SOT FDA Colloquia

The Evolving Research Landscape of Low- and No-Calorie Sweeteners—December 7, 2023

Presentation Slides

Welcome and Opening Remarks
Namandjé Bumpus, PhD, US FDA Principal Deputy Commissioner, Silver Spring, MD

Cannabidiol Overview: Clinical Considerations, Regulatory Status, and Marketplace Concerns
Robert Welch, PharmD, University of Mississippi, Oxford, MS

Pharmacokinetics of Cannabidiol
Ryan Vandrey, PhD, Johns Hopkins University, Baltimore, MD

Central Nervous System Effects of Cannabidiol
Ethan Russo, MD, CReDO Science, Vashon, WA

Effects of Cannabidiol on the Male Reproductive System
Renata Mazaro-Costa, PhD, Federal University of Goias, Goiânia, Brazil

Beyond CBD: Exposure, Chemistry, and Toxicity of “Minor” Cannabinoids
Michael Santillo, PhD, US FDA/CFSAN/OARSA, Laurel, MD
All speakers

Roundtable Discussion
Moderator: Luísa Camacho and Barbara Kaplan
All speakers

SOT FDA Colloquium Organizing Committee

David C. Dorman, DVM, PhD, DABT, DABVT, ATS, 2023-2024 Colloquium Series Chair, North Carolina State University, Raleigh, NC
Jason R. Richardson, PhD, DABT, ATS, 2024-2025 Colloquium Series Chair, University of Georgia, Athens, GA
Jason L. Aungst, PhD, FDA Liaison, US FDA, College Park, MD
Omari Bandele, PhD, US FDA, Rockville, MD
Patrick Crittenden, PhD, US FDA, Rockville, MD
Alex Eapen, PhD, Cargill Inc, Wayzata, MN
Suzanne C. Fitzpatrick, PhD, DABT, US FDA, College Park, MD
Esther M. Haugabrooks, PhD, The Coca-Cola Company, Atlanta, GA
Rayetta Henderson, PhD, ToxStrategies Inc., Katy, TX
Alexandra Lobach, PhD, Givaudan, Mississauga, ON, Canada
Willie McKinney, PhD, DABT, McKinney Regulatory Science Advisors, LLC, Henrico, VA
Jeffrey J. Yourick, PhD, DABT, ATS, US FDA, Laurel, MD
Chidozie Amuzie, Johnson and Johnson, Toronto, Canada, 2023-2025 Council Contact
Betty Eidemiller, PhD, SOT Staff Liaison, Reston, VA

Co-Chairs: Anne Macgregor-Das, PhD, US FDA CFSAN, and Daniele Wikoff, PhD, ToxStrategies LLC

Overview

Many different types of sweeteners used in the US are utilized broadly across food products. By law, these must be safe for consumption. Companies are responsible for ensuring the safety of ingredients and rely on standard approaches to substantiate safety. This involves utilization of standard toxicological experimental studies investigating the potential for adverse effects following acute and repeated-dose exposure, and to assess potential risk associated with use of the sweetener as intended by the ingredient use. More recently, the scientific community has begun to explore additional health outcomes and to assess novel aspects of exposure/outcome relationships via observational studies in human populations. This colloquium will survey modern aspects of low- and no-calorie sweetener research, including the emerging literature pertaining to sweeteners and their effects on the microbiome, and the potential impact of these changes on human health; and consideration of data types other than traditional toxicology testing in animals, including epidemiological and mechanistic data. The recent re-evaluation of aspartame will serve as a case study for how these emerging studies are being considered by risk assessors. Finally, the colloquium will conclude with a panel discussion on the key issues and knowledge gaps identified by the speakers and questions from participants.

