University of Nebraska - Lincoln DigitalCommons@University of Nebraska - Lincoln Dissertations, Theses, & Student Research in Food Science and Technology Food Science and Technology Department 5-2013 Risk Assessment of Trace and Undeclared Allergens in Processed Foods Benjamin C. Remington University of Nebraska-Lincoln, [email protected] Follow this and additional works at: https://digitalcommons.unl.edu/foodscidiss Part of the Other Food Science Commons Remington, Benjamin C., "Risk Assessment of Trace and Undeclared Allergens in Processed Foods" (2013). Dissertations, Theses, & Student Research in Food Science and Technology. 32. https://digitalcommons.unl.edu/foodscidiss/32 This Article is brought to you for free and open access by the Food Science and Technology Department at DigitalCommons@University of Nebraska - Lincoln. It has been accepted for inclusion in Dissertations, Theses, & Student Research in Food Science and Technology by an authorized administrator of DigitalCommons@University of Nebraska - Lincoln. RISK ASSESSMENT OF TRACE AND UNDECLARED ALLERGENS IN PROCESSED FOODS By Benjamin C. Remington A DISSERTATION Presented to the Faculty of The Graduate College at the University of Nebraska In Partial Fulfillment of Requirements For the Degree of Doctor of Philosophy Major: Food Science and Technology Under the Supervision of Professors Stephen L. Taylor and Joseph L. Baumert Lincoln, Nebraska May, 2013 RISK ASSESSMENT OF TRACE AND UNDECLARED ALLERGENS IN PROCESSED FOODS Benjamin C. Remington, Ph.D. University of Nebraska, 2013 Advisers: Stephen L. Taylor and Joseph L. Baumert Minimal eliciting doses for objective allergic reactions were found for 13 priority allergens and over 1800 individuals from published clinical literature or unpublished clinical data. Allergic populations did not vary when analyzed by age or geographic region. Results of this study show there are sufficient clinical data from food allergic individuals to use for risk assessment purposes for several allergenic foods. Of 186 food products bearing advisory statements regarding peanut or 16 products that had peanut listed as a minor ingredient, 8.6% and 37.5% contained detectable levels of peanut (>2.5 ppm whole peanut). An additional market survey of 215 nutrition bars with peanuts as a minor ingredient and/or an advisory statement for peanuts found 24.6% tested positive for peanut compared to 4% of products with no mention of peanuts on the label. Probabilistic risk assessment showed the risk of reaction among peanut allergic consumers from advisory labeled nutrition bars was significant but brand- dependent. The probabilistic approach provides the food industry with a quantitative method to assist with determining when advisory labeling is most appropriate. Agricultural commodity cross-contamination of soybean was detected in 62.8% of samples representing all forms of wheat flour. Conservative probabilistic risk assessments predict a risk of allergic reaction occurring in the most sensitive soy-allergic individuals. Experimental milling and stream separation with spiked soy in wheat samples did not produce a soy-free wheat flour stream. Additional cleaning measures will be needed to remove soy before wheat milling begins. LC-MS/MS identified fourteen known allergens in industry representative soy product samples, including all subunits of Gly m 5 (β-conglycinin) and Gly m 6 (glycinin), the Kunitz trypsin inhibitor, Gly m Bd 28K, and Gly m Bd 30K. Method refinements or different techniques might be necessary to detect low abundance proteins such as Gly m 3 and 4. The relative amount of an allergen in a sample correlated positively to the intensity of IgE binding at the expected molecular weight using sera from soy-allergic individuals. iv For my parents, Glen and Jamae. Thank you for your constant support while I explore the parts of life that make me happy. v ACKNOWLEDGEMENTS I would like to thank my advisers Drs. Steve Taylor and Joe Baumert for their support and guidance during the completion of my graduate program. Both have been outstanding mentors and their willingness to expose me to multiple aspects of the Food Allergy Research and Resource Program has offered invaluable experience as a graduate student. I will forever be grateful for opportunities and involvements they let me explore and push to be a part of. I would also like to thank many other members of FARRP. Lynn and Deb, thank you for the endless help and teachings throughout my time in the lab. Julie, thank you for the friendship, lab expertise, and honest conversations over the years. Jamie and Pat, thank you for your patience, support, and ability to make everything run smoothly. To my fellow graduate students, especially Jelena Spiric, Kaye Ivens, Poi-Wah Lee, and Rakhi Panda, thank you for the advice, assistance, and making the office a fun place to work every day. Special thanks goes to Sean, Anna, Ferlie, and all of the analytical lab members that helped with kit techniques and other analytical issues. I would like to acknowledge Dr. Geert Houben of TNO, Dr. René Crevel of Unilever, and the FARRP Board of Directors for their contributions, comments, and critiques on different aspects of the food industry and food allergen risk assessment within my project. Finally, I would like to thank my parents, siblings, and other friends and family for their support during my dissertation. I would not be where I am today without them and I am truly grateful for the influences they have had on my life. vi TABLE OF CONTENTS LIST OF TABLES ............................................................................................................. xi LIST OF FIGURES ...........................................................................................................xv CHAPTER 1: LITERATURE REVIEW .............................................................................1 I. INTRODUCTION ...................................................................................................1 II. FOOD SENSITIVITIES ..........................................................................................1 a. Food Intolerances .........................................................................................3 i. Anaphylactoid Reaction ...................................................................3 ii. Metabolic Food Disorders................................................................3 iii. Idiosyncratic Reactions ....................................................................4 b. Food Hypersensitivity ..................................................................................5 i. Immune System Overview ...............................................................5 ii. Cell-Mediated Hypersensitivity .......................................................9 iii. IgE-mediated Hypersensitivity and Food Allergy .........................10 c. Prevalence of IgE-Mediated Food Allergy ................................................13 d. Diagnosis of Food Allergy .........................................................................16 e. Treatment of Food Allergy ........................................................................18 f. Legume Allergy .........................................................................................20 g. Soy Proteins and Allergens ........................................................................25 III. FOOD ALLERGEN LABELING AND THRESHOLDS .....................................38 a. Importance of Thresholds ..........................................................................39 b. Interval-Censoring Survival Analysis ........................................................43 vii IV. ADVISORY LABELING OF FOOD ALLERGENS IN PROCESSED FOODS ..................................................................................................................46 a. History of Use ............................................................................................46 b. Regulatory Guidance .................................................................................47 c. Previous Examples/Studies ........................................................................49 V. COMMODITY CONTAMINATION WITHIN FOOD SUPPLY ........................50 a. History of Use ............................................................................................50 b. Regulatory Guidance .................................................................................50 c. Previous Examples/Studies ........................................................................51 VI. FOOD ALLERGEN RISK ANALYSIS ................................................................52 a. Risk Assessment ........................................................................................55 i. Hazard Identification .....................................................................55 ii. Hazard Characterization .................................................................56 iii. Exposure Assessment.....................................................................57 iv. Risk Characterization .....................................................................58 1. NOAEL-Based Safety Assessment Method ......................59 2. Benchmark Dose method ...................................................61 3. Quantitative Risk Assessment............................................63 b. Risk Management ......................................................................................68 i. Preliminary Risk Management