (green), and Weibull -Poisson (red) -Poisson (orange), log -logistic . 4.1.4 SECONDARY PROCESSING AND FOOD MANUFACTURING As described in Chapter 6, spices may undergo a number of processes such as removal of debris, cracking/grinding, blending, p athogen reduction treatment, and/or re -packing at secondary spice processing facilities and may be added to foods in food manufacturing facilities. Once added to foods, the spice may be subjected to a pathogen reduction treatment, such as cooking. Because spices are shelf -stable, they are commonly warehoused . in spice lots in ASTA member spice processing facilities was Salmonella Information about the prevalence of the Federal Register Notice and is discussed below in provided by data submitted by ASTA in response to Salmonella Section 4.1.4.1. Sagoo et al . (2009) found a prevalence of 1 % (135 g; 95% CI 0.2-5% ) for a wide es) in the variety of spices collected from spice “production” facilities (secondary spice processing faciliti United Kingdom, Table 4.1 -positive spice samples in the study reported by the Food Salmonella . Two of the Safety Authority of Ireland ( FSAI, 2005) were from (1) an “import or production or packing premises or wholesaler” and (2) an “establishment[s] using large amounts of herbs/spices for food preparation .” A study FDA Draft Risk Profile | 52

65 Prevalence and Concentration of Salmonella and Filth in Spices | 4 Salmonella examining spices in processing plant facilities in Belgium found no samples contaminated with ; EFSA, 2006a), Table 4.1. The FDA 10% RFR also provides data on (25 g; 95% CI 0- the frequency of -registered facilities, which include facilities that distribute, Salmonella -positive spice samples found in FDA process, pack/re . -pack, and store spices. Data from the first three years of the RFR are described below Spice/food recalls as sociated with Salmonella -positive samples may arise from samples collected from pre- -associated U.S. recalls is provided in Section 4.1.6. retail sites or retail/end user sites. Information about spice SALMONELLA PREVALENCE IN SPICE SAMPLES COLLECT ED IN SPICE INDUSTRY 4.1.4.1 MANUFACTURING FACILI TIES (ASTA MEMBERS) ASTA submitted a large set of microbiological testing data on spice lots (ASTA, 2010; Ruckert, 2010) in rt development of response to the Federal Register Notice requesting scientific data and information to suppo the risk profile on pathogens and filth in spices (FDA, 2010e). According to the submission, “The ASTA members that provided the information handled more than 50% of the spices distributed during the reporting period (August 1, 2007- 31, 2009)” (Ruckert, 2010), i.e., domestic and imported spices sold in July the United States (Van Doren, 2011) . Unfortunately, it is not possible to determine from the information provided, the fraction of spice distributed that are represented by this data se t. However, this data set does and generic E scherichia coli in spice lots Salmonella provide some information on the relative prevalence of that had not undergone a pathogen reduction treatment as compared with those that had undergone such a formation that is not easily determined from FDA surveillance data. treatment, in Salmonella screening tests varied somewhat among the Methods of analysis and sample mass tested in the (Ruckert, 2010). submission Specifically, the different contributing ASTA members, according to the ASTA submission indicates that at least one composite sample was tested for for each result, that “a Salmonella number of participants followed the Bacteriological Analytical Manual FDA Category II or Category III testing Salmonella ,” and that the mass of that composite sample “ranged between 25 to 375 grams.” procedures for (Ruckert, 2010) the sensitivity of the test . No other method/sample -mass information was provided. Because depends strongly on the mass of spice analyzed and can also depend on the sample compositing scheme (Bassett et al. , 2010), the absence of this information complicates interpretation of the Salmonella lot prevalence values derived from these data and quantitative comparisons within this data set and with other data . sets Salmonella Table 4.9 summarizes the data ASTA provided on the prevalence of in spice lots that had not been subjected to a pathogen reduction treatment and includes an average prevalence value for all spice lots tested and individual prevalence val ues for types of spice for which at least 55 lots were tested . We decided to use this slightly smaller cutoff for inclusion to allow more comparisons between pre/no treatment and post - Confidence limits are provided for a treatment spice from this data set. ll values. Table 4.9. Observed prevalence of Salmonella contamination in spice lots from some ASTA member companies to which no pathogen reduction treatment had been applied, August 1, 2007 -July 31, 2009 95% Confidence Lot Salmonella a # Positive Spice N a b Prevalence (%) Interval - 228 12178 1.64 2.13 All Spices 1.87 Specific Spices 0 Cassia 877 0 0.0 - 0.3 Cloves 0 60 0 - 5 0 33 Cumin Seed 50 191 26 20 - Parsley 1032 0 0 0.0 - 0.3 Paprika 155 9731 1.59 1.35 - 1.86 19 Pepper, Black 55 35 22 - 49 All other spices 0.5 4 232 2 - 4 a Screening tests examined a total of 25 -375 g spice. b 95% exact confidence limit (Clopper and Pearson, 1934). FDA Draft Risk Profile | 53

66 Prevalence and Concentration of Salmonella and Filth in Spices | 4 Salmonella prevalence value for all spice lots examined (1.87%; 25 The average -375 g; 95% CI 1.64-2.13%) is strongly influenced by the prevalence among paprika lots because 80% of the lots tested were paprika . Assuming that the distribution of testing procedures were approximately the same for the different types of spice, these data suggest that lots of untreated black pepper and cumin seed are more likely to be than lots of other types of spice and that lots of untreated cassia, parsley, and Salmonella contaminated with rs used by the possibly also cloves, are unlikely to be contaminated, at least from the sources and supplie members of ASTA who contributed to this data set . Salmonella in spice lots that had been subjected to a Table 4.10 provides information on the prevalence of pathogen reduction treatment, including values for specific types of spice for which at least 65 lots were tested. contamination of spice lots from some ASTA member Table 4.10 . Observed prevalence of Salmonella -July 31, 2009 companies to which a pathogen reduction treatment had been applied, August 1, 2007 Lot Salmonella b a c # Positive 95% Confidence Interval N Spice b Prevalence (%) 3 18421 0.02 All Spices 0.0 - 0.5 Specific Spices - 0 0.00 0 155 2 Anise 0 1383 0.00 Basil - 0.2 0.0 123 0.00 0 0 - 2 Bay Cassia/Cinnamon 460 0.00 0.0 - 0.6 0 Celery 0 310 0.00 0.0 - 1.0 0 488 0.00 0.0 - 0.6 Cloves 0.0 488 0.00 - 0.6 Coriander 0 0 795 0.00 0.0 - 0.4 Cumin Dill 170 0.00 0 - 2 0 533 0.00 Fennel 0.0 - 0.6 0 Ginger 91 0.00 0 0.00 - 0.03 0.8 Marjoram 0 354 0.00 0.0 - Nutmeg 256 0.00 0 - 1 0 0 0.0 1192 0.00 - 0.3 Oregano 0.0 903 0.00 - 0.3 Paprika 0 0 95 0.00 0 - 3 Parsley 0.0 5456 0.02 - 0.1 1 Pepper, Black 0 971 0.00 0.0 - 0.3 Pepper, White 2363 0.04 1 0.0 - 0.2 Pepper, Red 312 0 Rosemary 0.00 0 - 1 Sage 597 0.00 0.0 - 0.5 0 141 0.00 Savory 0 - 2 0 Thyme 436 0.00 0 0.0 - 0.6 Turmeric 0 136 0.00 0 - 2 - All other spices 213 0.5 0.01 1 3 a Spice categories include all lots described by this name, e.g., “Pepper, Red” includes lots described as “Pepper, Red” and “Pepper, Red – High Heat” and “Dill” includes lots described as “Dill”, “Dill Seed”, or “Dill Weed .” b Screening tests examined a total of 25 -375 g spice. c 95% exact confidence limit (Clopper and Pearson, 1934). Only three lots of treated spices tested positive post treatment during the two- year period: one lot each of black pepper, red pepper, and tarragon leaves. Of these lots, two had been treated with steam (one lot treated in the United States and the other lot treated in the source country) and one had been treated with ethylene oxide outside the spice source country (non -source/”other” country) . There are not enough n. Salmonella -positive results to compare prevalence values by either treatment type or locatio FDA Draft Risk Profile | 54

67 Prevalence and Concentration of Salmonella and Filth in Spices | 4 Salmonella member pathogen reduction treated spice lots sampled is The overall prevalence of in the ASTA- statistically smaller than the value for imported spice shipments sampled at the point of entry to the United States during FY2007- FY2009. The dif ference is so large that it cannot be fully explained by a difference in sample size examined in the screening tests (25 -375 g versus 750 g). Assuming that the methods of analysis used by ASTA members were validated and are comparable with the data from FD A and that the distribution of contamination within lots was not dramatically different than that found in the shipments examined by FDA, a plausible explanation for the difference observed is a difference in the sampled lots/shipments that had undergone a pathogen reduction treatment. ASTA members also tested spice lots for generic Escherichia coli post treatment during this time period, Table 4.11. As with sampling and testing data , contributing members used a number of different Salmonella nalysis for E scherichia coli . “Typically,” two methods with similar detection limits were methods of a 4 employed (AOAC method 991.14 (< 10 CFU/g; as reported by Ruckert, 2010) and AOAC method 966.24 (< 3 MPN/g; as reported by Ruckert, 2010) . We presume both methods exa mined 50 g of sample (AOAC method 966.23, referenced in methods 991.13 and 966.24) . Method descriptions are available from AOAC International (2005a, 2005b, 2005c) . The three lots that tested positive for Salmonella post -treatment were . scherichia coli not tested for the p resence of E The data on the prevalence of generic scherichia coli post -treatment in Table 4.11 provide insights into the E effectiveness of bacterial reduction treatments and post . The predominance of -treatment preventive controls black pe pper lots in the data set (representing 30% of all lots sampled and 78% of lots testing positive) strongly influences the summary statistics and confounds other factors such as spice form (ground/whole) or the type of pathogen reduction treatment applied . The observations of positive E scherichia coli tests on spice lots after pathogen reduction treatment indicate that either the treatments were not totally effective or post- treatment preventive controls were ineffective in preventing contamination or growth of remaining Escherichia coli in the spice. Further research is needed to determine the cause(s) for these observations and whether the cause could have implications for contamination of spice lots with other pathogens. also indicate that lots of ground black pepper sampled had a statistically The sampling results in Table 4.11 larger prevalence of scherichia coli when compared with raw/whole black pepper. This differs from the E result found for Salmonella prevalence among sampled shipments of black pepper offered for entry to the United States (Table 4.4). These same data are reflected in the summary data for all raw/whole spices and ground spices in Table 4.11. Additional data are needed to determine the reason for the difference. 4 TM Ruckert (2010) reported AOAC method 991.1 but it is likely the method was 999.14, which is the Petrifilm Escherichia TM method. /Coliform Count Plate coli FDA Draft Risk Profile | 55

68 Prevalence and Concentration of Salmonella and Filth in Spices | 4 Escherichia contamination in spice lots in some coli Table 4.11. Frequency and prevalence of generic AS TA member companies to which a pathogen reduction t reatment had been applied, August 1, 2007 - July 31, 2009 coli Escherichia 95% Confidence a N # Positive Lot Preva lence Spice b Interval a (%) b 25604 213 All Spices 0.83 - 0.95 0.72 Spices subjected to different processes c 0.18 11119 30 0.27 Raw/Whole spices - 0.39 c 170 1.83 9291 1.57 - 2.12 Ground Spices c 18 0.48 3742 0.28 - 0.76 Whole Black Pepper c Pepper Ground Black 3966 138 3.48 2.93 - 4.10 0.03 Spice treated with Ethylene Oxide 11601 4 0.01 - 0.09 1.97 Spice treated with Steam 12086 208 1.72 1.50 - Spice treated with Irradiation 0 0.0 0.0 - 0.9 345 0.01 1 0.3 Spice treated with PPO - 2 303 Spice treated with unspecified pathogen 0.0.2 - 1270 0 0.0 0.0 d reduction process a We presume both methods examined 50 g of sample (AOAC method 966.23, referenced in methods 991.13 and 966.24). b 95% exact confidence limit (Clopper and Pearson, 1934). b Test data for one lot was excluded because of ambiguity as to whether the lot had undergone a pathogen reduction treatment before testing. c Test data on lots for which raw/whole/ground status could not be determined were excluded in this analysis. d Test data on lots for which a unique pathogen reduction process was not specified were grouped into this category. REPORTABLE FOOD REGI 4.1.4.2 FREQUENCY OF STRY ENTRIES ASSOCIA SALMONELLA TED WITH –CONTAMINATED SPICES AND SEASONINGS. The Reportable Food Registry was established by Section 1005 of the Food and Drug Administration 85), which amended the FD&C Act by creating a new s ection 417 of the Amendments Act of 2007 (Pub. L. 110- , Reportable Food Registry [21 U.S.C. 350f.] (U.S.C. 2007) FD&C Act Reportable Food Registry tracks patterns of adulteration of food in the United States by requiring The FDA industry (responsible parties) (FDA, 2010b) to submit reportable food (FDA, 2010c) reports when “there is reasonable probability that the use of, or exposure to, such a rticle of food will cause serious adverse health consequences or death to humans or animals” (FDA, 2010c) and accepting voluntary reports from federal, . More details about the program are provided i n Section 8.1.3 .4. state and local public health officials Within the “Spices and Seasonings” category, described in the RFR Commodity Definitions document (FDA, Salmonella contamination led all other hazards reported in the first three years of the program 2012e), . This catego ry includes spices identified at CFR 182.10 (FDA 2013f), and also lists examples of products such as 21 whole and ground spices, rooibos, sesame seeds, poppy seeds, caraway, anise, fenugreek seeds, meat coatings and rubs, seafood seasonings, dried herbs, and dried ginger (FDA, 2012e.) The number of primary entries, or the initial reports submitted by industry (responsible party) (FDA, 2010b) about a reportable food (FDA, 2010c) to FDA, reported for Salmonella in “Spices and Seasonings” was 16, 23, and 5 for years 1 (September 8 -2009-Sept ember 7, 2010), 2 (September 8, 2010 – September 7, 2011), and 3 (September 8, 2011 – September 7, 2012), respectively . The frequency of primary entries for Salmonella in “Spices and Seasonings” was the largest among all 28 food categories in Year 1, secon d largest in Year 2 and tied for fourth largest (with two other RFR food commodities) in Year 3. However, it is difficult to interpret frequency values and relative rankings without knowledge of the total number of products/lots tested of each food commodi ty type. FDA Draft Risk Profile | 56

69 Prevalence and Concentration of Salmonella and Filth in Spices | 4 4.1.5 RETAIL/END USE R prevalence or concentration We were unable to identify any reports characterizing in spices at Salmonella retail (food service, grocery store, restaurants, or in the home) in the United States. Information from the FDA targ eted sampling assignment in 2010 established that shipments of imported spice offered for entry to the United States and packaged for retail may be contaminated and may comprise a significant percentage of the ~ 20% for imported cap sicum and sesame seed shipments sampled during the contaminated shipments ( Aug ; Van Doren et al ., 2013c) . Surveillance studies at retail have been conducted in a -Dec 2010 study period number of different countries, Tables 4.1 and 4.2 . Observed prevalence values ranged from 0% (wi th non- zero upper limits) to 10% with varying confidence limits listed in Table 4.1. Salmonella has been found in a wide variety of spices and spice blends at retail (listed in Table 4.1) . As mentioned previously, most of the studies examined small samples of spice, which limit the ability of the screening test to detect Salmonella at low concentration s. Determinations of concentration s in spices found at retail are listed in Table 4.2, with most arising Salmonella from outbreak investigations t concentration of Salmonella reported in a spice/spice blend was 11 . The larges MPN/g (Lehmacher et al ., 1995), sampled from the food manufacturer’s spice supply for the food implicated in the salmonellosis outbreak . A surveillance study from retail samples of black pepper and red pepper (capsicum) in Japan found mean concentration s of Salmonella of 0.086 MPN/g (86 MPN per 1000 g; Hara - Kudo et al ., 2006; see Table 4.2 for details of calculation) . Another surveillance s tudy in the United Kingdom s in sesame seeds and mixtures of seeds of <0.1 -0.2 MPN/g reported a range of Salmonella concentration (<10-20 MPN per 100 g; Willis et al . ., 2009) 4.1.6 FREQUENCY OF F D RECALLS IN THE UNI TED STATES ASSOCIATED WITH OO –C SALMONELLA ONTAMINATED SPICES Recalls of food products can provide insights into the prevalence of contamination in foods at retail but can also involve spice/spiced -foods collected at other stages of the farm -to-table continuum, e.g., during spice processing or food manufacturing . In the United States, recalls are typically initiated when analysis has identified that a food does not meet regulatory requirements, e.g., the product is contaminated or is , such as an outbreak . Class I recalls involve mislabeled, or when a spice/food has been linked to human illness “a situation in which there is a reasonable probability that the use of or exposure to a violative product will cause serious adverse health consequences or death ” whereas Class 2 recalls involve “a situation in which use of or exposure to a violative product may cause temporary or medically reversible adverse health consequences or where the probability of serious adverse health consequences is remote” (FDA, 2013c) . FDA further distinguishes recall events as either primary or secondary . Primary recall events are recalls initiated by the firm in which the triggering violation was found or that caused the violation whereas secondary recalls arise from firms that are recipients of the violative products for use as an ingredient in a final product . Salmonella From 1969-2003, FDA identified 20 primary recalls of spices, all of which were because of et al ., 2006) . The one other recall noted in the report, associated with Listeria contamination (Vij in bay leaves, was later determined to be a recall for fresh bay leaves, rather than dried bay monocytogenes Hogan, 2011) . Most of the recalls ( leaves ( 15/20) took place in the final four years of the study, 2001- 2003. The large increase in recalls associated with Salmonella -contaminated spices in the latter four years of the study was attributed primarily to an increase in surveillance of Florida spice companies following a contamination finding in 2001 (Vij et al., 2006) . None of the recalls were linked to outbreaks, desp ite the fact that some of the spice recalled had been marketed for some period of time (1 -18 months; Vij et al ., 2006). FDA Draft Risk Profile | 57

70 Prevalence and Concentration of Salmonella and Filth in Spices | 4 More recently, FDA has reviewed primary recall events associated with contaminated spices during the two year period January 1, 2008- cember 31, 2009 (that were classified by FDA by March 23, 2010) . Eight De primary recall events involving one hundred and sixteen different products were initiated because of the presence/potential presence of (Ma, 2013) . The eight spice- associated recalls represented 2% of Salmonella all Class I and II primary recall events and 26% of the Class I and II primary recall events associated with Salmonella . Products recalled in one spice -associated event contamination during that time period (Ma, 2013) were also implicated in or related to the Salmonella Rissen outbreak (described in Chapter 2) attributed to consumption of contaminated white pepper (Ma, 2013 ). Root causes for the spice recalls were determined by a panel of seven FDA scientists from an analysis of the data and information provided by industry and FDA. Lack of supplier control was identified as a contributing contamination of spices. In factor in each of the eight primary recall events associated with Salmonella addition, insufficient/inadequate san itation controls, environmental monitoring and training were also . identified as root causes for the recalls associated with the white pepper outbreak (Ma, 2013) The scope of spice recalls is not easily captured by the number of events or products recalled . For example, -to-eat salami products related to the Salmonella the single recall event in the United States involving ready Montevideo/Senftenberg outbreak associated with contaminated black and red pepper resulted in 234,686 pounds of salami products being recovered from the marketplace (USDA/FSIS, 2010) . In the Salmonella Wandsworth and Typhimurium outbreak associated with a contaminated broccoli powder ingredient in a bags of the snack food that had snack puff food, recalls focused on trying to capture some of the ~1.3 million been distributed in the United States and Canada (Hogan, 2010). 4.1.7 INTERNATIONAL REPORTS OF FOOD SAFE TY HAZARDS ASSOCIATE D WITH SALMONELLA –C ONTAMINATED SPICES - RASFF and Feed (RASFF) notifies member states of the The European Commission Rapid Alert System for Food “existence of a serious direct or indirect risk to human health deriving from food or feed, this information is DG SANCO immediately notified to the Commission under the RASFF” (EC/ . During the years 2 001- , 2012a) including Escherichia coli , 2011, 44.8% of RASFF notifications on selected biological hazards ( Salmonella, spp., Campylobacter spp. , Listeria monocytogenes, Shigella spp. , Staphylococcus aureus, Clostridium Bacillus Caliciviruses) in food of non botulinum, norovirus , a nd -animal origin were from the category Hepatitis A, “Herbs and Spices .” Eighty percent of the “Herbs and Spices” RASFF notifications during this time period roducts in the “Herbs Salmonella (Altieri were associated with and Robinson , 2013; EC/DG SANCO, 2012b ). P and Spices” category may include dry or fresh products. 4.2 FILTH Methods of analysis used to determine filth adulteration of spice vary with filth element and spice type and form (e.g., ground or whole). All methods of analysis used by FDA are described in the Macroanalytical ne whether the concentration of filth is less than the DAL (for Procedures Handbook (FDA, 1998a). To determi natural or unavoidable defects in foods), FDA typically examines six spice subsamples taken from different portions of the spice shipment/lot. For example, the DALs for ground black pepper include specifications for insect fragment parts (≥475 insect fragments per 50 - g spice) and rodent hairs (≥2 rodent hairs per 50 - g spice) . To determine whether a shipment of ground black pepper is adulterated with filth, FDA collects six 50 - g samples and exam ines each subsample for insect fragment and rodent hairs. The shipment would be adulterated if the average concentration of either of the filth elements was not smaller than the DAL. FDA Draft Risk Profile | 58

71 Prevalence and Concentration of Salmonella and Filth in Spices | 4 SPICE: FROM FARM TO TABLE OV 4.2.1. FILTH ADULTER ATION PREVALENCE OF ERVIEW Little experimental data have been reported on the prevalence or concentration of filth in spices throughout . FDA regularly samples imported foods including spices, for filth and these data the farm -to-table continuum were analyzed to provide a mea sure of the extent of filth contamination of imported spices at the point of import. 4.2.2. PRIMARY PRODU CTION - We were unable to identify any reports characterizing filth contamination in/on spice source plants pre or harvest, filth adulteration of spices, s of filth elements in spices at primary production sites. concentration spices are derived from parts of plants and are often dried in open air environments, the presence of Because ese types of filth are termed “natural or twigs, dirt and field insect parts are not unexpected (ASTA, 2011). Th s below the DALs . unavoidable defects” by FDA and are acceptable when found in spices at concentration 4.2.3. DISTRIBUTION AND STORAGE Surveillance data on the prevalence of filth adulteration of spices during dis tribution and storage is limited to evaluations of these quantities at the point of import; we were not able to identify any surveillance studies of located in storage facilities or at other points of the distr of the prevalence ibution filth adulteration of spice chain. However, inspections of spice processing/packing facilities and food manufacturing facilities provide information about the potential for adulteration of spice/food in the storage areas of the facilities . some Inspection s are discussed in Se ction 8.1.3 .1. 4.2.3.1 FILTH ADULTE RATION OF SHIPMENTS OF IMPORTED SPICE OF FERED FOR ENTRY TO T HE UNITED STATES Data reported in this section are derived from two studies of FDA sampling data (1) review of results from the annual sampling program for the years FY2007-FY2009 and (2) review of sampling results from a targeted sampling assignment in 2010 (August-December) that focused on examining imported shipments of capsicum and sesame seed offered for entry to the United States for potential filth adulte ration. Selection of shipments of imported spice/other food for examination under FDA’s annual field work plan is based on a number of factors including the inherent risk of the product, general surveillance activities described in the FDA work plan, FDA work performance goals and/or congressional work performance goals. All data examined in the FY2007 -FY2009 study presented below were drawn from “surveillance sampling activities”, as described above, as opposed to compliance activities. All shipments o f imported capsicum or sesame seed were eligible for sampling for the 2010 targeted study. A total of 299 shipments of capsicums and 233 shipments of sesame seeds were sampled at the point of import into the United States between August and December 2010. The shipments sampled constituted approximately 10 or 20 percent of all shipments of imported capsicum or imported sesame seed shipments, respectively, offered for entry to the United States. FDA Draft Risk Profile | 59

72 Prevalence and Concentration of Salmonella and Filth in Spices | 4 filth adulteration shipments of imported s pice o ffered for entry to the United States Observed in Summary results for prevalence of filth adulteration (defined in Section 3.2) in imported shipments of spices -FY2009 are presented in Table 4.12. The overall offered for entry to the United States during FY2007 (95% CI 10- % prevalence for filth adulteration of imported spice shipments during that time period was 12 . This value is 1.8 times (RR 95% CI 1.4- 2.2) the value found for all other shipments of imported FDA - 15%) regulated foods sampled during this time period. -regulated Table 4.12. Prevalence of filth adulteration in shipments of imported spice or other FDA -FY2009 foods offered for entry to the United States, FY2007 Filth Shipment 95% Confidence N Spice/Food # Positive a Interval Prevalence (%) b 82 665 Spices 12 9.9 - 15 All Imported b regulated Foods 585 All other Imported FDA - 8350 7.00 6.47 - 7.57 c Spices Subject to different processes 7.4 257 11 - 15 Ground/cracked Spice 28 24 165 Whole Spice 9.5 - 21 15 Specific Spices d 27 Capsicum 115 21 18 12 - Pepper, Black 54 2 0 - 10 1 Sesame Seed 71 10 7 4 - 19 e Spices/Spices and Seasonings, NEC 28 181 15 10 - 22 6.7 All other spices 25 244 10 - 15 a 95% exact confidence limit (Clopper and Pearson, 1934). b All shipments of imported FDA -regulated spices or other imported foods that were sampled during the study period. c Categorizations derived from product code and description. When description was insufficient to categorize, the sample was not included. Note that analytical methods used to determine filth in ground/cracked spices differs from those used to determine filth in whole spices. See text for details . d Capsicum includes paprika as well as hot and other sweet dried capsicum peppers. e Shipments r of spices “not elsewhere classified” (NEC) in the product code are assigned to “Spices, NEC”, “Spices and Seasonings, NEC”, o “Mixed Spices and Seasonings, NEC .” Our data indicate that the prevalence rates for imported shipments of ground/cracked spice d o not differ statistically from that of whole spice (p>0.05) . When comparing filth adulteration prevalence values for shipments of different types of spice, we find that the prevalence for shipmen ts of imported black pepper was smaller than that for shipme nts of imported capsicum, “spices/spices and seasonings, NEC”, or the category “all other spices” (Marascuilo procedure -FY2009. Results from the ) among those sampled during FY2007 2010 sampling assignment targeting imported shipments of sesame seeds and ca psicums found essentially the same filth adulteration prevalence for capsicum (18% 95% CI 14 -24%) but a much smaller filth adulteration prevalence for shipments of sesame seed (0.5%, 95% CI 0.0 -2.5%) than was observed for the period FY2007- FY2009. More dat a are needed to determine whether the smaller prevalence value reflects a sustained reduction in the prevalence of filth in imported sesame seed shipments. The types of filth adulteration found in sampled shipments of imported spices offered for import during the three year study period are presented in Table 3.4 . The most prevalent types of filth elements were insect fragments, whole/equivalent insects, and animal hair . As mentioned in Chapter 3, almost all of the insects found in these spice samples are stored product pests with some test portions analyzed containing four or more species of pests in a single test portion. The presence of the specific insects found indicates poor (Pharaoh ant), handling, storage, or cleaning of the spices . One of the species found, Mono morium pharaonis FDA Draft Risk Profile | 60

73 Prevalence and Concentration of Salmonella and Filth in Spices | 4 et al ., 2001) Acarus siro (grain mite), has been identified as a vector of food borne pathogens (Olsen . Another, . has been associated with allergic reactions in people handling products containing this mite (Olsen, 1998b) -FY2009 A review of the FDA sampling database for imported spice shipments offered for U.S. entry FY2007 showed that hair was detected in 253 (38% of sampled) shipments of imported spice (Table 4.13), although not all of these shipments were determined to be adulterated by filth . Of the hair found, 38% was identified to be from rodents. As discussed in Chapter 3, the presence of rodent hair without a hair root in spices generally is an indication that the spice had been contaminated with rodent feces . All h airs found in food are indicative GAPs of insanitary conditions and therefore failures in the application of Good Agricultural Practices ( ) and ound in shipments of i spice o ffered for entry to the United States, FY2007 - Table 4.13. Hairs f mported FY2009 FY -09 Hair Summary # Test Portions # Shipments 07 Human hair 47 35 Bat 1 1 19 Cat 32 Cow 1 1 Dog 1 1 Mammalian 23 11 244 85 Mouse/Rat 10 Other 19 Rabbit 3 3 1 Rat 1 Rodent 15 11 Non - striated 13 7 Sheep 1 1 Striated 37 18 Unknown 129 49 All Hairs 567 253 Current Good Manufacturing Practices ( ). For example, human hair in spice could arise when workers CGMPs he spice fail to use hair nets while cat/dog hair could arise if the spice processing/packing/storing handling t nimals for rodent control . In addition, direct evidence of animal fecal and/or insect facility employs these a fecal contamination was found in a small number of the samples. Foreign substances found in spices ranged from twigs and sticks to staples, stones, and various fibers (T able 3.4) . Most of these materials can be classified as hard and/or sharp objects; e.g. sticks, stones, staples; which are physical hazards in foods (Olsen, 1998a) and are classified as action Category 1 analytes (indicators of a potential food safety haza rd) according to the 1999 revised filth strategy , and violate s ection 402(a)(1) of the FD&C Act. Others, such as fibers or rubber bands, are action category 2 (detectable and objectionable to the section 402(a)(4) of the FD &C Act. consumer), potentially violating 4.2.4. SECONDARY PROCESSING AND MULTI -C OMPONENT FOOD MANUFA CTURING We were unable to identify any reports characterizing the prevalence or concentration s of filth adulteration in spice found in processing, packing or food manufacturing facilities . Spice manufacturers regularly apply . However, physical cleaning techniques to remove filth elements from raw spice during secondary processing inspections of spice processing/packing facilities and food manufacturing facilities provide information about FDA Draft Risk Profile | 61

74 Prevalence and Concentration of Salmonella and Filth in Spices | 4 the facility environment and the potential for adulteration of the spice/food within that environment. Inspection Review of FDA inspection data for a group of 59 domestic spice s are discussed in Section 8.1.3 .1. firms inspected as part of a special assignment to support this risk profile revealed that the presence of pests was among the most common findings reported. 4.2.5. RETAIL/END US ER We were unable to identify any reports characterizing the prevalence or concentration s of filth in spice at et al. re et al. , 1986) which were tail other than the surveys FDA conducted in the 1980s (Gecan , 1983; Gecan . FDA generally set DALs to values that would reflect used to set the DALs for the spices listed in Table 3.3 significant deviation from the best prac tices of industry and agriculture at that time. TH SALMONELLA 4.3 PREVALENCE OF BO ON OF SPICES AND FILTH ADULTERATI In 1960, Kenton Harris wrote in Food and Drug Technical Bulletin No. 1: “Often the line of demarcation between a harmful and a filthy food is exceedingly narrow . Many of the sources of filth in food products are potential sources of disease organisms . It is well known that rodents are vectors of several diseases transmissible to man, including typhus, plague, infectious jaundice, and Salmonella infection . Flies and roaches may harbor . Rodents, flies, and other insects closely pathogenic bacteria and transmit infection to foods associated with filth and insanitary conditions are capable of mechanically transferring pathogenic and spoilage organ isms from such filth directly to food products . Therefore, certain forms of filth contamination of food carry implications of danger to health although the demonstration of specific agents of disease may be difficult or impossible” By 2001, the body of s cientific evidence demonstrating a relationship between some types of filth and specific agents of disease had grown significantly, as described in detail in FDA’s 2001 review of the scientific ., 2001). Insects, rodents and other an et al literature (Olsen imals possessing the following five attributes: “synanthropy, endophily, communicative behavior, attraction to filth and to human food, and harborage of pathogens in the natural (wild) populations” are recognized as having the potential to spread pathogens to et al ., 2001 and references therein). As a consequence, it is possible that the presence of human food (Olsen filth and pathogens in spices could be correlated, at least at some points along the farm -to-table continuum. In 1989 FDA performed a limited study comparing the microflora recovered from samples of spice and fecal pellets found in spice from shipments of spice offered for entry to the United States and reported no correlation (Satchell et al ., 1989). Interpretation of these data with regard to the correlation between filth and spice contamination with pathogens is limited because the results were based on a very small data set . In the 1989 study, 1- 4 fecal pellets from each of nine shipments were examined for microflora and compared with microb iological test results on two 375 g samples from each shipment. E scherichia coli (generic) was found in two pellets but neither Salmonella nor Escherichia coli was found in spice samples from the nine shipments (Satchell ., 1989). et al In order to address whether adulteration of spice by filth and Salmonella are correlated at the point of entry to the United States, we analyzed FDA sampling data for shipments of imported spices and food offered for entry during the years FY2000- FY2009 (except FY2002 for which there were incomplete data) . A total of 883 shipments of imported spice were examined for both Salmonella and filth during this time period. Results of FDA tests are presented in Table 4.14 . Evaluation of the Fisher exact p -value indicates that the cor relation between Salmonella and filth contamination of imported spices at the point of import is not significant and filth Salmonella (p>0.05) for the sampled shipments examined. In contrast, correlation between FDA Draft Risk Profile | 62

75 Prevalence and Concentration of Salmonella and Filth in Spices | 4 -regulate d food shipments examined for both contaminants during this contamination in other imported FDA same time period (4557 shipments) was found to be highly significant (p<0.001), as shown in Table 4.15. ion of Salmonella Table 4.14. Examination of relationship between presence of filth and adulterat -FY2009 (except) FY2002 shipments of imported spice offered for entry, FY2000 # Negative for Fisher Exact # Positive for a Salmonella Salmonella - Value Filth p # Positive for 13 100 na Filth # Negative for 711 na 59 Filth Fisher Exact na na 0.195 a Value p - a Fisher -value (SAS, 2012) . “na” indicates measure is not applicable for the cell. exact p Salmonella adulteration of Table 4.15. Examination of relationship between presence of filth and shipments of imported foods offered for entry, FY2000 -FY2009 (except) FY2002 # Positive for Fisher Exact # Negative for a Salmonella p - Value Filth Salmonella # Positive for 234 25 na Filth # Negative for 151 4147 na Filth Fisher Exact <0.001 na na a p- Value a Fisher exact p -value (SAS, 2012) . “na” indicates measure is not applicable for the cell. The absence of a correlation for shipments of imported spices offered for entry to the United States may result from a lack of statistical power (data for a small number of shipments are compared) or may signify that spices or the spice supply chain practi ces before import are characteristically different (on average) with -regulated products and filth from those of other imported FDA regard to contamination with Salmonella (among those sampled). It is common for spice producers and/or processors to physically clean raw spices to remove visible filth; this often takes place at primary production, while additional cleaning can take place during secondary processing (see Chapter 6). Pathogen reduction treatments are also commonly applied to some spices . Such treatments are performed in the secondary processing phase of the spice farm -to-table e place before or after import continuum, which may tak . The combination of these practices may remove any correlation between the presence of Salmonella and filth in shipments of imported spice at the point of entry to the United States, if any existed initially. More research is needed to understand how the prevalence of filth and Salmonella adulteration of spices changes along the supply chain from farm to the consumer table. FDA Draft Risk Profile | 63

76 5. CHARACTERIZATION OF CONTAMINANTS Salmonella The goal of this section is to highlight the characteristics of and filth adulteration that impact their potential risk to public health when found in spices . The sections below are not meant to reproduce or comprehensively review the vast literature on Salmonella or filth but rather provide general/representative references for key statements. a on the survival of Salmonella in spices and the potential for growth of Salmonella in wet spices were very Dat limited. In order to begin to address this data gap, FDA scientists undertook a series of experiments to evaluate these properties in ground black pepper . A full description of the experiments and results can be et al . In sections 5.1.2 and 5.1.3, we present key results and conclusions and compare found in Keller . (2013) our results with related reports in the literature. SALMONELLA 5.1 5.1.1 GENERAL CHARACTERISTICS OF SALMONELLA There are two species of Salmonella : S. enterica and S. bongori (WHO, 2007) . Salmonella enterica is further divided into six enterica (I), salamae (II), arizonae (IIIa), diari zonae ovars: subspecies, each with many ser (IIIb), houtenae (IV), and indica (VI) (WHO, 2007) . As shown in Table 3.2, all of the Salmonella strains isolated from spices in the United States have been Salmonella enterica and have included strains from five of the six S. enterica subspecies. W hile the primary habitat for Salmonella is considered to be the intestinal tract of vertebrates such as birds, animals, rodents, reptiles, and humans (FDA, 2012d) most variants can survive for extended periods in non- host environments . For example, it has been shown that Salmonella can survive in soil (Garcia et al ., 2010; ., 2012), plants (Franz et al Bech et al ., 2010), water (Ceballos et al ., 2003; Skariyachan et al ., 2012; Micallef and van Bruggen, 2008; Barak et al et al ., 2013), manure and s oil amended with manure (Ongeng et ., 2011; Gu ., 2011; Bech al ., 2010; Semenov et al ., 2009; Islam et al ., 2004; Garcia et al ., 2010), on et al equipment/surfaces (Mattick et al ., 2003; Castelijn et al ., 2013), and in low moisture foods (Podolak et al. , 2010; Ristori ., 2007; Beuchat and Scouten, 2002; Komitopoulou and Penaloza, 2009; Lehmacher et al ., et al 1995; Uesugi et al ., 2006; Keller et al ., 2013; FDA, 2012d) . Indeed, a key characteristic of Salmonella related to spice contamination is its ability to resist dry, desiccation conditions for extended periods ( Beuchat and Scouten, 2002; Hiramatsu et al ., 2005; Du et al . 2010; Beuchat and Mann, 2010; Podolak et al ., 2010; Kimber et al., 2012; Blessington et al., 2012) . Salmonella has been found in and on insects, which can transport the bacteria from one location to another -Ripoll et al et al ., 2007; Wang et al ., 2011; Hoelzer et al (Crumrine ., 1971; Holt et al ., 2012) . ., 2011; Pava Beyond survival, most va riants of Salmonella can grow in a variety of non-host environments, given sufficient water, nutrients, and other appropriate environmental conditions (Combase Consortium, 2012; Harris et al ., 2003; Brandl, 2006; Danyluk et al. et al. , 2009a; Beuchat and Mann, , 2008; Franz and van Bruggen, 2008; Du 2010; Keller ., 2013) . This adaptability enables Salmonella to cycle between animal host and et al environment, thereby extending the lifetime of the bacteria/bacterial colony and “ensuring its passage to the next host” (Winfield and Groisman, 2003; Foster and Spector, 1995; Podolak et al ., 2010). A direct consequence of Salmonella ’s ability to survive in non -host environments is that it is widely dispersed -contaminated material (animate or inanimate) comes in contact with the Salmonella in nature and that when FDA Draft Risk Profile | 64

77 Characterization of Contaminants | 5 spice source plant or spice before human consumption it may be a potential source of viable bacterial contamination . PICES 5.1.2 ANTIMICROBIAL PROPERTIES OF SOME S Essential oils of some spices possess anti microbial properties which can inhibit the growth of bacteria E , Salmonella , and , scherichia coli under some conditions (Al - including Bacillus cereus Staphylococcus aureus et al. , 1976; Shelef et al. , 1980; Shelef, 1983; Shele f, et al. , 1984; Aktug and Delaimy and Ali, 1970; Farbood -Palmer et al. , Karapinar, 1986; Karapinar and Aktug, 1987; Zaika, 1988; Billing and Sherman, 1998; Smith 1998; Arora and Kaur, 1999; Hammer et al. , 1999; Dorman and Deans, 2000; Ceylan and Fung, 2004; Burt, et al. , 2009a; Du et al. , 2009b; Tajkarimi 2004; Du , 2010; Weerakkody et al. , 2011). For example, Al - et al. Delaimy and Ali (1970) reported that 1% v/v garlic extract inhibited growth of scherichia coli and E Typhi while Smith-Palmer et al. (1998) reported that essential oils of bay, cinnamon, clove and Salmonella Enteritidis at a concentration of 0.075%. thyme inhibited growth of Salmonella Many studies have demonstrated that the strength of the inhibitory effect depends on the essential oil, its concentration, and the p athogen (including strain), among other factors (Al -Delaimy and Ali, 1970; Farb ood , 1976; Shelef et al. et al. et al. , 1984; Aktug and Karapinar, 1986; Karapinar and , 1980; Shelef, 1983; Shelef Aktug, 1987; Zaika, 1988; Billing and Sherman, 1998; Smith mer et al. , 1998; Arora and Kaur, 1999; -Pal et al. , 1999; Dorman and Deans, 2000; Ceylan and Fung, 2004; Burt, 2004; Tajkarimi et al. , 2010; Hammer , 2011) 10 Weerakkody et al. needed . For example, Shelef et al. (1980) reported that Salmonella Typhimurium times more sage for inhibition in broth than . Karapinar and Aktug (1987) reported that eugenol, B. cereus which is the key antimicrobial compound in cloves, had a smaller minimum inhibitory concentration for Salmonella Typhimurium than thymol or anethole, essen tial oils in thyme and anise seed, respectively. Spices containing essential oils with strong inhibitory effects towards may limit the growth of the Salmonella pathogen in some foods if the concentration of the spice/essential oil is sufficient and other conditions are appropriate . What is not known is the extent to which the presence of antimicrobial essential oils in some spices impact survivability of Salmonella in low moisture foods in general or the spice itself. The relatively large preva lence found by FDA for shipments of oregano and allspice offered for import to the Salmonella United States during FY2007 -FY2009 demonstrates that the antimicrobial activity against Salmonella is not sufficient to eliminate Salmonella contamination from shipments of these types of spices (as discussed in Section 4.1.3.1). PICES 5.1.3 SURVIVABILITY IN S It is well established that salmonellae survive long periods in low moisture foods and dry environments et al ., 2005; Du et al . 2010; Beuchat and Mann, 2010; Podolak et al ., (Beuchat and Scouten, 2002; Hiramatsu . Lehmacher et al. (1995), analyzing samples of paprika, 2010; Kimber et al., 2012; Blessington et al., 2012) Salmonella can survive for at least 8 months in samples of that spice but the spe demonstrated that cific conditions under which the spice was stored and how these impacted survival were not recorded. FDA undertook a series of experiments to characterize how survival of in a spice depends on storage Salmonella conditions (Keller et al ., 2013) . Samples of ground black pepper were inoculated with a cocktail of Salmonella ° strains, held at 35 or 25 C, and stored under either high relative humidity (RH, 97%) or under low RH (typically ≤ 40%) . Results for these experiments are presented in Figures 5.1 -5.4. FDA Draft Risk Profile | 65

78 Characterization of Contaminants | 5 9.00 1.0 1 9.00 0.9 8.00 0.9 8.00 0.8 0.8 7.00 7.00 0.7 0.7 6.00 6.00 water activity water activity 0.6 0.6 5.00 5.00 0.5 0.5 4.00 log cfu/g 4.00 Log(cfu/g) 0.4 0.4 3.00 3.00 0.3 0.3 2.00 2.00 0.2 0.2 1.00 0.1 1.00 0.1 0.00 0.0 0 0.00 10 80 70 60 50 40 30 20 0 60 40 20 0 120 100 80 Time (day) Time (day) C and ° at 25 Salmonella Figure 5.1. Survival of Salmonella C and ° at 35 Figure 5.2. Survival of high (97%) RH. Mean and standard deviation of Mean and standard deviation of high (97%) RH. population ( ▲ Salmonella ); black pepper water population ( ); black pepper water ▲ Salmonella aw, (∆). Error bars represent the standard aw, (∆). Error bars represent the standard deviation calculated from three replicate samples; deviation calculated fr om three replicate samples; absence of detection was assigned a value of zero. absence of detection was assigned a value of zero. ) for the analysis was 1.69 LOD Limit of detection ( LOD for the analysis was 1.69 log CFU. log CFU. 9.00 1.0 9.00 1.0 0.9 8.00 0.9 8.00 0.8 7.00 0.8 7.00 0.7 6.00 0.7 water activity 6.00 0.6 5.00 water activity 0.6 0.5 5.00 4.00 0.5 Log(cfu/g) 0.4 4.00 log(cfu/g) 0.4 3.00 0.3 3.00 0.3 2.00 0.2 2.00 0.2 1.00 0.1 1.00 0.1 0.00 0.0 0.00 0.0 0 50 150 200 250 300 100 350 200 300 0 250 150 50 400 100 Time (day) Time (day) Figure 5.4 . Survival of Salmonella C and ° at 35 ° at 25 Salmonella Figure 5.3. Survival of C and ambient (≤40) RH. Mean and standard deviation ambient (≤40) RH. Mean and standard deviation of ); black pepper water ▲ population ( Salmonella population ( of Salmonella ▲ ); black pepper water aw, (∆). Error bars represent the standard aw, (∆). Error bars represent the standard deviation calculated from three replicate samples; deviation calculated from three replicate samples; absence of detection was assigned a value of zero. absence of detection was assigned a value of zero. LOD for the analysis was 1.69 log CFU. LOD for the analysis was 1.69 log CFU. was observed (Figures 5.1 Under high humidity conditions, a rapid decline in the population of Salmonella o o o and 5.2) and was faster at 35 C, the surviving Salmonella population fell below detection C. At 35 C than at 25 o limits (1.69 log CFU/g) after 60 days, while at 25 C, Salmonella decreased below this point after 100 days of FDA Draft Risk Profile | 66

79 Characterization of Contaminants | 5 Salmonella survival storage. In contrast, at low RH, population reduction rates were much smaller, with o o exceeding 280 days at 35 C and 365 days at 25 C (the length of the experiments), as illustrated in Figures 5.3 and 5.4. Figures 5.1-5.4 also illustrate how the humidity of the environment affects the water activity (a ) of w the exposed black pepper and suggests that the population reduction rate is related to the water Salmonella activity of the black pepper. B euchat and Scouten (2002), investigating Salmonella population reduction rates in alfalfa seeds, also found that population reduction rates decreased with decreasing water Salmonella activity or temperature et al . (2007), examining Salmonella Rubi slaw in black pepper, also found . Ristori Salmonella population reduction rates increased with storage temperature but did not find statistically different population reduction rates for a in the range 0.663-0.937. The absence of a significant a w w dependence for the population reduction rate in their experiments may be related to the short time scale of the experiment (15 days) and the limited a range examined (Ristori ., 2007) . Similarly slow population et al w C, Salmonella , o r walnut kerne ls held at 23 reduction rates have been found for ° on almonds, pistachios -24 after initial drying following addition of a wet inoculum (Kimber et al. , 2012; Blessington et al. , 2012) . Although the humidity of the storage environment may vary from location to location and in some locations, may not be well controlled, it may not often reach the high levels examined in the FDA study that resulted in reduced survival of Salmonella . Storage conditions meeting spice industry standards (ASTA, 2011; ESA, 2011) will result in spice with relatively low water activity, a condition that can result in long -term survival of Salmonella, if present. The mechanism by which Salmonella is able to surviv e desiccation so efficiently is an active area of research. Some studies have pointed to that Salmonella morphological changes such as the formation of filamentous cells and multicellular morphology (rdar) during desiccation are critical for its survival (White et al. , 2008; , 2000), while other studies have identified that the o -antigen capsule determined by Mattick et al. et al. extracellular polysaccharides is critical for Salmonella persistence in dry environments (Garmi , 2008; et al. , 2006; Fin et al. , 2012) . Transcription analysis at genomic level suggests the involvement of Gibson n , et al. fatty acids metabolism and osmotic compatible solutes in Salmonella desiccation stress response (Li 2012). The relative importance of these and other factors in facilitating the survival of Salmonella in low moisture foods has yet to be determined. Resistance to heat, irradiation, and disinfectants. Salmonellae are desiccated/dehydrated when in low moisture foods such as spices and desiccation/ e strains of dehydration of som has been shown to increase the organism’s tolerance to heat, UV Salmonella irradiation, and disinfectants (Doyle and Mazzotta, 2000; Hiramatsu et al., 2005; Podolak et al., 2010; Gruzdev -desiccated organism et al., 2011; Keller et al., 2012; Harris et al., 2012) as compared with the non . For o example, Gruzdev et al . (2011) found that application of 100 C for 1 hour to desiccated enterica Salmonella serovar Typhimurium was insufficient to eliminate all viable bacteria in the sample . Other studies have shown that heat and irradiation tolerance are related to water activity of the food/sample (Barrile and Cone, 1970; Goepfert et al ., 1970; Jeong et al ., 2012) . The extent of tolerance can also be dependent on serotype and food matrix (Gruzdev et al et al ., 2012) and decimal reduction s during thermal pathogen ., 2011; Nascimento -linear behavior where the rate of decline decreases with increasing reduction treatments can exhibit non et al. , 2012; Blessington et al. , 2012) . Gruzdev et al. (2011) found that time (Beuchat and Mann, 2012; Abd rehydration of previously desiccated Salmonella may not fully restore susceptibility to heat. These observations indicate that application of pathogen reduction and disinfection methods developed for foods ces may not be as effective as anticipated when applied to spices. other than spi 5.1.4 POTENTIAL FOR GROWTH IN MOISTENED SP ICES AND SPICE -C ONTAINING FOODS The threshold water activity for growth of Salmonella is reported to be 0.94 (ICMSF, 1996) which is much higher than the water activity recommended for storage of spices by the spice industry (≤0.75, ASTA, 2011; Salmonella will not grow in spice when maintained at recommended water 0.65, ESA, 2011) . Therefore, FDA Draft Risk Profile | 67

80 Characterization of Contaminants | 5 . However, we wanted to determine whether Salmon could grow in spice when water is added, activities ella are there sufficient nutrients in spice to support growth when wet that could potentially lead to increased i.e., concentration Salmonella in spice or create Salmonella niches in the spice supply chain environment that s of Whole black pepper could be exposed to moisture during the drying could facilitate cross -contamination? process, if not protected from rain, or during storage, if the packing material is not waterproof . Ground black pepper, either in the production line or in the spice /food manufacturing environment, could become wet during processing/packing as a result of wet cleaning or poor facility design/maintenance . Ground black pepper could also become wet during storage if the material in which it is packaged or stored is not waterproof and the environment in which it is stored is not designed and maintained properly (e.g., holes in the roof, condensation, or high humidity) . In addition, ground black pepper could become wet during food . To minimize the occurrence of preparation in a home or restaurant, e.g., when exposed to steam or humid air (Codex) these possibilities, Codex Alimentarius has developed guidance for spice production, processing and (Codex Alimentarius, 1995) . has developed the Current Good Manufacturing Practices (FDA, use , the U.S 2012a) and the spice and food industries have developed guidance for processing and food manufacturing facilities handling low moisture foods (ASTA, 2011; ESA, 2011; GMA, 2009) . esigned experiments to determine whether Salmonella FDA scientists d can grow in moist/wet black pepper at temperatures typical of spice processing, storage and use (excluding cooking) and if so, whether growth rates are comparable to those in optimized media (Keller et al ., 2013). The water activity threshold for o growth in ground black pepper at 35 C was determined to be 0.979 ± 0.003 (Keller et al ., 2013) which is in other food products (ICMSF, 1996) Salmonella higher than the threshold (0.94) reported for . The difference between the threshold for Salmonella growth in ground black pepper and the threshold reported in other foods may be related to the presence of antimicrobial compounds in ground black pepper but also could be related to other differenc es in the black pepper growth environment as compared with an optimized growth . environment Salmonella generation times in ground black pepper under permissive water activity conditions were short, similar to maximum growth rates recorded in optimal grow th media (ICMSF, 1996) . Therefore, growth of Salmonella could represent a substantial risk to the food industry should the pepper become wet, that is, when industry standards for spice water activity are exceeded. These experiments demonstrated that ground black pepper at water activities near the threshold fo r growth of Salmonella may not be noticeably wet, as shown in Figure 5. 5. Small, local areas of high water activity may be able to develop if condensate or other small drops of water are allowed to contaminate stored black pepper or black pepper dust that may accumulate in the spice processing/packaging or food manufacturing environments . These local areas may also develop from the condensation of moisture from insect respiration (Williams et al. , 2004) . Such small localized areas may not be obvious during storage and manufacture but could result in a significant risk of Salmonella growth in contaminated black pepper products or in the creation of environmental niches. However, generation and lag times increased when the water activity of the ground black pepper was lowered below the optimal value (Keller et al ., 2013). This means that in the case of an accidental addition of water to ground black pepper, growth may be limited if the time for evaporation is shorter than the lag time for growth initiation. Sp ice -containing foods can exceed the threshold water activity value for growth and provide nutrients and an environment that support growth (Combase Consortium, 2012). However, not all moist foods will support growth due to intrinsic characteristics of the food such as pH and salt content. For example, Fedoruk (2011) estimated the risk of salmonellosis from consumption of dairy- based snack food dips made from contaminated spice and found that the acidity of the food limited growth. FDA Draft Risk Profile | 68

81 Characterization of Contaminants | 5 Figur e 5.5. Appearance of ground black pepper at different water activities (a ). w S OF THE NON -TYPHOIDAL SALMONELLO SIS 5.1.5 CHARACTERISTIC Salmonella Dose -Response While there is no dose-response model specifically derived from outbreak investigations or challenge studies Salmonella in spices or low moisture foods, the WHO/FAO developed a dose -response model for of Salmonella in 2002 based on 20 outbreaks associated with food (WHO/FAO, 2002) . Figure 5.6 illustrates the WHO/FAO beta -Poisson model and the insert shows predictions for low dose, illustrating a nearly linear dose -response relationship predicted for doses up to ~20 CFU. Low dose exposures are expected from reported in spices (Section Salmonella consumption of contaminated spices based on the concentration s of 4.1.1 and Table 4.2) and the typical serving size for spice per eating occasion (Section 7.2.2). This beta -5 CFU) would infect 1% of -Poisson model predicts that a dose of approximately 4 CFU (95% CI 3 the exposed population (ID1) while a dose of approximately 63 CFU (95% CI 44- 90 CFU) would infect 10% of the exposed population (ID10). Although data used to develop the dose odel did not include -response m spices, the ID1 predicted by the WHO model is consistent with the rough estimate made by Lehmacher et al . (1995) of 4-45 MPN, based on data from the 1995 salmonellosis outbreak attributed to consumption of contaminated paprika in papri ka -powdered potato chips. Low doses of Salmonella from consumption of contaminated spices would be anticipated from the concentration Salmonella found in contaminated spices of (Table 4.2) and the typical amounts of spice consumed in a single eating occasi on (Section 7.2.2). FDA Draft Risk Profile | 69

82 Characterization of Contaminants | 5 Salmonella . Solid line is expected value; dashed lines Figure 5.6. WHO/FAO dose -response model for bracket 95% confidence limits, derived from WHO/FAO, 2002. Inserted graph is an expansion of the main -60 CFU. graph in the dose range 0 Teunis et al . (2010), analyzing an expanded data set from that used by WHO/FAO and using more complex -level dose- modeling strategies that included a two response model, predicts the ID1 for illness to be 0.395 CFU (95% CI: 0.01-89.7 CFU) response relationship differed by . The study examined whether the dose- serotype or susceptibility (defined as less than 12 years of age or older than 65 years of age) and reported no statistically significant differences in models for different serotypes or susceptibility categories among those 5 considered. Bollaerts . (2008), also using a two -level dose- response model, re- examined the dataset used by WHO et al food matrix combination Salmonella and found differences in dose -response models for different s. serotype- Spices were not among the foods in the data set but an outbreak involving one low moisture food (cheddar . The models developed by Bollaerts et al . (2008) were not able to separate the effects of cheese) was included serotype and food matrix. The dose -re sponse models of Bollaerts et al. (2008) predict larger probabilities of illness for susceptible populations (>60 years of age) for certain ranges of dose. For the serotype -food matrices with the steepest dose- response relationships, susceptible individual s are predicted to have a greater probability of illness at low dose than non- -food matrices susceptible individuals. For the serotype -response relationships, differences in susceptible and non- susceptible populations are with less steep dose 5 Teunis et al. (2010) used his model to estimate the number of people exposed in the outbreak attributed to consumption (1995) of contaminated paprika -powdered potato chips . However, the estimated attack rate taken from Lehmacher et al. quoted in Teunis et al. (2010) was incorrect. FDA Draft Risk Profile | 70

83 Characterization of Contaminants | 5 et al ., 2008) -susceptible predicted for high doses (Bollaerts . For all other doses, susceptible and non populations have similar responses. -response models address the severity of illness or health outcome and whether these None of the three dose differ with age. Primary Disease and Sequelae The onset of symptoms of salmonellosis, a gastrointestinal disease, typically occurs 12 -72 hours after infection and typically lasts 4 -7 days, although times outside the general ranges have been reported (see for example, . Symptoms often include diarrhea, fever and abdominal that, 2003 (reporting on Guthrie, 1992)) pain (CDC, 2013b). Antibiotic resistant strains of can cause complications in patients (Lynch and Salmonella . Death may occur when the infection spreads . Tauxe, 2009) beyond the intestines to other parts of the body Infants, elderly, and immuno -compromised individuals are most likely to have severe symptoms (CDC, 2013b). In addition to these factors, some data suggest that the severity of illness may also depend on se et al ., 2008) . Overall estimates of hospitalization and mortality rates among infected rotype (Jones individuals are 2% and 0.03% , respectively, based primarily on 2000- 2008 public health data (value includes correction for underreporting; Scallan et al ., 2011) and are shown in Table 5.1. . Estimated percentage of salmonellosis cases associated with different health endpoints and Table 5.1 typical duration of illness. a Fraction of Cases Typical Duration Health Endpoint 0.966 4 - 7 days Gastroenteritis: unconfirmed c - confirmed 0.034 11 days Gastroenteritis: culture c 0.019 16 days Gastroenteritis: Hospitalization Mortality in general population 0.0003 n/a b d Reactive Arthritis - ≥7 years 0.5 a et al . (2011b) unless otherwise noted. Data from Scalla Hospitalization and mortality fractions include the correction for n underreporting. Sum of unconfirmed and culture -confirmed cases of gastroenteritis percentages is 1. Percentages for individuals who were hospitalized, died, or later acquired reactive arthr itis are relative to the full set of salmonellosis cases. b Value not well established. See text for details. c Data from Kemmeren et al confirmed illness equated with illness . (2006) based on data collected in the Netherlands; duration of culture- associated with a visit to a medical doctor. d Data from Curry et al . (2010) for reactive arthritis regardless of etiology. See text for details. A breakdown of hospitalization and mortality rates by age from CDC’s FoodNet Surveillance Report for 2011 (CDC, 20 12b) is illustrated in Figure 5.7 . These data suggest that hospitalization rates generally increase with age, with largest rates for individuals who are ≥80 years of age. However, infants (<1 year of age) have an increased risk of hospitalization relative to older children . Fatality rates also increased with age for older adults beginning at ages >40 years old (CDC, 2012b). Reactive arthritis can develop several weeks after initial illness (Locht et al ., 1993; Dworkin et al ., 2001; et al ., 2002; Town es et al ., 2008) in some cases, however the incidence rate is not well established Hannu et al ., 2008; Kemmeren et al. , 2006). Curry et al (Townes, 2010; Townes . (2010), examining reactive arthritis cases among U.S. military personnel, found that reactive arthri tis symptoms can last for years; 35.5% of cases (Reiter’s disease or post -dysenteric arthropathy) still had symptoms after two years and ~30% had symptoms after seven years. Inflammatory bowel disease (IBD) has been associated with salmonellosis (see for example, Helms et al ., 2006; Gradel et al ., 2009; Kemmeren et al ., 2006) but there is disagreement in the literature as to whether a person’s relative risk for IBD is increased following infection with Salmonella (Jess et al ., 2011; Mann and Saeed, 2012). FDA Draft Risk Profile | 71

84 Characterization of Contaminants | 5 . Age dependence of hospitalization and fatality rates for foodborne salmonellosis in the Figure 5.7 . Hospitalization rate (%) (  white bars) and Fatality Rate (%) (  United States, 2010 black bars) as a function of age of the individual with Salmonella -caused illness . Data from FoodNet 2011 Surveillance Report (CDC, 2012b), based on 8273 total laboratory -confirmed salmonellosis infections . 5.2 FILTH Filth can be broadly broken down into three categories, each of which has different health and regulatory et al ., 2001) . In the first category are adulterants that can be direct food safety hazards . This impacts (Olsen group would include hard and sharp ob jects that can cause physical injury to the consumer . This group also contains those insects that exhibit attributes for a contributing factor (synanthropy, endophily, communicative behavior, attraction to excrement and to human food, and ability to harbor pathogens in wild populations; Olsen et al ., 2001), for the spread of food- borne pathogens when there is no effective control in place to eliminate or neutralize the hazard . For example house flies, Musca domestica , are attracted to filth . They also travel between the outside and inside of homes nd readily move between them and human food a and processing facilities and have a close association with people . Most importantly, they are vectors for human diseases and the disease organism can be found in the wi ld populations of the insect . Pava -Ripoll et al . (2012) found Salmonella spp. (6% of the flies tested), Cronobacter spp. (14%) and Listeria monocytogenes (3%) in wild populations of M. domestica . Rats and mice are attracted to excrement, to other pathoge n reservoirs, and to human food. Wild populations harbor food-borne pathogens, especially disease causing strains of scherichia coli , Salmonella , and Listeria . E These diseases can be transmitted from rodent to rodent . Rodents have been implicated in at least nine documented outbreaks of salmonellosis in humans (Olsen et al ., 2001) . Rodents can also be vectors for plague, murine typhus, and Weil’s disease (Vazquez, 1977) . Evidence of their presence in foods, e.g., rodent . hairs and feces, is indicative of insanitary conditions, suggesting failures in the application of GAPs or CGMPs FDA Draft Risk Profile | 72

85 Characterization of Contaminants | 5 The second category includes those filth elements that are alive and/or are clearly detectable and objectionable to the consumer . This category would include live infestation of insects/mites in the food or adulteration with foreign matter associated with objectionable conditions or practices in production, storage, or distribution that are clearly visible to the consumer. The third categor y includes those filth elements that are natural or unavoidable filth and would include hair . The same filth element could be classified in fragments, whole insects or insect fragments, mold filaments, etc all three categories based on its size, life stage, life status (alive/dead), and whether the product has been et al., subject to a microbial kill step (Olsen 2001) . FDA has analyzed spices that were adulterated by all three categories of filth elements at the same time. FDA Draft Risk Profile | 73

86 Overview of Spice Farm -to-Table Continuum a nd Potential Sources of Contamination | 6 6. OVERVIEW OF SPIC E FARM - TO - TABLE CONTINUUM AND POTENTIAL SOURCES OF PATHOGEN AND FILTH C ONTAMINATION An overview of the farm -to-finished product storage continuum for spices created by ASTA is shown in Figure 6.1. This comprehensive figure illustrates the basic processes i nvolved in primary production and secondary processing of spices. Not all spice products pass through each of the processes, e.g., some spices are not subjected to a pathogen reduction treatment, some spices are not ground, and some spices are not . ASTA has included in the figure some of the key ted by ship because they are grown domestically transpor preventive practices that may be used during these phases to support the food safety of spices such as Good ractices (GMPs), moisture control (of dried product), Agricultural Practices (GAPs), Good Manufacturing P process validation, warehouse sanitation, container inspection, and a Hazard Analysis Critical Control Point system . The diagram also notes product cleanliness specifications such as the DALs and the A STA Cleanliness Specifications. Fig -finished product continuum for spices including transport ure 6.1. Typical stages in spice farm -to and processing options and control points . Figure developed by ASTA for “Clean, Safe Spices: Guidance from the American Spice Trade Association” ( Figure 1) published in 2011 by ASTA. Reprinted with permission. FDA Draft Risk Profile | 74

87 Overview of Spice Farm -to-Table Continuum a nd Potential Sources of Contamination | 6 The supply chain from finished spice product- ly simple or very complicated, as to-consumer can be relative illustrated by Figure 6.2. Spice manufacturers may sell /transfer their spice products wholesale to a seasoning manufacturer, food manufacturer, food wholesaler, institutional food service, or restaurant, each of which . Spice manufacturers may also package their own spice will further handle and possibly also process the spice . for retail sale, selling directly to grocers, or retail food establishments where consumers may purchase them Figure 6.2 . Possible pathways for spice from spice manufacturer to consumer. ON 6.1 PRIMARY PRODUCTI Spices are a large, diverse group of plants, some of which have been domesticated, cultivated, and used since the times of the pharaohs to enhance the flavor of foods or as drugs . It is impossible to describe in this report the wide variety of agricultural practices involved for each of the spices . Instead, we provide a brief overview of spices, typical growing practices, and potential sources of pathogen or filth contamination during primary production. Spice and lifecycle diversity Any part of a particular plant can be used as a spice . Table A3 in Appendix A provides a list of over 80 different plants that are used as spices and the part of the plant used or sold in commerce . For this report , they have been grouped into broad categories of bark, flowers, fruit/seeds, leaf, o r roots . These terms are not of the term . For example, the flower group used in their narrow botanical definitions but in the colloquial use FDA Draft Risk Profile | 75

88 Overview of Spice Farm -to-Table Continuum a nd Potential Sources of Contamination | 6 contains whole dried flowers such as ) or just part of the flower such as the calendula ( Calendula officinalis saffron Crocus sativus ( saffron) ; or the dried flower bud such as cloves, Syzygium aromaticum . n of stame ); bulbs such as onion ( Allium Similarly, the root group includes rhizomes such as ginger ( Zingiber officinale . The part of the Allium sativum s such as horseradish ( Armoracia lapathifolia ) ); or true root ) or garlic ( cepa plant used has a great impact on how it is harvested, dried, processed, and the kinds of pests that may affect it. g as well . Some plants are annuals, Likewise, the life cycle of the plant has a great influence on its processin coriander ( Coriandrum sativum Myristica fragrans ), while others are ); others are perennials, nutmeg/mace ( Capsicum annuum, C. frutescens ). long lived annuals or perennials that are grown as annuals, chili peppers ( . Some The growth pattern of the plant influences the ease of harvest and exposure to potential pathogens spices grow on vines, e.g., black pepper ( ), others are leafy shrubs, e.g., oregano ( Lippia spp. ), Piper nigrum Myristica fragrans ). while others are the fruits of a tall tree, e.g., nutmeg or mace ( In some cases may not be known. For example, spices sold as , the species of the plant that sold in commerce regano ” may be any of over 200 species of herbs, shrubs, or small trees of the family Verbenaceae, genus, “o . “Oregano ” may also be of the family Labiatae, Origanum vulgare but the same species may also be Lippia 2012f) of “Spices and other natural named “marjoram .” FDA regulations at 21 CFR 182.10 ( FDA, provide a list seasonings and flavorings” by common and botanical name that are considered to be “Generally Recognized as Safe” (GRAS) substances. To add to the confusion regarding precise identification of source plant materials, there have been significant taxonomic changes since the last revision of 21 CFR 182.10 (FDA, 2012f) . Growing practices As discussed in more detail in Chapter 7, many types of spices grow in tropical or semi . -tropical environments A few are tem perate crops (garlic, onion, mustard, horseradish) . The size of the farm and the agricultural techniques used to grow spices varies with the particular spice and growing region. For example, many spice farms in India are comprised of an acre or less and la rge farms typically contain less than 100 acres. In contrast, in the United States spice -producing farms are typically larger, where small farms are typically comprised of tens of acres and large farms are typically comprised of hundreds of acres. Of cours e, only a few types of spices can be easily grown on farms in the United States (see Chapter 7 for a discussion of spice production). Spices can be grown in monoculture (chili peppers, garlic), intercropped with other species (black pepper grown with nutm eg/mace, rubber, cocoa, etc.), wild -crafted (collected in the wild) or semi -wild -crafted (oregano/marjoram). Many spices are produced on very small farms where farm animals are used to plow, irrigation water is taken from nearby surface water sources, fert ilization is achieved with manure/soil - amended manure, and crops are harvested by han d. Spice source plants on these farms are on mats, cement , but may in some cases be left to dry directly on the ground. slabs, or on raised platforms in the sun spices (e.g., capsicum in India or dehydrated garlic in the United States) a larger spice company may For some and supply them with seed, fertilizers, pesticides, and technical expertise on contract with growers agricultural and food safety growing and harvesting practices . Spice farms in the United States producing dehydrated onion and garlic are generally owned by or contracted with a single spice company that dictates/controls growing and harvest practices and may even provide their own proprietary seed . Use of automated equipment to plant, grow and harvest the spice source plant crops, and temperature/moisture to dehydrate source plants is more common on large farms. controlled ovens Spice s are typically cleaned to remove foreign matter and extraneous materials at the primary production site but may also undergo additional cleaning at one or more points along the supply chain. The cleaning process can range from hand sorting to remove sticks, stones, or other extraneous materials to the use of simple . The technology for cleaning brushing, or sieving machines to remove the extraneous materials winnowing, FDA Draft Risk Profile | 76

89 Overview of Spice Farm nd Potential Sources of Contamination | 6 -to-Table Continuum a spices typically involves simple milling and sieving employed during primary . Metal detectors are commonly processing to remove extraneous metallic material that may have inadvertently been added to the spice during harvest or processing (e.g., a staple). Potential s ources of pathogens or filth in spices during production A variety of animals including birds, animals, rodents, reptiles, insects, and humans may introduce Salmonella or filth into the spice production environment. Once present in the environment, Salmonella may remain viable for long periods and may possibly e ven grow in the soil, irrigation water, manure or soil- amended manure (Chapter 5 and references therein). Spice source plants may become contaminated with Salmonella imals or environmental materials come in contact wi th or other pathogens when contaminated an them. During the traceback investigation for one spice -related outbreak, the importing company declared that manure fertilizer used during production was the likely contamination source ( Koch et al. , 2005; Chapter 2) . In addition to fertilizer source, water quality, application method (overhead, flooding, or drip), and irrigation timing, as well as animal access to the crop are likely to be critical parameters in determining whether the spice source plant or (dry) sp ice could become contaminated. In a review of risk factors for microbial contamination of fruits and vegetables, Park et al. (2012) identified contaminated irrigation water and soil as among the most critical and the prevention and control of contamination in irrigation water and soil as the most effective targets for pre- harvest risk management. The drying phase for spices is another critical point where filth and pathogen contamination may occur, particularly for spices that are dried in the open environment on mats or directly on the gro und for extended periods (1 -7 days) . During drying, the spice may be exposed to possible rodent, bird, flies, and field pests. If the spices are not dried quickly enough or adequately, mold growth may take place . Some strategies for drying spice source pl ant material can reduce the risk of contamination during this phase, for example, use of raised platforms with simple tarp roofs will reduce the risk of contamination of spices by bird feces as compared with drying on mats on the ground without a roof. Cr oss -contamination from equipment to spice source plants or spices may take place if equipment used to plant, harvest. dry or store the spice source plants becomes contaminated and is not adequately cleaned. Human transfer of pathogens or filth is possible when harvest or other aspects of the production process are primarily manual and personal hygiene is insufficient. Filth is not a major issue during the pre e the spice has not developed. As the plants -cultivation step becaus y important parts start to develop , the risk of contamination by filth get older and the economicall such as insects and animals increases (Table 6.1) . Cross -contamination from equipment or field workers can also be an issue during primary production. Contamination of the spice of inte rest with other parts of the dried source plant may occur if appropriate cleaning/harvesting methods are not applied. The ranking in Table 6.1 was derived by FDA from site visits, knowledge of source plants and pests, and data on filth adulteration of e. spic The extent to which the identified potential sources of contamination contribute to contamination of spice depends on the specific production practices employed. FDA Draft Risk Profile | 77

90 Overview of Spice Farm nd Potential Sources of Contamination | 6 -to-Table Continuum a Table 6.1. Evaluation of risks for filth contamination at different stages during the production of spices 1 Production steps Filth - cultivation - Pre Field Cultivation + ++ Harvest Intermediate storage +++ Transportation (+) Processing (cleaning/cutting/drying/packaging) + 3 Final product (package/stored) to ++ - 1 Explanation of symbols: - usually no risk, (+) no to low risk, + low to medium risk, ++high risk, +++ very high risk. 3. The risk depends on the packaging of the spice and how it is stored. 6.2 DISTRIBUTION AND STORAGE The distribution system can be ver y complex and as a result, storage may occur at many different points. Some crops are harvested, processed, and sold relatively quickly because their quality starts to decrease immediately upon picking (for example, capsicum) . Other crops, if left whole, have a long shelf life . For . FDA personnel learned -7 years before it is sold example, whole black pepper can be held in storage for 5 during their visits to India that because black pepper is a readily sold cash crop, small farmers may keep the d) spice on site for years, to serve as an emergency fund for unexpected events. whole (drie . In India, black pepper is often sold Producers may sell to a local buyer or directly to a spice processor/packer . The buyer consolidates small lots from tens to to a local buyer, sometimes in lots as small as one kilogram . The regional buyer hundreds of farms to create a 50 -100 kilogram lot, which is then sold to a regional buyer s spice into a much larger lot to sell on the NCDEX (National Commodity and Derivatives Exchange Ltd., collect Mumbai; 1 metric tonne needed ) or directly to a spice processor/packer. Larger farms may produce sufficient volumes of spice to avoid some of the aggregation steps (that may increase the risk for contamination of the spice) and the ensuing delay to market associated with it. Some spice manufacturers who contract groups of farmers for production of spices may coordinate and control aggregation of spices from contractors. Spice processing may take place before and/or af ter export. For example, the Spices Board of India has their spices to undergo filth and pathogen reduction created “spice parks” where producers can bring Spices Board India, treatments as well as microbiological testing to ensure compliance with U.S. standards ( 2013; see discussion of the Indian EIC certificate program in Chapter 8 for more details on processing of black pepper ). Individual shipments of imported spice offered for import to the United States often contain large amounts of Table C1; Van Doren et al. , 2013c ). After arrival, the spice, e.g., thousands or tens of thousands of kilograms ( -packaged and distributed multiple times before being used in food lot may be processed, and/or re preparation . Potential s ources of pathogens or filth in spices during distri bution and storage At each stage of the often complex and lengthy stored for some period. spice distribution process, spice is This characteristic of the spice farm -to-table continuum makes proper packaging and storage a critical issue for preventing conta mination. When improperly packaged or stored, the spice may become contaminated through contact with animals or contaminated soil, water, or equipment, or may become wet, which can facilitate the growth of pathogens such as Salmonella and/or mold. Re -use o f storage bags/boxes may enhance the potential for contamination of spice, particularly if the bag is in direct contact with the spice. FDA Draft Risk Profile | 78

91 Overview of Spice Farm -to-Table Continuum a nd Potential Sources of Contamination | 6 FDA observed problems with storage conditions during some of its site visits and inspections. Some facilities es in walls, ceilings, or roofs. These facility had gaps in walls or around doors, open unscreened windows, hol provide opportunities for insects, rodents , birds, an d water to enter the facility. FDA analysis of filth features in shipments of imported spice offered for entry to the United States during the three adulteration of spices - FY2009 found that most of the insect adulterants were stored product pests, indicative of year period FY2007- poor handling, storage, and cleaning of the spices. Transportation can also be a source of contamination if trucks and cargo holds of ships are not maintained, cleaned or sanitized, and spice packaging allows the spice itself to come in contact with contaminated . Adulteration has been documented for other commodities surfaces . in transit The extent to which the identified potential sources of contamination contribute to contamination of spice depends on the specific distribution and storage practices employed. AND MULTI - C 6.3 SECONDARY PROCESSING OMPONENT FOOD MANUFACTURING As with the other stages of the spice supply, the practices involved in processing, packing and food . Spice secondary processing typically includes additional cleaning steps manufacture can vary tremendously hogen reduction treatment, and for some spices, grinding, to remove element of filth, application of a pat practices can vary tremendously among facilities and firms. cracking and/or blending procedures. Processing For example, some spice processors/packers may pack finished spice product manually while other use a completely automated system. Smaller firms tend to use less automation and may use common pieces of equipment or lines for different spices or processing activities. Combinations of practices in a single firm has also been observed. majority of spices in U.S. commerce are used by food onversations with ASTA, we know that a Based on c manufacturers as ingredients in the production of multi -component foods. These secondary manufacturers -national corpora tions. Some spice is also sold to foodservices and range in size from very small firms to multi to retail outlets for consumers, as shown in Figure 6.2. restaurants (or restaurant chains) as well as -component foods can be as complicated as the myriad of foods curren tly Manufacturing processes for multi available on the U.S. market. However, three basic scenarios illustrate the spectrum of possibilities with regard to the application of a pathogen reduction step 1) a manufacturing process that does not include any : ( pathogen reduction e dry spice blends); ( 2) a manufacturing process that includes a pathogen step (e.g., som reduction 3) a step after the spice ingredient has been added to the food (e.g., canning of low acid foods); ( manufacturing process that includes a pathogen reduction step before add ition of the spice ingredient(s) to the food (e.g., spice coatings on deli meats/cheeses, snack food coatings, garnish). In the case of (1) and (2), manufacturers typically use spice that has been already subjected to a pathogen reduction step (e.g., by th e spice processor). ources of pathogens or filth in spices during secondary processing and multi -component food Potential s manufacturing In a recent review published in the Journal of Food Protection, Podolak et al . (2010) identified five factors contrib uting to contamination by Salmonella in low -moisture food manufacturing: ( 1) contamination associated with poor sanitation practices; ( 2) contamination associated with poor facility and equipment design and maintenance; ( 3) contamination associated with lack of GMPs; ( 4) contamination associated with poor ingredient control and handling; and ( 5) contamination associated with poor pest control. The review provided many examples from foodborne outbreaks attributed to these types of system failures. FDA Draft Risk Profile | 79

92 Overview of Spice Farm nd Potential Sources of Contamination | 6 -to-Table Continuum a Cleaning and sanitation is particularly challenging in facilities processing low moisture foods because the presence of water, used to clean equipment, floors and walls, may facilitate growth of Salmonella or other pathogens, once present in the facility environment , which could lead to sustained opportunities for cross - Salmonella niches . For this reason, spice processors and food contamination through the creation of tation methods, particular in the manufactures of low moisture foods generally apply dry cleaning and sani Salmonella et -pathogen reduction treatment area in the facility (Chen “Primary Control Area (PSCA),” the post ., 2009b; GMA, 2009) . In some instances, wet cleaning is used, e.g., after grinding dehydrated garlic and al prep aring to grind cinnamon with the same grinder. If the equipment cannot be disassembled, it is cleaned in place. FDA personnel observed excess water on floors and near spice grinding/mixing equipment during site visits to both domestic and foreign spice processors. The potential for to actively grow under Salmonella and create niches in the processing environment from which cross these specific conditions -contamination . may occur cannot be ruled out without further study for food contact surfaces may not remove all spice particles or eliminate Dry cleaning and sanitation methods all Salmonella . As a result, use of common equipment for processing different spices or foods, such as a common grinder or common transfer line, can lead to cross -contamination of previously uncontaminated spice with contaminated spice. During a visit to one facility, FDA personnel observed that the same piping ce to the finished product area and the was used to transfer raw and pathogen reduction treated spi processing worker was una ware that the system allowed for cross -contamination of treated spice with untreated spice. For spices, grinding/crushing/cracking of whole spices creates a lot of spice dust that, if not contained, may lead to cross -contamination in a processing facility . For example, widespread spice and Salmonella -contamination was suspected as a contributing contamination of the grinding room was found and cross cause of the 2009 Salmonella . Salmonella was also Rissen outbreak associated with ground white pepper in the environment of 10% of domestic spice manufacturing/packing/re- packing facilities inspected in found 2010 (Aug -Dec) . When air, personnel and material flow is not adequately controlled, “raw” spice that may be contaminated with Salmonella may contaminate sp ice in the PSCA (after it has undergone a pathogen reduction treatment) (see examples in Podolak , 2010 and GMA, 2009). et al. As noted above, FDA has learned that some spice does not undergo a pathogen reduction treatment during the secondary processing phase. If contaminated spice does not undergo such a treatment or kill step before consumption, consumers may become ill. In many cases, spice processors sell untreated spice to a food manufacturer who will apply a lethality step to the spice before allowi ng it to reach the consumer. Ineffective or inefficient pathogen reduction treatments may allow some Salmonella to survive. Pathogen reduction treatments that have not been validated or for which the process parameters are not monitored and verified, have the potential for insufficient treatment. Spice processors as well as seasoning and food manufacturers that purchase spice that has not been produced, transported, distributed, or stored using appropriate preventive controls may have a higher risk of pur chasing contaminated spice. inspections of domestic spice facilities found that pests were the most often c ited CGMP violation . FDA Surprisingly, most of the facilities inspected for which information was available, did have established pest control prog rams. Pests can transfer Salmonella or other pathogens from one location to the spice . Poor facility design and lack of control of movement of people and material in areas where finished product is located can enhance opportunities for contamination of t he environment or cross -contamination to the product (see for example, Podolak et al. , 2010 and Beuchat et al. , 2013). The extent to which the identified potential sources of contamination contribute to contamination of spice -component food manufacturing practices employed. depends on the specific spice processing and/or multi FDA Draft Risk Profile | 80

93 Overview of Spice Farm nd Potential Sources of Contamination | 6 -to-Table Continuum a 6.4 RETAIL/END USER Retailers (institutional foodservices, restaurants, and retail food stores) may source their spices from a rehouses, re- packers, secondary processers diversity of company types including importers, wa (grinders/blenders) and wholesalers . Depending on the retail facility type, spice may be stored in a large warehouse, small storage room or directly in the kitchen area and/or customer access areas. Consumers purc hasing spice for home use may obtain their spice products in small pre -packaged retail containers or from bulk bins via direct purchase from retail stores, markets, internet venders, etc., or from home gardening (limited by climate) . Storage in consumers’ homes can be in the kitchen, pantry or elsewhere, in the original . When adding spice retail packaging or transferred into other containers (e.g., spice rack specific containers) to foods, it is not uncommon for food preparers to shake the spice out of its container directly into the food or cooking pot rather than using a utensil to do so. Potential s ources of pathogens or filth in spices in the retail or home environment The greatest concern for spice at the retail/home setting is the potential for growt h of Salmonella in foods to which contaminated spice has been added when food is not maintained at an appropriate temperature. It is suspected that growth contributed to the illness rates observed in several of the spice -related outbreaks, such -containing tea (Chapter 2). It is not known whether the practice of as the outb reaks associated with spice shaking a spice container over a pot during cooking can add sufficient moisture to the container to allow growth of . Keller et al . (2013) found that initiation of Salmonella growth in contaminated ground Salmonella black pepper at permissive water activities and room temperature generally includes a long lag -time. In such a case, evaporation of added moisture may reduce the water activity of the spice below the t hreshold for growth before growth begins. (Keller et al. , 2013). Cross -contamination may also take place, if the spice is allowed to come in contact with contaminated . surfaces in the food preparation area such as the surfaces of common utensils used for spices and other foods Contamination of spice by insects or rodent feces/hairs may take place if the spice is kept in open con tainers for extended periods and insects and rodents can enter the facility . These pests, if allowed access to the spice, can int roduce pathogens into the spice. The extent to which the identified potential sources of contamination contribute to contamination of spice depends on the specific distribution and storage practices employed. FDA Draft Risk Profile | 81

94 7. SPICE PRODUCTION AND CONSUMPTION Y 7.1 U.S. SPICE SUPPL N 7.1.1 U.S. PRODUCTIO Only five spices are produced in the United States in large quantities: dehydrated onion, dehydrated garlic, capsicum, mustard seed, and sesame seed (USDA/ERS, 2012a -c; ASGA, 2012) . Dry weight production values . The value for are available from the USDA Economic Research Service and are shown for 2010 in Table 7.1 garlic in Table 7.1 includes production for both the dehydrated and fresh markets (converted to dry weight); . As of 2010, imports of four out of five of these spices separate values are not available (USDA/ERS, 2012b) exceeded U.S. production (USDA/ERS, 2012a -c). Table 7.1. U.S. production of s pices in 2010: Dehydrated onion, dehydrated (and fresh) garlic, capsicum, mustard seed, and sesame seed. U.S. Production Spice (million lbs., dry weight) a 104.3 Dehydrated Onion b Dehydrated and Fresh Garlic 138.4 c Capsicum 93.0 c 41.9 Mustard Seed d Sesame Seed >22 a Dehydrated weight, estimated by dividing fresh weight by factor of 9 . Data and conversion factor from USDA/ERS (2012a) b Dehydrated weight for combined dehydrated and fresh garlic supply, estimated by dividing fresh weight by factor of 2.7 Data and conversion factor from USDA/ERS (2012b). c Data from USDA/ERS (2012c). d Data from ASGA (2012) which reported “over 11,000 tons .” Domestic production of dehydrated onions is much larger than import, and has been for at least the past 30 total U.S. supply was produced domestically (USDA/ERS, 2012a) years, Figure 7.1. As of 2010, 90% of the . Production far exceeds U.S. needs for the food supply; approximately half of U.S. production is exported (USDA/ERS, 2012a) rated onion imports have grown over the last . Although small in a relative sense, dehyd . decade in both absolute and relative terms (USDA/ERS, 2012a) Domestic production of garlic (dehydrated and fresh) accounted for all of the U.S. supply until 1969 and then ~85% of the U.S. supply until 1997, F igure 7.2 . After 1997, the relative contribution of domestically produced garlic began to decrease annually, until 2006 . Comparing absolute production and import values for the period after 1997, one finds that the observed change arose from an acceleration of garlic imports and a relatively stagnant , then decreasing , domestic production (USDA/ERS, 2012b) . Since 2006, imports have surpassed domestic production, but only slightly . A change in U.S. import restrictions issued in 2011 may expand garlic imports even further by allowing importation from the European Union and several other countries (39 countries in all) (USDA/APHIS, 2011). FDA Draft Risk Profile | 82

95 Spice Production and Consumption | 7 Figure 7.1 . Relative contributions of domestic and imported dehydrated onion to the total annual U.S. supply, 1970 to 201 0. Total annual supply values used to calculate relative contributions only include new crop and imports; beginning stocks and loss of domestic product during processing were excluded. Data derived from USDA/ERS 2012a. Figure 7.2 . Relative contributions of domestic and imported garlic to the total annual U.S. supply, . Data includes California production only (the major producing state) and combines 1960 to 2010 dehydrated and fresh garlic . Data derived from USDA/ERS (2012b). The relative contributions of domestic production and importation of capsicum to the total U.S. spice supply have varied over the years, Figure 7.3, while the total supply has increased more than 750%, from 41.5 million pounds in 1966 to 320.8 million pounds in 2010 (peak supply was 382.9 million pounds in 2006; USDA/ERS, 2012c). The increase in the relative contribution of domestic capsicum production to the supply from 1966 to 1980, Figure 7.3, is a reflection of increased domestic production; imports wer e approximately . After 1980, both domestic and importation supplies constant during that period (USDA/ERS, 2012c) FDA Draft Risk Profile | 83

96 Spice Production and Consumption | 7 increased through 1992 but after 1992, domestic production generally decreased while imports continued to increase in volume (USDA/ERS, 2012c) . The contribution of imported capsicum to the total supply has exceeded domestic production since 1998 . In 2010, domestic production of capsicums constituted 20% of the total capsicum supply (USDA/ERS, 2012c) . Figure 7.3 . Relative contributions of domestic and imported capsicum (including paprika) to the total annual U.S. supply, 1966 to 2010. Data includes California production and New Mexico production (beginning 1976) . Data derived from USDA/ERS (2012c). The U.S. supply of mustard seed is also primarily derived from imports, Figure 7.4 . From 1966 to 2010, imports have contributed more than 60 % of the total U.S. supply (except for 2002, when U.S. production was uced domestically exceptionally large; USDA/ERS 2012c). In 2010, 20% of the mustard seed supply was prod (USDA/ERS, 2012c). Production of domestic sesame seeds has recently increased from approximately 5 million pounds per year to over 22 million pounds in 2009 and 2010 (ASGA, 2012) . As a proportion of the supply, the domestic 2010 represents at least 21% of the total supply (USDA/ERS 2012c; ASGA, 2012) production in . Part of this growth in production can be attributed to the development of non -dehiscent varieties, which allow drying in the field and mechanical harvest techniques to be used (ASGA, 2012) . Several other types of spice source plants can grow effectively in the United States, e.g., basil, oregano and thyme, and are even wild harvested (see for example, Oregon’s Wild Harvest, 2012) but production of the (dried) spices is small. FDA Draft Risk Profile | 84

97 Spice Production and Consumption | 7 Figure 7.4 . Relative contributions of domestic and imported mustard seed to the total annual U.S. supply, 1966 to 2010. Domestic mustard seed production weights used to calculate relative contribution is determined from the previous year’s production m . Data derived from USDA/ERS inus product used as seed (2012c). 7.1.2 U.S. IMPORTS The United States is the single largest export market for spices (International Trade Center UNCTAD/WTO, . Import data for 2006), importing more than 1.1 billion pounds of spices in 2009 (USDA/ERS 2010, 2011a) individual spices are provided by the USDA Economic Research Service (USDA/ERS, 2010) and data for 2009 is provided in Table 7.2 . The relative contributions to total imports are calculated for each spice with the caveat that garlic has been excluded (because the relative proportions of imports intended for the dehydrated market is not available) . While five spices (capsicum, mustard seed, black and white pepper (tabulated together), and ginger root) accounted for one half of the 2009 imports by weight, a much large r number of . Indeed, the USDA Economic Research Service found in its spices and spice blends account for the other half 2007 report that “the share of traditional spices, such as peppers, cinnamon, and vanilla de clined [between 1998 and 2007] as the U.S. palate increasingly sought diverse tastes and increased its demand for such products as nutmeg, saffron, fennel and turmeric” (Brooks et al. , 2009). Spices are primarily produced in developing countries (Internat ional Trade Centre UNCTAD/WTO, 2006). However, d ata from the USDA Foreign Agricultural Service (FAS) on U.S. imports of spices show that spice imports to the United States came from over 140 countries (USDA/FAS, 2011) . Table 7.3, derived from FAS tables, i dentifies the top 20 countries for 2010 U.S. spice import, based on value; dehydrated onion and garlic are not included in these figures . The table also provides a comparison of imports from the same countries one decade earlier . Comparing 2010 with 2000, we see that total spice imports increased by nearly 60% by value over this time period, with imports valued at more than 1 billion dollars in 2010 . The relative contribution to spice imports from different countries has also changed with time . FDA Draft Risk Profile | 85

98 Spice Production and Consumption | 7 7.2 . Spice imports in 2010 by weight. Table a b 2010 Import Weight (million 2010 Percent of Total Spice Imports Spice pounds) (%) c 227.8 Capsicum 18.7 Mustard Seed 169.3 13.9 Pepper, Black and White 12.8 155.4 Ginger Root 97.4 8.0 Sesame Seed 81.6 6.7 Cassia 54.3 4.5 and Cinnamon 22.7 1.9 Cumin Seed d 1.5 17.8 Dehydrated Onion Coriander Seed 10.6 0.9 Poppy Seed 10.2 0.8 Fennel Seed 8.6 0.7 0.6 Turmeric 7.8 Caraway Seed 0.5 6.2 0.4 Sage 5.0 Anise Seed 4.7 0.4 Celery Seed 4.7 0.4 Vanilla Beans 3.9 0.3 Nutmeg 3.9 0.3 Pimento (Allspice) 2.8 0.2 Cloves 2.8 0.2 Mace 0.1 0.7 e e Dehydrated and Fresh Garlic – 159.6 317.7 26.1 Other Spices Total Spice Imports (excluding dehydrated garlic) 1215.9 100.0 a USDA/ERS (2012c), unless noted otherwise Data from b Total spice weight used to calculate percent values excludes garlic. c Capsicum includes dried capsicum and paprika. d Dry weight equivalent. Data from USDA/ERS (2012a). e /ERS (2011b). Dry weight equivalent. Data from USDA FDA Draft Risk Profile | 86

99 Spice Production and Consumption | 7 2010. Table 7.3. Spice imports by value, 2000- Change in Percentage 1 1 2000 Import Value 2010 Import Value 2010 Percent of All of All Imports, 2000- Country Imports (million $) (million $) 2010 101.9 161.8 16.1 - 0.1 India Indonesia 146.2 14.6 - 6.5 132.4 109 China 10.9 6.6 26.9 Canada 30.2 70.9 7.1 2.3 Mexico 42 64.3 6.4 - 0.3 Vietnam 64.3 6.4 3.4 18.6 4.9 49.5 Peru 4.7 1.5 Spain 17.7 42 4.2 1.4 Brazil 40.7 39.9 4 - 2.5 2.8 Madagascar 28.3 30.6 - 2.0 Guatemala 20 23.7 2.4 - 0.8 Turkey 18.4 20.4 2 - 0.9 0.7 Egypt 7.3 19.2 1.9 Germany 15.6 1.6 0.9 3.9 1.5 15.4 Sri Lanka 0.3 7.4 1.3 Israel 12.6 10.4 - 0.4 France 5.9 10.4 1 0.1 Colombia 0.5 10.3 1 1.0 Syria 7.5 8.1 0.8 - 0.4 Pakistan 1.8 7.2 0.7 0.4 Other Countries 102.4 83.3 8.3 - 8.0 World Total 1002.4 100 627.9 - 1 Data from USDA/FAS (2011). China’s share increased by 6.6 percentage points from 2000 to 2010 while that of Indonesia decreased by . Smaller gains in import share during this period were observed for Peru, Vietnam, and nearly that amount Canada, in decreasing order of gain . In 2010, India, Indonesia and China together provided nearly 42% of . Ten countries supplied 77% of spice imports by imported spices (excluding dehydrated onion and garlic) dehydrated onion and garlic) . It is also noteworthy that some countries , for example, value in 2010 (excluding that are not major spice producers, are major exporters of spice to the United States Germany, . These lend, or re -package it before exporting it countries import spice from developing countries and may process, b to the United States . In 2007, crushed black pepper imports from Germany were valued at $8 million (Brooks et al. , 2009). The relative contributions from each country to U.S. supplies of individual spices have be en reviewed by the USDA Economic Research Service for 1980 -1994 (Buzzanell , 1995) and 1998- 2007 (Brooks et al. , 2009) . et al. In 2007, capsicums were primarily imported from China, Mexico, Peru and India whereas black pepper was imported from Brazil, Vietn am and India (Brooks, et al. , 2009) . Mustard seed is primarily imported from Canada (Buzzanell et al. , 1995) while ginger is primarily imported from China (Brooks et al. , 2009) . More than 70% of vanilla imports in 2007 were from Madagascar with smaller contributions from Uganda, Indonesia, . Cumin seeds are imported from a number of countries including India, Syria, India and Papua New Guinea Turkey, China and Pakistan while cinnamon is imported from Indonesia, Sri Lanka, Vietnam, Brazil and China . The co untry- spice import matrix for the United States continues to evolve . Appendix B lists the main spice - producing countries and their absolute and relative contributions to world -wide production for 2010. Review of the tables included in Appendix B (from FAO 2013a -b) demonstrate the wide diversity of production countries and illustrates the potential for future growth and evolution of the U.S. import market. FDA Draft Risk Profile | 87

100 Spice Production and Consumption | 7 7.2 SPICE CONSUMPTIO N IN THE UNITED STAT ES OPULATION 7.2.1 CONSUMER P in July 2009, A large fraction of the U.S. population consumes spices. Based on a retail study of household use an estimated 86% of households in the United States use fresh or dried herbs, spices, or seasoning blends (Mintel International Group, 2009). A similarly large fraction, 78%, o f households report using herbs, spices and seasoning blends beyond salt and pepper (Mintel International Group, 2009). Small differences in . Among the survey household use by gender, age, ethnicity/race, and household income are reported -65+ years), a slightly larger percentage of women (84%), people in the age range 25 participants (aged 18 -34 (82%), Hispanic households, and households with annual incomes in the range $100K- 149K (84%) report using herbs, spices and seasoning blends other than salt and pepper (Mintel International Group, 2009) . These estimates do not include the additional percentage of the population that may only consume spices in foods prepared or seasoned outside the home, e.g., by food manufacturers, food services, restaurants or other prepared food suppliers . Indeed, a majority of the spice supply is sold wholesale and most is ultimately ., 1995). et al incorporated into prepared foods (Buzzanell 7.2.2 CONSUMPTION MA REQUENCY SS AND F n the United States is provided by the USDA Economic An estimate of annual per capita spice consumption i This estimate is based on annual food availability data and the U.S. population. From 1966 Research Service. to 2010, per capita consumption of spices other than dehydrated onion and garlic, increased ne arly 300%, with an average rate of increase of 0.5 lbs./decade (USDA/ERS, 2012c), Figure 7.5 . Per capita consumption of garlic, dry and fresh, has also increased dramatically with a rate of increase of ~0.3 lbs./decade (dry weight equivalent rate), between . In contrast, per capita consumption of 1970 and 2010 (USDA/ERS, 2012b) dehydrated onion, as estimated from the total net supply, has been approximately constant since 1970 (USDA/ERS, 2012a) . In 2010, annual per capita consumption of spices excluding dehy drated onion and garlic was approximately 3.47 lbs. (1575 g) and including dehydrated onion was approximately 3.64 lbs. (1653 g; USDA/ERS, 2012c) . Assuming spices are consumed in three meals per day, the per capita spice consumption is estimated to be 1.4 g per eating occasion. FDA Draft Risk Profile | 88

101 Spice Production and Consumption | 7 Figure 7.5. Annual per capita spice c onsumption in the U.S excluding dehydrated onion and garlic, 1966- Data from USDA/ERS (2012c). 2010. The FDA/CDC National Health and Nutrition Examination Surveys (NHANES), employing the U.S. EPA Food Commodity Intake Database (FCID), which includes commodity -specific intake data derived from the What We Eat in America daily spice intake for spice consumers in the United (WWEIA) survey, provide estimates of States . For 2003- 2006, average daily consumption was approximately 1 g for spices other than capsicum and 5 g for spices including capsicum (Di Novi and Edwards, 201 3; EPA, 2012a) . These estimates include consumption of fresh herbs and chili peppers and are derived from standard recipes for foods consumed and . Based on these estimates, the mean spice consumption per eating occasion is 0.3 -1.7 g reported to WWEIA for 3 eating occasions per day (Di i and Edwards, 201 3; EPA, 2012a). The inclusion of fresh herbs and chili Nov peppers (in capsicums) positively biases this estimate while the use of standard recipes, which do not necessarily include minor spice ingredients, increases its uncertainty . Daily or eating occasion consumption estimates for certain individual spices are available from the NHANES database while others can be derived from food availability data . The NHANES database indicates that the highest mean eating occasion consumption estimates for individual spices are for sesame seeds and dried basil, at approximately 150 mg/eating occasion (Di 3; EPA, 2012a) . Capsicum Novi and Edwards, 201 consumption is larger, ~1.4 g/eating occasion, but this value includes dry and fresh . Table 7.4 provides estimates for daily consumption of a wide range of spices based on food availability data . Except for dehydrated onion and the combined estimate for dehydrate and fresh garlic, where net supply estimates are available, the consumption estimates in Table 7.4 provide upper limits to the per capita daily consumption of each spice because the values are derived from gross supply data. Further, the per capita estimates assume all consumer. These spices in the supply are consumed each year and that everyone in the population is a FDA Draft Risk Profile | 89

102 Spice Production and Consumption | 7 assumptions increase the uncertainty in these values as measures of true consumption. Finally, the food availability -based daily consumption estimates for spices that are infrequently consumed or consumed by . only a small segment of the pop ulation, will provide particularly poor estimates of actual consumption a Table 7.4 . Estimated per capita spice consumption based on food availability, 2010 . lbs./yr. g/day Spice b Capsicum 1.0 1.3 1.0 1.3 Other spices c Dehydrated and Fresh Garlic 0.9 1.1 Mustard 0.7 0.8 Black and white pepper 0.6 0.5 0.4 Sesame seed 0.3 Ginger 0.3 0.4 Dehydrated Onion 0.2 0.2 Cassia 0.2 0.2 Cumin 0.07 0.09 Coriander 0.03 0.04 Poppy 0.04 0.03 Fennel 0.03 0.03 0.03 0.03 Turmeric 0.02 0.02 Caraway 0.02 0.02 Sage 0.02 0.02 Anise Seed 0.01 0.02 Vanilla Beans 0.02 0.02 Celery 0.01 Cloves 0.01 Allspice 0.01 0.01 Mace 0.003 0.002 a , Based on gross supply (USDA/ERS, 2012c) except for dehydrated onion and garlic, where net supply data was available (USDA/ERS 2012a -b). See text for discussion. b Includes paprika c ated by dividing fresh weight by factor of 2.7 Data and Dehydrated weight for combined dehydrated and fresh garlic supply, estim conversion factor from USDA/ERS (2012b). Estimates of the variability and frequency of spice consumption for all spices, for individual spices, and for different segments of the population are not av ailable . We know that some dishes or foods contain amounts of spice larger than the per eating occasion means listed above, e.g., black pepper encrusted foods such as salami, and when consuming these foods, exposure may be larger if the food is contaminated with Salmonella . Despite the absence of data variability, based on experience we do not expect consumption of any particular spice during a single eating occasion to exceed more than a few grams . The most important data gap with regard to consumption of spices is a measure of the fraction of spices that are cooked sufficiently to provide Salmonella an effective kill step for microbial pathogens such as . FDA Draft Risk Profile | 90

103 8. CURRENT MITIGATION AND CONTROL OPTIONS U.S. R AND P ROGRAMS 8.1 EGULATORY STANDARDS In this section we briefly review major regulatory standards and discuss regulatory programs that address the food safety of spices with respect to adulteration by pathogens or filth. , AND COSMETIC ACT 8.1.1 FEDERAL FOOD, DRUG FDA can take action against a food if it is adulterated, misbranded, or otherwise not in compliance with all applicable federal laws . Four main sections in the Federal Food, Drug, and Cosmetic Act (FD&C Act) address spice adulteration: For spices adulterated with any poisonous or deleterious substance: s ection 402(a)(1) of the FD&C Act – “A food shall be deemed adulterated if it bears or contains any poisonous or deleterious substance which may render it injurious to health.” This means that a spic Salmonella or another human pathogen violates the e containing FD&C Act. For spices adulterated with filth: s “A food shall be deemed adulterated if it ection 402(a)(3) of the FD&C Act – consists in whole or in part of any filthy, putrid, or decomposed substance or is otherwise unfit for food.” The Defect Action Levels describe the maximum concentration s of natural or unavoidable defects in foods that present no health hazards for humans . If the Defect Action Levels (DALs) 21 CFR 110.110 (FDA, 2012h) are exceeded, FDA would consider that spice to be adulterated. For spices manufactured under insanitary conditions section 402(a)(4) of the FD&C Act – “ A food shall be : ereby it may have deemed adulterated if it has been prepared, packed, or held under insanitary conditions wh become contaminated with filth, or whereby it may have been rendered injurious to health.” : section 801(a)(3) of the FD&C Act authorizes FDA to detain For spices offered for import into the United States to be adulterated or misbranded. a regulated product that appears 8.1.2 PUBLIC HEALTH SERVICE ACT The Public Health Service Act (42 U.S.C., Chapter 6A, Subchapter II, Part G, Section 264; FDA, 2013p) allows the Surgeon General, with approval of the Secretary of Health and Human Services, “to make and enforce such regulations as in his judgment are necessary to prevent the introduction, transmission, or spread of communicable diseases from foreign countries into the States or possessions, or from one State or possession ate or possession.” into any other St 8.1.3 U.S. REGULATORY MECH ANISMS 8.1.3.1 CURRENT GOOD MANU FACTURING PRACTICES (CGMPS), INSPECTIONS AND ENVIRONMENTAL SAMPLI NG FDA provides regulatory oversight of food through its field staff . Current Good Manufacturing Practices (CGM P) regulations for manufacturing, packing or holding human food describe general food safety principles can be regulations currently and specific aspects of production that impact the safety of a product . These FDA Draft Risk Profile | 91

104 Current Mitigation and Control Options | 8 21 found ; proposed ch anges to these regulations can be found in proposed 21 CFR CFR at 110 (FDA, 2012i) 117 (78 Federal Register 3646, January 16, 2013) (FDA, 2013s ). FDA performs both foreign and domestic inspections of food (including spice) manufacturing, packing, and . Some inspections include environmental sampling . While most of the spice supply storage facilities each year is imported, domestic firms handling imported spice may process (e.g., treat, grind, crack, and/or blend), pack -pack the spice before the product is made available to the consumer/ . and/or re customer Domestic inspections differ from foreign inspections in a number of ways, including the fact that domestic inspections can be unannounced, whereas foreign inspections need to be planned and coordinated well in advance. Addit ionally, domestic inspections may include environmental and/or product sampling, whereas, except in very limited circumstances (i.e., outbreak investigations), FDA inspectors do not currently take environmental or product samples during foreign inspections . in preventing contamination of spice Effectiveness of CGMPs, Inspections and Environmental Sampling with pathogens or filth. FDA evaluates compliance of food facilities with CGMPS through inspections, which may include environmental sampling. Data from FDA inspection reports on firms that manufacture, pack or re -pack spices for the years FY2007-FY2012 are shown in Table 8.1. Each inspection is assigned one of three Official Action Indicated (OAI), Voluntary Action Indicated (VAI), or No Action Indicated (NAI). classifications: In addition, FDA evaluates all the evidence collected during inspections and determines whether additional actions are warranted, e.g., issuing a warning letter, recall, or regulatory meeting. Table 8.1 provides the average annual percentage of FDA domestic or foreign inspections of firms that manufacture, pack, or re -pack spices that were classified as OAI or VAI . In addition, FDA evaluates all the evidence collected during inspections and determines whether additional actions are warranted, e.g., issuing a warning letter, recall, or regulatory meeting. FY2012, FDA inspected 2649 domestic firms that manufacture, pack, or re -pack spices, with During FY2007- the annual total inspections for this group of firms in the range of 321-555. Between FY2007 -FY2010, there were too few foreign inspections of firms that manufacture, pack, or re- pack spices to provide a meaningful FY2012, 70- 73 foreign inspections of firms that . However, during FY2011- rate for these classifications manufac ture, pack, or re -pack spices were performed annually and rates for OAI and VAI classifications are provided. Table 8.1 -pack spices, FY2007 - . Classification of inspections of firms that manufacture, pack or re FY2012 a Foreign Firms Domestic Firms OAI Classification Fiscal VAI Classification OAI Classification VAI Classifications Percentage (%) Year Percentage (%) Percentage (%) Percentage (%) 2007 0.3 33 NA NA 2008 0 31 NA NA 2009 1 38 NA NA 2010 1 35 NA NA 2011 3 34 0 49 2012 0.7 26 6 60 a No statistics are calculated for years in which fewer than 30 inspections were performed. As illustrated in Table 8.1, only a small percentage of domestic or foreign inspections of firms that manufacture, pack, or re -pack spices during the years FY2007 -F Y2012 identified significant objectionable conditions or practices . A substantial percentage of inspections were classified as VAI, with a significantly larger proportion of foreign inspections in FY2012 resulting in this decision as compared with domestic inspections during that year. Because the observations that lead to a VAI classification do not necessarily pertain to an immediate food safety issue, interpretation of the VAI classification rates is difficult. FDA Draft Risk Profile | 92

105 Current Mitigation and Control Options | 8 Comparison of the inspection statistics for firms that manufacture, pack, or re -pack spices with those for . Table 8.2 provides statistics for other food sectors provides a relative measure of compliance with CGMPs domestic inspections of firms that manufacture, pack, or re -pack spices as well as f irms that manufacture, pack, or re -pack other low moisture foods. Annual numbers of domestic inspections for the firms in the food -758 during this time period sectors listed in Table 8.2 ranged from 78 . Also provided in Table 8.2 are the average statistics for inspections of all other FDA regulated foods sectors, which numbered annually in the 24,000 for FY2007- range ~17,000 – FY2012. The rate of OAI and VAI classifications for inspections of statistically different (p>0.05) from rates -packing spices is not domestic firms manufacturing, packing or re for firms manufacturing, packing or re -packing other low moisture foods, such as cereals, chocolate, coffee/tea, nuts/edible seeds, milled whole grain, or the average rate for firms handling other categories of foods. . Classification of domestic inspections of firms that manufacture, pack or re Table 8.2 -pack low moisture foods, average annual rates FY2007- FY2012 Average Annual Percentage of FY2007 - FY2012 Domestic Inspections VAI Classifications OAI Classifications Percentage of firms Percentage of firms Product Group (SD) mean % (SD) mean % 1.0 (1.0) 33 (4) Spices Cereal prepared/Breakfast food (0.3) 32 (5) 0.1 Chocolate/Cocoa Powder 0.5 (0.4) 34 (2) (5) Coffee, Tea 0.7 (0.4) 33 Nuts/Edible Seeds (1.0) 38 (6) 1.3 Whole grain, milled 1.4 (1.5) 29 (5) All Other FDA - regulated Food Categories 1.9 (1.1) 38 (3) -packing environments, a special In order to learn more about spice manufacturing, packing and re assignment was issued by FDA in 2010 for inspections of 59 domestic firms of varying sizes that manufacture, pack and/or re -pack spices. Each inspection included environmental sampling and the collection of additional information . Inspectors were instructed to restrict environment al sampling to non- food contact surfaces in order to gauge the potential for cross -contamination in the facility. Sampling was focused in processing and packing areas positioned after the pathogen reduction step in the product flow, if such a step took pl ace in the firm, which has been referred to by the food industry as the “Primary Salmonella Control Area (PSCA)” et al . Inspectors were instructed to sample areas where cross contamination (Chen ., 2009b; GMA, 2009) between the floor or other surfaces and food contact surfaces and equipment may take place as well as -treatment products (e.g. spice dust) may be transported to the post- treatment locations/pathway where pre areas inadvertently where moisture was observed or . Inspectors were also asked to sample and identify areas was likely to occur in the processing area. Ten percent of spice firms inspected (6/59) were found to have Salmonella -positive environmental samples. Among the six firms with Salmonella -positive environmental samples, two were very sm all (<$100,000 annual sales), three were medium size ($1,000,000 –$9,999,999 annual sales), and one was very large . Most of the firms (5/6) processed spices and many also packed/re -packed (>$50,000,000 annual sales) spices; one firm was engaged in only pac king/re -packing spices . Multiple Salmonella -positive environmental samples were found in two of the firms, with 7% (14/193) and 23 % (24/103) of environmental samples collected in these firms testing positive, respectively . Salmonella - positive swab samples obtained in the six spice firms were recovered from three different zones: zone 2 (non-product contact surfaces in close proximity to product such as the exterior of spice grinding equipment, product contact surfaces in the spice processing/handling areas of the facility floors or walls), zone 3 (non- FDA Draft Risk Profile | 93

106 Current Mitigation and Control Options | 8 - that are not in close proximity to food contact surfaces such as forklifts, drains, or walls) and zone 4 (non product contact surfaces far from the spice processing/handling areas of the facility such as locker rooms, . Most samples, including most positive samples, were collected from bathrooms, hallways, and stairways) areas classified by inspectors as Zone 2 Salmonella -positive samples were in the . Common locations for grinding and packing/re -packing areas, where cross -contamination from the environment to the product could occur. Salmonella was found in the environment had undergone FDA environmental Two of the firms in which sampling in past inspections and one of them had had Salmonella -positive en vironmental samples during the past inspection Salmonella -positive . Some of the samples that tested positive in the firm with a past history of environmental samples contained the same strain (identical PFGE) as that found two years earlier. Salmonella s observation raises the possibility that the strain was never eradicated from the environment Thi Salmonella after the first inspection or that a common/frequent source of contamination is responsible for re - te that serotyping Salmonella contamination of the facility. These data demonstra isolates found in the environment (or product) provides additional information about the contamination that may be useful in investigating possible contamination sources . Product samples were not taken as a part of this study so a relationship between the observation of positive environmental samples and the likelihood of contamination of finished product could not be determined. -reduction processes, and product testin Data on CGMP practices, applications of pathogen g were - and pest collected for many of the firms . The most commonly reported CGMP citations listed on the FDA Form 483’s . Citation frequencies ranged from 2 to 12 firms issued to the firms in these inspections are listed in Table 8.3 among the 59 inspected . Grouping citations into major CGMP categories, these inspections identified a number of areas of concern: (1) cleaning (e.g., accumulation of food particles on equipment or within the facility, equipment not easily cleanable, insufficient cleaning; 21 firm s, 23% of all FDA Form 483 citations), (2) pests (17 firms, 19% of citations), (3) employee hygiene issues (e.g., using bare hands on spices, lack of hand washing, failure to provide hand washing facilities at each necessary location; 16 firms, 17% of citations) and (4) issues with the facility design or state of repair (e.g., holes in the ceiling, cracks in floors, no bathroom doors, product debris a in unreachable areas; 19 firms, 15% of citations). Even though pests were often identified in CGMP citations, majority of firms reported having a regular pest -prevention/reduction program (28/29 inspected firms for which this information was available) . FDA Form 483 citations for moisture (e.g., leaking water from ceiling, dripping water from air conditioning vent, standing water) were issued to 6 firms. One inspector observed whole dried capsicums being sprayed with water and was told the practice was used to reduce the likelihood of cracking/breaking during packaging . Information on the frequency that spic es handled by each firms underwent a pathogen reduction treatment . Of the 26 firms for which this information was gathered, 23 firms reported some (10/23) was also gathered . In most cases (15/23 firms), spice was treated before or all (13/23) of the spice handled by the firm treated reaching the facility . Information on environmental sampling and Salmonella product sampling and testing programs within firms was recorded in 25 of the inspections . Among these, a larger percentage of large spice firms (>$10 million annual sales) reported having environmental sampling programs (73% (11/15)) and/or product sampling programs (87% (13/15)) than smaller spice firms (<$10 million annual sales) where 10% (1/10) of firms reported having environmental sampling program and 30% (3/10) of firms reporting having product sampling programs. FDA Draft Risk Profile | 94

107 Current Mitigation and Control Options | 8 eporte Table 8.3. Sixteen most frequent citations r d on FDA Form 483 issued during domestic spice -December 2011 nspections, August firm i 21 CFR a Citation Short Description Long Description Rank Reference Effective measures are not being taken to [exclude pests from Lack of effective 1560 110.35c 1 the processing areas] [protect against the contamination of pest exclusion food on the premises by pests]. Failure to provide adequate screening or other protection 1306 110.20(b)(7) Screening 2 against pests. The plant is not constructed in such a manner as to allow Floors, walls and 110.20B4 3 [floors] [walls] [ceilings] to be [adequately cleaned and kept 1422 ceilings clean] [kept in good repair]. Failure to maintain [buildings] [fixtures] [physical facilities] Buildings/good 110.35a 4 1553 in repair sufficient to prevent food from becoming repair adulterated. Failure to provide [hand washing] [hand sanitizing] facilities 3652 110.37e1 Suitable locations 5 at each location in the plant where needed. Failure to conduct cleaning and sanitizing operations for Cleaning and utensils and equipment in a manner that protects against 110.35a 6 sanitizing 1554 - contact surfaces] [food - contamination of [food] [food operations packaging materials]. e] [package] [store] foods under Failure to [manufactur Manufacturing 110.80b2 7 conditions and controls necessary to minimize [the potential 1695 conditions for growth of microorganisms] [contamination]. Maintenance of Failure to maintain [equipment] [ute nsils] [finished food equip., utensils, and 2392 8 110.80b1 containers] in an acceptable condition through appropriate finished food cleaning and sanitizing. packaging Materials and The [design] [materials] [workmanship] of [equipment] 110.40a 9 1125 workmanship [utensils] does not allow proper [cleaning] [maintenance]. contact surfaces] Proper precautions to protect [food] [food - Contamination [food - packaging materials] from contamination with with 110.20b2 10 1293 [microorganisms] [chemicals] [filth] [extraneous material] microorganisms, cannot be taken because of deficiencies in plant [size] chemicals, filth, etc. [construction] [design]. Effective use of hair Failure to wear [hair nets] [head bands] [caps] [beard covers] 1406 110.10b6 11 restraint [appropriate hair restraints] in an effective manner. - type [light bulbs] [lighting fixtures] Failure to provide safety Safety lighting and 1427 110.20b5 12 [skylights] [glass] suspended over exposed food. glass Failure to maintain buildings, fixtures, or other physical 1552 110.35a Buildings/sanitary 13 facilities in a sanitary condition. Failure to [construct] [handle] [maintain] equipment, Equipment, 1701 110.80b7 14 containers and utensils used to [convey] [hold] [store] food in containers, utensils a manner that protects against contamination. Failure to store raw materials in a manner that [protects 15 2386 110.80a1 Storage against contamination] [minimizes deterioration]. Contamination by Failure to take effective measures to protect finished food raw materials, 2394 110.80b6 ination by [raw materials] [refuse] [other 16 from contam refuse, other ingredients]. ingredients a The citation number is an FDA number for the specific observation described in the corresponding long description. Several different observations may be associated with the same section of the CFR, so the CFR reference is not sufficient to identify the observation . In summary, when measured by FDA inspection classifications, ≤ 3% of domestic firms that manufacture, pack, or re -pack spices were found to be out of compliance with FDA regulations regarding food safety and sanitation during the years FY2007 -FY2012 . The annual percentage of domestic firms that manufacture, pack, -pack spices that were inspected and found to be out of compliance during the years FY2007 -FY2012 or re FDA Draft Risk Profile | 95

108 Current Mitigation and Control Options | 8 was not statistically different from the annual percentages for inspections of firms that manufacture, pack, or re -pack other low moisture foods. More data are needed to evaluate the rate of compliance among foreign firms. Information gathered in 2010 from 59 ins pections of domestic firms that manufacture, pack, or re -pack spices provide additional information about the potential for contamination within firms and preventive control by firms. programs and practices used was found in the environment of t en percent of firms Salmonella inspected including in the PSCA and most contamination sites were in locations where cross -contamination to spice product is most likely to occur (Zone 2). Among the 26 firms for which this information was available, 88% reported that s ome (38%) or all (50%) of the spice handled by the firm had been or would be subjected to a pathogen reduction treatment before leaving the firm. Regular environmental and product sampling programs were common in large firms (≥73%) but not as common in small firms (≤30%) . 8.1.3.2 PRODUCT SAMPLING, REFUSALS, AND RECOND ITIONING within Product sampling is a mechanism used General Compliance Program, which the FDA Import Foods - covers imported food entries, and within the FDA Domestic Food Safety - Complianc e Program, covering food products in domestic commerce. Spices may be sampled as part of either of these programs . Because spices are primarily produced outside the United States, the majority of sampling activities related to spices target nts of spice offered for entry to the United States. In addition to general surveillance imported shipme activities, FDA can issue field assignments to request targeted activities for a particular food . Field assignments are often used to gather data regarding a specific problem or product that are not addressed directly in a routine compliance program. Additionally, s pices may be sampled at different points along the food chain, e.g., as part of a foodborne illness outbreak investigation. The FDA regulatory programs help prevent contaminated spices from reaching the U.S. consumer by (1) directly identifying contaminated spice shipments/lots and either having them removed from the food supply to meet food safety requirements, (2) placing importers with shi pments found or reconditioned contaminated on import alert and (3) indirectly encouraging the spice industry to prevent/remove contamination and eliminate/mitigate practices that would lead to contamination to avoid FDA enforcement actions for shipments found violative. W hen a food is found to be adulterated with pathogens or filth, it is refused admission . When a product is initially refused admission, the importer can (1) export the product; (2) destroy the product; or (3) request roduct to bring the product into compliance. If the importer permission from FDA to recondition the p requests reconditioning, the reconditioning proposal is approved by FDA and the reconditioning is successful in remedying the violation, FDA will release the product into U.S. commerce. Effectiv eness of product sampling, refusals and reconditioning in preventing contaminated spice from entering the U.S. food supply. Refusal of or reconditioning contaminated shipments identified by the FDA product sampling program prevents the contaminated spice f rom entering the U.S. supply or eliminates the contamination from the spice. During the period FY2007-FY2010, 906 imported spice shipments (including Salmonella and/ or sesame seeds) were refused entry on the basis of the presence or potential for presence of filth . Among these shipments, 749 shipments of spice were refused entry because of the presence or potential presence of Salmonella and 238 shipments were refused because of the presence or potential presence of filth . Data on reconditioned imported shipments is provided in section 8.2.1.1. While only a small fraction of shipments of imported spice offered for entry to United States are examined by FDA for the presence of Salmonella (~1%) or filth (~0.05%), when a shipment is found violative, the importer can be placed on import alert . Once on import alert, all subsequent shipments of the same spice from that importer would be subject to “detention without physical examination. ” FDA’s decision to remove a product from detention without physical examinati on is based on evidence establishing that the conditions that gave rise to the appearance of a violation have been resolved. FDA’s decision to remove the product from the FDA Draft Risk Profile | 96

109 Current Mitigation and Control Options | 8 Import Alert is based on evidence that provides confidence that future entries will be in compliance with the FD&C Act. In this way, the product sampling program can identify and prevent importers of contaminated spice from impacting the food safety of spice in the United States . Import Alerts related to shipments of spice Salmonella th contaminated wi or filth are discussed in the next section (8.2.1.3). The indirect deterrent effect of regulatory sampling is difficult to measure but comparisons of compliance on of spices with rates among surveillance samples provide insights into the extent of contaminati Salmonella and/or filth; these were discussed in Sections 4.1.3 and 4.2.3. Finally, FDA has examined the efficacy of its sampling protocol for spices (Andrews and Hammack, 2003) in detecting shipments of imported spice contaminated with Salmonella . Based on models developed from Salmonella prevalence and enumeration data collected for shipments of imported capsicum and sesame seed, the sampling protocols employed by FDA to test samples of spice for the presence of Salmonella are predicted to be efficient in detecting the more highly contaminated spice shipments, which contain the majority of the Salmonella et al. , 2013c). Additional research is in the imported supply (Appendix C, Table C3; Van Doren these predictions to other types of imported spice. needed to determine the applicability of 8.1. 3.3 IMPORT ALERTS, GREEN LISTS AND COUNTR Y AGREEMENTS Import Alerts . An Import Alert is a communication tool developed by FDA to disseminate import information (problems, violations, trends, etc.) for inspectional and compliance operating instructions to FDA field (such as the Center for Food Safety and Applied Nutrition) and the Office of Regulatory personnel, Centers Affairs headquarter units . FDA’s use of Import Alerts results in effective and uniform import coverage nationwide, as well as significantly improving the uniformity of enforcement in import problem areas . The subject of an Import Alert may be a specific hazard, commodity, geographical area, firm, or any combination thereof. Historical ly, FDA has decided that issuance of an Import Alert is appropriate when ( 1) there is evidence of the importation of violative products; ( 2) there is evidence of the importation of products that may appear violative; or ( that future entries of an imported product may appear 3) when other information indicates violative . For example, when an imported product is found to be adulterated or misbranded, FDA can use that . FDA &C Act information as evidence that future shipments from that manufacturer appear to violate the FD can subject future entries to “Detention Without Physical Examination” (DWPE), and list the manufacturer . If there is no existing import alert to address the violation, FDA can create a and product on an import alert new import alert. Products subject to DWPE will be detained without examination when they are offered for entry to the United . Firms have the opportunity to submit evidence to overcome the appearance of the violation . If they are States successful, the product will be allowed entry . If they are unable to overcome the appearance of the violation, the product will be refused admission. For spices, the most common causes for DWPE are filth and pathogens . Table 8.4 lists the import alerts ssoc iated with spices and address involving DWPE that are primarily/exclusively a issues of pathogen and/or filth adulteration (FDA, 2013h) . Import Alert 99 -19 (Detention Without Physical Examination of Food Products Due to the Presence of Salmonella which evidence has indicated the likelihood of ; FDA, 2013i) lists firms and the specific foods for Salmonella contamination . Firms importing shipments of imported spices other than black pepper from India and white and black pepper from Brazil (which are covered by Import Alerts 28 -02 and 28-04, respectively) may be listed on this import alert . As can be seen from Table 8.5, a majority of the firms on Import Alert 99 -19 contamination of spices and/or sesame seeds are cited for the likelihood Salmonella , even though the import alert is not limited to spices and sesame seeds. The names and numbers of firms on the import alert have FDA Draft Risk Profile | 97

110 Current Mitigation and Control Options | 8 contamination of Salmonella changed through time but the proportion of firms cited for the likelihood of spices remains large. Table 8.4. Import Alerts involving DWPE that are primarily/exclusively associated with spices and ilth adulteration. address issues of pathogen and/or f a b Number Problem Type Action Years Active DWPE particular foods from each 19 1994 - present 99 Salmonella Firm - firm Salmonella , filth, mold, 1987 - present DWPE of Indian Pepper 28 - 02 Country/World Wide foreign matter DWPE of Black and White Pepper Salmonella 1989 - present 04 Country/World Wide 28 - from Brazil 24 - 11 1988 - present excessive mold Country/World Wide DWPE Dried Peppers from Mexico DWPE Sesame seeds from Mexico Filth (mammalian and 1977 - present - 28 03 Firm and surveillance of sesame seeds other excreta, insect filth) from other countries a First year in range is date when the Import Alert was initiated. For the “Firm” type Import Alerts, this data corresponds to the date when the import alert was initiated . The date when each food/firm was put on the Import Alert is listed in the Import Alert. b DWPE means “detention without physical examination.” Table 8.5. Number of f -19 for DWPE in October 2010 and June 2013 irms listed on Import Alert 99 Number of Firms on a,b b,c # Firms (2010) # Firms (2013) Import Alert 99 - 19 Total firms with one or more products identified for DWPE 882 733 Firms with spices cited as industry code 28 520 (71%) 595 (67%) Firms with spices cited as industry code 23K - 02 110 (15%) 83 (9%) a 19 as of October 2010 (FDA, 2013i). Data taken from Import Alert 99- b Included in the count may be multiple listings of the same parent company because the company used several FEI numbers, listed different addresses or spelled its name differently. c Data taken from Import Alert 99 -19 as of June 2013 (FDA, 2013i). The firms listed on Import Alert 99 -19 are from many different countries. Table 8.6 lists the countries with the largest number of firms identified for DWPE of one or more types of spices (sum of firms with industry 28 1, 2011 and June 26, 2013. The largest number of firms on Import and/or product code 23K02) as of July Alert 99 Salmonella contamination of spices are from India and the “top ten” list -19 cited for the likelihood of of countries in Table 8.6 is nearly the same in 2013 as it was in 2011 (nine out of the ten countries listed are the same) . The numbers of firms listed for each country is in part a reflection of the numbers of shipments -FY2009 study comparing prevalence in Salmonella offered for import and sampled. Based on the FDA FY2007 shipment s of imported spice offered for import to the United States by export country, the prevalence of Salmonella , 2013a; discussed in et al. in shipments is not strongly dependent on export country (Van Doren Section 4.2.3 and Table 4.5). Green Lists and Count ry Agreements. If certain conditions are met, FDA may allow exemptions to DWPE for some firms. For example, for Import Alert 28 -02, imports of Indian black pepper that are accompanied by an official Indian Export Inspection Council certificate will not be subject to DWPE when the Indian EIC certificate indicates that the spice shipment has been sampled and tested for compliance with U.S. Salmonella -02 for a detailed list of requirements for , filth, mold and foreign matter (see Import Alert 28 information th e certificates must include; FDA, 2013j) Another example is Import Alert 24 -11 where firms that provided information to overcome the appearance of a continued violation for foods, particularly mold, can apply for exemption from DWPE (FDA, 2013k). Regardless of importer status, FDA may monitor or sample any shipment of regulated product offered for import to the United States. FDA Draft Risk Profile | 98

111 Current Mitigation and Control Options | 8 a pices Table 8.6 -19 for DWPE of s . Countries with the largest number of firms listed on Import Alert 99 Salmonella ” due to “presence of 2011 2013 b,c c,d Country Country # Firms # Firms 172 India 187 India Mexico 36 Mexico 37 34 Turkey 37 Turkey Syrian Arab Republic 33 Syrian Arab Republic 34 Vietnam 29 Vietnam 30 26 Egypt 29 Egypt China 25 26 China Indonesia 15 Indonesia 18 Thailand Thailand 18 15 Pakistan 16 Lebanon 14 a Spices identified as industry code 28 or product code 23K02 (sesame seeds) b Data taken from Import Alert 99 -19 as of 7/1/2011 (FDA (2013i). c Included in the count may be multiple listings of the same parent company because the company used several FEI numbers, liste d different addresses or spelled its name differently. d Data taken from Import Alert 99 -19 as of 6/26/2013 (FDA, 2013i). Effectiveness of Import Alerts and Country Agreements in preventing contaminated spice from entering the Shipments subject to DWPE at entry to the United States must be accompanied by evidence U.S. food supply . that the shipment meets U.S. requirements before the product is allowed to enter U.S. commerce. Typical Salmonella evidence for compliance with the and filth requirements includes results from third party microbiological or filth tests and/or certification that the shipment has been subjected to an e ffective microbial reduction treatment. In this regard, import alerts are expected to be highly effective in reducing the risk of contamination in the particular products from the particular firms/countries identified. FDA periodically examines the effec tiveness of exemption programs for imports by sampling spice in shipments from exempted firms. An audit of the exemption program for Import Alert 28 -02, took place in 2010. For a period of one month, FDA examined all 55 Indian black pepper shipments offered for entry to the United States during that time period. Most of the shipments were accompanied by an Indian EIC certificate (51/55), although some of the certificates were out of date or had other discrepancies. (750 g et Using FDA sampling and testing protocols ; Andrews and Hammack, 2003; Andrews Salmonella for al ), ., 2011; 6 x 50 g spice for ground black pepper and ~ 4kg (8 x 500 g) for whole black pepper; FDA, 1998a Salmonella and filth adulteration the 55 shipments were tested for the presence of . None of the samples from Salmonella or to be adulterated by contain the 51 shipments accompanied by an EIC certificate were found to filth. Of the four shipments that were not accompanied with a certificate, two were adulterated by Salmonella, none were adulterated by filth, and two were not actually Indian black pepper, but rather were imported to India from Vietnam. -02, which requires assurance of This audit provides evidence that the exemption program for Import Alert 28 food safety be provided by a certificate from the government of the country of origin, does provide some assurance that the black pepper shipment will comply with U.S. regulations for and filth in spices. Salmonella Salmonella with EIC certificates indicates that the Specifically, the absence of or filth in all of the shipments Salmonella or filth in these shipments is in the range of 0.0 prevalence of .). More data -5.7% (750 g; 95% C.L are needed to determine whether the exemption program provides added food safety value, i.e., shipments accompanied by an EIC certificate have a smaller likelihood of being contaminated with Salmonella or filth per from India. Collecting these data would be difficult because it appears than other shipments of black pep that most of the shipments of black pepper from India offered for entry to the United States are accompanied by an Indian EIC certificate (51/55 in this study). FDA Draft Risk Profile | 99

112 Current Mitigation and Control Options | 8 8.1.3.4 REPORTABLE FOOD REGISTRY The Food and Drug Administration Amendments Act of 2007 required FDA to establish an electronic portal by which instances of reportable food may be submitted; this is the Reportable Food Registry (FDA, 2013d) . Under section 417(a)(2) of the FD&C Act, a reportable food is “an article of food... for which there is a reasonable probability that the use of, or exposure to, such article of food will cause serious adverse health consequences or death to humans or animals.” FDA interprets the definit ion of a reportable food to include those foods that would meet the definition of a Class I recall situation, for example, spice contaminated with Salmonella . Reportable foods must be reported by industry (responsible party) (FDA, 2010b) while federal, state, and local public health officials have the option to submit voluntary reports . Public health officials with knowledge of a reportable food can inform a food facility that it may be required to submit a food report. -identified pur pose of the Reportable Food Registry is to provide a reliable mechanism to The congressionally track patterns of adulteration in food in order to support efforts by FDA to target limited inspection resources to protect public health. Effectiveness of the Reportable Food Regi stry in preventing contaminated spice from entering the U.S. food supply . Data on primary entries (initial reports) submitted during the first three years of the Reportable Food Registry program are listed in Table 8.7 . Reports for all FDA -regulated foods except dietary supplements and infant formula (for which FDA has other mandatory reporting systems) are included in the RFR . The FDA - regulated food commodities covered by the RFR have been separated into 28 types. “Spices and Seasonings” . is the food commodity type that includes spices Most of the primary entries associated with “Spices and Seasonings” reported contamination with Salmonella . . Other hazards reported No other pathogens were associated with “Spices and Seasonings” primary entries for “Spices and Seasonings” during this time period included undeclared allergens (4), presence of a foreign object (1) and presence of lead (1). As seen in Table 8.7, the number of primary entries reported for “Spices and Seasonings” during the first two years of the program were larger than that for most of the other food commodity types for all hazards and for Salmonella in particular . However, the absolute and relative (e.g., rank) number of primary entries for “Spices and Seasonings” were much smaller in Y ear 3 of the program. As mentioned previously, the absence of information about the total number of tests performed or lots examined, makes it difficult to interpret the meaning of these data, including changes from year to year . However the publication of the reports and summary statistics has been effective in alerting the industry to reported problems. Each primary entry may be followed by many related “subsequent reports” (defined as a report by either a supplier (upstream) or a recipient (downstream) of a food/feed (including ingredients) for which a primary ). The number of subsequent reports depends on whether the primary report has been submitted; FDA, 2013d report is on a widely used ingredient or a finished food distributed to many different locations. For example, a Salmonella and find that it is contaminated . Subsequent reports will food manufacturer may test a spice for then be expected from the supplier of the spice and downstream recipients of spice from the implicated lot, if applicable . In this w ay, the Reportable Food Registry, with the help of industry, is able to identify and remove contaminated spice from the food supply. Data from the RFR on spices and other commodities has increased the speed with which FDA and its state and local partners investigate reports and take appropriate follow -up action, including removing reportable foods from commerce when necessary ( FDA, 2013d) . The data has also improved FDA’s understanding of how ly chains, increasing FDA’s ability to trace products including spices are distributed through commodity supp FDA Draft Risk Profile | 100

113 Current Mitigation and Control Options | 8 . Data from the RFR has also supplied information reportable foods upstream and downstream (FDA, 2013d) . to help FDA target inspections, plan work, and identify and prioritize risks (FDA, 2013d) Table 8.7. Primary entries reported to the FDA Reportable Food Registry September 8, 2009 - September 7, 2012 a a a Year 1 Year 2 Hazard Year 3 Reportable Food Registry Food Commodity - all 229 All FDA 225 224 regulated Food Categories “Spices and Seasonings” all 17 25 8 Rank out of total number of primary entries for “Spices and th th nd rd all 3 -4 2 10 b Seasonings” among all 28 RFR food commodity types All FDA - regulated RFR Food Categories Salmonella 86 86 63 23 “Spices and Seasonings” Salmonella 16 5 Rank of number of primary entries for “Spices and th nd st 2 Salmonella 4 (tied) 1 Seasonings” among all 28 RFR food commodity types a Year 1 included September 8, 2009 -September 7, 2011; Year 3 included -September 7, 2010; Year 2 included September 8, 2010 2011 -September 7, 2012. September 8, b Dietary supplements and infant formula are excluded. c Tied with two other RFR food commodities. 8.1.3.5 ACTICES GOOD AGRICULTURAL PR Good agricultural practices (GAPs) are a collection of science -farm produ ction and -based principles of on post -production processes that, when used, result in safer food. GAPs criteria are developed and applied based, in part, on the type of agricultural production system in use. Although many GAPs principles (such as worker health and hygiene) are a pplicable to any agricultural system, GAPs guidance in the United States has been developed mainly for the fresh produce industry (FDA, 1998b; USDA/ARS, 2013) . The FDA Guide to Industry: Guide to Minimize Microbial Food Safety Hazards for Fresh Fruits and Vegetables (FDA, 1998b) has relevance for spice crops grown in systems similar to fresh produce crops (e.g., capsicums) as does the Produce GAPs Harmonized Food Safety Standards (USDA/ARS, 2013). While FDA and USDA/ARS currently have no GAPs guidance for small -cropping and/or -scale, multi/inter -craft’ agricultural systems, which are internationally used to grow spice crops, FDA has ‘managed wild worked with WHO to create guidance for rural workers who grow fresh fruits and vegetables (WHO, 2012). Five keys to growing safer fruits and vegetables: promoting health by decreasing microbial contamination The manual was designed “to be easy to use, adopt and adapt so that community and health educators can tailor the training materials to meet local needs” (WHO, 2012) . The target audience for this guidance is “rural workers, including small farmers who grow fresh fruits and vegetables for themselves, their families and for sale in local markets” but could also be used by small- scale spice producers (WHO, 2012) . Effectiveness of Good Agricultural Practices in preventing contamination of spices with Salmonella and/or filth during primary production. WHO, FDA, and USDA guidance documents were developed based on the best available science, and as a result, it is expected that application of the principles and recommendations outlined in these guidance documents should reduce the risk of contamination of fresh produce (including capsicums) with microbial pathogens and filth . We are unaware of any systematic studies that have measured changes in the prevalence of microbial or filth contamination in capsicums or other spice source plants as a result of applications of these principles or any surveys that measure the extent to which these practices have been adapted by th e food industry in general or the spice industry in particular . However, FDA commissioned a study to examine the cost -effectiveness of practices intended to prevent tomato -related foodborne illness, which quantified the predicted relative impact specific g rowing and harvest practices have on the risk of Salmonella contamination (Robert et al ., 2009) . In support of the proposed produce rule (FDA, 2013e), FDA also completed a quantitative assessment of the impact of Enterohemorrhagic Escherichia coli (EHEC) . contamination of irrigation water on the risk of illness from consumption of leafy greens (FDA, 2013e) FDA Draft Risk Profile | 101

114 Current Mitigation and Control Options | 8 8.1.3.6 RETAIL ESTABLISHMENT AND CONSUMER GUIDANCE FDA Food Code The code developed and regularly updated by FDA that “ assists food control is a model jurisdictions at all levels of government by providing them with a scientifically sound technical and legal basis for regulating the retail and food service segment of the industry. Local, state, tribal, and federal regulators use the FDA Food Code as a model to develop or update their own food safety rules and to be consistent with national food regulatory policy” (FDA, 2013m) Nearly all of the U.S. states have adopted the FDA F ood Code as the basis for their food safety regulatory ov ersight of retail food and institutional facilities (FDA, 2013b) . The FDA F ood Code uses the term “Potentially Hazardous Food” (PHF) to define foods that should have time/temperature controls for safety to limit pathogen growth or toxin formation. The defi nition of PHF takes into consideration pH, water activity (a ), w pH and a interaction, heat treatment, and packaging. Several decision trees and tables are included in the w FDA Food Code to aid in determining if a food is considered a PHF . Acco rding to the FDA Food annex to the algorithms (FDA, 2013n), spices would not be classified as a PHF because the typical a Code is too small. w - The U.S. Government provides consumers general safe food handling information such as the current multi media Advertising Council campaign Safe Food Families that provides messages on cleaning utensils and surfaces, preventing cross -contamination, safe cooking and proper chilling of food. Education campaigns also provide product/pathogen -specific advice for high profile, recu rring hazards (e.g., egg safety, or food safety for pregnant women). The information and learning materials are disseminated through the media, E - newsletters to health educators, school -based programs, and FDA Consumer Updates, food safety agency agency displays at regional food shows and health fairs, and health care provider offices. websites, FoodSafety.gov is a “Gateway to Federal Food Safety Information” website that provides information on outbreaks and recalls, as well as feature articles delivering messages to consumers. Guidance for consumers regarding the safe handling of low -moisture foods, such as spices has not been addressed. Effectiveness of retail establishment and consumer guidance in preventing contamination of spices with or filth in retail establishments, including consumer homes, and in preventing consumption and/ Salmonella of contaminated spice . While neither the nor consumer guidance developed by FDA currently FDA Food Code provide specific guidance on preventive practices for spices, these documents provide general information on practices that are designed to reduce the likelihood of contamination of food with pathogens (such as Salmonella ) and filth and practices that limit growth and survival of pathogens in foods ends . FDA evaluated tr in food safety practices in retail food establishments (institutional foodservice, restaurants, and retail food stores) during the period 1998 -2008, evaluating compliance with 42 different foodborne illness risk factors 2010d ). All but one (nurs ing homes) of the facility types investigated, showed a statistical improvement (FDA, in applying food safety practices that reduce the prevalence of risk factors for foodborne illness (e.g., o maintaining food at 5 C or below except during preparation, cooking, c ooling or when time is used as a public health control). All major education campaigns for consumers are developed through the use of formative evaluation with the ve food safety target audiences, and each program is evaluated with the end users. Because consumers recei information through a variety of outlets, it is difficult to evaluate the impact of a particular educational campaign on the population as a whole. 8.1.3.7 FDA FOOD SAFETY MODERNIZ ATION ACT The FDA Food Safety Modernization Act (FSMA) was s igned into law January 4, 2011 (FDA, 2011a ). FSMA (3) address five areas of food safety (1) preventive controls (2) inspection and compliance es imported food safety (4) response and (5) enhanced partnerships. Some of the provisions of FSMA have been implemented while other r egulations and guidance documents required by FSMA were either under developme nt by FDA or under review by appropriate authorities when this report was written. Below we briefly describe the FSMA provisions that have been implemented and which are expected to significantly impact the food safety FDA Draft Risk Profile | 102

115 Current Mitigation and Control Options | 8 . The of the U.S. spice supply information provided below was gathered from the FDA FSMA information website available to the public (2013o), unless otherwise noted. FDA is increasing the fr equency of domestic and foreign inspections pursuant to section 201 of FSMA. FDA also has the authority to detain food if, during an inspection, examination, or investigation, FDA “has reason tion 207 of FSMA). FDA to believe” that the product is “adulterated or misbranded” (sec has the authority also to deny entry of products to the United States from foreign food facilities that refuse access to FDA inspectors or third party inspectors authorized by the agency (s ec tion 306 of FSMA ). In general, b efore an imported food can enter the United States, a prior notice must be submitted to FDA (21 CFR 1. 279; FDA, 2013r). Implementation of section 304 of FSMA adds the requirement that the notice provide the name of “any country to which the article has been refused entry.” This requirement should help FDA stop refused shipments from being allowed entry to the United States by a different U.S. port . FDA now has the authority to mandate food recalls for all FDA -regulated foods (section 206 of FSMA). Prior to FSMA, FDA only had the authority to mandate recalls of infant formula. This authority allows FDA to require recalls of foods to protect the public health in cases when industry does not voluntarily do so. FDA has developed an International Food Safety Capacity -Building Plan (FDA, 2013q) to “expand technical, scientific and regulatory food safety capacity of foreign governments and their respective food industries” (section 305 of FSMA) (FDA, 2013q) . Building capacity is an important part of FSMA (Section 305). As one part of its capacity building efforts, FDA has begun to set up new and expand established international posts in a range of countries and regions including China, India and Latin American. Important new rules to implement Sections 103 and 301 of FSMA related to spice safety ( proposed rule -Based Preventive Controls for Human “Current Good Manufacturing Practice and Hazard Analysis and Risk Food” (78 Federal Register 3646; January 16, 2013) (FDA, 2013s) and ign Supplier Verification “Fore Program s for Importers of Food for Humans and Animals ” (78 Federal Register 45730; July 29, 2013) (FDA, 2013t) are discussed under future efforts since they were not finalized at the time this report issued. Effectiveness in improving spice food safety. Data addressing the of the FDA Food Safety Modernization Act effectiveness of each of the provisions of FSMA described above was not available at the time this report was written because of the brief period since implementa tion. 8.2 INDUSTRY PROGRAM S TION 8.2.1 PATHOGEN REDUC 8.2.1.1 INTRODUCTION While post -harvest treatments such as physical cleaning and garbling (inspecting and removing refuse) of raw spices may reduce filth and possibly sources of pathogenic bacteria, the y are not sufficient to eliminate or reduce microbial populations associated with the spices . The most common spice processing treatments that impact the viability of microorganisms, including human pathogens such as Salmonella , can generally be grouped in to three categories: 1) steam treatment, 2) gamma radiation, and 3) fumigation with ethylene oxide (EO) . These treatments are also commonly used for other materials such as pharmaceuticals and biologics as described by the U.S. Pharmacopeia (USP, 2011 ). Other treatment options have been studied and are described in the scientific literature; however, they are not currently used or are only minimally used on a commercial basis for spice treatment . These include dry CO heat, microwave radiation, high pressure processing, supercritical carbon dioxide ( ), ozone, pulsed light, 2 FDA Draft Risk Profile | 103

116 Current Mitigation and Control Options | 8 and an alternative steam treatment “controlled condensation.” These technologies are explained in more detail in Section 8.2.1.8 which describes alternative pathogen reduction treatments. As mentioned in Section 8.1.3 .2, imported spice shipments initially refused for import on the basis of microbial hazards may be accepted for entry after reconditioning. Between January 2007 and December ditioning proposals for spices (Table 8.8) 2012, CFSAN accepted 50 out of 155 recon . Thirty -seven proposals (amaranth [1], anise seed [1], basil [1], black pepper [4], Salmonella (74%) addressed contamination with [1], dill seeds [1], ginger celery seed [1], chili pepper powder/flakes [5], coriander powder [1], cumin powder [1], onion granulated [1], parsley powder [1], sage leaves [1], sesame seeds [16], turmeric [1]). Ten proposals (22%) were for contamination with filth (chili/paprika powder/flakes/whole [7], cumin [1], ginger [1], and Salmonella. . One sesame seed proposal (2%) addressed contamination with both filth and sesame seeds [1]) . Accepted reconditioning proposals for s Table 8.8 2012 (December) pices, 2007 – CFSAN ng Country of Origin Adulteration Product Type of Reconditioni Review Year Controlled condensation steam India Salmonella Amaranth 2012 treatment 2012 Turkey Anise Seeds Salmonella Irradiation Basil 2011 Egypt Salmonella Irradiation Black Pepper 2008 Mexico Irradiation Salmonella Black Pepper 2010 Vietnam Salmonella Irradiation Indonesia Black Pepper Salmonella Ethylene Oxide 2011 Black Pepper 2011 Indonesia Salmonella Propylene Oxide Celery Seeds 2011 India Salmonella Ethylene Oxide and Steam Chili pepper flakes 2008 Mexico Filth Cold treatment Chili pepper flakes 2012 Mexico Salmonella Irradiation Chili pepper, whole dried Separate/sort/treat and visible Filth/Mold 2012 Mexico (Ancho) inspection Chili pepper, whole dried Separate/sort/treat and visible Filth 2011 India (Ghost) inspection whole dried Separate/sort/treat and visible Chili pepper, 2012 Mexico Filth inspection (Habanero) Separate/sort/treat and visible Chili pepper, whole dried Filth Mexico 2012 inspection (Puya) 2011 China Filth/Mold Steam/sort, visual inspection Chili pepper, whole dried 2011 Chili powder India Salmonella Irradiation Chili powder 2011 India Salmonella Irradiation Mexico Chili powder Salmonella Irradiation 2011 Chili powder 2009 Mexico Filth Blend and sort Irradiation Chili powder 2012 Mexico Salmonella Coriander powder 2012 India Salmonella Irradiation Cumin powder 2011 India Salmonella Irradiation Cumin Seeds 2008 Turkey Filth Aspirate and sort India Dill Seeds 2012 Salmonella Ethylene Oxide Steam; clean (separate/sift) and India Filth 2012 Fennel mill Controlled condensation steam 2011 Nigeria Salmonella Ginger, dried split treatment Propylene oxide (mold); tumble; 2008 Ginger, whole dried China Filth/Mold aspirate FDA Draft Risk Profile | 104

117 Current Mitigation and Control Options | 8 CFSAN Country of Origin Adulteration Type of Reconditioni ng Product Review Year Egypt Salmonella Irradiation Onion, granulated 2011 Separate/Sort and visible Paprika peppers, dried 2012 China Filth/Mold mild inspection whole 2010 Hungary Salmonella Irradiation Parsley powder Paprika peppers, dried Filth/Mold/Mi Separate/Sort and visible Peru 2012 tes inspection and fumigation whole mild 2011 Germany Salmonella Propylene Oxide Sage Leaves Salmonella , ); Scalp Salmonella Irradiation ( 2009 Sesame Seeds Mexico and sift, hull, dry (filth) Filth 2010 India Salmonella Irradiation Sesame Seeds India Salmonella Ethylene Oxide Sesame Seeds 2010 2010 India Salmonella Ethylene Oxide Sesame Seeds Sesame Seeds India Salmonella Ethylene Oxide 2010 Salmonella Venezuela Sesame Seeds Ethylene Oxide 2007 Sesame Seeds 2010 India Salmonella Irradiation Irradiation Sesame Seeds 2011 Guatemala Salmonella Sesame Seeds India Salmonella Irradiation 2011 Salmonella India Sesame Seeds Irradiation 2011 Sesame Seeds 2012 India Salmonella Irradiation Sesame Seeds, hulled 2011 India Salmonella Irradiation Controlled condensation steam Salmonella India 2011 Sesame Seeds, hulled treatment Sesame Seeds, hulled 2011 India Salmonella Irradiation Sesame Seeds, hulled 2011 Guatemala Salmonella Irradiation Sesame Seeds, hulled 2011 India Filth Cold treatment Controlled condensation steam Sesame Seeds, hulled India Salmonella 2012 treatment 2011 India Salmonella Ethylene Oxide Turmeric Indigenous Spice Microflora. The microflora of different spices is highly variable in size and scope . Not only will the population of microorganisms differ among various spices, it will also differ within a spice category based on cultivation, handling, storage and processing conditions . Spices are derived from botanic sources typically cultivated outside and exposed to environmental contamination such as dust, water, insects, animals, and human con tact . Additionally, spices are subject to various handling, storage and processing techniques that expose them to other possible contamination sources . Because they are agricultural commodities, it should not be surprising that spices have a large and varied microflora including occasional contamination with pertinent human pathogens. Salmonella in various spices is well established (Chapters 4 and 5). The presence and survival of While numerous researchers have reported the presence of Salmonella in s pices, few have provided enumeration data . Based on available data (Table 4.2) and analysis (Section 4.1.3; Figures 4.1 and 4.2; Van Doren et al. , 1 2013c), the Salmonella in adulterated spices is thought to be low, typically averaging less than bioburden of MPN/g but documented as being as large as 11 MPN/g (Lehmacher et al ., 1995) in samples associated with a spice -attributed salmonellosis outbreak . FDA Draft Risk Profile | 105

118 Current Mitigation and Control Options | 8 D TREATMENTS 8.2.1.2 COMMONLY USE To evaluate the efficacy of processes designed to inactivate pathogens, a review of scientific refereed . Information below in text and related literature related specifically to treatment of spices was conducted . Data on changes in microbial populations before and after treatment were tables reflect this analysis ob tained from graphs, tables and text in the refereed papers . Because of the widespread utilization of steam, gamma radiation and EO treatments, direct comparisons of results from these processes were made for the -four publications related to spice treatments were obtained as microbial populations reported. Seventy refereed journal articles or book chapters after a review of literature, including 11 related to steam ve heating, treatment, 42 to gamma radiation, 14 to EO, and 35 related to other treatments such as microwa dry heat, hydrostatic high pressure, pulsed light, pulsed electric field, high pressure CO , x -rays and electron 2 beam . (The sum of individual treatments is greater than the total reviewed because many papers conducted than one treatment.) A number of these refereed papers did not contain original direct comparisons of more treatment data because they were review articles or addressed other spice issues such as toxicology or quality effects al data that were used to construct the . The number of publications with original microbiologic . The reviewed refereed papers and book tables were five for steam, five for EO, and 19 for gamma radiation chapters were published between 1942 and 2010. Data from an individual refereed paper was selected for analysis when the numerical size of a microbial population was clearly presented in tabular or graphical form for spice samples taken before and after . The decimal reduction for a specific spice and treatment combination was calculated from these treatment data pairs . Because some “after” treatment results were reported as “zero”, it was assumed the microbial In those cases, the decimal population was below the limit of detection for the enumeration method used. reduction beginning population. This assumption was modified only was assumed to be “greater than” (>) the if the paper indicated that the lower limit of detection was greater than 1 CFU/g . Most data pairs reported and were for total aerobic plate counts (APC) while those for yeasts and molds, coliforms, E sch erichia coli Enterobacteriaceae were also included data were obtained from APCs . The more valuable decimal reduction they are generally several logs higher than other measurable populations before treatment . Having a because ncreased chances of obtaining a measurable population after treatment therefore larger initial population i yielding a discrete decimal reduction . It was noteworthy that none of the reviewed studies involved experiments on spices inoculated with a pathogen or pathogen surrogate . Whi le reductions in the overall microbial populations (APCs) observed in these studies may provide a relative comparison of the efficacy of different treatment types, results do not Salmonella Salmonella reductions . Specific treatment validation studies using predict expected or appropriate surrogates are needed and highly recommended. 8.2.1.3 STEAM TREATMENT Steam treatment of foods is a well -known traditional technology used to address both quality and safety issues. It is well characterized and has been the subject of considerable scientific study for many decades . According to Pflug and Holcomb (2001), there are three general factors affecting the thermal resistance of microorganisms to heat: 1) microbial inherent res istance, 2) environmental influences during cell growth and/or sporulation, and 3) environmental influences during the heating cycle . Microbial thermal resistance is traditionally measured in terms of D - and z -values where D, standing for Decimal Reduction Time, is the time at a specific temperature needed to reduce the target population by one log (90%) and z -value, representing the reciprocal of the slope of the line in a Thermal Death Time curve is the change interval in temperature need ed for the line t o pass through t o increase/decrease the D -value by one log . Environmental influences during cell growth and spore formation of vegetative cells and spores impact the cell physiological state, which has an impact on the thermal resistance . These influences include issues such as incubation temperature, nutrient medium composition, and cell age . Environmental influences during the heat cycle may FDA Draft Risk Profile | 106

119 Current Mitigation and Control Options | 8 include, among others, medium pH, ionic strength, substrate composition, and the presence of antimicrobial compounds that might impact cell survival. Perhaps the best known and studied steam process for foods is retorting whereby canned foods are rendered commercially sterile using pressurized, saturated steam . As an example, cans of low acid foods are packed team chamber and subjected to steam at 121°C and pressure of 15 psig for a set time period . Microbial into a s death (lethality) occurs based on numerous factors including, among others, the time and temperature of treatment and thermal resistance characteristics ( . D and z values) of the target organism In steam treatment of spices, lethality arises from the time and temperature of exposure of the spice microflora to steam . Treatments that provide thorough exposure of spice particles to steam for an appropriate ti me should successfully eliminate vegetative bacterial pathogens (e.g., Salmonella ). Steam system designs vary greatly in their abilities to fully expose spice particles to steam, and may or may not . Traditional steam tr include pressure and saturated steam eatments expose spice to steam that consists of vaporized water and usually a very small portion of liquid water (saturated steam) at a pressure (or vacuum) m- steam -vacuum process create an . Steam treatments employing a vacuu to control its temperature ronment that removes the gases from within the chamber and allows for the steam to penetrate envi throughout the product. it is saturated steam, will be dependent on the The steam temperature, because vacuum held within the processing chamber . A final vacuum st ep is used for these processes to remove any water that may have condensed onto the spice . Steam treatments that include supplemental electrical or indirect heat employ saturated steam condensation and heat conduction to both heat the spice to remove any microbial contamination and control the moisture level of the spice so that it does not change during the process . These dual heating systems may not include a drying step, but could include a cooling step to cool -vacuum and dual heating processes aim to the spice back to pre- processing conditions . Both vacuum -steam reduce the undesirable effects of excessive wetting of spice that may take place during traditional steam treatment. Two basic methods used for steam treatments include batch and continuous proc essing . In batch processing, packages of spices are palletized, loaded into a treatment chamber followed by steam injection into the chamber with or without pressure . Due to variations in bulk density among spices (as well as other factors such as packing permeability and stacking configuration), there is no set of conditions for steam treatments that would be effective for all spices; therefore, processor s should determine treatment time that will ensure steam penetration throughout the package for an adeq uate time period to reduce the number of vegetative pathogens. Continuous steam processing involves equipment designed to continually move spice through a system where steam is injected . System designs differ in the way in which the unpackaged product is exposed to steam and conveyed through the system . Some may use rotational devices to provide tumbling action for enhanced exposure of spice particles to the steam and to convey the spice through the steam chamber . Others may layer spices on a conveyor belt without enhanced mixing action of the spice particles as they traverse the steam chamber . Other systems may use different conveyance systems . In a properly designed and operated . Continuous systems system, all particles will be directly exposed to steam for an appropriate time period that agitate spice particles within the steam chamber theoretically need less exposure time than the batch . A continuous system that has less mixing action (e.g., method, which relies on passive steam penetration conveyor belt ) would need longer exposure time to ensure complete coverage as compared to continuous systems that use mixing action. of steam treatments. Steam treatments can effectively reduce microbial Applicability and Practicality populations in dried spices but may impact spice quality . Advantages are that the technology is well established and effective when properly applied, and equipment is readily available. Disadvantages are that some systems are not designed to provide the most effective reduction in microb ial populations, and physicochemical quality parameters related to color and flavor may be negatively impacted by steam. FDA Draft Risk Profile | 107

120 Current Mitigation and Control Options | 8 Effectiveness of steam treatment Refereed publications that address spices in reducing Salmonella in spices. Salmonella inoculated with populations are limited to presence/absence data after steam treatment and do not discuss enumeration in low moisture foods are . However, data on thermal inactivation of Salmonella ce of salmonellae in chocolate, a low . In a review by Doyle and Mazzotta (2000), the thermal resistan available . For example, D -values at 71°C moisture food, was shown to be much higher than for higher moisture foods ranged between 210 and 1,200 min for S. Anatum in chocolates with various moisture contents between 0 Typhimurium in roast beef had a D S. . As discussed in Section and 4% wher eas -value of 0.095 min at 70°C any refereed publications have established that salmonellae in low moisture foods have significantly 5.1.3, m - and z higher D gher moisture levels (Podolak et al. , 2010; Hiramatsu -values compared to other foods with hi et al. , 2011; Keller et al. , 2012; Harris et al. , 2012) , It has also been shown that reductions et al. , 2005; Gruzdev et al. ; Abd are not always linear and that significant tailing may occur (Beuchat and Mann, 2010 , 2012; Blessington et al. , 2012). Reductions of different microbial populations in spices (aerobic plate counts, yeast/mold counts, total , and Enterobacteriaceae ) by steam treatments were reviewed in coliforms, fecal coliforms, E scherichia coli . four refereed publications (Table 8.9) Table 8.9. Decimal reductions of microbial populations in spices from heat t reatments STEAM Trmt Type Trmt Pressure Decimal Process a a Time Temp Spice Adapted from: of c Type (psig) Reduction b (°C) Count (min) 0.1 160 15 APC C 2 Almela et al. ,2002 Paprika 0.1 160 30 APC C > 4.8 Almela et al., 2002 Paprika Paprika 0.1 160 15 CF C > 3.5 Almela et al., 2002 > 160 30 CF C 0.1 3.5 Almela et al., 2002 Paprika 2002 Paprika 0.1 160 15 EB C > 3.9 Almela et al., Paprika 160 30 EB C > 3.9 Almela et al., 2002 0.1 Yesair and 115 10 APC B 4.8 20 Pepper, black ground Williams (1942) Yesair and 15 121 15 APC B 7.9 Pepper, black ground Williams (1942) Yesair and 108 5 APC 4.3 5 Pepper, black ground B Williams (1942) 16 ~100 0 APC B 2.6 Waje et al., 2008 Pepper, black ground Pepper, black ground 16 ~100 0 CF B 4.2 Waje et al. , 2008 Pepper, black ground ~100 0 YM B 16 2.3 Waje et al. , 2008 0 3 130 2010 APC Pepper, black whole U 0.8 Sádecká, assumed Pepper, red ground 16 ~100 0 APC B 1.3 Rico et al. , 2010 Pepper, red ground 16 ~100 0 YM B 2.7 Rico et al. , 2010 FDA Draft Risk Profile | 108

121 Current Mitigation and Control Options | 8 DRY HEAT Trmt Trmt Type Pressur Decimal Process a a Adapted from: Time Spice Temp of 2 Reduction Type e (psig) 1 (°C) Count (min) 15 70 0 APC B 1.9 Anise seed Farag Zaied et al. , 1996 70 0 YM B 15 2.5 Farag Zaied et al. , 1996 Anise seed 15 70 0 APC B Coriander Farag Zaied et al. , 1996 2 Coriander 15 70 0 YM B 2.3 Farag Zaied et al. , 1996 70 0 APC B 3 Farag Zaied et al. , 1996 Fennel seed 15 15 70 0 YM B Fennel seed 3 Farag Zaied et al. , 1996 Paprika 0.1 152 0 APC 1.6 Almela et al. , 2002 C Paprika 0.1 152 30 APC C 1.8 Almela et al., 2002 Paprika 152 0 CF C 1.3 Almela et al. , 2002 0.1 152 30 CF C 2.4 Almela et al. , 2002 Paprika 0.1 0.1 152 0 EB C Paprika 3.8 Almela et al. , 2002 Paprika 0.1 152 30 EB C > 3.9 Almela et al. , 2002 Pepper, black whole 15 70 0 APC B 3 Farag Zaied et al. , 1996 Pepper, black whole 70 0 YM B 15 3.1 Farag Zaied et al. , 1996 Turmeric 15 70 0 APC B 2.9 Farag Zaied et al. , 1996 Turmeric 15 70 0 YM B 2.7 Farag Zaied et al. , 1996 MICROWAVE Trmt Trmt Decimal Pressure Process Type of a a Spice Adapted from: Time Temp 2 1 (psig) Type Count Reduction (°C) (min) 1.2 0 APC Oregano 100 Legnani et al. , 2001 15 C 15 100 0 EC Oregano C 0.2 Legnani et al. , 2001 100 0 FC 15 3.8 Legnani et al. , 2001 Oregano C 0.67 160 0 APC B Pepper, black ground Emam el al. , 1995 1.3 Pepper, black ground 1.25 240 0 APC B 3.5 Emam el al ., 1995 100 0 APC C 0.1 Legnani et al. , 2001 Pepper, black whole 15 15 100 0 EC Pepper, black whole 0.2 Legnani et al. , 2001 C Pepper, black whole 15 100 0 FC C 2.5 Legnani et al. , 2001 2001 Pepper, red chili 15 100 0 APC C 1.3 Legnani et al, Pepper, red chili 15 100 0 EC C 0.7 Legnani et al. , 2001 C 100 0 FC 15 3.6 Legnani et al. , 2001 Pepper, red chili Rosemary 15 100 0 APC C 1.6 Legnani et al. , 2001 Rosemary 15 100 0 EC C 0.2 Legnani et al. , 2001 C Rosemary 15 100 0 FC 3 Legnani et al. , 2001 Sage 100 0 APC C 1.5 Legnani et al. , 2001 15 C Sage 100 0 EC 15 0.8 Legnani et al. , 2001 Sage 15 100 0 FC C 3.7 Legnani et al. , 2001 a Trtmt = treatment. b APC = total aerobic plate count, CF = coliforms, EB = Enterobacteriaceae, EC = Escherichia coli fecal coliforms, YM = yeasts and , FC = molds. c B = batch, C = continuous, U = unknown APC population reductions ranged from 1.3 log for a 16 min continuous process at 100°C at atmospheric pressure to 7.9 log for an autoclave process in saturated steam at 121°C for 15 min. Data in Table 8.9 indicate that steam treatment produces a relatively higher reduction of spice microflora than dry heat or microwave treatment; however, this comparison is limited by the small number of steam -treated spices in the studies (bl ack pepper, red pepper and paprika), the small number of studies published in scientific literature with usable data, especially for dry heat and microwave treatments, and the different study conditions and thermal e, some studies used steam chambers with pressure while others . For exampl processes used in the studies FDA Draft Risk Profile | 109

122 Current Mitigation and Control Options | 8 . Another noteworthy issue is that all studies reviewed for this used only flowing steam without pressure the native microflora of test spices rather than inoculating with specific microorganisms of document used . concern or a surrogate Salmonella . Despite this difficulty in making Therefore, none of the published studies specifically address direct comparisons among the studies, conclusions can be drawn: • Some steam treatments effectively reduc e microbial populations on dried spices, and based on APC decimal reduction s achieved appears to be more effective than dry heat or microwave treatment; Steam systems that use • saturated steam and pressure under specific time/temperature constraints reduce microbial populations more than those that do not. Those not utilizing pressure reduced APCs between <1 and 4 logs depending upon time/temperature and exposure conditions whil e APC reductions in steam systems that used pressures ranged from 2 logs in a continuous system to almost 8 logs in a batch system with 15 psig pressure . Microbial reductions from dry heat and microwave logs, respectively. treatments ranged from 1.3 to 3.9 logs and 0.1 to 3.7 Early tests conducted by Yesair and Williams (1942) established that ground black pepper could be . They autoclaved at various temperature/pressure combinations to yield low total counts of microorganisms per sensory quality . Treatment conditions ranged from 5 min at 108 °C (5 psig reported minimal change to pep pressure) to 15 min at 121°C (15 psig pressure) yielding 4.3 and 7.9 decimal reduction s in APC, respectively . Pepper quality was determined using subjective sensory methods and di . d not incorporate chemical analyses Sádecká (2010) reported that heat treatment of black pepper for 3 min with dry steam at 130 °C produced “a remarkable decrease in the overall aroma of heat sterilized black pepper” which is counter to the report from Yes air and Williams (1942) . The Sádecká study used gas chromatographic instrumentation (GC/FID, GC/MS) including a combined instrumentation/sensory technique (GC olfactometry, or GC/O) to establish changes in volatile compounds in the pepper, whereas Yesair a nd Williams conducted qualitative human sensory evaluation without instrumentation. A unique continuous process designed and tested by Almela et al. (2002) used dry nitrogen with and without 2 and pressure of 1 or 2 kg/cm various amounts of steam at a constant temperature of 160°C (15 or 30 psig) steam combined with dry nitrogen was more effective at for 6 seconds . Treatment combinations that used , 2002). et al. reducing microbial populations than the use of dry nitrogen alone (Almela et al. °C ) of dried whole red peppers (2010) determined that atmospheric steam treatment (16 min, 100 Rico re -drying and grinding into powder produced a reduction in APC of in a commercial tumbling chamber before ical properties compared to gamma radiation or less than 2 logs with greater negative impact on physicochem control pepper . This laboratory also studied these same treatments on black pepper with similar results , 2008) et al. . APC, coliform and yeast/mold counts were reduced 2.6 log, 4.2 log, and 2.3 log, (Waje resp ectively, with significant loss of color and flavor of the black pepper due to steam treatment. An alternative steam treatment that relies on “ is discussed below in 8.2.1.8. This controlled condensation” t on sensory quality of spices while also type of treatment was designed to reduce the impac . It appears that this type of steam reducing/eliminating salmonellae that might be present in the spice treatment may produce an acceptable reduction in Salmonella while having a reduced impact on the spice sensory qualities as compared to more rigorous steam treatments. ION TREATMENT 8.2.1.4 GAMMA RADIAT Radiation is an efficient method to eliminate pathogens from foods . Cobalt -60 and cesium -137 are commonly used sources of gamma rays to which pre -packaged foods are exposed for specific time periods to provide a dose that effectively reduces microbial populations . Dosage of gamma rays decreases with wave penetration . For this reason, gam into a food such that food particles closer to the source receive a higher dose ma irradiators usually increase penetration efficiency with use of a system whereby food packages are not static FDA Draft Risk Profile | 110

123 Current Mitigation and Control Options | 8 but are moved past the gamma ray source during the exposure time to ensure thorough coverage of the package . Suggested minimum doses for a variety of spices are found in the ASTM Standard Guide for Irradiation of Dried Spices, Herbs, and Vegetable Seasonings to Control Pathogens and Other Microorganisms (ASTM International, 2010) and range from a low of 3 to 8 kilogray (kGy) for caraway, cinnamon, paprika, red pepper and turmeric to a high of 7 to 15 kGy for onion powder . Ranges for minimum doses are necessary to -to-lot variability in initial microbial populations . address lot section 201(s) of the FD&C Act, sources of irradiation used on food Under are included in the definition of food additives . FDA reviews the . Food additives are subject to premarket review and approval by FDA to determine whether a food additive is safe for its intended use in food. FDA evidence regulations permit the irradi ation of spices up to a 30 kGy maximum absorbed dose (21 CFR 179.26(b)(5) (FDA, 2012k) . As with all permitted food additives, the dose used on spices should be no greater than that needed to achieve the desired technical effect. Three sources of radiation may legally be used; gamma sources (which include the isotopes cobalt -60 and cesium -137), electron beam sources with a maximum energy of 10 MeV, and X -ray sources with a maximum energy of 7.5 MeV . Although electron beam and x od -ray sources are allowed for fo treatment under 21 CFR 179 (FDA, 2012l), these technologies have to date not been described in proposals submitted for FDA review on reconditioning of violative spices . Published information on the effectiveness for these technologies is covered at the end of this section under Alternative Pathogen Reduction Treatments. FDA s also specify the types of packaging materials allowed for irradiation treatment of foods (21 regulation CFR 179.45) (FDA, 2012m) . Package labeling to indicate the spice has been irradiated is required under 21 CFR 179.26(c) (FDA, 2012n); however, the labeling requirement does not apply to a food that contains ingredients irradiated before being incorporated into the food. Applicability and Practicality of gamma radiation treatments. Gamma radiation is described in literature as a cost effective method of microbial inactivation that provides minimal impact on physicochemical characteristics of spices compared to either steam or EO . In a review by Kiss and Farkas (1988), numerous citations were given for research that demonstrates “no substantial changes” in the volatile oil content of most spices treated up to 15 kGy . Steam treatment adds moisture to spices that may have detrimental quality effects while EO may cause chemical chan ges that impact quality (Kiss and Farkas, 1988) and toxicity (e.g., EO . The major disadvantage with gamma radiation is consumer resistance to the use of this technology residues) on foods . Effectiveness of gamma radiation treatment Salmonella in spices . Effects of gamma radiation on in reducing Salmonella various strains of Although little published information in foods have been reported in literature. exists for the irradiation kinetics of Salmonella inoculated into spices, D -values (kGy dose that reduc es a population by 1 log) exist for a variety of products . Salmonella D- value results for a few low moisture products that might be considered representative for spices are 1.0 kGy (alfalfa seeds; Thayer , 2003), et al. 0.7 to 1.1 kGy (broccoli seeds; Rajko wski et al , . 2003), 0.9 kGy (bone meal; calculated from Ley et al. , 1963) and 1.5 kGy (desiccated coconut; calculated from Ley et al. , 1963) . Notably, reported D -values are lower for Salmonella inoculated onto produce and meats before . irradiation, ranging from about 0.2 to 0.7 kGy Among the refereed publications reviewed, 19 contained original treatment data related to gamma radiation . When viewed as a of at least 25 spices at various dosage levels ranging between 2 and 20 kGy (Table 8.10) function of dosage level across all spices, observed APC decimal reduction s fall within the following ranges: • 1.6 to 5.8 decimal reduction for doses between 2 and 5 kGy (n=52) • 2.2 to >6.9 decimal reduction for doses between 6 and 10 kGy (n=49) • 3.5 to >6.9 decimal reduct ion for doses between 11 and 20 kGy (n=8) The differences in spice results at any particular dosage level likely reflect treatment and biological variability within the experimental conditions for a particular study . Differences within a spice category and specific . Issues such as accurate dosimetry and dosage level suggest that other elements of the studies impact results FDA Draft Risk Profile | 111

124 Current Mitigation and Control Options | 8 dose mapping, the type of enumeration method and medium, the type of spice, and diversity of microbial species in the spice could impact final population counts after treatment. pices Table 8.10. Decimal reductions from gamma radiation for microbial populations of various s D - value kGy Decimal Type of a Spice (kGy/decimal Adapted from: b Reduction dose Count reduction) 3.0 1.7 APC Kiss and Farkas, 1988 Allspice 5 4.9 8 1.6 APC Vajdi and Pereira, 1973 Allspice 2.1 1.9 APC 4 Grecz et al., 1986 Anise seed 5 2.8 1.8 APC Farag Zaied et al., 1996 Anise seed 5 3.5 1.4 APC Kiss and Farkas, 1988 Anise seed 7 3.9 1.8 APC Grecz et al., 1986 Anise seed 10 5.2 1.9 APC Farag Zaied et al., 1996 Anise seed 5 2.8 1.8 YM Farag Zaied et al., 1996 Anise seed c > 10 2.9 > 3.4 YM Farag Zaied et al., 1996 Anise seed 2 1.6 Cardamom 1.3 APC Grecz et al., 1986 Cardamom 5 1.6 3.1 APC Sharma et al., 1984 10 > 2.6 > 3.8 APC Sharma et al., 1984 Cardamom APC 8 3.7 2.2 Vajdi and Pereira, 1973 Celery seed 5 2.4 2.1 APC Chili et al., 1987 Munasiri 4.5 1.1 5 Singh et al., 1988 Chili APC 5 4.0 1.3 Chili Alam et al., 1992 APC Chili 10 5.1 2.0 APC Munasiri et al., 1987 APC 6.3 1.6 Alam et al., 1992 Chili 10 5 1.2 4.2 Cinnamon APC Sharma et al., 1984 Clove 5 1.4 3.6 APC Sharma et al., 1984 1996 Coriander 5 1.6 3.1 APC Farag Zaied et al., Coriander 1.8 2.8 APC Munasiri et al., 1987 5 5 1.6 3.1 APC Alam et al., 1992 Coriander 5 4.0 1.3 Coriander Kiss and Farkas, 1988 APC > 4.1 > 2.4 10 APC Farag Zaied et al., 1996 Coriander 10 > 4.2 > 2.4 APC Munasiri et al., 1987 Coriander Coriander 4.1 2.4 APC Alam et al., 1992 10 > 2.8 > 1.8 YM Farag Zaied et al., 1996 Coriander 5 10 > 2.8 > Coriander 3.6 YM Farag Zaied et al., 1996 Cumin 2 3.0 0.7 APC Grecz et al., 1986 Cumin 5 2.6 1.9 APC Alam et al., 1992 4.1 Cumin 5 1.2 APC Kiss and Farkas, 1988 Cumin > 4.0 > 2.5 APC Alam et al., 1992 10 APC 2.3 1.7 Grecz et al., 1986 Curry 4 10 > 5.0 > Curry APC Munasiri et al., 1987 2.0 Fennel seed 5 2.7 1.9 APC Farag Zaied et al., 1996 Fennel seed 10 4 2.5 APC Farag Zaied et al., 1996 Fennel seed 3.3 1.5 5 YM Farag Zaied et al., 1996 Fennel seed 10 > 3.3 > 3.0 YM Farag Zaied et al., 1996 1.3 Garlic 3.0 4 APC Vajdi and Pereira, 1973 Ginger 5 2.5 2.0 APC Farag et al., 1995 1995 Ginger 10 3.0 3.3 APC Farag et al., FDA Draft Risk Profile | 112

125 Current Mitigation and Control Options | 8 D - value kGy Decimal Type of a Spice (kGy/decimal Adapted from: b dose Reduction Count reduction) 2.9 APC Farag et al., 1995 Marjoram 1.7 5 1.1 APC 4.6 Kiss and Farkas, 1988 Marjoram 5 2.1 4.8 APC Farag et al., Marjoram 1995 10 5 1.8 2.8 APC Sharma et al., 1984 Nutmeg APC 10 3.1 > 3.2 > Sharma et al., 1984 Nutmeg 4 2.5 1.6 APC Kiss and Farkas, 1988 Onion powder 4 1.8 2.2 APC Silberstein et al., 1979 Onion powder 4 Onion powder 2.1 1.9 APC Silberstein et al., 1979 APC 2.9 1.7 Kiss and Farkas, 1988 5 Onion powder 8 2.3 3.5 APC Onion powder et al., 1979 Silberstein 3.5 2.3 APC Silberstein et al., 1979 Onion powder 8 APC 9 1.1 8.2 Silberstein et al., 1979 Onion powder 9 2.2 Onion powder 4.1 APC Silberstein et al., 1979 Onion powder 9 2.0 4.5 APC Silberstein et al., 1979 10 3.3 3.0 APC Kiss and Farkas, 1988 Onion powder 10 3.1 3.2 APC Silberstein et al., 1979 Onion powder 10 4.5 2.2 APC Silberstein et al., 1979 Onion powder 13 4.8 2.7 APC Silberstein et al., 1979 Onion powder APC 4.6 2.8 Silberstein et al., 1979 Onion powder 13 15 5.5 2.7 APC Silberstein et al., 1979 Onion powder 15 4.8 3.1 APC Silberstein et al., 1979 Onion powder 15 5.5 2.7 APC Silberstein et al., 1979 Onion powder APC 4.8 3.1 Silberstein et al., 1979 Onion powder 15 5 5.0 1.0 Oregano APC Legnani et al., 2001 Oregano 6 3.2 1.9 APC Vajdi and Pereira, 1973 Oregano 5.4 1.9 10 APC Legnani et al., 2001 2.5 Paprika 5 2.0 Kiss and Farkas, 1988 APC Paprika, added oil 2.2 3.0 APC Franco et al., 1986 6.5 APC 2.8 2.3 Franco et al., 1986 Paprika, fine grind 6.5 6.5 2.7 2.4 APC Franco et al., 1986 Paprika, granulated 4.3 Paprika 1.9 APC Vajdi and Pereira, 1973 8 3.5 2.6 Paprika APC Kiss and Farkas, 1987 9 3.1 Paprika 3.5 11 APC Kiss and Farkas, 1988 Pepper, black ground 4 2.8 1.4 APC Soedarman et al., 1984 Pepper, black ground 3.0 1.3 APC Singh et al., 1988 4 5.8 Pepper, black APC Legnani et al., 2001 5 0.9 Pepper, black 5 3.2 1.6 APC Kiss and Farkas, 1988 Pepper, black ground 5 2.3 2.2 APC Farkas and Andrássy, 1984 2.2 Pepper, black ground 2.3 5 APC Farkas and Andrássy, 1984 Pepper, black ground 5 3.8 1.3 APC Farkas and Andrássy, 1984 Pepper, black ground 5 3.8 1.3 APC Farkas and Andrássy, 1984 Pepper, black ground 5 4.1 1.2 APC Sharma et al., 1984 Pepper, black ground 2.7 1.9 APC Grecz et al., 1986 5 5 3.3 1.5 APC Munasiri et al., 1987 Pepper, black ground APC 1.1 4.5 Emam et al., 1995 Pepper, black ground 5 5 2.1 2.4 Pepper, black whole Farag Zaied et al., 1996 APC Pepper, black whole 5 > 6.0 > 0.8 APC Sádecká, 2010 ground 6 4.1 1.5 APC Soedarman et al., 1984 Pepper, black Pepper, black ground 7.5 5.0 1.5 APC Singh et al., 1988 Pepper, black ground 5.9 1.4 APC Soedarman et al., 1984 8 Pepper, black ground 5.0 1.8 9 APC Grecz et al., 1986 Pepper, black ground 10 > 6.2 > 1.6 APC Soedarman et al., 1984 1.8 Pepper, black ground > 5.7 > 10 APC Sharma et al., 1984 10 > 5.5 > 1.8 APC Munasiri et al., 1987 Pepper, black ground 1995 Pepper, black ground 10 3.3 3.0 APC Emam et al., FDA Draft Risk Profile | 113

126 Current Mitigation and Control Options | 8 D - value kGy Decimal Type of a Spice (kGy/decimal Adapted from: b dose Reduction Count reduction) Legnani 6.8 10 APC et al., 2001 Pepper, black 1.5 10 > Pepper, black > 1.4 APC Shigemura et al., 1991 6.9 3.9 2.6 10 Waje et al., 2008 Pepper, black powder APC 10 4.7 2.1 APC Farag Zaied et al., Pepper, black whole 1996 Pepper, black ground 12 5.0 2.4 APC Vajdi and Pereira, 1973 > 6.9 > 2.5 APC Shigemura et al., 1991 Pepper, black 17 20 > 6.9 > 2.9 APC Shigemura et al., 1991 Pepper, black Pepper, black whole 2.4 2.1 YM Farag Zaied et al., 1996 5 2.7 > 3.7 > Pepper, black YM Shigemura et al., 1991 10 Pepper, black powder 10 2.8 3.6 YM Waje et al., 2008 Pepper, black whole > 3.4 > 2.9 YM Farag Zaied et al., 1996 10 > 3.7 > 4.6 YM Shigemura et al., 1991 Pepper, black 17 20 > 3.7 > 5.4 YM Shigemura et al., 1991 Pepper, black Pepper, black ground 2.3 1.7 EB Soedarman et al., 1984 4 1.9 > 4.2 > Pepper, black ground EB Soedarman et al., 1984 8 Pepper, black whole 5 > 0.9 > 5.6 COL Farag Zaied et al., 1996 Pepper, black powder 4.6 2.2 COL Waje et al., 2008 10 11.1 > 0.9 > Pepper, black whole COL Farag Zaied et al., 1996 10 Pepper, red chili 5 5.7 0.9 APC Legnani et al., 2001 Pepper, hot (red) 4.5 1.1 5 APC Farag et al., 1995 10 4.8 2.1 APC Farag et al., 1995 Pepper, hot (red) 2001 Pepper, red chili 10 6.0 1.7 APC Legnani et al., Pepper, red powder 10 5.1 2.0 APC Rico et al., 2010 YM 2.3 4.3 Rico et al., 2010 Pepper, red powder 10 5 3.0 1.7 APC Kiss and Farkas, 1988 Pepper, white > Pepper, white 6.8 > 1.5 APC Shigemura et al., 1991 10 > 6.8 > 2.5 Pepper, white APC Shigemura et al., 1991 17 Pepper, white 20 > 6.8 > 2.9 APC Shigemura et al., 1991 Rosemary 3.9 1.3 APC Legnani et al., 2001 5 Rosemary 4.1 2.4 10 APC Legnani et al., 2001 Sage 5 5.4 0.9 APC Legnani et al., 2001 Sage 4.9 2.0 10 APC Legnani et al., 2001 Thyme 4 1.8 2.2 APC Grecz et al., 1986 Thyme 7 3.5 2.0 APC Grecz et al., 1986 Turmeric 3.1 1.6 APC Farag Zaied et al., 1996 5 APC 3.7 1.4 Munasiri et al., 1987 Turmeric 5 5 4.0 1.3 APC Singh et al., 1988 Turmeric Turmeric 3.5 1.4 APC Alam et al., 1992 5 5.5 1.4 7.5 APC Singh et al., 1988 Turmeric Turmeric 10 > 3.2 > 3.1 APC Farag Zaied et al., 1996 Turmeric > 5.0 > 2.0 APC Munasiri et al., 1987 10 1.5 Turmeric > 6.5 > 10 APC Alam et al., 1992 Turmeric 5 > 2.8 > 1.8 YM Farag Zaied et al., 1996 Turmeric > 2.8 > 3.6 10 YM Farag Zaied et al., 1996 a Spice descriptors taken from references . b Enterobacteriaceae , YM = yeasts and molds APC = total aerobic plate count, COL = coliforms, EB = c "> " symbol used when microbial count after treatment is below the detectable limit. Number represents the population before treatment based on the enumeration method. Decimal reduction s in Table 8.10 were calculated by subtracting the log of the microbial population after treatment from that of the population before treatment. When the final microbial population after treatment was below detectable limits, the decimal reduction was calc ulated based upon the type of enumeration method used and the initial population, and was expressed with a “greater than” symbol . When initial , and the populations were small, such as typically seen for yeast/mold, coliforms or Enterobacteriaceae population after treatment was not detectable; it is difficult to draw inferences about the actual decimal FDA Draft Risk Profile | 114

127 Current Mitigation and Control Options | 8 In theory, the actual decimal reduction for “greater than” results could have been significantly reduction. s higher than what was reported . In some instances, large initial APC counts were reduced to concentration below detection after treatments . For example, black and white pepper with initial counts of log 6.8 APCs had e t al., 1991) . With the assumption non-detectable populations after treatment at 17 or 20 kGy (Shigemura that the method of detection allowed an enumeration estimate of 1 colony per gram, the decimal reduction was reported in Table 8.10 as “>6.8.” The average D -proce ss enumerations were available -value for APCs across all spices for which discrete post . D- is 2.2 ± 1.0 kGy (n=102) values are commonly generated for a specific species or strain of organism rather than a general group count such as APCs or YM counts, as was done here . With that noted, D -values for irradiation data may provide a useful relative comparison with other treatments but should be interpreted with care . Research on irradiation treatment using Salmonella or a suitable surrogate is needed. Numerous individual refereed publications refer to a range of kGy doses roughly between 3 and 10 for s deemed “acceptable.” reduction of overall microbial populations to concentration One publication states that a dose of 20 kGy will reduce microbial populations to less than 10 CFU/g and render a spice “sterile .” In a re et al. (1991) reported kGy doses that resulted in a 3 decimal view article on gamma radiation, Sjöberg reduction for 35 spices. These ranged from a low of 3 kGy to a high of 10 kGy with an average of around 6 kGy to achieve a 3 decimal reduction in APCs . As mentioned earlier, ASTM International (2010) provides ranges of minimum doses to achieve “acceptable levels” (acceptable concentrations) of microorganisms in 19 spices dosage levels ranging between 3 and 15 kGy . with There exists considerable variability in dose responses reported in Table 8.10 . For example, decimal reduction s for ground black pepper at 5 and 10 kGy range between 1.1 to 4.1 log and 3.3 to >6.9 log, respectively. This large degree of variability within a single dose suggests additional factors influence the . Based on the understanding that significant variability exists in published efficacy of gamma radiation refereed data, additional research would likely be necessary in order to ensure achievement of a desired decimal reduction to Salmonella in specific spices . related DE TREATMENT 8.2.1.5 ETHYLENE OXI Ethylene oxide (EO or EtO) is a colorless gas that chemically reacts with components of vegetative cells and spores thereby resulting in cell death . Alkylation of nucleic acids in cells treated by EO has been demonstrated (Parisi and Young, 1991) and is thought to contribute to cell inactivation . EO is commonly used as an alternative to heat treatments and has provided a method for sterilization of heat sensitive materials -based medical devices, drugs, and treatment of spices or other foods . Use of EO as an such as plastic antimicrobial treatment is more complex than for steam and irradiation due to the large number of variables that should be controlled for the treatment to be effective. According to USP, variables include temperature, exposure time, humidity, vacuum/positive pressure and gas concentration (USP, 2011) . Gilbert et al. (1964) demonstrated that desiccation of various organisms increased their resistance to EO treatment and re sulted in non-linear inactivation curves . Other variables are the permeability of packaging in which spices are packed and the loading designs of individual pallets and the treatment chamber itself . Variations in package ensity and chamber/pallet loading patterns will impact the ability of the material permeability, spice bulk d . In some gas to penetrate the most inaccessible points within the packs thereby affecting the treatment time cases, such as with foil lined film, packaging material will essentially block penetration of EO rendering the Additionally, inert balance gases, such as CO technology ineffective. or N , and a series of chamber air washes 2 2 at the end of a cycle are needed to address concerns about EO flammability and mutagenic properties of toxic EO residues . While toxic residues of EO in treated materials remains a concern, an assessment of cancer risk (Fowles , 2001) from EO residues in spices concludes that “risks are practically negligible” based on et al. current understanding of exposure from concentration s of EO found in spices . Factors described here demonstrate the complexity of conducting validation studies for EO treatment chambers and conditions . Despite these limitations, EO is a well -established technology that is commonly used fo r sterilization of . On the medical devices and pharmacological products resulting in reductions of at least 6 log (USP, 2011) FDA Draft Risk Profile | 115

128 Current Mitigation and Control Options | 8 other hand, due to concerns about toxicity and safety, EO is banned for fumigation of foods in the European Union and Australia. . Packaged spices are placed into a Leistritz (1997) provides an overview of steps used in EO processing . This is followed by a vacuum step and heating of the chamber to the process chamber, which is then sealed temperature . Humidity is introduced into the chamber followed by the EO / inert gas mixture. After holding for a specified time period, usually several hours to ensure gas penetration into the package interior, gas is removed from the chamber, which is then flushed with air several times . After the c hamber returns to atmosphere pressure, product is removed. Applicability and Practicality of ethylene oxide treatments. The use of EO as a treatment method for spices is well established although the effectiveness at reducing Salmonella may be less than for irradiation or steam . Research opportunities exist to demonstrate clearly the expected decimal reductions of treatments in spices from EO Salmonella be controlled with this technology, as . Due to the larger number of variables to compared to steam or irradiation, validation studies would be more complex, but it should be possible to design scientific studies that will specify variables such as gas concentration, exposure time/temp, humidity, and product type and density to achieve successful results. Under the U.S. Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) (EPA, 2012b) the Environmental Protection Agency (EPA) regulates substances intended for preventing, destroying, repelling, or mitigating . Ethylene oxide is used to reduce p ests and microbiological contamination any pest . In 2008, the EPA reregistered ethylene oxide as a legal pesticide that may be used on spices. Spices may be decontaminated using ethylene oxide consistent with EPA’s regulation under 40 CFR 180.151 (EPA, 2012c) . Appl ication of ethylene oxide treatment to spices in prohibited in some countries . in spices. Effectiveness of ethylene oxide treatment in reducing Salmonella Five refereed studies on EO treatment of spices were reviewed . Decimal reduction nd in refereed scientific journals s of spice APCs fou . Several data points were available for paprika range from 1.3 log to >6 log with an average of about 3.0 log and ground black pepper with only one data point each for allspice, celery seed, cinnamon, garlic and oregano . A comparison of results among the studies is difficult due to substantial differences in gas concentrations, exposure time, temperature and moisture. As stated above, EO treatment involves control of several variables . One data point in Table 8.11 was dete rmined from pre - and post -treatment APC counts provided by a company to FDA after a reconditioning treatment accepted by FDA in 2010 was applied. Farkas and Andrássy (1984) demonstrated that EO fumigation was more effective at water activities of 0.75 and 0.50 than at 0.25, which supports results by Gilbert et al. (1964), mentioned above . Michael and Stumbo (1970) studied the effect of EO on lyophilized Salmonella Senftenberg (alone and in egg solids) and E . Treatment conditions included 40°C, 700 mg/L gas concentration, and relative scherichia coli . D- humidity between 11 and 73% values (min) for lyophilized cells alone were 2.2 at 11% RH, 3.4 at 23% RH, 4.0 at 33% RH, 5.0 at 53% RH and 5.9 at 73% RH indicating that fumigation was more effective at lower relative humidity which is counter to results of Farkas and Andrássy (1984) and Gilbert el al. (1964). The reasons for differences in results in these studies is unknown . When cells were lyophilized in an egg solids mixture, the D -value at 11% RH increased from 2.2 to 4.5 min thereby indicating that the food matrix can influence cell survival. FDA Draft Risk Profile | 116

129 Current Mitigation and Control Options | 8 Table 8.11. Decimal reductions of APC counts in spices treated with ethylene o xide Time Decimal or % A Temp w Gas Conditions Adapted from: Spice Reduction (°C) Moisture (Hr) Allspice, Vajdi and Pereira, O/160 10% EO + 90% CO 150 mL H 2 2 a 3 ground 57 cu. ft. 4.6 1973 12 (w/w)/4.5 m 150 mL H O/160 10% EO + 90% CO Vajdi and Pereira, Celery seed, 2 2 3 57 ground 4.7 16 1973 (w/w)/ 4.5 m cu. ft. Cinnamon, b 80 15cc/11.4 L NR ground 2.9 Yesair et al., 1942 5 Vajdi and Pereira, O/160 150 mL H 10% EO + 90% CO 2 2 3 (w/w)/ 4.5 m 5 cu. ft. 3.5 1973 Garlic, ground 57 10% EO + 90% CO 150 mL H O/160 Vajdi and Pereira, Oregano, 2 2 3 57 cu. ft. > 16 3.5 ground 1973 (w/w)/ 4.5 m 10% EO + 90% CO Paprika, 150 mL H O/160 Vajdi and Pereira, 2 2 3 16 57 (w/w)/ 4.5 m cu. ft. > 6 ground 1973 Paprika, Reconditioning 54 470 mg/L 23% RH 3 1.7 ground treatment Paprika, Kiss and Farkas, NR NR NR NR 2.2 ground 1988 Paprika, 3 c 1986 granulated 48 25 750 g/m 11.12% mois. 1.5 Franco et al., Paprika, added 3 25 750 g/m 6.64% mois. 1.3 Franco et al., 1986 oil 48 Paprika, fine 3 25 750 g/m grind 7.05% mois. 1.8 Franco et al., 1986 48 150 Pepper, black O/160 mL H 10% EO + 90% CO Vajdi and Pereira, 2 2 3 ground (w/w)/ 4.5 m cu. ft. 3.4 57 1973 16 Pepper, black 80 15cc/11.4 L NR ground 5 3 Yesair et al., 1942 Pepper, black Farkas and 3 6 22 600 g/m 0.25 Aw; 8.5% 2.1 ground Andrássy, 1984 Pepper, black Farkas and 3 22 600 g/m ground 0.50 Aw; 11.0% 3.8 6 Andrássy, 1984 Pepper, black Farkas and 3 22 600 g/m 6 0.75 Aw; 15.0% 3.8 ground Andrássy, 1984 a Study by Vajdi and Pereira 1973 described gas and moisture conditions based on chamber geometry of 160 cubic feet. b NR = Not Reported, likely ambient c 3 g/m is equivalent to mg/L F TREATMENT EFFECTIV ENESS 8.2.1.6 COMPARISON O . Recent studies on red and black peppers Several publications compare gamma radiation to steam and/or EO suggest gamma radiation of 5 or 10 kGy produces a larger reduction in microbial populations than selected steam treatments with a reduced impact on physicochemical quality (Waje et al. , 2008; Rico et al. , 2010, Sádecká, 2010); however, the type of steam treatment used in these studies is less effective at reducing microbial populations when compared to the more aggressive steam treatments of other studies (Yesair et al. , 1942; Almela ., 2002) . In another comparison of gamma radiation with saturated steam, Kispéter et al. et al (2003) concluded that ionizing radiation was more appropriate than steam treatment of paprika due to changes in quality parameters associated with steam. In a comparison of EO and gamma radiation, Vajdi and Pereira (1973) concluded that irradiation was more effective at red ucing spice microflora with insignificant changes in volatile oil composition or color of paprika compared to EO . Franco et al. (1986) also found that irradiation was more effective than EO at reducing paprika microflora. Narayanan et al. (2000) concluded that gamma radiation is a superior technology to . They indicated that EO was least desirable due to its flammability and toxic nature . steam, microwave or EO FDA Draft Risk Profile | 117

130 Current Mitigation and Control Options | 8 While all three major treatment types will reduce microbial populations to some degree, an evalu ation of data and expert opinion published in the scientific literature suggests that gamma radiation is the most efficient method of pathogen elimination while causing the fewest changes in physicochemical quality parameters of spices . The major disadvantage for gamma radiation is lack of public acceptance whereas steam and EO have disadvantages related to changes in spice quality, e.g., color, flavor, and aroma, while EO has additional and is prohibited from being applied to disadvantages related to toxicity, complexity of treatment operations, spices in some countries . The data in tables 8.9, 8.10, and 8.11 demonstrate that large reductions in microbial populations can be achieved by these treatments under certain circumstances. Data are needed to erize achievable reductions of charact , or an appropriate surrogate, in spices and the conditions Salmonella to achieve such reductions. necessary 8.2.1.7 TREATMENT VA LIDATIONS The lack of data specifically related to the impact of treatment options on Salmonella in spices indicates there is a critical need for comprehensive validation research related to the effects of various treatments on Salmonella , and on selection of appropriate surrogates for spice matrices. There is also a need to establish an performance standard for treatments to destroy pathogens to achieve an appropriate level acceptable of protection. Information about methods to validate processes have been published (Scott, 2005; Codex, 2008; NACMCF, 2010; USP, 2011) thereby providing guidance on ho w to plan and conduct a validation to ensure that a process will inactivate Salmonella in spices and meet a relevant food safety objective. Companies that treat spices with an antimicrobial process should validate that the process is effective at eliminating the pertinent pathogen(s) . Generally speaking, steps involved in ensuring that a process will provide a desired kill step include establishing that the equipment and process control instruments will operate within identified parameters, and determining the processing conditions necessary to achieve elimination of the identified hazard to an . Determination of these conditions may involve reviewing scientific or or protection appropriate level technical literature, reviewing previous validation studies, reviewing government documents, mathematical . Alternatively, experiments may be designed and conducted to modeling, or operational data and surveys produce relevant reproducible data on process conditions necessary to eliminate the food hazard. s should be repeated to provide a statistically sound view of variability. Finally in the validation Experiment companies should document successful completion of the steps taken in the protocol. process, In those instances when a pathogen cannot safely be used duri ng a validation challenge study, the pathogen should be replaced with a surrogate -pathogenic and have inactivation . Surrogates should be non characteristics and kinetics that can be used to predict behavior of the target pathogen exposed to the inactivatio n technology . Other desirable characteristics of surrogates include having stable and consistent growth characteristics, easy preparation and enumeration, being genetically stable, and lack of spoilage characteristics if used on equipment in a production area. (FDA, 2000) Of critical importance in the validation is determination of the amount of kill needed to achieve the desired objective . For example, the juice HACCP regulation (21 CFR 120) (FDA, 2012o) requires that juices receive a process capable of producing a 5- . USP standard sterilization decimal reduction of the pertinent pathogen -6 achieve at least a 10 treatments (USP, 2011) are to /unit microbial survivor probability (i.e., greater than a 1 in 1 million chance that a viable cell survives treatment per unit of product) . Such a numerical standard is not et al . (2013) provides some discussion about which issues to established for spices although Schaffner consider when setting standards for low moisture foods . A typical USP -like validation protocol would be implemented in different stages including 1) an installation qualification stage to ensure that equipment is properly designed, installed and calibrated; 2) an operational stage that includes test qualification stage to ensure that the equipment functions properly; 3) a confirmatory treatments of materials using appropriate measurements to ensure treatment uniformity that is adequate to FDA Draft Risk Profile | 118

131 Current Mitigation and Control Options | 8 final stage whereby all supporting information and data produce the pathogen reduction desired ; and 4) a to execute the validation is properly documented. used An additional resource for information on process validations is the report, “Parameters for Determining Inoculated Pack/Challenge Study Protocols” published by the National Advisory Committee on Microbio . Although this report largely addresses growth inhibition logical Criteria for Foods (NACMCF, 2010) challenge studies, portions related to inactivation studies are pertinent to development of studies on . The report provides information on factors related to the product, target organisms, treatment of spices s and preparation, inoculation method, sampling considerations, sampling intervals, concentration inoculum ust be and interpretation of test results . Additionally, the report recommends that “challenge studies m designed and evaluated by an expert food microbiologist” thereby emphasizing the need for companies to engage experts in the validation process . Other validation information is available from additional sources ; Codex, 2008). (GHTF, 2004; Hardin, 2012; Taormina, 2012; FDA, 2011b REATMENTS 8.2.1.8 ALTERNATIVE PATHOGEN REDUCTION T Research on a variety of alternative processing methods applied to the treatment of spices has been . A steam method in which condensation and evaporation are controlled to prevent harmful effects published s of salmonellae on spice quality while reducing concentration has been developed and is currently available . Other processes, such as electron beam and x -ray radiation, high hydrostatic pressure with commercially heat, ozonation, and high pressure CO with heat, appear to produce significant reductions in microbial 2 populations. Controlled condensation (CC) steam processes are commercially available whereby condensation and evaporation are controlled to allow thermal inactivation of microorganisms while reducing negative physicochemical quality changes usually associated with pressurized or atmospheric pressure steam . Expe riments on almonds inoculated with treatment (Koco Inc., 2008; Perren, 2008) Enterococcus faecium NRRL B 2354 as a surrogate for Enteritidis PT30 showed decimal reduction s of 2.5, 3.6, 5.0 and Salmonella e for use on 6.1 after CC treatment for 1, 2, 5 and 10 min, respectively. This technology may be appropriat spices, but should properly validated. be Zhao and Cranston (1995) investigated the effect of ozonized air (6.7 mg/L ozone) on various E microorganisms in ground black pepper or water containing whole black pepper scherichia . Reductions in col i, Salmonella , of 3 to 4 logs were produced in ground pepper while similar reductions in APCs were seen for treatment of for whole peppercorns . Researchers concluded that this technology would be best used whole peppercorns in ozonized water . Treatment of ground black pepper could result in unacceptable changes in volatile oils depending upon the moisture content of the pepper . Emer et al. (2008) reported that in whole and ground bl scherichia coli an ozone concentration of 0.1 ppm for 360 min could reduce ack E pepper approximately 7 log without a negative impact on product quality. Butz et al. (1994) showed that a three cycle high pressure processing (HPP) treatment at 70 ̊ C for 30 min at 80 MPa followed by 30 min at 350 MPa successfully inactivated the micr oflora of spice mixtures . It was necessary to raise the water activity to 0.91 to achieve microbial inactivation possibly making the process less . Skapska desirable for spices et al. (2003) demonstrated the application of combined dry heat and high hydrost . A atic pressure to eliminate vegetative cells from black pepper with minimal impact on volatiles minimum treatment of 1000 MPa under argon for 30 min at 60 ̊C reduced the mesophilic population of the native microflora less than one log . The same treatment at 140 ̊C reduced the mesophilic population 3.4 logs . Finally, Neetoo and Chen (2011) determined that a two phase treatment using dry heat followed by 600 MPa for 2 min produced a 5 decimal reduction of Salmonella spp. and E scherichia coli O157:H7 inoculate d onto alfalfa seeds, a commodity similar in characteristics to some spices. Dry heat and microwave heat treatments were addressed by a variety of researchers (Emam et al. , 1995; general, dry heat and microwave , 2002). In Faraq Zaied et al. , 1996; Legnani et al. , 2001; and Almela et al. FDA Draft Risk Profile | 119

132 Current Mitigation and Control Options | 8 techniques were less effective than steam at reducing microbial populations with reductions ranging from 1.3 to >3.9 log and from 0.1 to 3.8 log, respectively as compared to steam which ranged from 0.8 to 7.9 decimal s (Table 8.9) . Neetoo and Chen (2011) reported that dry heat of 65°C for 10 days or 70°C for 24 hr. reduct ion on alfalfa seeds, a low moisture product similar to spices such as celery seeds by reduced Salmonella approximately 5 log. Such extreme treatments may not be viable for spices due to changes in volatile oil (2000) suggests that microwave treatments concentration and quality et al. . A review article by Narayanan 3 will reduce microbial populations by a factor of 10 to 10 . Results in Table 8.9 generally fall within that range further indicating that microwave treatment may not provide an adequate reduction of pathogens. Supercritical CO is a method of using pressurized liquid CO as a processing method for foods and has been 2 2 populations in a variety of foods achieving decimal reduction s of <1 to >8 Salmonella demonstrated to reduce Gonzalez et al. , 2007) . This process method is also currently used to extract volatile oil constituents (Garcia- . The usefulness of supercritical CO from spices yielding liquid spice extracts as an antimicrobial process for 2 raw paprika was investigated by Calvo and Torres (2010) who reported that mild process conditions that would not affect extractable volatiles or color (25 -30% moisture, 85-90°C, 60- 100 bar pressure) “were sufficient to achieve the disinfection and total count reduction required by the most exigent clients.” Data appeared to suggest that the heat used during this treatment was a major contributor to the microbial reductions observed needed to determine the effect of pressurized CO . Further studies would be on 2 in spices. Salmonella . Although a 7 Pulsed UV light was studied for microbial inactivation in wheat flour and black pepper -log inactivation of occurred on glass beads and quar tz plate, pulsed UV light treatment Saccharomyces cerevisiae for wheat flour or black pepper (Fine under the conditions of study produced less than 1 decimal reduction and Gervais, 2004) . Further refinements will be needed before this technology would be useful for inactivation of microorganisms in food powders . The effect of another pulsed technology, pulsed electric field, on microflora of spices was investigated by Keith et al. (1997) and found to produce no more than a 1 decimal in APCs of dried onion, dill and basil powders. reduction Electron beam and x . Proctor et al. -ray radiation treatments of foods have been studied since the 1940s (1950) reported on the impact of supervoltage cathode rays on the native microflora of several spices and dry food ingredients ced between 3 and >6 logs after treatment . Van Calenberg et al. (1998) . APCs were redu found that reductions in microflora of spices were similar for electron beam and x- ray radiation and appeared to be >4 log for APCs in white pepper, 3 to 4 log in paprika, and 2 to 3 lo g in nutmeg at doses of 7.5 kGy . Hayashi (1998) showed that “soft electrons” (electrons with an energy of 300 keV or lower; defined by et al. study authors) would reduce the total microbial load in black pepper, white pepper, turmeric, coriander and basil to below detectable concentration s (<10 CFU/g) . Nieto -Sandoval et al. (2000) reported minimum electron beam irradiation D -values of 2.12 kGy for APCs, 2.66 kGy for Enterobacteriaceae , 3.15 kGy for -reducing clostridia, and 3.36 kGy for yeasts/molds coliforms, 3.84 kGy for sulfide . The D -value represents the kGy dosage -decimal reduction. They further reported no impact on the red color level needed to produce a 1 of paprika after treatment. 8.2.1.9 APPLICATION OF PATHOGEN REDUCTION TREATMENTS ASTA “recommend s the use of validated microbial reduction techniques” (ASTA, 2011) and many spice processing and packing/re -packing facilities apply such treatments to their spices. However, it is not known what fraction of the total U.S. supply is treated other than it is not 100%. Treatment may take place in the source country, another country or in the country of import, e.g., in the United States information shared by spice producers and manufacturers during our site visits and information gathered during FD A inspecti ons (see Section 8.1.3.1.) indicate that practices differ among spice manufacturers/packers/re- and packers among spices treated . Some spice manufacturers /packers/re- packers subject all or nearly all of the spice they handle to a pathogen reduction treatmen t (either before acquisition or during their processing) while others subject the spice to a pathogen reduction treatment only when the customer request s it. Some types of spices per, than others, e.g., are more commonly treated with pathogen reduction treatments, e.g., black pep FDA Draft Risk Profile | 120

133 Current Mitigation and Control Options | 8 . Many spices will be subjected to one or more treatments capable of killing dehydrated onion and garlic during food preparation (canning or cooking). However, some spices pathogenic bacteria such as Salmonella consumption . receive no antimicrobi al treatment before More data are needed to determine treatment conditions to ensure elimination of vegetative pathogens in . The data on concentration Salmonella in imported capsicum or sesame seed shipments offered for s of spices e United States (Van Doren, 2013c) and those found in samples of spices associated with foodborne entry to th Salmonella . Table 8.12 provides estimates of the number of outbreaks (Table 4.2) provide some guidance Salmonella - illnesses resulting from a population consuming raw spi ce from a single 40,000 lb. (18144 kg) and serving size, assuming the contaminated shipment/lot as a function of mean shipment/lot concentration - and between -shipment contamination is Poisson -distributed within the lot. The FDA study examining within in imported shipments of capsicum or sesame seeds provides some support for this Salmonella distribution of et al ., 2013c). (Van Doren assumption Salmonella illnesses resulting from a population consuming Table 8.12. Estimates of the number of raw spice from a single 40,000 lb. (18144 kg) Salmonella -contaminated lot as a function of mean lot and serving siz e, assuming the contamination is Poisson concentration -distributed within the lot Lot . Mean S Decimal reduction Serving Estimated Number of Illnesses to reduce illnesses Concentration a if all spice eaten raw Size (g) to <1 (MPN/g) 1 45,133 5 1 1 0.1 4,556 4 0.01 1 456 3 1 46 2 0.001 5 1 0.15 45,541 0.1 4,561 4 0.15 0.01 0.15 456 3 0.001 0.15 46 2 a Salmonella dose -response model (WHO/FAO, 2002). Based on the WHO/FAO 8.2.2 INDUSTRY GUIDANCE FROM TRADE ORGANIZATION S ON PRACTICES IMPACTI NG FOOD SAFETY OF SPICE S Spice and food trade associations have developed and published guidelines on the production, handling and packing of spices and low moisture foods that address food safety issues including mitigation and control programs and practices that prevent/reduce t he risk of contamination of spice with pathogens and filth . These include: • American Spice Trade Association (ASTA) o , 2011 Clean, Safe Spices: Guidance from the American Spice Trade Association , February , 2006 o HACCP Guide for Spices and Seasonings Clean Spices: A Guidebook for Shippers of Products to the U.S. Spice Trade o , May, 2008 • American Dehydrated Onion and Garlic Association, Official Standard and Methods, 14th edition , April 2005. • International Organization of Spice Trade Associations, General Guidelines for Good Agricultural Practices Spices , April 2008 • Grocery Manufacturing Association, Control of Salmonella in Low -Moisture Foods , Feb . 2009 In addition to the guidance documents identified above, the Grocery Manufacturer Association (GMA) published a series of reports of their research and best practices for controlling Salmonella in low moisture foods: FDA Draft Risk Profile | 121

134 Current Mitigation and Control Options | 8 Control of in Low -Moisture Foods I: Minimizing Entry of Salmonella into Processing • Salmonella ., 2009) et al Facility (Scott Control of Salmonella in Low -Moisture Foods II: Hygiene Practices to Minimize Salmonella • ., 2009a) Contamination and Growth (Chen et al Control of Salmonella in Low • -Moisture Foods III: Process Validation and Environmental Monitoring (Chen et al ., 2009b) Sources and risk factors fo r contamination, survival, persistence, and heat resistance of • in Salmonella Low et al ., 2010). -moisture foods (Podolak The Clean, Safe Spices: Guidance from the American Spice Trade Association (ASTA, 2011) document was developed to “assist the spice industry in developing programs that minimize the risk for contamination -processing storage, helping industry firms during growing, harvesting, drying transport, processing, and post n, safe spices to their industrial, food service and consumers customers” (ASTA, 2011). This to provide clea spice industry guidance provides five major recommendations: Minimize the risk for introduction of filth throughout the supply chain. 1. -processing contamination ination, cross -contamination, and post 2. Prevent environmental contam during processing and storage. 3. Use validated microbial reduction techniques. 4. -treatment testing to verify a safe product. Perform post 5. ment. Test to verify a clean and wholesome manufacturing environ The guidance identifies the specific programs and practices that should be established in order to implement the recommendations including • Good Agricultural Practices for growing and harvesting spices • Supply chain approval and re -evaluation program s • Good Manufacturing Practices (FDA CGMPs and Codex General Principles of Food Hygiene) • Hazard Analysis Critical Control Point (HACCP) Plans. • Validated microbial reduction process • ASTA Cleanliness Specifications • Post -treatment product sample and testing p rogram • Environmental sample and test program The guidance describes key elements of each program (e.g., evaluation of each potential supplier’s implementation and use of preventive controls such as GAPs, GMPs, and HACCP plans as part of a supplier from this guidance document, illustrates approval program). Figure 6.1, copied with permission recommended preventive controls to be applied at each stage of the farm to finished product continuum. ASTA Cleanliness Specifications, described in the guidance document, identify limits for macroscopic extraneou s matter for spices similar to FDA DALs. The concentration s in these specifications are in some cases smaller than the FDA DALs and provide limits for some spices for which specific FDA DALs were not . established Clean Spices: A Guidebook for Shippers of Products to the U.S. Spice Trade (ASTA, 2008) provides descriptions of U.S. regulations regarding importation of spice (including relevant food safety regulations), an overview of CGMPs and HACCP, FDA DALs and ASTA Cleanliness Specifications, warehouse/st orage sanitation practices, and cleaning practices to remove extraneous material. This guide describes specific equipment that can used to remove extraneous material from spice and a chart to link spice, filth element, and equipment. FDA Draft Risk Profile | 122

135 Current Mitigation and Control Options | 8 s and Seasonings (ASTA, 2006) identifies pre HACCP Guide for Spice -requisite programs, HACCP principles, HACCP plan implementation and documentation as it applies to spices and seasonings. It describes hazards ons of how to conduct a hazard analysis. including microbial and physical, and provides examples and suggesti Salmonella in Low GMA 2009 guidance and related reports (Scott, et al. , 2009; Chen Control of -Moisture Foods et al. et al. , 2009b) identify seven control elements to minimize the risk of Salmonella , 2009a; Chen co ntamination of low moisture foods in the manufacturing environment: 1. Prevent ingress of spread of Salmonella in the processing facility. 2. Enhance the stringency of hygiene practices and controls in the PSCA . 3. Apply hygienic design principles to building and equipment design. Prevent or minimize growth of Salmonella 4. within the facility. 5. Establish a raw materials/ingredients control program. 6. Validate control measures to inactivate Salmonella . controls and corr 7. Establish procedures for verification of Salmonella ective actions. These documents also describe common industry practices associated with implementation of each element. in a facility handling low moisture foods such as spices is defined as “the area where handling of PSCA The ingredient and product re quires the highest level of hygiene control . In a facility where products receive a pathogen inactivation treatment, the PSCA is the area subsequent to the terminal pathogen reduction step. In a facility where no inactivation step is employed, the entire process area may become the (lethality) et al. , 2009a) . PSCA” (GMA, 2009; Chen General Guidelines for Good Agricultural Practices Spices (IOSTA, 2008) addresses preventive controls to limit the introduction mycotoxins, heavy metals, pesticide residues, al lergens, undeclared colors, and processing aides from spices. The International Organization for Standardization (ISO) has issued over 50 standards for sampling and testing of spices. These recommendations are concerned with quality standards rather than food safety . standards guidance from trade organization s in preventing contamination of spices with Effectiveness of industry and/or filth and in preventing contaminated spice from entering the spice supply. The guidance Salmonella documents represent the spice and food manufacturing industries’ best practices. The guidance has evolved as data have demonstrated the ability of Salmonella to survive in low moisture foods and research has revealed causes for contamination n ot previously recognized, particularly for low -moisture foods. As a result, it is expected that application of the principles and recommendations outlined in these documents would reduce the risk of contamination of spices with microbial pathogens and filth. We are not aware of any surveys that have measured compliance with guidance recommendations or changes in contamination preva lence in spice production sites. As discussed in Section 8.1.3.4 and illustrated in Table 8.7, the number of RFR primary entries “Spices and Seasonings” in Year 3 of the program, was smaller than that found the for previous two years. It is noteworthy that the ASTA guidance Clean, Safe Spices: Guidance from the American Spice Trade Association was issued during Year 3. Unfortunatel y, absence of information about the total number of tests performed or lots examined , makes it difficult to interpret the significance of the in each year observed changes. As seen in Table 8.7, the number of primary entries reported for “Spices and Seas onings” during the first two years of the program were larger than that for most of the other food commodity types for all hazards and for Salmonella in particular . However, the absolute and relative (e.g., rank) number of primary entries for “Spices easonings” were much smaller in Y and S ear 3 of the program. As mentioned previously, the absence of information about the total number of tests performed or lots examined, makes it difficult to interpret the FDA Draft Risk Profile | 123

136 Current Mitigation and Control Options | 8 year . However the publication of the reports and meaning of these data, including changes from year to summary statistics has been effective in alerting the industry to reported problems. 8.2.3 RECALLS -containing foods were conduc Until FSMA was enacted in 2011, r of spices or spice ecalls ted on a firm's own initiative or by FDA request . FDA did not have the authority to mandate a recall. Classification of recalls and . discussion of recent recalls were described in Section 4.1.6 ning in the U.S. food supply Effectiveness of recalls in preventing contaminated spice from entering or remai . Recalls remove contaminated product or potentially contaminated product from the commercial market. As such, they directly impact public health by avoiding illnesses that would otherwise have been realized, if the contaminated had been consumed . Estimates of (potential) illnesses prevented for each spice- associated food recall event is hampered by lack of information about the serving size for each of the products recalled. Development and reporting such a metric would allow comparison of “illnesses prevented’ from recalls to other mitigation strategies. US AND FAO/WHO 8.3 CODEX ALIMENTARI , as a joint effort of the WHO and the Food and Agriculture Organization (FAO) Codex Alimentarius (Codex) , serves to assemble experts from it s member nations who set global standards for the safety and quality of foods. A number of guidance documents provided by Codex (Codex Alimentarius, 2013) address practices important to ensure spice food safety including • (CAC/RCP 1 -1969) (CAC, 2003) General Principles of Food Hygiene • -1995) (CAC, 1995) Code of Hygienic Practice for Spices and Dried Aromatic Plants (CAC/RCP 42 • Guide for the Microbiological Quality of Spices and Herbs Used in Processed Meat and Poultry -1991) (CAC, 1991) Products (CAC/GL 14 • de of Hygienic Practice for Fresh Fruits and Vegetables (CAC/RCP 53 -2003) (CAC, 2010) Co These documents provide broad requirements for hygienic production and harvesting, establishment design and hygiene, personnel hygiene, establishment hygienic processing, -product specifications. The and end spice -specific code is currently being revised by the Codex Committee on Food Hygiene (USDA, 2012). WHO has established WHO guidelines on good agricultural and collection practices (GACP) for medicinal plants and create Five keys to growing safer fruits and vegetables: promoting health by decreasing microbial d contamination which may be applicable to spice production (WHO, 2003 ; WHO, 2012) . The latter document, which was discussed briefly in Section 8.1.3.5, targets rura l workers and adapts the strategy of “Five keys to safer food manual” by providing graphics as well as text to communicate better with the intended audience. of the United Nations has also developed general GAP principles for all commodities that addre FAO ss soil, water, crop selection and rotation, and crop protection from pests (FAO, 2013a) . A “ is now available from the Joint FAO/WHO Expert Meetings Microbiological Sampling Plan Analysis Tool” on Microbiological Risk Assessment 2013) and t he Co dex Committee on Food Hygiene is developing ( JEMRA, detailed examples for the revised Principles and Guidelines for the Establishment and Application of Microbiological Criteria for Foods to aid in its implementation . in preventing contamination of spices with Salmonella Effectiveness of Codex and FAO/WHO guidance and/or filth and in preventing contaminated spice from entering the spice supply. These general guidance documents provide guidance for the spice and food industries based on sound scientific evidence and most have been revised to reflect current knowledge in food safety . As a result, it is expected that application of the principles and recommendations outlined in these guidance documents should reduce the risk of Code of Hygienic Practices for Spices and Dried . The contamination of spices with microbial pathogens and filth FDA Draft Risk Profile | 124

137 Current Mitigation and Control Options | 8 Aromatic Plants is not based on currently available data and information but is being revised. We are unaware of any systematic studies that have measured changes in the prevalence of contamination in microbial or filth spices as a result of applications of these guidance documents or any surveys that measure the extent to which these practices have been adapted by the food industry in general or the spice industry in particular. FDA Draft Risk Profile | 125

138 9. GENERAL CONCLUSIONS AND POTENTIAL FUT URE MITIGATION AND CONTROL OPTIONS 9.1 GENERAL CONCLUSI ONS Salmonella Bacillus spp. (including B. A wide diversity of pathogens have been found in spices including , ), Clostridium perfringens , Cronobacter cereus Shigella, and Staphylococcus aureus . Human illness spp., outbreaks attrib -contaminated spice have most commonly been associated uted to consumption of pathogen Salmonella or Bacillus with amination. Ten of fourteen (71%) spice -associated outbreaks identified spp. cont worldwide during the period 1973 -2010 and 87% of the documented human illnesses in the outbreaks attributed to consumption of contaminated spices were caused by serotypes of . Salmonella was Salmonella only pathogen associated with reported spice the -associated outbreaks, food recalls, and Reportable Food Registry reports in the United States , for the review periods covered in this report. The absence of spice- associated Bacillus spp. out breaks or food recalls reported in the United States is somewhat surprising, particularly in light of reports of Bacillus spp. outbreaks associated with consumption of contaminated spice in the European Union during the 1973 his report, and additional Bacillus -2010 review period covered in t spp. outbreaks (4) reported in the European Union in 2011 (EFSA, 2013). The apparent differences in the types of outbreaks attributed to contaminated spice and most commonly reported in the United States and the European Union or other regions/countries may arise in part from differences in awareness, surveillance (including test methodology), regulations, clinical diagnoses of suspected foodborne illnesses, and reporting requirement for different kinds of illnesses . Diff erences in diet, food preparation, and food storage practices may also contribute to the observed differences in types of reported outbreaks. into/on spice Evidence described in this report demonstrates the potential for introduction of Salmonella during primary production, distribution and storage, secondary processing and food manufacturing, and at Salmonella periods and retail. can survive in the natural environment (outside of an animal host) for extended persist in production environments for years. may , contact between the spice During primary production source plant during growth, harvest, or drying and Salmonella - contaminated materials in the environment , including soil, water, insects, animals, or animal feces, has the potential to contaminate the spice. Once in /on the spice, can continue to survive for long periods . Salmonella Most spices consumed in the United States are imported. The overall prevalence of Salmonella - contaminated shipments of imported spice offered for entry to the United S tates was 6.6% (750 g sample size ; 95% CI 5.7- 7.6%) for FY2007-FY2009. This value is 1.9 times (95% CI 1.6-2.3) the prevalence found for other shipments of FDA -regulated foods examined during the same period. was found in shipments of many Salmonella rent types of spices, in a variety of forms (whole, cracked diffe , ground or blended) and from many different Salmonella is a general problem in the spice supply countries. As a result, we conclude that the presence of rather than a problem of a specific t ype/form of spice or source country. A few differences in chain prevalence rates with spice type, form, or country were significant and these should be explored further to better understand the increased/decreased contamination rate. Salmonella s r anging from 0.0007 to 11 MPN/g -spice (7 MPN per 10,000 g to 11 MPN per g) concentration have been reported. Observations and models developed from an FDA 2010 study of shipments of imported capsicum (299 shipments) or sesame seed (233 shipments) offered for entry to the United States predict wide variability in the mean concentration of contamination among contaminated shipments of these types of spices and that many contaminated shipments contain very low concentrations of Salmonella . Estimated prevalence values based on sampling results are likely to be underestimates. S ampling plan design, particularly selections of an appropriate sample size and validated method of analysis, are critical t o ensure efficient surveillance. FDA Draft Risk Profile | 126

139 General Conclusions and Potential Future Mitigation and Control Options | 9 has also been found in the environment of spice/food facilities , including spice/food facilities Salmonella identified in the United States -associated outbreaks - associated with two of the three spice . Cross contamination from the spice/food manufacturing environment to the spice product was su spected to have been a contributing factor in both of these . An FDA surveillance study involving environmental outbreaks sampling in 59 spice manufacturers/packing/re-packing facilities in the United States during 2010 found 10% of the facilities contained Salmonella in the environment. In that study, Salmonella was found on non- product contact surfaces in close proximity to product such as the exterior of spice grinding equipment, floors or walls . The relatively large prevalence of Salmonella -positive facility environments observed in the survey indicates that Salmonella presence in spice manufacturers/packing/re-packing facilities is not uncommon. Experiments have shown that Salmonella can grow quickly in some spices when moistened/wet (in the other nutrients) which means that environmental niches may be created in facilities where absence of Salmonella is present in the environment and moisture is not controlled (e.g., where wet cleaning is used). Site visits and conversations with the spice industry revealed that not all spices sold by spice manufacturers have been treated with a pathogen reduction step. Food manufacturers and food preparers who purchase ction step that would limit the potential for the spice , if initially spice may subsequently apply a pathogen redu contaminat ed , to cause illness. However, investigations of spice- associated outbreaks revealed that in at least three of the outbreaks, the consumed spice had not undergone a pathogen reduction treatment before reaching the consumer . Addition of spices to foods after cooking is not uncommon in the United States (e.g., addition of capsicum or Italian seasoning to a pizza and black pepper to salads, steaks, and other foods). Once a moist food, pathogens from spice ingredients may grow if appropriate time/temperature present in conditions are not maintained. Growth of the pathogen in the food was suspected to have contributed to the numbers of illnesses in some of the outbreaks. Many of the -associated outbreaks during 1973 -2010 were associated with consumption of low - spice Salmonella moisture foods, including outbreaks leading to large numbers of illnesses. Large numbers of illnesses can occur from consumption of spices when the exposed popu lation is large, even when the concentration of Salmonella in the spice is small. This was the case for the1993 outbreak associated with consumption of contaminated paprika -powdered potato chips. A single contaminated shipment/lot of spice can contain mill ions to tens of millions of servings. A diversity of filth adulteration has been found in spices offered for import to the United States that includes insects, excrement, hair, and other materials. Filth shipment prevalence during FY2007 -FY2009 was 12% (95% CI 10- 15%) which was 1.8 times (RR 95% CI 1.4-2.2) the value found for all other imported shipments of FDA -regulated foods sampled during this time period. Filth was found in shipments of many different types of spices, in a variety of forms (whole, cracked, ground or blended) and from many different countries. As a result, we conclude that the presence of filth is a general problem in the spice supply chain rather than a problem of a specific type/form of spice or source country. However, shipments of imported black pepper FY20 09 and sesame seeds during FY2010 had significantly smaller violation rates than many during FY2007- other types of spice. The most prevalent types of filth were storage product insects/insect parts and animal hair (especially rodent). These types of filth are indicative of insanitary conditions and failures in the application of CGMPS. Current mitigation and control options to prevent or control adulteration of spice by pathogens and filth include GAPs, CGMPS, inspections of and environmental sampling in spice manufac turing/packing facilities, product sampling, refusals and reconditioning, import alerts (with or without green lists and country agreements), recalls, application of pathogen reduction treatments, and guidance from FDA, other U.S. federal agencies, interna tional agencies and industry trade organizations. Many of the current enforcement and regulatory strategies are effective but, with modification, could have greater impact on compliance. One - example is Import Alert 28 -02 for Indian Black Pepper, which includes an agreement that leverages in country regulatory authority to improve the food safety of shipments of the imported spice offered for entry FDA Draft Risk Profile | 127

140 General Conclusions and Potential Future Mitigation and Control Options | 9 to the United States. This combination of incentives appears to be effective in reducing the prevalence of Salmonella . or filth contamination in shipments of Indian black pepper offered for entry to the United States Expansion of this type of mechanism to other spices and/or to other countries should lead to further improvements. The FDA Food Safety Modernization Act provides important new tools to mitigate and control Salmonella , including authority to contamination and post treatment cross contamination of spices with ndards and mandate recalls and increase in the frequency of foreign and domestic inspections. Prevention sta import safety mandates required by FSMA are included in the potential future mitigation and control options, because they were still in development when this report was written. Failures identified in the farm -to-table food safety system potent ially leading to adulteration of consumed spice generally arose from poor/inconsistent application of appropriate preventive controls , such as failing to limit animal access to the source plant during harvest and drying phases, failing to limit insect and rodent access to spice during storage, and tment (or failing to subject all spice to an effective pathogen reduction trea . other lethality step) On the basis of our research, we concluded that the knowledge and technology is available to significantly reduce the risk of illness from consumption of contaminated spices in the United States . Capacity building through the creation of partnerships with stakeholders can facilitate improvements in spice safety and reduce the risk of illness from consumption of path ogen -contaminated spices . Specifically, enhanced communication between FDA and the spice industry and within the spice and food manufacturing industry itself, combined with training across the spice supply chain are needed to ensure understanding of appropriate preventive controls and how to implement and maintain them. 9.2 POTENTIAL FUTURE MITIGATION AND CONTROL OPTIONS We developed the following list of potential future mitigations and control options for consideration based on and a review and analysis of the scientific data and information available about the prevalence, concentration public health risk of pathogen (primarily ) and filth adulteration of spices and our assessment of Salmonella the efficacy of current mitigation and control options list includes mitigation and control options that . The FDA, the spice industry, government agencies, food manufacturers/preparers , and the consumer s may consider to reduce the prevalence and concentration of Salmonella , other pathogens, and filth in spices and to reduce the public health burden resulting from consumption of contaminated spices or foods containing contaminated spices. Mitigation and control options identified include capacity building, guidance, enforcement and regulatory strategies, communicatio n, education, and training . Research ne eded to explore additional potential mitigations is described in Chapter 10. For each mitigation and control option, we briefly describe the observation/data that motivated it, provide a brief description of the option, identify expected benefits/effectiveness, and provide additional comments about implementation (practicality), as needed . -to-table continuum in which it would be Mitigation and control options are organized by the stage in the farm implemented or the pa rt of the continuum that would be most highly impacted. More data are needed to rank the relative importance of the different kinds of system failures identified in the report and the potential impact of the proposed mitigation and control options. 9.2.1 PRIMARY PRODUCTION Update and produce industry and government guidance documents to reflect current knowledge and practices and improve utility of these documents by creating flexible communication platforms . Poor/inconsistent application of industry and g overnment guidance was identified as one of the contributing factors leading to spice contamination with pathogens and filth. Some of the guidance documents for spice production, storage, distribution, processing, and use described in Chapter 8 do not desc ribe the most up -to- date science -based principles for preventing/limiting contamination during on- farm production and post - production processes of spices (e.g., the Codex Code of Hygienic Practices for Spices and Dried Aromatic FDA Draft Risk Profile | 128

141 General Conclusions and Potential Future Mitigation and Control Options | 9 .) The tandards for the Growing, Harvesting, Packing, and Holding of Produce for Herbs proposed rule “S ” (78 Federal Register 3504, January 16, 2013) (FDA, 2013e ), which woul d im plement Human Consumption , provides information on mitigation in connection with pre -har vest commodities. It may section 105 of FSMA be applicable to certain types of spice source plant production and could be relevant to updated guidance documents. Each guidance document should be reviewed and updated, as necessary. To improve the utility of these documents, tools should be developed to allow individuals/organizations to create customized extracts/compilations of the guidance(s) to review, share, discuss, and educate with particular groups. For example, one could create a single extract that collects all the s ections of Codex documents that are relevant to the primary production of spices from the numerous relevant Codex food hygiene guidance documents. Some of this work is underway (e.g., development of a proposed revision of the Codex Code of Hygienic Practices for Spices and Dried Aromatic Herbs; FDA, 2012f) . Alternatively, an alliance of stakeholders could work together to harmonize standards for the industry, as has been done in the produce industry (United Fresh, 2013). Creation of flexible and comprehensive resources, such as the examples described above, would require resources to complete, but may improve adoption by clarifying recommendations. Enhance education and training for spice primary producers . Poor/inconsistent application of industry and gov ernment guidance was identified as one of the causes of spice contamination with pathogens and filth. While a number of guidance documents have been developed and have been reviewed in Chapter 8, some may not be accessible to all primary producers for a variety of reasons, e.g., not available, culturally insensitive, too general, wrong language, or uses the written word. New/revised versions of these documents could be developed to address limitations, perhaps building off of the novel GAPs tools developed by WHO (2013b) and the National GAPs Program at Cornell University (2013). Further improvements in application of guidance may be realized if practical examples are provided, either as part of the guidance or in another document/media format. For example, possible strategies for implementing guidance for primary production could address issues specific to different spices, growing practices/environments, and different available s should be shared as they resources. Best practices for training and education resulting from these effort could be used to enhance the efficacy of other training/education initiates. Development of these new educational tools will require resources and would likely benefit from a collaboration that includes primary econdary spice processors, experts in GAPs, and experts in communication. Members of the spice producers, s spice industry have invested much time and effort to understand local regulations, practices, and traditions in different spice producing regions and this information should inform education and training development. Collaborative initiatives in place that might consider taking part in this work include the industry -academia - government Preventive Controls Alliance (FDA, 2013f) or the Joint Institute for Food Safety and Nutrition )- country specific food safety training partnership (JIFSAN, 2013) . The development of a Collaborative (JIFSAN Training Centre for Food Safety and Supply Chain Management in Spices and Botanical Ingredients in India is already in progress. The par tners in this initiative are the Confederation of India Industry Food Agriculture Centre of Excellence (CII -FACE), Spices Board India, and JIFSAN (Food Agriculture Centre of Excellence, 2013.) FDA participated in the initial “train the trainer” programs b y training individuals from the CII -FACE, Spices Board India, Indian government officials, and industry representatives who will support the new initiative. 9.2.2 DISTRIBUTION A ND STORAGE FDA work with governments of spice producing countries to enhance food safety oversight by developing and formalizing programs such as the Indian EIC certificate program . FDA audits of the Indian EIC certificate program suggest that the program is effective in reducing the incidence of contamination in imported Indian bl ack pepper, although some discrepancies in its application were found, as described in Chapter 8 . Therefore, it is anticipated that reductions in the prevalence of pathogens and filth in imported spice shipments offered for import to the United States may be realized by expanding (and improving) the current program to include other spices imported from India and developing similar programs with other Salmonella -shipment countries that are major sources of spice in the United States. The relatively large FDA Draft Risk Profile | 129

142 General Conclusions and Potential Future Mitigation and Control Options | 9 valence for shipments of Indian spices other than black pepper found in the FDA study of FY2007 -FY2009 pre import surveillance data, argues for expansion of the program. The current program provides market e shipments to the United States are no longer subject advantage to black pepper industry participants becaus to DWPE at the border . In the future, the preventive controls, foreign supplier verification program, and voluntary qualified imported program provisions of FSMA (sections 103, 301, and 302 of FSMA) wo uld provide additional incentives and may impact the nature and structure of food safety oversight programs The imported food certification provision of FSMA (section 303 of FSMA) provides FDA with the developed. authority to require a certificate of compl iance for imported foods. Strengthen the capacity of regulatory systems in spice source countries . Many major spice source countries are developing nations with developing food safety systems. Improvements in countries’ food safety systems can significant ly improve the quality of spices consumed in the country as well as exports. One strategy employed by India is the creation of “spice parks” where producers and aggregators may bring spice to be cleaned, treated and tested. Capacity -building major recommendations made by the was one of the Institute of Medicine of the National Academies in its report “Ensuring Safe Foods and Medical Products through stronger regulatory systems abroad,” (IOM, 2012) and is an area of emphasis in FSMA. FDA has developed a comprehensive International Food Safety Capacity -Building Plan (FDA, 2013q; discussed in Section 8.1.3.7) to engage both government and industry leaders in food source countries to improve the quality of food produced and exported. As one part of these capacit y building efforts, FDA has begun to set up new and expand established international posts in a range of countries and regions including China, India and Latin America. Improve storage practices for spices. The prevalence of stored product pests in spices observed in shipments of imported spices offered for entry to the United States during FY2007 -FY2009 indicates that insanitary storage conditions are not uncommon. Efficient improvement of storage practices would involve a ployed and prevalence of stored-product pests in spices across the systematic review of the practices em farm -to-table continuum (or other indicators of poor storage practices) to identify the stages and type of e most to the presence of stor ed- product pests in spices (see research Chapter practices that contribute th 10). . Nearly three quarters (71%) of the firms listed on the FDA to improve Import Alert communication generalized Import Alert 99 -19 for Salmonella contamination of imported foods were cited for violations in one or more spices. One option is to consider creating a commodity specific import alert for Salmonella and/or filth in spices to enable industry to more easily identify firms on detention and to facilitate tracking and trending analyses . This will communicate to all stakeholders that these specific contaminants may be found in spices. It is not known whether this option would significantly reduce the prevalence of Salmonella or filth in imported shipments of spice because shipments from im porters on either the current or proposed import alert would be subject to DWPE. Improvements might be realized if this modification more clearly communicated to the food industry the magnitude of the problem and thereby triggered new efforts to prevent co ntamination of spice . In addition, FSMA includes import food safety mandates that may lead to reductions in the prevalence of pathogen contamination or filth adulteration in shipments of imported spice in the future, e.g., the preventive controls rule for human food (section 103 of FSMA), the foreign supplier verification program (section 301 of FSMA), the prior notice provision (section 304 of FSMA, final rule issued), and possibly also the imported food certification provision (section 303 of FSMA). Final rules and their implementation may determine the extent to which these mechanisms reduce the prevalence of pathogen or filth adulteration in shipments of imported spices. FDA Draft Risk Profile | 130

143 General Conclusions and Potential Future Mitigation and Control Options | 9 CONDARY PROCESSING 9.2.3 PRIMARY AND SE FDA , industry and academic experts work together to develop regulations , and potentially guidance , for the spice industry (manufacturers, processors including treatment facilities, packers and holders of ventive controls spice) on developing food safety plans that include pre . Poor/inconsistent application of appropriate preventive controls was identified as one of the contributing factors leading to contamination of spice with Salmonella or filth. Section 103 of FSMA “ Hazard analysis and risk -based preventive controls ” requires food facilities to evaluate hazards that could affect food safety, identify and implement preventive controls to prevent hazards, monitor controls and maintain monitoring records, and conduct verification activities . FDA issued the proposed rule “ Current Good Manufacturing Practice and Hazard Analysis and Risk - Based Preventive Controls for Human Food” (78 Federal Register 3646, January 16, 2013) that would, when finalized, implement s ection 103 of FSMA . The proposed rule proposes to require facilities to conduct a hazard analysis, identify hazards reasonably likely to occur, and establish preventive controls for such hazards. There are also proposed requirements for a food safety plan, monitoring and corrective actions for preventive controls, validation of preventive controls, and records. In addition the proposed rule “ Foreign Supplier Verification Programs for Importers of Food for Humans and Animals ” (78 Federal Register 45730, July 29, 2013) (FDA, 2013t) proposes to require that importers verify that the foods they import are produced using processes and procedures that ensure the same level of safety as food produced in the United States. Guidance could also be developed to support the FSMA rulemakings. Guidance may be specific for spices or included in preventive controls guidance for low -moisture foods and should address environmental sampling. preventive controls . Guidance would be Such guidance would i mprove awareness of hazards and effective science -based and built off of s -based industry guidance and best practices. Implementation of the cience guidance by the spice industry may be improved if the guidance is accompanied by outreach following its . For example, ASTA has been actively engaging the spice ind ustry in webinars about the ir initial publication guidance and presented a webinar on environmental sampling to interested parties in April 2013 (ASTA, 2013). . Poor/inconsistent Enhance education and training for primary and secondary spice processors application of appropri ate preventive controls was identified as one of the contributing factors leading to contamination of spice with Salmonella or filth. This option is analogous to that described for primary producers in 9.2.1. A number of guidance documents and reports have been developed by the spice and food industries on preventive controls for primary and secondary processing of spices and low moisture foods (see Section 8.2.2). However, observations and conversations between some spice processors and members of the risk profile development team engaged in educational or inspectional visits revealed lack of awareness . Education and or understanding of some provisions in industry spice processing guidance documents training efforts could include development and application of new strategies to make the information in the documents accessible to all primary and secondary spice processors. Development of practical tools or examples for implementing the guidance for spice processors may also expand implementation of preventive controls . For example, providing floor plans for hygienic design for operations of differing sizes and available resources, ideas on how to adapt facilities and equipment to improve food safety (e.g., sanitary equipment design), and identification of the best approaches for appropriate cleaning and sanitation of spice processing facilities and equipment may be helpful. Already in progress is the development of a Collaborative Training Centre for Food Safety and Supply Chain Management in Spices and Botanical Ingredients in India, described in 9.2.1 (Food Agriculture Centre of Excellence, 2013). FDA develops guidance for industry on the criteria recommended for validation of spice pathogen reduction treatment processes . A significant percentage of reconditioning proposals are rejected by FDA each year and it is suspected that some pathogen reduction treatments applied to spices may not be efficient in reducing the microbial population (evidence that spice shipments/lots that had been subjected to a thogen reduction treatment were contaminated, although this could have arisen from post -process pa FDA Draft Risk Profile | 131

144 General Conclusions and Potential Future Mitigation and Control Options | 9 FDA, possibly in collaboration with appropriate professional societies, could establish best contamination). the process and protocols used to treat spices to practices and develop guidance for testing and veri fying reduce microbial loads. Such guidance would clarify FDA expectations for validation studies and is also likely to help industry improve their treatment processes to deliver consistent effective pathogen reduction treatments and thereby reduce the incidence of contamination across the entire U.S. spice supply . Implementation of the guidance by the spice/processing industry may be improved if the guidance is accompanied by outreach following its initial publication. Increase (or mandate) application of validated pathogen reduction treatments for reduction of Salmonella to all spices intended for human consumption in the United States at an appropriate point before or after packaging . Our research revealed that some raw spice reaches the consumer. The spice and food manufacturing industries could develop new strategies to increase the application of validated pathogen reduction treatments to spice . As mentioned previously, the proposed rule “ Current Good Manufacturing Practice and Hazard Analysis and Risk -Based Preventive Controls for Human Food” ( 78 Federal Register (FDA, 2013s) proposes to require validation of food safety preventive controls as 3646; January 16, 2013) part of verification. Such a requ a final rule w ould increase the application of validated pathogen irement in reduction treatment of spices for reduction of Salmonella . Because research discussed in this document has revealed that pathogen reduction treatmen spices reaching the consumer, ts have not been applied to all success of such initiatives would likely decrease consumer exposure to potential life threatening microbial diseases. FDA and spice industry increase inspections of foreign and domestic spice warehouses, spice processing, an d spice pathogen reduction treatment facilities that include environmental sampling and assess compliance with CGMPS . Our review of spice facility inspections demonstrated that review of hazard analysis and preventive controls during inspections can identify potential problems before contamination In addition, appropriate and regular environmental sampling within a facility provides an additional occurs. assessment of the facility environment, one that is not necessarily captured by an observational inspect ion Salmonella -positive environmental sample, additional sampling in the facility can help alone. In the event of a the source of contamination. Serotyping Salmonella -positive to characterize the spatial extent and possibly samples can determine whether the organism has been found previously in the facility. This environmental information can also help with identifying and eliminating the contamination source . Such an initiative could also involve training for inspectors on hazards and pre ventive controls for spices (or low moisture foods) and how to conduct preventive control inspections. Such training would improve awareness of hazards and preventive controls among inspectors. FDA is currently implementing an increase in frequency of foreign and domestic food facility inspections, as required by FSMA. As mentioned above, ASTA presented a webinar on environmental sampling in April 2013, which may encourage adoption and improved application of this food Accred itation of Third -Party Auditors/Certification Bodies to Conduct Food safety tool. The proposed rule “ Safety Audits and to Issue Certifications ” ( 78 Federal Register 45781, July 29, 2013) ( FDA, 2013u), which, when finalized would implement section 307 of FSMA , would increase the capacity for regulatory and consultative audits of spice warehouses, processing and pathogen reduction facilities, once implemented. 9.2.4 RETAIL/END USE R FDA work with CDC and states to develop method s to facilitate collection of spice consumption and purchase i nformation from individual cases and restaurant sub -clusters during outbreak investigations. Attribution of foodborne illnesses to foods, particularly m inor ingredients such as spices, is difficult and is often not accomplished during routine outbreak investigations. This information would improve our ability to . New tools/methods could be characterize the public health risk associated with consumption of spices developed for use by state and local partners that will promote rapid collection of key information for traceback investigations. These tools should consider the potential role of ingredients such as spices in food FDA Draft Risk Profile | 132

145 General Conclusions and Potential Future Mitigation and Control Options | 9 contamination and could include improved patient/food preparer questionnaires/interviews that would include The question(s) about use and consumption of spices and seasonings in the outbreak investigation. team should also explore methods of using adjunct data sources (e.g., shopper loyalty cards or photo menu ategies will enhance the flow of cards of dishes consumed at restaurants) to aid investigations. These new str product information to public health and regulatory agencies during traceback investigations, thereby expediting identification of any common food source. Development and implementation of new tools and methods for outbreak investigations could be facilitated through collaboration between the FDA Coordinated the CDC outbreak and response team. Outbreak Response and Evaluation Network (CORE) and Increase efforts and improve strategies to identify the root cause of ingredient contamination including whether growth in the food or environment contributed to the outbreak. As revealed by the analysis of spice -associated outbreaks presented in this report, root cause of contamination was rarely identified in -associated outbreaks. spice This information is critical for reducing the burden of illness associated with consumption of contaminated spices because it identifies failure(s) in the food safety system . Once failures . As have been identified, they can be addressed, thereby improving/strengthening the food safety system illustrated by the extensive research efforts that went into trying to reveal the location/root cause of contamination in the Salmonella Montevideo outbreak attributed to consumption of black or red pepper - coated s alami products, finding the root cause can be extremely difficult, particularly for such a complex . Increased efforts could include increased sampling of products and supply chain as is typical for spices environment at different points in the traceback diagram with serotype determined and NGS analyses or other appropriate subtyping analysis performed e development of new . FDA’s CORE would likely lead th to better obtain root cause information strategies . Public health agency scientists involved in outbreak investigations enumerate pathogens in samples of food and ingredients in the food -chain that have been identified as having strains identical to the Salmonella . Enumeration of pathogens such as outbreak strain is rarely pursued during outbreak investigations but this information can provide data to indicate the relative role of CGMP and supply -chain of in a spice could be indicative of conditions failures in the outbreak (e.g., a high concentration Salmonella . Enumeration of the implicated food in an outbreak will also that supported growth of the microorganism) provide a measure of the actual “dose” consumed, which can be used to estimate the size of the exposed population or to explore the impact of food/patient properties on the probability for illness . This information is critical for application of quantitative risk assessment efforts and can be used to characterize the public health burden associated with pathogen contaminated spice as well as the impact of different mitigation and control options on that burden . Enumeration data gathered during outbreak events could be added to the data resources available for FDA’s risk ranking tool iRisk , which is a public ly available rapid risk assessment and risk ranking tool developed by FDA. Develop new strategies to identify related illnesses attributed to spices or other low -moisture/long shelf -life foods . Retail packages of spices and other low moisture or shelf -stabl e products have the potential of being used by a large number of consumers over very long periods (years). As a result related illnesses may be spread out in time and space . Serotype/PFGE data are very helpful in identifying related illnesses, when clustered in time. When serotypes are rare, related illnesses may be able to be linked particularly . However, when common serotypes are involved, sequencing information, such as across time and space afforded by Next Generation Sequencing, are likely needed to li nk these illnesses across time and space . NIH/NCBI's Sequence Read Archive (SRA) is currently being developed to collect these data (NCBI, 2013). The data deposited in the SRA will be available for public download without geographic and/or political ctions . The SRA is part of the international partnership of archives (INDSC) at NIH/NCBI, the European restri Bioinformatics Institute, and the DNA Database of Japan. Data submitted to any of these 3 sites will be shared among them. These new tools will enable re searchers to identify more outbreaks, which would lead to a better characterization of the public health risk associated with consumption of spices. The data collected may also provide information such as the regional origin of the pathogen causing illness , which can significantly aid in the determining of root cause/system failures. FDA Draft Risk Profile | 133

146 General Conclusions and Potential Future Mitigation and Control Options | 9 FDA, spice industry, and foreign governments work together to develop guidance , and potentially . The complexity of the spice to improve traceability during outbreaks of illness from spices regulations, Montevideo Salmonella supply chain complicated the development of an accurate traceback diagram in the . Improved outbreak in the United States associated with black or red -pepper coated salami products traceability would help in identifying and eliminating contaminated spice from the supply and has the potential to identify the cause of contamination, which could prevent future contamination events . Improved traceability would also decrease the time needed estigation and as a result, could reduce for the traceback inv the numbers of illnesses by more quickly identifying and removing/remediating all potential contaminated spice lots in the supply . Once developed, such guidance may be more effectively implemented if a companion tra ining program is developed and implemented. In implementing section 204(a) of FSMA, FDA established product tracing pilots, which were conducted by IFT . One of these product tracing pilots included an exploration of scenarios involving processed foods cont aining spice ingredients and this pilot project has provides been completed about the product tracing pilots (McEntire and Bhatt, 2012) , which report . IFT’s recommendations on strategies that FDA can use to improve product tracing , was made available for p ublic comment by FDA (FDA, 2013v) . FDA intends to use the findings from this report and other recent tracing - related efforts to help inform the development of the rulemaking on tracing mandated in Section 204 of FSMA . That rulemaking will establish additio nal recordkeeping requirements for facilities that manufacture, process, pack or hold foods that FDA designates as high -risk. If FDA designates spices as high -risk, then the requirements established by the rulemaking will improve the traceability of spices . Report recalls arising from contamination based on serving size of the product recalled in addition to the amount recalled . It is currently very complicated, if not impossible, to determine the number of servings the product is an ingredient in many different foods . of a product that has been recalled when Characterization of recalls on the basis of standard serving size would help to better define the public health impact of each recall event and would enable FDA and others to characterize each recall o n the basis of potential foodborne illnesses prevented. 9.2.5 GENERAL Increase surveillance of pathogens other than Salmonella in spices and in human cases of foodborne illness . The absence of evidence for spice- associated illnesses, food recalls, or RFR primary entries linked to Salmonella in the United States may arise from lack of surveillance. First efforts should pathogens other than Bacillus focus on was the seco nd most common pathogen associated with spice -associated spp., which outbreaks -2010. Additional pathogen targets could include Clostridium reported during the period 1973 perfringens , which was identified in one of the possible spice -associated outbreaks discussed in Section 2.4 and pathogenic E scherichia coli , which has been shown to be able to survive for long periods in low moisture foods (Kimber et al et al ., 2012). ., 2012; Blessington ade organizations to Educate and train regulatory partners, and reach out to countries and food tr communicate common spice hazards and available preventive controls . Initial efforts could involve developing a variety of communication strategies to effectively share the present risk profile with regulatory partners and stakeholders . Scientific publications and public presentations , including webinars, are one forum open to all stakeholders and FDA has used these forums to communicate results ahead of publication of this report. Additional efforts could include the creation of partner ships with regulatory partners and stakeholders to craft communication tools to improve awareness of common spice hazards and application of available preventive controls . Collaborative initiatives in place that might consider taking part in this work -country specific food ude the industry -academia- government Prevent ive Controls Alliance or the JIFSAN incl safety training partnerships. FDA Draft Risk Profile | 134

147 General Conclusions and Potential Future Mitigation and Control Options | 9 Improve understanding and application of appropriate sample designs and analytical protocols for spice (and environmental) . In light of the small concentration s of Salmonella sampling for pathogens reported in spices, it is critical that public health agencies and the spice and food industries use effective Salmonella product sampling plans (including sample size) when screening spice (or the environment) for . Guidance for sample designs is availabl e in the published scientific literature (e.g., ICMSF, 2002) and also online (JEMRA, 2013) . The Codex Committee on Food Hygiene is developing detailed examples for the revised Principles and Guidelines for the Establishment and Application of Microbiologic al Criteria for Foods to aid in its implementation . Guidance on analytical protocols for detection of Salmonella in spices is provided in the FDA Bacteriological Analytical Manual (Andrews , 2011) . These new tools build on the extensive scientific et al. li terature on product sampling . All resources noted here are free and public ly available . Education and training on sampling plan design and laboratory methods of detection, isolation and confirmation of Salmonella would enhance capacity, improve data qualit y and most importantly, would ultimately improve detection efficiencies when appropriate plans and methods are used . FDA alert/communicate with the spice industry as a whole when observations suggest that the application of current preventive controls fo r pathogens and filth in spices may not be adequate . Observations that might warrant communication could include an increasing or significantly larger - prevalence of pathogens or filth in all spices or a particular type of spice as compared with other FDA regulated foods, an increase or unusually large number of inspections with poor CGMP compliance, or a new . The form of the communication could vary or unusual system failure identified as part of an investigation depending on the urgency and scope of the problem . For example, FDA could issue a constituent update, . Such industry letter, publication, or give a webinar or presentation at a public or scientific meeting communication s would heighten awareness across the industry to potential problems and would provide the industry with an opportunity to develop systemic reforms to reduce/eliminate contamination in spices to minimize the public health impact . FDA has already used some of these mechanisms to share key results of this report ahead of publication. FDA alert/communicate with spice producing countries when observations suggest that the application of current preventive controls for pathogens and filth in spices may not be adequate . Observations that might warrant communication might include an unusual ly large number of spice firms on Import Alert, or a Salmonella sudden increase in the prevalence of -positive spice shipments from that country. Such communications would a lert countries to potential systemic or new problems in the spice supply chain that threaten public health in the United States and possibly also the source country . Overhaul FDA product codes to allow for better identification of products and more precise tracking and trending of products by FDA . Current product codes complicate tracki ng and trending . Revisions could include providing unique identifiers for low moisture foods such as spices, foods that had undergone a pathogen reduction step, and foods packaged for retail . Such revisions would help FDA to more precisely characterize and compare contamination findings across the spice/food spectrum, such as prevalence in imported shipments offered for import, and would improve the ability to identify emerging food safety problems with spices or other FDA -regulated products and improve FDA’s ability to target the types of . shipments that pose the greatest public health risk for sampling FDA Draft Risk Profile | 135

148 SEARCH NEEDS 10. DATA GAPS AND RE adulteration of The development of the risk profile revealed many gaps in information and data regarding spices by pathogens and filth and the potential for this contamination to impact public health . Below we identify these gaps and the research needed to fill them, particularly focusing on research that will improve our ability to assess the public health risk posed by consumption of spices in the United States, to better characterize system failures that lead to spice contamination, and to explore additional potential future mitigations. 10.1 DATA GAPS 10.1.1 FOODBORNE OUT BREAKS • What stage of the farm -to-table continuum did the spice contamination take place? Where specifically did contamination take place? • What were the root cause(s)/failure(s) that allowed the spice to be contaminated? • Were there additional failures in the food safety system that allowed the initial contamination to reach the consumer? • Did cross -contamination contribute to the outbreak or was it the major cause? • Did growth of the pathogen in the spice/food contribute to the public health burden (increased numbers of illnesses)? • What was the concentration of contamination in the spice implicated in causing illness? (was it significantly larger than that found in surveillance?) • What percentage of foodborne outbreaks attributed to complex foods or for which the food could not be determined were caused by contaminated spice? D CONCENTRATION OF PATHOGENS AND FIL TH IN SPICES 10.1.2 PREVALENCE AN What is the prevalence, concentration and distribution of Salmonella • hogens in spices or other pat (domestic and imported) at different stages of the farm -to-table continuum? Where is the most common point of entry? Are there large differences among spices (including whether it is whole or ground?) • What is the prevalence of filth in spices (domestic and imported), particularly storage pests, at different stages of the farm -to-table continuum? Which is the most common point of entry and what is the most common cause of contamination? Has the prevalence of filth in spices at retail in the United States changed since last measured in the 1980’s? If so, why? • Salmonella in imported shipments of raw spice offered for import to the How does the prevalence of United States compare with that for shipments of spice that have undergone a patho gen reduction treatment? Is this dependent of the type of spice? How do these measures compare for spice at retail? How does contamination prevalence in raw domestic spice differ from domestic spice at retail? • In which stages of the farm -to-table continuum do the presence of filth and Salmonella in spice correlate (if any)? FDA Draft Risk Profile | 136

149 Data Gaps and Research Needs | 10 CS OF CONTAMINANTS 10.1.3 CHARACTERISTI Are the survival of Salmonella in (dry) spice and the growth of • in wet spice strongly Salmonella dependent on spice type? • What are the survival and growth characteristics of other pathogens in spice? • How does survival of Salmonella differ at low concentration s of contamination; are the antimicrobial compounds sufficient in concentration/number to kill the little Salmonella p resent? 10.2.4 MITIGATION AND CONTR OL O PTIONS 10.2.4.1 CGMPS AND E NVIRONMENTAL SAMPLIN G Salmonella or other pathogens are found in the facility • What is the risk for spice contamination when environment? (What is the relationship between prevalence of in the environment and Salmonella prevalence of Salmonella or other pathogens in the product? What are typical transfer rates from equipment or surfaces in spice processing/packing facilities to spice?) • What is the prevalence of Salmonella or other pathogens in foreign spice processing/packing facility environments? • What percentages of spice processing/packing firms follow the guidelines for spices and low moisture foods? Which practices are least often adopted and why? Which CGMP recommendations redictive of adulteration of the spice product? are most p • What percentage of spice processing/packing firms perform regular environmental sampling? Does Salmonella ? Other pathogens? this sampling include testing the environment for What are the economic and social/c onsumer costs/concerns associated with requiring filth • reduction treatments for all spices and seasonings? 10.2.4.2 PATHOGEN RE DUCTION • What is the efficacy of commonly applied pathogen reduction treatments on the population of Salmonella in spice? • What a re the economic and social/consumer costs/concerns associated with requiring pathogen reduction treatments for all spices and seasonings? • What percentage of spice in the U.S. supply subjected to a pathogen reduction treatment before reaching the consumer? How does this percentage vary by spice type, size of spice/food firm, and stage in the farm -to-table continuum? 10.2.4.2 SAMPLING • How would the efficacy of a three- class attribute system for filth in spices differ from the current system? 10.2.4.3 IMPORT ALERTS • What is the effectiveness of firm -type import alerts? Does this differ from country -wide commodity specific import alerts? 10.2.5 CONSUMPTION • What is the distribution of consumption patterns for spice in the U.S. population? How does this depend on the type of spice or consuming population? FDA Draft Risk Profile | 137

150 Data Gaps and Research Needs | 10 • What is the relative frequency of consuming uncooked spice among the various U.S. populations? Are there spices that are more frequently consumed raw or added to foods near the end of cooking? Are ther e cuisines or specific foods in which raw/lightly cooked spice is generally included? 10.2 RESEARCH NEEDS 10.2.1 FOODBORNE OUT BREAKS Research novel methods/strategies to efficiently identify the contaminated ingredient in foodborne illness outbreaks . Such methods would improve foodborne illness attribution. Research novel methods/strategies to efficiently identify the root cause in a foodborne outbreak le involving spices . Such methods would identify failures in the spice food safety system, which would enab the spice industry to improve these systems. Research novel methods/strategies to efficiently traceback spice ingredients to their original source . Traceback for spices can be very complicated because of the multiple sources, suppliers, processors, pac kers, food manufacturers and retail establishments that may be involved . Novel strategies are needed to more quickly understand the complex web of relationships. 10.2.2 PREVALENCE AN D CONCENTRATION OF PATHOGENS AND FIL TH IN SPICES Determine the distribution and concentration of Salmonella in spices at critical points in the farm -to - . Much data are needed to determine the relative importance of contamination at different table continuum stages of the spice supply chain, including studies of spices at production, before undergoing a pathogen reduction treatment, and at U.S. retail . Interpretation of analyzed data would be enhanced if the data collected tion would distinguish pathogen reduction treated spices and spices that had not undergone a pathogen reduc treatment as well as spice type. Determine the prevalence and concentration of pathogens other than Salmonella in spices at critical points in the farm -to -table continuum . A wide diversity of pathogens have been identified in spices outside the United States including Bacillus spp. which have been reported to have caused human illness from consumption of contaminated spice . Research should include pathogens detected in spices as well as pathogenic Escherichia coli strains (e.g., O104) which have been identified in sprouts of seeds commonly used as spices. Surveillance data are especially needed at the point of import, in spice/food processing facilities, and at retail in the United States. Determine the prevalence of different kinds of filth at critical points in the farm -to . The -table continuum prevalence of stored product pests in spices observed in shipments of imported spices offered for entry to the FY2009 indicates that insanitary storage conditions are not uncommon . A United States during FY2007- systematic review of the practices employed and prevalence of stored -product pests in spices across the farm -to-table continuum (or other indicators or poor storage practices) w ould be able to identify the stages and type of practices that contribute the most to the presence of stored -product pests in spices . Similarly, prevalence data on other types of filth along the farm -to-table continuum may reveal additional weaknesses in t he food safety system. Determine the prevalence of filth at retail in the United States . These data would reveal whether spice . contamination with filth has improved since the establishment of DALs FDA Draft Risk Profile | 138

151 Data Gaps and Research Needs | 10 of Salmonella Determine the relationship between prevalence and concentration in the spice processing in spices - Salmonella environment and . These data would better characterize the potential role of cross contamination from the spice -processing environment to the spice in facilities where Salmonella is pr esent, and could include quantitative measures of transfer (e.g., coefficients) . Determine the percentage of firms that receive pathogen reduction treated spice or that treat spice to eliminate pathogens and the percentage of firms that perform regular e nvironmental sampling for Salmonella . These data would provide information about extent of application of these preventive controls in the spice industry. CS OF CONTAMINANTS 10.2.3 CHARACTERISTI Determine how survival of in dry spice and growth of Salmonella in wet/moist spice varies Salmonella . with spice type This research extends the research initiated by FDA on black pepper and would provide a more comprehensive understanding of survival and potential for growth in spices. Determine whether Salmonella s urvival in spice is strongly dependent on the initial . Contamination concentrations numbers/concentration introduced detected in “naturally” contaminated samples are small compared with the concentration s used in survival and growth studies. Data are needed to determine whether at low concentration s of contamination, other factors, such antimicrobial compounds present in the spice, lead to different survival rates. Determine survival and potential for growth of other pathogens in spices . Research should in clude scherichia coli pathogens detected in spices as well as pathogenic strains (e.g., O104) which have been E identified in sprouts of seeds commonly used as spices. 10.2.4 MITIGATION AN D CONTROL OPTIONS Identify and characterize appropriate surrogate microorganisms that can produce similar inactivation results as Salmonella for specific technologies in specific spices. Optimal surrogates should be nonpathogenic, have inactivation kinetics that can predict reductions in Salmonella populations, be stable and exhibit consistent growth characteristics, easy to prepare in high -density populations, easy to enumerate and differentiate from other microflora, and have injury susceptibility similar to Salmonella . Measure the relative effic acy of Salmonella reduction processes commonly used on spices and validate mitigation treatments . The study should include evaluation of the impact of spice form Salmonella (whole/cracked/ground), equipment design, and critical parameters on the efficacy of reduction using a variety of treatment processes commonly used on spices . This effort should also address surrogate selection, inoculum preparation, and detection/enumeration of desiccation -stressed salmonellae in spices . Data from such a study would provide critical information to FDA and the spice industry. Develop new and improved methods of dry cleaning and sanitation that are effective in reducing the prevalence and concentration of Salmonella (and other microbial pathogens). The research should include efficacy and validation studies. Determine the economic and social/consumer costs/concerns associated with requiring pathogen reduction treatments for all spices and seasonings . The research should include a survey that assesses consumer acceptance of spices treated with the most commonly applied pathogen reduction treatment . technologies and study to determine the economic impact of a mandate FDA Draft Risk Profile | 139

152 Data Gaps and Research Needs | 10 Determine the economic and social/consumer costs/concerns associated with requiring all spices receive trea tment to remove filth . This research would be needed before a new regulation could be developed. The research should include a survey to assess consumer tolerance of natural and unavoidable defects in food. Develop a rapid accurate method to measure mold . Analysis for mold, especially in ground spices, in spices is time consuming and complex . Development of a rapid method for detection of mold in spices would allow more samples to be analyzed more accurately and would lead to a better characterization of the prevalence of mold in spices across the supply chain . Develop a rapid method for screening and/or quantifying filth in spices . Current methods are labor intensive and time consuming, thereby limit the annual capacity for filth sampling by FDA, the spice and food industries . Development of a rapid analytical method would increase capacity for filth analysis. Optimize methods for detection and enumeration of Salmonella . (and other pathogens) in spices Detection of pathogens such as Salmonella in spices is challenging for a number of reasons including the desiccated state of bacteria and the presence of antimicrobial compounds in some spices . Contamination concentration is needed to determine probability of illness, efficacy of pathogen reduction trea tments, magnitude of growth, and other factors that can help determine root cause in outbreak/contamination investigations yet is rarely collected . Current methods are slow and labor intensive. Rapid reliable analytical methods for both detection and enume ration would improve capacity for government agencies and the spice/food industry to collect these data. Determine the impact of a three -class attribute system for the evaluation of filth in foods on the quality ld eliminate marginally compliant foods from the food supply . Such a system wou and food safety of foods and thereby improve the quality and food safety of foods . A three -class system increases the ability to detect s of filth . food lots that have widespread but low concentration Determine metrics and develop plans to assess the efficacy of mitigation and control options including . Better measures of the public health impact of different mitigation and control options will lead to guidance a better characterization of the relative reduction in publi c health risk afforded by different types of options and will ultimately lead to the development of more effective options . 10.2.5 CONSUMPTION Determine the fraction and type of spices consumed that had never received a pathogen reduction step (including . These data should distinguish among spice type, cuisine, type of use, and food cooking) preparation setting (e.g., food manufacturers, institution, restaurant, or home). This information will help to characterize the public health risk posed by contaminated spices and help to identify the most likely populations to consume contaminated spices. Further characterization could be realized if the fraction and type of spices consumed as “partially cooked” spice (spice added to foods near the end of cooking whe re the heat treatment may be inefficient) could be estimated. Determine the distribution and variability of spice consumption servings among general and susceptible U.S. populations . This information cannot be accurately determined with NHANES data. Such data are needed to quantitative characterize the public health risk associated with spice consumption and would be most useful if it included additional data about high consumers and susceptible populations. . Research should assess the Conduct research to determine the fraction and type of spices eaten raw fraction of spices consumed in the United States that never undergo a pathogen reduction treatment (including cooking), preferably by type of spice. FDA Draft Risk Profile | 140

153 Data Gaps and Research Needs | 10 10.2.6 GENERAL Develop a quantitative risk assessmen t to estimate the risk of illness from consumption of spices and determine the relative effectiveness of potential control options to minimize the risk of illness from s or groups of consumption of spices . The risk assessment would have to address differences among spice spices. Comparison of the impact of different potential mitigation and control options on predicted risk of illness estimates (e.g., risk of illness per spice serving or annual per capita risk of illness) will provide . However, much of the data information for all sta keholders to ma ke appropriate risk management decisions that would be needed . FAO is currently engaged in evaluating the risk for a fully quantitative model is lacking posed by consumption of spices (FDA, 2012f). FDA Draft Risk Profile | 141

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184 Spice List | Appendix A IST APPENDIX A: SPICE L The list of plants in this appendix was compiled from Over 100 different plants are commonly used as spices. 21 CFR 182.10 (FDA, 2012f), EPA, and on -line lists of spices maintained by the American Spice Trade . Spices are listed by botanical name (Table A1) and by Association and the Seasoning and Spice Association . Each is also categorized by the plant part used (Table A3) common name (Table A2) . Typical spice use in foods is characterized in Table A4. Not all plants used as spices are listed in these tables. ame Table A1. Spice list by botanical n a Botanical Name Common Name Plant Part Used Source b root Onion Allium cepa ASTA, SSA c root ASTA, SSA Allium sativum Garlic Chives leaf 21CFR182.10 Allium schoenoprasum Greater Galangal root SSA Alpinia galanga Greater Galangal seed fruit/seed SSA Alpinia galanga Galanga (Galangal) root 21CFR182.10 Alpinia officinarum fruit/seed 21CFR182.10 Amomum melegueta Grains Of Paradise c Dill leaf Anethum graveolens ASTA, SSA c Dill Anethum graveolens seed fruit/seed ASTA, SSA d leaf ASTA Anethum sowa Dill d Dill seed ASTA fruit/seed Anethum sowa Angelica leaf 21CFR182.10 Angelica archangelica Angelica Root root 21CFR182.10 Angelica archangelica seed Angelica archangelica 21CFR182.10 Angelica Seed leaf 21CFR182.10 Angelica spp. Angelica spp. Angelica Root root 21CFR182.10 Angelica Angelica spp. seed 21CFR182.10 Angelica Seed Anthemis nobilis Camomile (Chamomile), English Or flower 21CFR182.10 Roman 21CFR182.10 Anthriscus cerefolium Chervil leaf Apium graveolens fruit/seed 21CFR182.10 Celery Seed Horseradish root 21CFR182.10 Armoracia lapathifolia Tarragon leaf 21CFR182.10 Artemisia dracunculus c fruit/seed ASTA Bixa orellana Anatto Mustard, White Or Yellow fruit/seed 21CFR182.10 Brassica hirta Mustard, Brown fruit/seed 21CFR182.10 Brassica juncea Brassica nigra Mustard, Black Or Brown fruit/seed 21CFR182.10 flower 21CFR182.10 Calendula officinalis Calendula Marigold, Pot flower Calendula officinalis 21CFR182.10 Calendula officinalis Pot Marigold flower 21CFR182.10 Capparis spinosa Capers flower 21CFR182.10 Capsicum Capsicum annuum fruit/seed 21CFR182.10 Capsicum annuum fruit/seed 21CFR182.10 Cayenne Pepper fruit/seed 21CFR182.10 Capsicum annuum Paprika Pepper, Cayenne fruit/seed 21CFR182.10 Capsicum annuum Capsicum annuum fruit/seed 21CFR182.10 Pepper, Red Capsicum frutescens Capsicum fruit/seed 21CFR182.10 Capsicum frutescens Cayenne Pepper fruit/seed 21CFR182.10 Capsicum frutescens fruit/seed 21CFR182.10 Pepper, Cayenne Capsicum frutescens Pepper, Red fruit/seed 21CFR182.10 Carum carvi Caraway fruit/seed 21CFR182.10 Cinnamomum burmanni Cassia, Padang Or Batavia bark 21CFR182.10 21CFR182.10 Cinnamomum cassia Cassia, Chinese bark FDA Draft Risk Profile | 172

185 Spice List | Appendix A a Source Botanical Name Common Name Plant Part Used 21CFR182.10 Cinnamomum cassia bark Cinnamon, Chinese Cassia, Saigon bark 21CFR182.10 loureirii Cinnamomum bark 21CFR182.10 Cinnamomum loureirii Cinnamon, Saigon Cinnamomum zeylanicum 21CFR182.10 Cinnamon, Ceylon bark d leaf SSA Kaffir Lime Citrus hystrix d Citrus hystrix fruit/seed SSA Kaffir Lime Coriander 21CFR182.10 Coriandrum sativum fruit/seed 21CFR182.10 Coriander Coriandrum sativum leaf Saffron flower 21CFR182.10 Crocus sativus Cumin (Cummin) fruit/seed 21CFR182.10 Cuminum cyminum Turmeric root 21CFR182.10 Curcuma longa Zedoary root 21CFR182.10 Curcuma zedoaria c Cymbopogon citratus Lemon Grass leaf SSA Elettaria cardamomum Cardamom (Cardamon) fruit/seed 21CFR182.10 Fennel, Common fruit/seed 21CFR182.10 Foeniculum vulgare Fennel, Sweet (Finocchio, Florence fruit/seed 21CFR182.10 Foeniculum vulgare var. duice Fennel) Angostura (Cusparia Bark) bark 21CFR182.10 Galipea officinalis Ambrette Seed fruit/seed 21CFR182.10 Hibiscus abelmoschus leaf 21CFR182.10 Hyssopus officinalis Hyssop Anise, Star fruit/seed Illicium verum 21CFR182.10 Illicium Star Anise fruit/seed 21CFR182.10 verum c fruit/seed ASTA, SSA Juniperus communis Juniper Bay leaf 21CFR182.10 Laurus nobilis Lavandula officinalis flower 21CFR182.10 Lavender Lippia spp. Oregano Oreganum, Mexican leaf 21CFR182.10 Oregano, Mexican Sage, Origan) 21CFR182.10 Majorana hortensis Marjoram, Sweet leaf Majorana onites leaf 21CFR182.10 Marjoram, Pot leaf 21CFR182.10 Majorana onites Pot Marjoram Horehound (Hoarhound) leaf 21CFR182.10 Marrubium vulgare Camomile (Chamomile), German Matricaria chamomilla flower 21CFR182.10 Or Hungarian Alfalfa Herb And Seed leaf 21CFR182.10 Medicago sativa Medicago sativa Alfalfa Herb And Seed seed 21CFR182.10 Melissa officinalis leaf 21CFR182.10 Balm (Lemon Balm) leaf Mentha piperita 21CFR182.10 Peppermint Mentha spicata Spearmint leaf 21CFR182.10 Myristica fragrans Mace fruit/seed 21CFR182.10 Myristica fragrans Nutmeg fruit/seed 21CFR182.10 Nigella sativa Caraway, Black (Black Cumin) fruit/seed 21CFR182.10 Nigella sativa Cumin, Black (Black Caraway) fruit/seed 21CFR182.10 Ocimum basilicum leaf 21CFR182.10 Basil, Sweet leaf 21CFR182.10 Ocimum minimum Basil, Bush c leaf Origanum vulgare ASTA, SSA Oregano Papayer somniferum fruit/seed 21CFR182.10 Poppy Seed Pelargonium spp. Geranium leaf 21CFR182.10 Petroselinum crispum Parsley leaf 21CFR182.10 Pimenta officinalis fruit/seed 21CFR182.10 Allspice fruit/seed Pimpinella anisum 21CFR182.10 Anise Piper nigrum Pepper, Black fruit/seed 21CFR182.10 Piper nigrum Pepper, White fruit/seed 21CFR182.10 Rosmarinus officinalis Rosemary leaf 21CFR182.10 Sage leaf 21CFR182.10 Salvia officinalis 21CFR182.10 Salvia sclarea Clary (Clary Sage) leaf FDA Draft Risk Profile | 173

186 Spice List | Appendix A a Source Botanical Name Common Name Plant Part Used leaf 21CFR182.10 Salvia triloba Sage, Greek Elder Flowers flower 21CFR182.10 Sambucus canadensis Savory, Summer leaf 21CFR182.10 Satureia hortensis (Satureja). Savory, Winter leaf 21CFR182.10 Satureia montana (Satureja). c Schinus terebinthifolia fruit/seed ASTA, SSA Pink Pepper Sesamum indicum Sesame fruit/seed 21CFR182.10 c flower ASTA, SSA Cloves Syzygium aromaticum e Thyme, Wild Or Creeping leaf Thymus serpyllum 21CFR182.10 e Thymus vulgaris Thyme leaf 21CFR182.10 21CFR182.10 Linden Flowers Tilia spp. flower Trifolium spp. leaf 21CFR182.10 Clover - Trigonella foenum Fenugreek fruit/seed 21CFR182.10 graecum Vanilla planifolia Vanilla fruit/seed 21CFR182.10 Vanilla tahitensis Vanilla fruit/seed 21CFR182.10 b SSA Sichuan Pepper Zanthoxylum piperitum fruit/seed Zingiber officinale root 21CFR182.10 Ginger a Plants listed as spices in commerce as cited by 21CFR182.10 (FDA, 2012f), ASTA (2012), or SSA (2012). b Common name is from Herbs of Commerce et al. , 2000). (McGuffin c Common name is from Herbs of Commerce (McGuffin et al. , 2000) as per 21 CFR101.4(h) (FDA, 2012q) d Common name from source(s) noted. e ASTA (2012) includes the species Thymus satureioides (thyme) on their list of spices . There is no history of use as a food in either GRIN, World Spice Plants, or Mansfeld’s World Database of Agricultural and Horticultural Crops . It is a valid scientific name in the Missouri Botanical Garden Tropicos database as Thymus saturejoides Coss. FDA Draft Risk Profile | 174

187 Spice List | Appendix A ame Table A2. Spice list by common n Plant Part a Botanical name Common name Source Used leaf 21CFR182.10 Alfalfa Medicago sativa seed 21CFR182.10 Alfalfa Medicago sativa Pimenta officinalis 21CFR182.10 Allspice fruit/seed Hibiscus abelmoschus 21CFR182.10 Ambrette Seed fruit/seed c fruit/seed ASTA Anatto Bixa orellana Angelica leaf 21CFR182.10 Angelica archangelica Angelica spp. Angelica 21CFR182.10 leaf Angelica archangelica root 21CFR182.10 Angelica Angelica spp. root Angelica 21CFR182.10 seed 21CFR182.10 Angelica Angelica archangelica Angelica spp. seed 21CFR182.10 Angelica Galipea officinalis bark 21CFR182.10 Angostura (Cusparia Bark) Anise Pimpinella anisum fruit/seed 21CFR182.10 Illicium verum fruit/seed 21CFR182.10 Anise, Star Melissa officinalis leaf 21CFR182.10 Balm (Lemon Balm) Ocimum minimum leaf 21CFR182.10 Basil, Bush Ocimum basilicum leaf 21CFR182.10 Basil, Sweet leaf 21CFR182.10 Bay Laurus nobilis Calendula officinalis flower 21CFR182.10 Calendula Camomile (Chamomile), English Or Anthemis nobilis flower 21CFR182.10 Roman Or Camomile (Chamomile), German Matricaria chamomilla flower 21CFR182.10 Hungarian Capparis spinosa flower 21CFR182.10 Capers fruit/seed Capsicum 21CFR182.10 Capsicum annuum fruit/seed Capsicum 21CFR182.10 Capsicum frutescens Caraway Carum carvi fruit/seed 21CFR182.10 Black (Black Cumin) Caraway, 21CFR182.10 Nigella sativa fruit/seed Cardamom (Cardamon) fruit/seed 21CFR182.10 Elettaria cardamomum Cinnamomum cassia Cassia, Chinese 21CFR182.10 bark Cinnamomum burmanni bark 21CFR182.10 Cassia, Padang Or Batavia Cinnamomum loureirii bark Cassia, Saigon 21CFR182.10 fruit/seed 21CFR182.10 Cayenne Pepper Capsicum annuum Capsicum frutescens fruit/seed 21CFR182.10 Cayenne Pepper fruit/seed Apium graveolens Celery Seed 21CFR182.10 Chervil Anthriscus cerefolium leaf 21CFR182.10 leaf 21CFR182.10 Chives Allium schoenoprasum Cinnamomum zeylanicum bark 21CFR182.10 Cinnamon, Ceylon Cinnamon, Chinese bark 21CFR182.10 Cinnamomum cassia Cinnamon, Saigon Cinnamomum loureirii bark 21CFR182.10 Clary (Clary Sage) Salvia sclarea leaf 21CFR182.10 Trifolium spp. Clover leaf 21CFR182.10 c Cloves Syzygium aromaticum flower ASTA, SSA leaf 21CFR182.10 Coriander Coriandrum sativum Coriandrum sativum fruit/seed 21CFR182.10 Coriander Cuminum cyminum fruit/seed 21CFR182.10 Cumin (Cummin) Cumin, Black (Black Caraway) fruit/seed 21CFR182.10 Nigella sativa c Dill Anethum graveolens leaf ASTA, SSA c Anethum graveolens fruit/seed ASTA, SSA Dill d Anethum sowa leaf Dill ASTA, SSA d Dill Anethum sowa fruit/seed ASTA, SSA Elder Flowers Sambucus canadensis flower 21CFR182.10 Fennel, Common Foeniculum vulgare fruit/seed 21CFR182.10 Fennel, Sweet (Finocchio, Florence 21CFR182.10 fruit/seed Foeniculum vulgare var. duice Fennel) FDA Draft Risk Profile | 175

188 Spice List | Appendix A Plant Part a Common name Source Botanical name Used 21CFR182.10 graecum fruit/seed Trigonella foenum Fenugreek - c Alpinia galanga root Galangal SSA Greater c Alpinia galanga fruit/seed SSA Greater Galangal seed Alpinia officinarum root 21CFR182.10 Galanga (Galangal) c Allium sativum root Garlic ASTA, SSA Geranium Pelargonium spp. leaf 21CFR182.10 Zingiber root 21CFR182.10 Ginger officinale Amomum melegueta fruit/seed 21CFR182.10 Grains Of Paradise Marrubium vulgare leaf Horehound (Hoarhound) 21CFR182.10 Horseradish Armoracia lapathifolia root 21CFR182.10 Hyssop Hyssopus officinalis leaf 21CFR182.10 c ASTA, SSA Juniperus communis fruit/seed Juniper d leaf SSA Kaffir Lime Citrus hystrix d fruit/seed SSA Kaffir Lime Citrus hystrix Lavandula officinalis flower 21CFR182.10 Lavender c Cymbopogon citratus leaf SSA Lemon Grass Tilia spp. flower 21CFR182.10 Linden Flowers Myristica fragrans fruit/seed 21CFR182.10 Mace Calendula officinalis 21CFR182.10 flower Marigold, Pot Marjoram, Pot leaf 21CFR182.10 Majorana onites leaf Marjoram, Sweet 21CFR182.10 Majorana hortensis Mustard, Black Or Brown Brassica nigra fruit/seed 21CFR182.10 Mustard, Brown Brassica juncea fruit/seed 21CFR182.10 Mustard, White Or Yellow Brassica hirta fruit/seed 21CFR182.10 Nutmeg Myristica fragrans fruit/seed 21CFR182.10 b Onion Allium cepa root ASTA, SSA c Oregano leaf ASTA, SSA Origanum vulgare Oregano Oreganum, Mexican Oregano, Lippia spp. leaf 21CFR182.10 Mexican Sage, Origan) fruit/seed 21CFR182.10 Paprika Capsicum annuum Petroselinum crispum leaf 21CFR182.10 Parsley Piper nigrum fruit/seed 21CFR182.10 Pepper, Black Cayenne Capsicum annuum fruit/seed 21CFR182.10 Pepper, Capsicum frutescens fruit/seed 21CFR182.10 Pepper, Cayenne Capsicum annuum fruit/seed 21CFR182.10 Pepper, Red Capsicum frutescens fruit/seed 21CFR182.10 Pepper, Red Piper nigrum 21CFR182.10 fruit/seed Pepper, White leaf 21CFR182.10 Peppermint Mentha piperita c fruit/seed ASTA, SSA Schinus terebinthifolia Pink Pepper Papayer somniferum fruit/seed 21CFR182.10 Poppy Seed Calendula officinalis flower Pot Marigold 21CFR182.10 Pot Marjoram Majorana onites leaf 21CFR182.10 Rosemary leaf 21CFR182.10 Rosmarinus officinalis Crocus sativus flower 21CFR182.10 Saffron leaf 21CFR182.10 Sage Salvia officinalis Salvia triloba leaf Sage, Greek 21CFR182.10 Savory, Summer Satureia hortensis (Satureja). leaf 21CFR182.10 Satureia montana (Satureja). leaf 21CFR182.10 Savory, Winter Sesame Sesamum indicum fruit/seed 21CFR182.10 b Sichuan Pepper Zanthoxylum piperitum fruit/seed SSA Mentha spicata leaf 21CFR182.10 Spearmint Star Anise Illicium verum fruit/seed 21CFR182.10 Tarragon Artemisia dracunculus leaf 21CFR182.10 Thyme Thymus vulgaris leaf 21CFR182.10 Thyme, Wild Or Creeping Thymus serpyllum leaf 21CFR182.10 21CFR182.10 Turmeric Curcuma longa root FDA Draft Risk Profile | 176

189 Spice List | Appendix A Plant Part a Source Common name Botanical name Used Vanilla planifolia Vanilla 21CFR182.10 fruit/seed Vanilla Vanilla tahitensis fruit/seed 21CFR182.10 root Zedoary Curcuma zedoaria 21CFR182.10 a Plants listed as spices in commerce as cited by 21CFR182.10 (FDA, 2012f), ASTA (2012), or SSA (2012). b Common name is from Herbs of Commerce (McGuffin et al. , 2000). c Herbs of Commerce Common name is from et al. (McGuffin , 2000) as per 21 CFR101.4(h) (FDA, 2012q) d Common name from source(s) noted. e ASTA (2012) includes the species Thymus satureioides (thyme) on their list of spices. There is no history of use as a food in either GRIN, World Spice Plants, or Mansfeld’s World Database of Agricultural and Horticultural Crops . It is a valid scientific name in the Missouri Coss. Botanical Garden Tropicos database as Thymus saturejoides FDA Draft Risk Profile | 177

190 Spice List | Appendix A y part of plant u sed Table A3. Spice list b Plant Part a Common name Source Botanical Name Used 21CFR182.10 bark Cassia, Padang Or Batavia Cinnamomum burmanni 21CFR182.10 Cinnamomum cassia bark Cassia, Chinese Cinnamon, Chinese 21CFR182.10 bark Cinnamomum cassia Cinnamomum loureirii Cassia, Saigon 21CFR182.10 bark Cinnamon, Saigon 21CFR182.10 bark Cinnamomum loureirii bark Cinnamon, Ceylon 21CFR182.10 Cinnamomum zeylanicum Angostura (Cusparia Bark) 21CFR182.10 bark Galipea officinalis Camomile (Chamomile), English Or Roman flower 21CFR182.10 Anthemis nobilis Calendula officinalis Calendula 21CFR182.10 flower Calendula officinalis flower Marigold, Pot 21CFR182.10 Pot Marigold 21CFR182.10 flower Calendula officinalis Capparis spinosa Capers flower 21CFR182.10 flower Crocus sativus Saffron 21CFR182.10 flower 21CFR182.10 Lavandula officinalis Lavender flower 21CFR182.10 Matricaria chamomilla Camomile (Chamomile), German Or Hungarian 21CFR182.10 Elder Flowers Sambucus canadensis flower c Cloves flower ASTA, SSA Syzygium aromaticum Tilia spp. Linden Flowers 21CFR182.10 flower c Alpinia galanga fruit/seed seed SSA Greater Galangal fruit/seed Amomum melegueta Grains Of Paradise 21CFR182.10 c Dill seed ASTA, SSA fruit/seed Anethum graveolens d Anethum sowa Dill seed fruit/seed ASTA fruit/seed Angelica Seed 21CFR182.10 Angelica archangelica fruit/seed Angelica spp. Angelica Seed 21CFR182.10 Apium graveolens fruit/seed 21CFR182.10 Celery Seed c fruit/seed Anatto ASTA Bixa orellana Brassica hirta Mustard, White Or Yellow 21CFR182.10 fruit/seed Mustard, Brown 21CFR182.10 fruit/seed Brassica juncea Brassica nigra Mustard, Black Or Brown fruit/seed 21CFR182.10 fruit/seed Capsicum annuum Capsicum 21CFR182.10 fruit/seed Capsicum annuum Cayenne Pepper 21CFR182.10 fruit/seed Capsicum annuum Paprika 21CFR182.10 fruit/seed Pepper, Cayenne 21CFR182.10 Capsicum annuum Pepper, Red fruit/seed 21CFR182.10 Capsicum annuum fruit/seed Capsicum frutescens Capsicum 21CFR182.10 fruit/seed Capsicum frutescens Cayenne Pepper 21CFR182.10 fruit/seed Capsicum frutescens Pepper, Cayenne 21CFR182.10 Capsicum frutescens Pepper, Red 21CFR182.10 fruit/seed fruit/seed Carum carvi Caraway 21CFR182.10 d fruit/seed Kaffir Lime SSA Citrus hystrix Coriander 21CFR182.10 fruit/seed Coriandrum sativum Cuminum cyminum Cumin (Cummin) 21CFR182.10 fruit/seed fruit/seed Cardamom (Cardamon) 21CFR182.10 Elettaria cardamomum fruit/seed Foeniculum vulgare Fennel, Common 21CFR182.10 fruit/seed Foeniculum vulgare var. duice Fennel, Sweet (Finocchio, Florence Fennel) 21CFR182.10 fruit/seed Ambrette Seed 21CFR182.10 Hibiscus abelmoschus Illicium verum Anise, Star 21CFR182.10 fruit/seed Illicium verum Star Anise 21CFR182.10 fruit/seed c Juniperus communis Juniper fruit/seed ASTA, SSA fruit/seed Medicago sativa Alfalfa Herb And Seed 21CFR182.10 Myristica fragrans Mace 21CFR182.10 fruit/seed 21CFR182.10 fruit/seed Myristica fragrans Nutmeg FDA Draft Risk Profile | 178

191 Spice List | Appendix A Plant Part a Common name Source Botanical Name Used 21CFR182.10 fruit/seed Caraway, Black (Black Cumin) Nigella sativa 21CFR182.10 Nigella sativa fruit/seed Cumin, Black (Black Caraway) Poppy Seed 21CFR182.10 fruit/seed Papayer somniferum Pimpinella anisum Anise 21CFR182.10 fruit/seed Allspice 21CFR182.10 fruit/seed Pimenta officinalis Piper nigrum Pepper, Black 21CFR182.10 fruit/seed Piper nigrum 21CFR182.10 fruit/seed Pepper, White c ASTA, SSA Schinus terebinthifolia fruit/seed Pink Pepper Sesame 21CFR182.10 fruit/seed Sesamum indicum Trigonella foenum - graecum Fenugreek 21CFR182.10 fruit/seed Vanilla Vanilla 21CFR182.10 planifolia fruit/seed Vanilla tahitensis Vanilla 21CFR182.10 fruit/seed b Zanthoxylum piperitum fruit/seed Sichuan Pepper SSA Allium schoenoprasum Chives 21CFR182.10 leaf c Anethum graveolens Dill ASTA, SSA leaf d Dill seed leaf ASTA Anethum sowa Angelica archangelica leaf Angelica 21CFR182.10 Angelica 21CFR182.10 leaf Angelica spp. Anthriscus cerefolium Chervil 21CFR182.10 leaf leaf Tarragon 21CFR182.10 Artemisia dracunculus d Kaffir Lime SSA leaf Citrus hystrix Coriandrum sativum Coriander 21CFR182.10 leaf c leaf Cymbopogon citratus SSA Lemon Grass leaf Hyssopus officinalis Hyssop 21CFR182.10 Laurus nobilis Bay 21CFR182.10 leaf Lippia spp. leaf 21CFR182.10 Oregano Oreganum, Mexican Oregano, Mexican Sage, Origan) Majorana hortensis Marjoram, Sweet 21CFR182.10 leaf Majorana onites leaf 21CFR182.10 Marjoram, Pot Majorana onites Pot Marjoram 21CFR182.10 leaf Marrubium vulgare Horehound (Hoarhound) leaf 21CFR182.10 Alfalfa Herb And Seed 21CFR182.10 leaf Medicago sativa Melissa officinalis Balm (Lemon Balm) 21CFR182.10 leaf Mentha piperita Peppermint leaf 21CFR182.10 leaf Mentha spicata Spearmint 21CFR182.10 leaf Basil, Sweet 21CFR182.10 Ocimum basilicum Basil, Bush 21CFR182.10 leaf Ocimum minimum c Origanum Oregano leaf ASTA, SSA vulgare Geranium leaf 21CFR182.10 Pelargonium spp. leaf Petroselinum crispum Parsley 21CFR182.10 21CFR182.10 leaf Rosmarinus officinalis Rosemary leaf Sage 21CFR182.10 Salvia officinalis Clary (Clary Sage) leaf 21CFR182.10 Salvia sclarea leaf Salvia triloba Sage, Greek 21CFR182.10 leaf Satureia hortensis (Satureja). Savory, Summer 21CFR182.10 leaf Satureia montana (Satureja). Savory, Winter 21CFR182.10 leaf Thymus serpyllum Thyme, Wild Or Creeping 21CFR182.10 vulgaris leaf Thymus 21CFR182.10 Thyme leaf Clover 21CFR182.10 Trifolium spp. b Allium cepa Onion root ASTA, SSA c Allium sativum Garlic root ASTA, SSA c Alpinia galanga Greater Galangal root SSA root Alpinia officinarum Galanga (Galangal) 21CFR182.10 21CFR182.10 root Angelica archangelica Angelica Root FDA Draft Risk Profile | 179

192 Spice List | Appendix A Plant Part a Botanical Name Common name Source Used Angelica spp. Angelica Root 21CFR182.10 root root Horseradish 21CFR182.10 Armoracia lapathifolia root Curcuma longa Turmeric 21CFR182.10 21CFR182.10 Zedoary root Curcuma zedoaria root Ginger 21CFR182.10 Zingiber officinale a Plants listed as spices in commerce as cited by 21CFR182.10 (FDA, 2012f), ASTA (2012), or SSA (2012). b Common name is from Herbs of Commerce (McGuffin et al. , 2000). c Common name is from (McGuffin et al. , 2000) as per 21 CFR101.4(h) (FDA, 2012q) Herbs of Commerce d Common name from source(s) noted. e ASTA (2012) includes the species Thymus satureioides (thyme) on their list of spices . There is no history of use as a food in either GRIN, World Spice Plants, or Mansfeld’s World Database of Agricultural and Horticultural Crops . It is a valid scientific name in the Missouri Coss. Botanical Garden Tropicos database as Thymus saturejoides FDA Draft Risk Profile | 180

193 Spice List | Appendix A se of spice in f oods Table A4. Common u Common use of spice in foods is characterized as raw, cooked or both . Spice use was assigned “raw” when dry spice is typically added to food without a microbial kill step. The term “cooked” was assigned when the . The term “both” was assigned when both cooking step is expected to provide an effective microbial kill step raw and cooked uses were identified or when the cooking step is not expected to always be sufficient to provide an effective kill step. Assignment of spice use is based on recipes and information on spice use . More research is needed to distinguish use by cuisine or culture. available on the internet Plant Part How used Common name Botanical name Used raw/cooked Medicago sativa Alfalfa leaf raw fruit/seed both Alfalfa Medicago sativa Pimenta officinalis fruit Allspice cooked Ambrette Seed Hibiscus abelmoschus fruit/seed both c Bixa orellana fruit/seed both Anatto Angelica archangelica leaf both Angelica Angelica spp. leaf both Angelica Angelica archangelica root cooked Angelica Angelica Angelica spp. root cooked Angelica seed cooked Angelica archangelica spp. seed cooked Angelica Angelica Galipea officinalis bark cooked Angostura (Cusparia Bark) Anise fruit/seed both Pimpinella anisum Anise, Star; Star Anise Illicium verum fruit/seed cooked Balm (Lemon Balm) Melissa officinalis leaf both Basil, Bush leaf both Ocimum minimum leaf Basil, Sweet both Ocimum basilicum Bay Laurus nobilis leaf cooked Calendula Calendula officinalis flower cooked Camomile (Chamomile), English Or Roman Anthemis nobilis flower both Matricaria chamomilla flower both Camomile (Chamomile), German Or Hungarian both Capers Capparis spinosa flower Capsicum fruit/seed both Capsicum annuum Capsicum frutescens fruit/seed both Capsicum fruit/seed both Caraway Carum carvi (Black Cumin) Nigella sativa Caraway, Black both fruit/seed Cardamom (Cardamon) Elettaria cardamomum fruit/seed both Cinnamomum cassia bark both Cassia, Chinese Cassia, Padang Or Batavia Cinnamomum burmanni bark both Cassia, Saigon bark both Cinnamomum loureirii Cayenne Pepper Capsicum annuum fruit/seed both Cayenne Pepper Capsicum frutescens fruit/seed both Celery Seed Apium graveolens fruit/seed both Chervil Anthriscus cerefolium leaf both Chives Allium schoenoprasum leaf both Cinnamon, Ceylon zeylanicum bark both Cinnamomum bark both Cinnamon, Chinese Cinnamomum cassia Cinnamomum loureirii bark both Cinnamon, Saigon Salvia sclarea leaf cooked Clary (Clary Sage) spp. leaf Clover both Trifolium c Cloves Syzygium aromaticum flower both Coriander leaf both Coriandrum sativum Coriander Coriandrum sativum fruit/seed both Cumin (Cummin) Cuminum cyminum fruit/seed both Cumin, Black (Black Caraway); Caraway, black both Nigella sativa fruit/seed (black cumin) Dill Anethum graveolens leaf both cooked Elder Flowers Sambucus canadensis flower FDA Draft Risk Profile | 181

194 Spice List | Appendix A Plant Part How used Common name Botanical name raw/cooked Used Foeniculum vulgare cooked fruit/seed Fennel, Common fruit/seed cooked Foeniculum vulgare var. Fennel, Sweet (Finocchio, Florence Fennel) duice - Fenugreek fruit/seed both Trigonella foenum graecum c Alpinia galanga root Galangal both Greater Alpinia officinarum root both Galanga (Galangal) c Garlic both root Allium sativum spp. leaf raw Pelargonium Geranium root both Ginger Zingiber officinale Grains Of Paradise fruit/seed both Amomum melegueta leaf both Horehound (Hoarhound) Marrubium vulgare Armoracia lapathifolia root raw Horseradish Hyssopus officinalis Hyssop leaf both c Juniperus communis fruit/seed cooked Juniper d Kaffir Lime cooked leaf Citrus hystrix d Citrus hystrix fruit/seed both Kaffir Lime Lavender flower both Lavandula officinalis c Cymbopogon citratus leaf both Lemon Grass Tilia spp. flower both Linden Flowers Mace fruit/seed both Myristica fragrans Calendula officinalis flower cooked Marigold, Pot; Pot Marigold leaf both Marjoram, Pot; Pot Marjoram Majorana onites Majorana hortensis leaf Marjoram, Sweet both Mustard, Black Or Brown Brassica nigra fruit/seed both Brassica juncea fruit/seed both Mustard, Brown both Mustard, White Or Yellow Brassica hirta fruit/seed Nutmeg fruit/seed both Myristica fragrans b Allium cepa root both Onion c Origanum vulgare leaf Oregano both Oregano Oreganum, Mexican Oregano, Mexican Lippia spp. leaf both Sage, Origan) Capsicum annuum fruit/seed both Paprika Parsley Petroselinum crispum leaf both Pepper, Black fruit/seed both Piper nigrum fruit/seed Pepper, Cayenne both Capsicum annuum Pepper, Cayenne Capsicum frutescens fruit/seed both Pepper, Red Capsicum annuum fruit/seed both Pepper, Red Capsicum frutescens fruit/seed both Pepper, White Piper nigrum fruit/seed both Peppermint Mentha piperita leaf both c Pink Pepper Schinus terebinthifolia fruit/seed both Papayer somniferum fruit/seed both Poppy Seed leaf both Rosemary Rosmarinus officinalis Crocus sativus flower Saffron cooked Sage Salvia officinalis leaf both Salvia triloba leaf both Sage, Greek Savory, Summer Satureia hortensis cooked leaf (Satureja). leaf cooked Savory, Winter Satureia montana (Satureja). Sesamum indicum fruit/seed both Sesame b Sichuan Pepper Zanthoxylum piperitum fruit/seed both Spearmint Mentha spicata leaf both Artemisia dracunculus leaf both Tarragon both Thyme Thymus vulgaris leaf FDA Draft Risk Profile | 182

195 Spice List | Appendix A Plant Part How used Common name Botanical name Used raw/cooked Thymus serpyllum leaf both Thyme, Wild Or Creeping Turmeric root cooked Curcuma longa Vanilla Vanilla planifolia fruit/seed cooked cooked Vanilla Vanilla tahitensis fruit/seed Zedoary root cooked Curcuma zedoaria a Plants listed as spices in commerce as cited by 21CFR182.10 (FDA, 2012f), ASTA (2012), or SSA (2012). b Common name is from Herbs of Commerce (McGuffin et al. , 2000). c Common name is from Herbs of Commerce (McGuffin et al. , 2000) as per 21 CFR101.4(h) (FDA, 2012q) d Common name from source(s) noted. e ASTA (2012) includes the species Thymus satureioides (thyme) on their list of spices . There is no history of use as a food in either GRIN, World Spice Plants, or Mansfeld’s World Database of Agricultural and Horticultural Crops . It is a valid scientific name in the Missouri Coss. Botanical Garden Tropicos databas e as Thymus saturejoides FDA Draft Risk Profile | 183

196 E SPICE PRODUCTION APPENDIX B: WORLDWID The worldwide spice production data for 2009 included in this appendix was obtained from the FAO . The top 20 producers are listed for each spice and the spice FAOSTAT Production website (FAO, 2013b) descriptions, country production, percent of worldwide production and data source listed were obtained from this FAO source. Worldwide Spice Production 2009 Table B1. Worldwide Production Spice (M etric Tonnes) 499,626 Anise, badian, fennel, coriander Chilies and peppers, dry 3,137,545 Cinnamon (canella) 155,400 Cloves 104,881 Garlic 22,282,060 Ginger 1,615,974 683,918 Mustard seed Nutmeg, mace and cardamoms 77,641 73,231,830 Onions, dry Pepper (Piper spp.) 451,220 Poppy seed 98,835 Sesame seed 3,976,968 a 1,588,807 Spices, nes Vanilla 9,815 a nes: not elsewhere specified Table B2. Anise, badian, fennel, coriander Include: anise ( Pimpinella anisum Illicium verum ); caraway ( Carum carvi ); coriander ); badian or star anise ( ( Coriandrum sativum ); cumin ( Cuminum cyminum ); fennel ( Foeniculum vulgare ); juniper berries ( Juniperus communis ). Seeds and berries from the various plants listed . They are normally used as spices, but also have ustrial (e.g. in distilleries) and medicinal applications. ind a Metric Tonnes Country Data Source % of Worldwide Production India 176,615 35.35 Im Mexico 50,000 10.01 F China 42,000 8.41 F Bulgaria 6.80 Im 33,957 31,431 6.29 Im Iran (Islamic Republic of) 30,829 6.17 Syrian Arab Republic 4.60 F Morocco 23,000 22,000 Egypt F 4.40 Russian Federation 11,200 2.24 1.96 Tunisia F 9,800 9,472 1.90 Turkey Afghanistan 8,904 1.78 Im Peru 1.44 F 7,194 1.41 F Canada 7,068 7,063 Romania 1.41 Viet Nam 5,080 1.02 Im Ukraine 4,509 0.90 Im Australia 2,940 0.59 Hungary 2,906 0.58 Im Occupied Palestinian Territory 2,706 0.54 F a FAO official data unless noted otherwise. Im: FAO data based on imputation methodology; F: FAO estimate. FDA Draft Risk Profile | 184

197 Worldwide Spice Production | Appendix B and peppers, dry Table B3. Chillies ; Capsicum frutescens C. annuum Red and cayenne pepper, paprika, chillies ( ); allspice, Jamaica pepper ( Pimenta officinalis ). Uncrushed or unground fresh pimentos are considered to be vegetables. a % of Worldwide Production Data Source Country Metric Tonnes India 43.155 F 1,300,000 260,000 8.29 F China 186,700 Pakistan 5.95 170,125 5.42 Thailand 140,216 4.47 Peru Im 118,514 3.78 Im Ethiopia 116,000 3.70 Myanmar F Viet Nam 112,937 3.60 Im 109,337 3.48 Bangladesh 93,641 F 2.98 Ghana 1.63 Im Mexico 50,988 50,000 1.59 F Nigeria Egypt 1.45 F 45,600 1.12 Im Romania 35,251 32,000 Democratic Republic of the Congo F 1.02 Benin 25,867 0.82 Im Bosnia and Herzegovina 20,429 0.65 Côte d'Ivoire 0.64 F 20,000 19,982 0.64 Hungary 18,265 0.58 Im Morocco a FAO official data unless noted otherwise. Im: FAO data based on imputation methodology; F: FAO estimate/ Table B4. Cinnamon (canella) Ceylon cinnamon ( ); Chinese, common cinnamon, cassia ( C. cassia ). The inner bark Cinnamomum zeylanicum . Includes cinnamon- tree flowers, cinnamon fruit and of young branches of certain trees of the Laurus family cinnamon waste (chips), whether whole, crushed or ground. a Metric Tonnes % of worldwide Production Data Source Country 43.25 Im Indonesia 67,209 37.32 China F 58,000 14,600 9.40 Sri Lanka Viet Nam 13,965 8.99 Im Madagascar 0.81 Im 1,253 - 133 0.09 Im Timor Leste Sao Tome and Principe 0.05 F 70 63 0.04 Seychelles Dominica 52 0.03 Im Grenada 37 0.02 F Comoros 18 0.01 Im a FAO official data unless noted otherwise. Im: FAO data based on imputation methodology; F: FAO estimate. FDA Draft Risk Profile | 185

198 Worldwide Spice Production | Appendix B Cloves Table B5. The whole fruit of the clove tree, including the flowers . Eugenia caryophyllata; Caryophyllus aromaticus picked before maturity and dried in the sun, and the stems of the clove flowers. a Data Source % of Worldwide Production Metric Tonnes Country 77.23 F Indonesia 81,000 7,594 7.24 Im Madagascar Tanzania 7,518 7.17 Im United Republic of 3,790 3.61 Sri Lanka 2.53 Im Comoros 2,658 1,159 1.11 Kenya Im China 900 0.86 F 249 0.24 Im Malaysia 13 0.01 F Grenada a FAO official data unless noted otherwise. Im: FAO data based on imputation methodology; F: FAO estimate. Garlic Table B6. . Numbers reflect fresh garlic production. Allium sativum a % of Worldwide Production Data Source Country Metric Tonnes 17,967,857 China 80.64 India 1,070,000 4.80 F F Republic of Korea 380,000 1.71 Russian Federation 1.02 227,270 0.90 Myanmar F 200,000 Ethiopia 179,658 0.81 * United States of America 178,760 0.80 Egypt 0.78 174,659 Bangladesh 154,831 0.69 Spain 154,000 0.69 Ukraine 150,100 0.67 Argentina 120,391 0.54 Im Turkey 0.47 105,363 Republic of Korea 0.45 101,347 Democratic People's Im 86,752 0.39 Brazil Thailand 71,433 0.32 Pakistan 0.30 67,204 Iran (Islamic Republic of) 64,002 0.29 Romania 63,245 0.28 Algeria 59,932 0.27 a FAO official data unless noted otherwise. Im: FAO data based on imputation methodology; F: FAO estimate FDA Draft Risk Profile | 186

199 Worldwide Spice Production | Appendix B Ginger Table B7. . It also is used for making beverages . Rhizome of a perennial herb . Includes fresh, Zingiber officinale provisionally preserved or dried, whereas ginger preserved in sugar or syrup is excluded. a Data Source Metric Tonnes Country % of Worldwide Production India 23.52 380,100 331,393 20.51 F China 192,500 11.91 F Indonesia Nepal 174,268 10.78 Im 10.53 Thailand 170,125 152,106 9.41 Im Nigeria Bangladesh 4.49 72,608 Japan 52,000 3.22 F Philippines 27,415 1.70 Cameroon 0.74 F 12,000 0.69 Malaysia 11,200 10,780 0.67 Sri Lanka 7,680 0.48 Im Côte d'Ivoire Ethiopia 6,834 0.42 Im Bhutan 3,766 0.23 Fiji 0.19 3,041 Republic of Korea 3,000 0.19 F Costa Rica 1,105 0.07 United 816 0.05 F States of America Mauritius 616 0.04 a FAO official data unless noted otherwise. Im: FAO data based on imputation methodology; F: FAO estimate. Table B8. Mustard Seed Brassica alba; B. hirta; Sinapis alba Brassica nigra; Sinapis nigra ) . In addition ); black mustard ( White mustard ( to the oil extracted from them, white mustard seeds, may be processed into flour for food use . Black mustard seeds also yield oil and are processed into flour that is used mainly in pharmaceutical products. a % of Worldwide Production ry Data Source Count Metric Tonnes Canada 30.46 208,300 Nepal 135,494 19.81 Myanmar 70,000 10.24 F Czech Republic 5.65 38,651 United States of America 22,391 3.27 Ukraine 118,200 17.28 Russian Federation 23,690 3.46 China 18,000 2.63 F 1.55 Romania 10,633 France 1.39 9,500 1.40 Hungary 9,568 7,411 1.08 Im Germany 0.55 3,785 Slovakia 2,924 0.43 Im Ethiopia 0.25 1,741 Bhutan Bulgaria 0.18 Im 1,222 300 0.04 Sri Lanka Kazakhstan 900 0.13 * Denmark 30 0.00 Im Mexico 16 0.00 a FAO official data unless noted otherwise. Im: FAO data based on imputation methodology; F: FAO estimate. FDA Draft Risk Profile | 187

200 Worldwide Spice Production | Appendix B Nutmeg, mace and cardamoms Table B9. ); cluster cardamon ( Myristica fragrans cardamons Elettaria cardamomum Nutmeg, mace ( ); other A. hambury ; ; A. cardamomum ); Malaguetta pepper, grains Aframomum angustifolium ( ; Amomun aromaticum ). Nutmeg is the inner brown kernel of the fruit of the nutmeg tree Aframomum melegueta of paradise ( . Mace is the net -like membrane between the outer shell and the kernel . Cardamon seeds are enclosed in the capsule produced by perennial herbs of the Zingiberaceae family. a Data Source Metric Tonnes Country % of Worldwide Production 30.65% Im Guatemala 23794 17000 21.90% F India 12.59% Im Nepal 9774 9082 11.70% Im Bhutan 8600 11.08% Indonesia F 3982 5.13% Im Lao People's Democratic Republic 2395 3.08% Grenada Im United Republic of Tanzania 795 1.02% Im 711 0.92% Im Malaysia 480 0.62% Sri Lanka 285 0.37% Honduras Im 192 0.25% Im Trinidad and Tobago 172 0.22% Im Saint Vincent and the Grenadines Malawi 0.17% F 133 0.13% F Ethiopia 100 60 0.08% Im Kenya Togo 0.05% F 35 Saint Lucia 30 0.04% F Madagascar Im 16 0.02% Dominica 0.01% F 5 a FAO official data unless noted otherwise. Im: FAO data based on imputation methodology; F: FAO estimate. Table B10. Onions, dried . Includes onions at a mature stage, but not dehydrated onions. Allium cepa a Country % of Worldwide Production Data Source Metric Tonnes 21,046,969 28.74% F China India 13,900,000 18.98% F United States of America 4.64% 3,400,560 Turkey 1,849,580 2.53% Egypt 1,800,000 2.46% F Pakistan 1,704,100 2.33% Russian Federation 1,601,550 2.19% Iran (Islamic Republic of) 1,512,150 2.06% Brazil 1,511,850 2.06% Netherlands 1.73% 1,269,000 1.73% Spain 1,263,400 1,200,000 1.64% F Republic of Korea Mexico 1.63% 1,195,820 Japan 1,154,000 1.58% Myanmar 1,050,000 1.43% F Algeria 1.34% 980,160 Indonesia 952,638 1.30% Ukraine 875,600 1.20% Uzbekistan 795,000 1.09% * Bangladesh 735,140 1.00% a FAO official data unless noted otherwise. F: FAO estimate; *: unofficial figure. FDA Draft Risk Profile | 188

201 Worldwide Spice Production | Appendix B Pepper ( Piper Table B11. spp.) ); long pepper ( Black, white pepper ( . Includes whole, P. longum Piper nigrum ). Perennial climbing vines crushed or ground berries . Black pepper is produced from partially ripe berries, while white pepper is from fully ripe berries, which have had the outer hull removed. a % of Worldwide Production Data Source Country Metric Tonnes 30.42% * 137,280 Vietnam 80,000 17.73% Indonesia F 14.49% Brazil 65,398 47,400 10.50% India 28,218 6.25% China F 25,300 5.61% Sri Lanka 23,210 5.14% Malaysia Thailand 6,730 1.49% 5,805 1.29% Im Mexico 3,949 Im 0.88% Madagascar 0.79% F Ghana 3,584 3,208 0.71% Im Philippines Cambodia 0.60% Im 2,704 0.58% Im Ecuador 2,626 2,408 0.53% Rwanda Im Niger 2,000 0.44% F Im Uganda 1,901 0.42% Zimbabwe 1,883 Im 0.42% 0.28% Bolivia (Plurinational State of) 1,263 1,040 0.23% Costa Rica a FAO official data unless noted otherwise. Im: FAO data based on imputation methodology; F: FAO estimate; *: unofficial figure. Table B12. P oppy Seed Papaver somniferum . The source of opium, poppy seeds are also used in baking and confectionery. a Metric Tonnes % Of Worldwide Production Data Source Country Turkey 34,194 34.60% 33.08% Czech Republic 32,692 Spain 7,000 7.08% F France 6,500 6.58% F Hungary 3.50% 3,458 Croatia 3,349 3.39% Germany 3,294 3.33% Im Occupied Palestinian Territory 2,200 2.23% F 1,956 Romania 1.98% Im Austria 1,504 1.52% Serbia 859 0.87% Im Slovakia 832 0.84% Im Netherlands 493 0.50% The former Yugoslav Republic of 504 0.51% Macedonia a FAO official data unless noted otherwise. Im: FAO data based on imputation methodology; F: FAO estimate. FDA Draft Risk Profile | 189

202 Worldwide Spice Production | Appendix B Spices, nes Table B13. ); dill seed ( Laurus nobilis Trigonella Anethum graveolens Including inter alia: bay leaves ( ); fenugreek seed ( Crocus sativus -graecum ); turmeric ( Curcuma longa ). Other spices foenum ); thyme ( Thymus vulgaris ); saffron ( that are not identified separately because of their minor relevance at the international level. Because of their limited local importance, some countries report spic es under this heading that are classified individually by FAO. This heading also includes curry powder and other mixtures of different spices. a Country Data Source Metric Tonnes % of Worldwide Production 1,100,000 69.23% F India 140,113 8.82% Bangladesh 87,028 Turkey 5.48% Im 85,987 5.41% F China 45,473 2.86% Im Pakistan 19,760 1.24% Im Colombia 1.10% Im Nepal 17,404 Iran (Islamic Republic of) 13,226 0.83% Im Burkina Faso 6,705 0.42% F 5,100 0.32% F Niger 4,959 0.31% F Nigeria 4,817 0.30% Sri Lanka Im 4,481 0.28% Im Indonesia 4,158 0.26% Bhutan Im Occupied Palestinian Territory 4,070 0.26% Im 0.21% Im Thailand 3,283 3,257 0.20% Zambia Im Spain 3,195 0.20% Im * Georgia 3,100 0.20% Morocco 3,000 0.19% F a FAO official data unless noted otherwise. Im: FAO data based on imputation methodology; F: FAO estimate; *: unofficial figure. Table B14. Sesame Seed Sesamum indicum . Va lued for its oil, but also as a food, either raw or roasted, as well as in bakery products r food preparations. the and o a Data Source % of Worldwide Production Country Metric Tonnes 21.81% Myanmar 867,520 657,000 India 16.52% 15.66% China 622,905 318,000 Sudan 8.00% 6.55% * 260,534 Ethiopia 4.48% 178,000 Uganda 2.77% * Nigeria 110,000 1.90% 75,632 Niger 1.63% Paraguay 65,000 64,445 Im Somalia 1.62% 1.41% 56,252 Burkina Faso 1.26% 50,008 Central African Republic 1.21% * United Republic of Tanzania 48,000 1.16% Thailand 46,039 * 41,000 Egypt 1.03% 0.88% * Chad 35,000 33,400 Pakistan 0.84% 32,306 Bangladesh 0.81% 0.80% * Afghanistan 32,000 0.78% F 31,000 Cambodia a FAO official data unless noted otherwise. Im: FAO data based on imputation methodology; F: FAO estimate; *: unofficial figure. FDA Draft Risk Profile | 190

203 Worldwide Spice Production | Appendix B Vanilla Table B15. Vanilla planifolia ; V. pompona . The fruit (or bean) of a climbing plant of the orchid family. Includes whole, crushed or ground. a Metric Tonnes % of Worldwide Production Country Data Source Indonesia 4,362 44.44% Im Madagascar 2,830 28.83% Im China 1,382 14.08% Im Mexico 524 5.34% Tonga 263 2.68% Im Im Turkey 215 2.19% French Polynesia 0.75% 74 Comoros 65 0.66% Im Uganda 48 0.49% Im Malawi 15 0.15% Im Kenya 12 0.12% Im Réunion 12 0.12% * Guadeloupe 8 0.08% F Zimbabwe 5 0.05% Im a FAO official data unless noted otherwise. Im: FAO data based on imputation methodology; F: FAO estimate; *: unofficial figure. FDA Draft Risk Profile | 191

204 APPENDIX C: FDA 2010 CONCENTRATION S AND STUDY OF OF SALMONELLA IN SHIPMENTS OF CAPI SCUM AND DISTRIBUTION SESAME SEED OFFERED FOR ENTRY TO THE UNI TED STATES. Salmonella in shipments of imported capsicum and The 2010 FDA study “Prevalence, level and distribution of sesame seed spice offered for entry to the United States: Observations and modeling results” was originally published in ( Van Doren et al. , 2013c ). Below we provide information from the study most Food Microbiology levant to the results discussed in the present risk profile document. re Material and Methods Sample Collection All imports of dried capsicum and sesame seeds were eligible for sampling during the study period. A total of 299 shipments of capsicums and 233 s hipments of sesame seeds were sampled at the point of import into the . The shipments sampled constituted approximately 10 or United States between August and December 2010 20 percent of all shipments of imported capsicum or imported sesame seed shipments, respectively, offered for entry to the United States. Sixty subsamples, each comprised of approximately 160 grams, were collected . Typically, each sub randomly from each shipment -sample was collected from a different container or sack of spice in the shipm ent selected at random. Samples were sent to U.S. Food and Drug Administration (FDA) laboratories for analysis . Sample Preparation, Screening, Isolation and Confirmation Salmonella Composite samples were prepared by dividing the 60 subsamples into four gr oups of fifteen . Twenty -five gram analytical units of product from each of the fifteen subsamples were combined to form a 375 g composite sample (Andrews and Hammack, 2003) . Each composite sample was screened for the presence of Salmonella using one of the following methods: AOAC’s Official Methods of Analysis (OMA): 2004.03, 2001.07, 2001.08, or 2001.09, which are available from AOAC International (2007a, 2007b, 2007c, 2007d) . All methods are validated and have similar performance criteria. Salmonella was isolated from each of the composite samples testing positive using the procedures described in Chapter 5 of the FDA Bacteriological Analytical Manual (BAM) (Andrews et al ., 2011; Jacobson, and Hammack, 2003) . Presumptive -positive Salmonella isolates were confirmed with OMA methods 978.24 or 991.13 (available from AOAC International (2005d, 2005e) Salmonella isolates recovered from the spices . were serotyped (Ewing, 1986) . Salmonella Enumeration A dilution assay was undertaken for composite samples of spi ce that were found to contain Salmonella by the screening test. The serial dilution protocol involved a three tube analysis on each of four different dilutions of spice . Spice sampled for the dilution assay analysis were drawn from a composite (thoroughly mixed) sample Salmonella - created from equal proportions of the same set of 15 subsamples used in the corresponding positive screening test. Separate composite spice product portions of 100, 10, 1, and 0.1 g were each rehydrated at a 1:9 ratio with a tryptic soy broth pre -enrichment medium by swirling or soaking as instructed et al ., 2011; Ja cobson, and Hammack, 2003). This procedure was repeated in the BAM method (Andrews three times (for three tubes) for each of the four different dilutions (100, 10, 1, and 0.1 g) . The enrichment tubes were kept at room temperature for 60 ± 5 min, pH adjusted to 6.8 ± 0.2, if necessar y, and then o incubated for 24 ± 2 h at 35 ± 2 C. Once incubation was complete, the BAM Salmonella culture method was followed (Andrews et al ., 2011; Jacobson, and Hammack, 2003) . The relative likelihood of each reported dilution assay pattern for a thoroughly mixed sample was evaluated on the basis of the rarity index (Blodgett, 2010a; Jarvis et al . 2010). FDA Draft Risk Profile | 192

205 FDA 2010 Study of Concentrations & Distribution of Salmonella in Shipments Offered for I mport | Appendix C Most Probable Number (MPN) values and 95% confidence intervals for each of the four composite samples were determined from the five results, screening test plus the four dilutions using the excel spreadsheet provided in the BAM (Blodgett, 2010b), where the screening test was treated as another “dilution” for the MPN analysis . For a few shipments, the procedure described above was not followed . For samples in one shipment of capsicum and six shipments of sesame seeds, the dilution assay result patterns were not reported Salmonella was reported for the enumeration experiment by the field labs but rather the presence/absence of . In these cases, we interpret the experiments as providing a second screening test with total spice as a whole mass of 333.3 g . For samples from two other shipments of sesame seeds with confirmed positive Salmonella samples, enumeration experiments were not performed . MPN estimates and confidence intervals for the mean Salmonella concentration in a shipment were calculated taking into account the full set of screening test and dilution assay results. The assumption of Poisson -distributed contamination within shipments, which was used to estimate the shipment mean concentration of contamination and is part of some of the parametric models developed, was examined. We evaluated for each of the 4 composite sample results, a rarity index (Blodgett, 2010a). Specifically we evaluated the probabi lity to obtain the pattern of results observed for one composite sample given the estimated mean shipment concentration divided by the probability to observe the most probable pattern of results in the composite sample given the estimated mean shipment con centration. This statistic has the advantage of being quantifiable for all of the outcomes obtained in this study including missing dilution assay results and binary dilution assay result outcomes. The second advantage is that this rarity index evaluates i n one statistic the adequacy of the assumption of within shipment Poisson distribution and s expectation that contamination concentration within dilution assay Poisson distribution . There is no a priori in different composites from the same shipment should be the same/similar because the spice contained in different composites are from different locations in the shipment. If the local concentration in a given composite is far higher or lower than the value estimate at the shipment level, the probability to o bserve the given pattern will be low with regards to the most probable one, leading to a low rarity index. We use the recommendations of Jarvis et al (2010) for thresholds of probability: the pattern of results is likely to occur if its rarity index is ≥0. 05; is expected to occur only rarely if the rarity index falls within the range 0.01< rarity index < 0.05; and is expected to occur extremely rarely if the rarity index is ≤ 0.01 Probabilistic Models Probabilistic models of imported spice shipment contami nation were examined for their ability to describe the Salmonella sampling data. Features included in the models were selected for their ability to describe Salmonella between - and within -shipment distributions of in spices. Each model was fit to the capsicum and sesame seed data separately, and evaluated for its quality of fit. Mathematical descriptions of the models, development of the likelihood functions, and derivation of the maximum likelihood solutions, where applicable, are presented in the Supplementary Material. All information gathered in this study, including positive and negative test results of screening and enumeration experiments, was used in determining model parameter estimates. Maximum likelihood estimates of model parameters were determined from the analytical solutions or determined numerically using the R general -purpose optimization function “optim” (R Development Core Team, 2008). Standard errors for model parameters were derived from the Hessian matrix while confidence intervals for model predications were estimated using a parametric bootstrap procedure . Models are compared for quality of fit on the basis of the Akaike information criterion (AIC). Deviations of model predictions from observations are compared in a number of ways. Model between -shipment contamination distributions are compared with observations graphically. Model predicted prevalence for the sampling plan used in the present study is compared with the observed one. Observed data on the distribution of contamination wit hin each shipment are compared with results predicted under a Poisson distribution assumption (see Section 2.2) . Finally, model fits, as quantified by the AIC, are compared with that of an empirical model. FDA Draft Risk Profile | 193

206 FDA 2010 Study of Concentrations & Distribution of Salmonella in Shipments Offered for I mport | Appendix C Model 1 Model 1 assumes (1) imported spice shipments offered for U.S. entry can be divided into two populations: uncontaminated shipments (zero probability of one or more bacterium in the shipment, designated “Population I”) and contaminated shipments (non-zero probability of one or more bacterium in the shipment, designated “Population II”) (2) contamination within Population II shipments is characterized by a Poisson distribution and (3) all contaminated spice shipments (Population II) have the same mean concentr ation of Salmonella . The explicit inclusion of a Salmonella -free population in this model and the additional models that -inflated distributions used by others to describe microbial distributions in foods follow is similar to the zero ., 2012). Model 1 is ales et al ., 2010; Bassett et al ., 2010; Jongenburger et al -Barron (see for example, Gonz characterized by two parameters, p and λ , which are the probability of being in Population II and the mean concentration of Salmonella in Population II shipments, respec tively. Model 2 Model 2 assumes (1) imported spice shipments at U.S. entry can be divided into two populations, i.e., uncontaminated shipments (Population I) and contaminated shipments (Population II) as defined in Model 1 - (2) contamination within Population II shipments is concentrated in isolated contamination clusters or “hot -zero while the probability outside the hot spots” (probability of at least one bacterium in each hot spot is non o f Salmonella and (4) the contamination spot is zero) (3) all hot spots have the same mean concentration within each hot spot is described by a Poisson distribution. This model is characterized by three parameters, p , h and λ , which are the probability of being in Population II, the probability that a sample taken from a shipment in Population II is from a hot spot, and the mean concentration of Salmonella in each hot spot, respectively. Models 3a -3d -3d assume (1) imported spice shipments offered for U.S. entry can be divided into two Models 3a populations, i.e., uncontaminated shipments (Population I) and contaminated shipments (Population II) as defined in Model 1 (2) contamination within Population II shipments is characterized by a Poisson s, where the distribution of distribution and (3) different shipments may have different mean concentration concentration s is defined by a gamma distribution (3a), lognormal distribution (3b), log -logistic mean dis tribution (3c), or Weibull distribution (3d). p , α, and β . p Models 3a, 3c, and 3d are characterized by three parameters, is the probability of being in Population II. In Models 3a, 3c, and 3d, is the shape parameter and β is the scale parameter. In Model 3b, α α Salmonella concentration and β is the standard deviation of the natural is the mean of the natural logarithm of logarithm of Salmonella concentration . Empirical Model Salmonella contamination of imported capsi cum and sesame seed Empirical models were developed for . These models assume (1) imported spice shipments offered shipments offered for entry to the United States for U.S. entry can be divided into two populations, i.e., uncontaminated shipments (Population I) and contaminated shipments (Population II) as defined in Model 1 (2) contamination within Population II shipments is characterized by a Poisson distribution and (3) different shipments may have different mean concentration s, where the distribution of mean concentration s is defined empirically from the within - shipment contamination concentration estimated from the observations. The fraction of uncontaminated shipments in each model is given by the fraction of shipments for which all four screening tests (4 composites of 375 g) tested negative, i.e., the observed prevalence. The distribution of mean concentration s among contaminated shipments is drawn from the discrete set of 10 (capsicum) or 23 (sesame seed) contaminated shipment estimated mean concentration s. Thus, the e mpirical models are saturated models . The empirical model for capsicum shipments includes 11 parameters and the empirical model for sesame seed shipments contains 24 parameters. FDA Draft Risk Profile | 194

207 FDA 2010 Study of Concentrations & Distribution of Salmonella in Shipments Offered for I mport | Appendix C Efficacy of Salmonella Sampling Plans in Reducing Risk contaminated spice shipments Salmonella Four sampling plans were evaluated for their ability to (1) identify offered for U.S. entry and (2) reduce Salmonella contamination in the imported spice supply, assuming identified shipments are reconditioned. Each sampling plan was a pplied to both the Model 1 and the best model identified among Models 3a -3d. In these analyses, we assumed the screening test has perfect sensitivity and specificity . FDA Draft Risk Profile | 195

208 FDA 2010 Study of Concentrations & Distribution of Salmonella in Shipments Offered for I mport | Appendix C Description of Sampled Shipments and Model Results Table C1. Description of s Salmonella -contaminated s hipments offered for U.S. entry ampled and a a Capsicum Sesame Seed Descriptor Contaminated Contaminated Sampled Sampled (233 Shipments) (299 Shipments) (10 (23 Shipments) Shipments) 5 4 - - 10 × 3.5 7.5 × 10 kg kg b Total Mass and Value for All Shipments 6 6 5 5 × 10 10 × $6.1 $5.3 $7.1 10 $1.6 × 10 × b 4 3 - : Mass - Mean Shipment Size kg 7.5 × 1.5 10 10 kg × b 3 4 - Size : Mass - Median Shipment kg 4.8 × 1.8 10 10 × kg b 4 4 : Mass - - Shipment Size Range 2.5 × 10 24 kg kg 125 - 3.8 × 10 - c Percentage of Shipments Retail ≥15 20 22 ≥11 d 46 80 Percentage of Shipments Ground/Cracked NA NA Fraction (Percentage) of Shipments Known ≥6/233 0/14 ≥14/299 0/7 to have Undergone a Pathogen Reduction (≤40%) (≤30%) (≥4.7%) (≥3%) e Treatment Fraction (Percentage) Fraction of Shipments 4/14 2/7 - - f ≥20%) Salmonella Neg. for ( with COA ( ≥17%) Percentage of Imported Shipments Sampled ~10 - ~20 - Observed Prevalence [95% CI] of 3.3% 9.9% - NA Contaminated Imported Spice Salmonella NA - [1.6 6.1%] [6.3 - 14%] g Shipments a Dash indicates the data were not available; NA indicates the descriptor is not applicable. b Mass and value determined from FDA sample collection report. c Retail defined as shipments packaged in bags/boxes containing ≤5 lbs (2.3 kg). d Percentages of ground/cracked and whole capsicum were determined by FDA product code and descrip . Information was available to assess form for 297 of the imported shipments tion e As determined by FDA product code and description for all imported shipments plus documents examined at import for contaminated shipments. Pathogen reduction treatment indications included “commercially sterile”, “heat treated”, “irradiated”, and “steam” or “eto” treated . The numbers of shipments identified is likely an underestimate because industry is not required to supply this information except for the case of irradiated spice and FDA officials are not required to record this information in their collection report. f COA means Certificate of Analysis . Documents provided at import for contaminated shipments were reviewed for COAs; information was available for 7 of the contaminated capsicum shipments and 14 of the contaminated sesame seed shipments. g 95% CI, exact confidence limits for the observed/apparent prevalence determined with the sampling protocol employed in this s tudy (Clopper and Pearson, 1934). Observed/apparent prevalence is a lower limit on the true preval ence. FDA Draft Risk Profile | 196

209 FDA 2010 Study of Concentrations & Distribution of Salmonella in Shipments Offered for I mport | Appendix C Model parameters and descriptors Table C2. S Mean . Concentration Hot Spot Mean b Prevalence Hot Spot Prevalence a in AIC on : Model Concentrati c [ S (SE) ]>0 (SE) c Contaminated (SE) Spice Shipments - Model #: # populations, Between (%) (%) (MPN/g) (unitless) (MPN/g) Within Distribution 3 - 3.4 (1.0) 241.4 1: 2 Populations, Poisson 10 × 3.64 Capsicum - 2 5.79 (1.54) x 10 2: 2 Populations, Hot Spot 3.5 (1.1) 217.9 7.2 (1.9) 3 - 1: 2 Populations, Poisson 9.9 (2.0) 405.7 10 × 3.53 d Sesame Seed - 2 5.9 (1.1) 7.75 (1.43) x 10 2: 2 Populations, Hot Spot 351.7 10.3 (2.1) -Shipment Distribution parameters Between e e α β (SE) (SE) f - 4 3a: 1 Population/gamma 100 - 174.7 Poisson 0.0384 (0.0315) 0.00833 (0.0031) 10 × 3.20 h g - 3 Poisson 7.3 (7.1) 175.1 2.445 (1.399) 3b: 2 Populations/lognormal - - 8.150 (3.067) × 5.74 10 Capsicum - 3 Poisson - 3c: 2 Populations/log - logistic 1.406 (0.465) 0.00231 (0.00062) 180.0 3.3 (1.0) 6.54 × 10 - 3 3d: 2 Populations/Weibull - Poisson 3.3 (1.0) 0.0053 (0.0028) 0.603 (0.153) 184.4 10 × 7.93 f - 4 3a: 1 Population/gamma 100 286.6 - Poisson 0.02073 (0.0105) 0.02977 (0.0076) × 6.17 10 h g - 3 Poisson 24.5 (19.3) 288.0 2.529 (1.078) 3b: 2 Populations/lognormal - - 8.543 (2.487) 10 × 4.77 d Sesame Seed - 3 Poisson 9.9 (2.0) - 301.9 3c: 2 Populations/log logistic - 1.319 (0.285) 0.00226 (0.00042) × 7.83 10 - 3 Poisson 9.9 (2.0) 3d: 2 Populations/Weibull 305.9 - 0.00474 (0.00136) 0.730 (0.136) 10 5.77 × - 2 3.3 (1.3 - 5.4) 167.8 Saturated Empirical Capsicum 10 × 1.13 d - 3 9.9 (6.0 - 14) 289.2 Sesame Seed Saturated Empirical × 5.93 10 a Following each model number is an abbreviated description of the model assumptions including the between -shipment distribution of Salmonella contamination (number of different populations) and the within -shipment distribution of Salmonella (Poisson or Hot Spot) . See text for detailed description. b Percentage of -contaminated shipments (as defined in the text) followed by s tandard error in parentheses. Salmonella c SE means standard error. d Models for contamination of sesame seed shipments use the revised data. See Table 2 and text for details. e Distribution parameters shape ( ) or scale ( β ) followed by standard error for that param eter in parentheses, unless otherwise noted. α f The optimized zero -Poisson model was degenerate with the two -parameter gamma- Poisson model, where shipment prevalence for Salmonella is 100%. See text for details. -inflated gamma g Mean of the of the natural l ogarithm of concentration followed by standard error for that parameter in parentheses. h Standard deviation of the natural logarithm of concentration distribution followed by standard error for that parameter in pa rentheses. FDA Draft Risk Profile | 197

210 FDA 2010 Study of Concentrations & Distribution of Salmonella in Shipments Offered for I mport | Appendix C Predicted Impact of Testing Shipments of Imported Capsicum or Sesame Seed Offered for entry to the United States for the presence Table C3. as a function of the mass of spice examined for contamination distributions in the incoming supply described by Model 1 and of Salmonella fit parametric model). 3a (the best- Model Model - Shipment Prevalence Spice Salmonella Screening Method a Size (95% CI) Effectiveness Measure 1500 g 25 g 375 g 750 g (kg) (%) c e d b FDA I COA FDA III FDA II Capsicum - Model 1 5.4) 3.4 (1.4 - Supply characteristics All sizes All sizes Expected value for percentage (95% CI) of - 0.3 (0.1 - 0.5) 2.5 (1.0 - 4.1) 5.4) - 5.1) 3.3 (1.3 3.1 (1.3 shipments detected (among all shipments) Expected value for percentage (95% CI) of All sizes 8.7 (6.5 - 11) 75 (63 - 83) 93 (87 - 97) 99.6 (98 - 99.9) contaminated shipments detected Expected value for percentage (95% CI) of All sizes captured in detected 99.9) 75 (63 Salmonella - 8.7 (6.5 - 11) - in supply 93 (87 - 97) 99.6 (98 83) shipments reduction (95% CI) of Expected value for log 10 All sizes 3.0) - 0.04 (0.03 Salmonella 2.4 (1.7 in spice supply if detected 0.05) 0.6 (0.4 - 0.8) 1.2 (0.9 - 1.5) - f shipments are reconditioned Capsicum - - Model 3a gamma -Poisson (Best Fit Model) 125 12) - 6.8 (3.3 3 18) 10 9.9 (4.7 - 7.5 x Supply characteristics 4 1.5 x 10 19) 10.8 (5.2 - Infinite 100 Expected value for percentage (95% CI) of 2.2 (0.9 All sizes 0.6 (0.1 - 1.1) - 3.6) 2.8 (1.2 - 4.5) 3.0 (1.7 - 5.4) shipments detected (among all shipments) - 41 (24 125 8.2 (1.8 - 15) 55) - 49 (33 33 (16 - 41) 48) (95% CI) of Expected value for percentage 3 - 34 (21 23 (10 7.5 x 10 39) - 29) 34) - 28 (15 5.6 (1.1 - 11) contaminated shipments detected 4 26 (14 - 32) 10) - 5.2 (1.0 - 1.5 x 10 21 (9.2 31 (19 - 36) 27) Expected value for percentage (95% CI) of Salmonella in supply captured in detected 99.5) All sizes 49 (10 - 76) 94 (64 - 98) 97 (78 - 99) 98 (88 - shipments Expected value for log reduction (95% CI) of 10 All sizes in spice supply if detected 2.3) - 1.8 (0.9 Salmonella - 0.6) 1.2 (0.4 - 1.7) 1.5 (0.7 - 2.0) 0.3 (0.05 f shipments are reconditioned FDA Draft Risk Profile | 198

211 FDA 2010 Study of Concentrations & Distribution of Salmonella in Shipments Offered for I mport | Appendix C Model - Shipment Prevalence Spice Salmonella Screening Method a (95% CI) Size Effectiveness Measure 1500 g 25 g 750 g 375 g (%) (kg) c b d e FDA I FDA II COA FDA III - Empirical Capsicum characteristics 3.3 (1.3 - 5.4) All sizes Supply Expected value for percentage (95% CI) of All sizes 0.5 (0.06 - 1.2) 1.9 (0.6 - 3.1) 2.4 (0.8 - 3.8) 2.9 (1.0 - 4.3) shipments detected (among all shipments) Expected value for percentage (95% CI) of All sizes 81) 14 (4.1 - 40) 56 (42 - 99) 72 (54 - 89) 85 (78 - contaminated shipments detected Expected value for percentage (95% CI) of All sizes captured in detected Salmonella in supply 99) 14 (4.1 - 40) 56 (42 - 81) 72 (54 - 89) 85 (78 - shipments Expected value for log reduction (95% CI) of 10 All sizes in spice supply if detected - 0.8 (0.7 2.0) Salmonella 1.0) 0.07 (0.02 - 0.2) 0.4 (0.2 - 0.7) 0.6 (0.3 - f shipments are reconditioned Model 1 Sesame Seed - 13.8) All sizes 9.9 (6.5 - Supply characteristics value for percentage (95% CI) of Expected 10.3) 0.8 (0.5 - 1.2) 7.3 (4.5 - All sizes 9.2 (5.8 - 13.0) 9.9 (6.4 - 13.7) shipments detected (among all shipments) Expected value for percentage (95% CI) of 99.8) - 99.5 (98.8 All sizes 8.4 (7.0 - 9.9) 73 (66 - 79) 93 (89 - 96) contaminated shipments detected Expected value for percentage (95% CI) of in supply captured in detected 99.8) All sizes 8.4 (7.0 - Salmonella 73 (66 - 79) 93 (89 - 96) 99.5 (98.8 - 9.9) shipments reduction (95% CI) of Expected value for log 10 Salmonella in spice supply if detected 2.7) - 2.3 (1.9 All sizes 0.04 (0.03 - 0.05) 0.6 (0.5 - 0.7) 1.2 (1.0 - 1.4) f shipments are reconditioned FDA Draft Risk Profile | 199

212 FDA 2010 Study of Concentrations & Distribution of Salmonella in Shipments Offered for I mport | Appendix C - Spice Model Shipment Prevalence Salmonella Screening Method a (95% CI) Effectiveness Measure Size 1500 g 25 g g 375 750 g (kg) (%) d e c b FDA I COA FDA II FDA III Model 3a - Sesame Seed - Poisson (Best Fit Model) gamma - - 17 (11 24) 24 4 31 (20 - 45) 1.5 x 10 Supply characteristics 4 47) 3.8 x 10 33 (21 - 100 Infinite 8.0 (5.0 Expected value for percentage (95% CI) of 1.2 (0.6 - 2.0) 6.3 (3.8 - 8.7) 14) - 11) 9.8 (6.0 - All sizes shipments detected (among all shipments) - 7.3 (3.6 - 12) 24 - 29) 47 (38 58 (50 37 (28 - 44) 53) Expected value for percentage (95% CI) of 4 1.5 x 10 35) 3.9 (1.8 - 20 (14 - 25) 30) - 26 (19 6.8) 31 (25 - contaminated shipments detected 4 24 (18 - 28) 6.4) - 23) 3.8 x 10 - 19 (13 30 (34 - 33) 3.7 (1.7 Expected value for percentage (95% CI) of in supply Salmonella 99) captured in detected - 97 (92 All sizes 35 (16 - 55) 89 (75 - 95) 94 (86 - 97) shipments value for log reduction (95% CI) of Expected 10 - 1.0 Salmonella All sizes in spice supply if detected 0.2 (0.08 - 0.3) (0.6 1.3) 1.2 (0.9 - 1.5) 1.5 (1.1 - 2.0) f shipments are reconditioned Empirical Sesame Seed - - 12) Supply characteristics All sizes 9.9 (4.7 Expected value for percentage (95% CI) of All sizes 1.2 (0.4 - 2.1) 5.4 (2.8 - 11) 6.9 (3.6 - 9.1) 8.3 (4.3 - 7.6) shipments detected (among all shipments) Expected value for percentage (95% CI) of - 84 (81 All sizes 12 (6.6 - 24) 95) 54 (48 - 75) 70 (64 - 86) contaminated shipments detected Expected value for percentage (95% CI) of - Salmonella in supply captured in detected 95) All sizes 12 (6.6 - 24) 54 (48 - 75) 70 (64 - 86) 84 (81 shipments Expected value for log reduction (95% CI) of 10 in spice supply if detected - 1.3) 0.8 (0.7 All sizes Salmonella 0.6 (0.03 - 0.1) 0.3 (0.3 - 0.6) 0.5 (0.4 - 0.9) f shipments are reconditioned a Shipment sizes selected are the smallest, mean and largest contaminated shipment sizes observed in this study for each particular spice type . b screening tests reported on industry Certificates of Analyses accompanying some of the spice shipments examined in this study . Sample mass examined for Salmonella c Typical sample mass used for FDA Category III foods which are foods that would normally be subjected to a process lethal to Salmonella between the time of sampling and consumption (Andrews and Hammack, 2003). d between the time of sampling and Salmonella Typical sample mass used for FDA Category II foods which are foods that would not normally be subjected to a process lethal to FDA Draft Risk Profile | 200

213 FDA 2010 Study of Concentrations & Distribution of Salmonella in Shipments Offered for I mport | Appendix C consumption (Andrews and Hammack, 2003). e Salmonella between the time of sampling and consumption Typical sample mass used for FDA Category I foods which are foods that would not normally be subjected to a process lethal to and are intended for consumption by the aged, the infirm, or infants (Andrews and Hammack, 2003). f Assumes reconditioning eliminates all Salmonella from the shipment. FDA Draft Risk Profile | 201

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