Colloquium Materials

The Evolving Science in Developmental Immunology and Immunotoxicity—May 4, 2023

Presentation Slides

Welcome from US FDA/SOT
Kristi Muldoon Jacobs, Acting Director US FDA CFSAN OFAS, Rockville, MD

An Introduction to Low- and No-Calorie Sweetener Uses in Foods and Beverages in the US
Corey Scott, PhD, Cargill, Plymouth, MN

Low- and No-Calorie Sweeteners and Metabolic Health: A Review of the Evidence from Acute Metabolic and Endocrine Responses to Long Term Clinical Outcomes
John Sievenpiper, MD, PhD, FRCPC, University of Toronto and St. Michael’s Hospital, Toronto, Ontario, Canada

Mechanistic and Epidemiological Studies and Their Role in the Safety Assessment of Low- and No-Calorie Sweeteners
Daniele Wikoff, PhD, ToxStrategies LLC, Asheville, NC

Aspartame as a Case Study in Re-evaluation of Sweetener Safety by the Joint FAO/WHO Expert Committee on Food Additives
Diane Benford, PhD, Chair 96th Joint FAO/WHO Expert Committee on Food Additives, Cheddington, Leighton Buzzard, United Kingdom

Roundtable Discussion and Conclusion
Moderator: Anne Macgregor-Das, PhD, US FDA CFSAN
All speakers

SOT FDA Colloquium Organizing Committee

David C. Dorman, DVM, PhD, DABT, DABVT, ATS, Colloquium Series Co-chair, North Carolina State University, Raleigh, NC
Jason R. Richardson, PhD, DABT, ATS, Colloquium Series Co-chair, University of Georgia, Athens, GA
Jason L. Aungst, PhD, FDA Liaison, US FDA, College Park, MD
Omari Bandele, PhD, US FDA, Rockville, MD
Suzanne C. Fitzpatrick, PhD, DABT, US FDA, College Park, MD
Esther M. Haugabrooks, PhD, The Coca-Cola Company, Atlanta, GA
Rayetta Henderson, PhD, ToxStrategies Inc., Katy, TX
Willie McKinney, PhD, DABT, McKinney Regulatory Science Advisors, LLC, Henrico, VA
Jeffrey J. Yourick, PhD, DABT, ATS, US FDA, Laurel, MD
Christine Perdan Curran, PhD, Council Contact, Northern Kentucky University, Highland Heights, KY
Chidozie Amuzie, Johnson and Johnson, Toronto, Canada, 2023-2024 Council Contact
Betty Eidemiller, PhD, SOT Staff Liaison, Reston, VA

Co-Chairs: Leigh Ann Burns Naas, Magnolia Toxicology Consulting LLC, and Patrick Crittenden, US FDA CFSAN

Overview

Over the past two decades the interest in developmental immunotoxicology (DIT) has grown substantially as a result of the need to more fully understand age-related susceptibility to a variety of potentially toxic compounds. The immature immune system is especially vulnerable to environmental insults, and immunotoxic exposures during critical prenatal and postnatal periods in development may lead to persistent immune dysfunction. Epidemiological evidence suggests that there is an increasing incidence of immune-mediated developmental disorders in children related to exposures to chemical substances in their environment. In recent years, the role of the microbiome in immune system development has also become evident and this extends to the role of the mother in seeding the fetal/infant microbiome both in utero and at birth, which may impact several aspects of development, including immune system maturation. Therefore, alterations in both maternal and fetal environmental exposures mediated by things such as nutrition and chemical exposure have the potential to result in varied risks to the developing immune system that can influence the risk of immune-related disease in children and adults. Understanding how to assess the risk to the developing immune system in animal studies is of high importance. As interest in DIT has grown, our understanding of the mammalian immune system has continued to swell, including a more sophisticated understanding of the developing immune system and the comparative developmental timelines across mammalian species. While the general stages of immune development are quite similar, it clear is that in terms of temporal development, a rat is not a dog is not a monkey is not a human. This makes it paramount to understand these differences when conducting and interpreting nonclinical safety studies. This colloquium will present the state of the science of developmental immunotoxicology and the challenges to supporting hazard identification and risk evaluation.

Colloquium Materials

Alternative Toxicological Approaches for Process-Formed Constituents in Food—January 19, 2023

Presentation Slides

Welcome from US FDA/SOT
Dori Germolec, PhD, 2023-2024 SOT President, NIEHS-NTP, Durham, NC

The Evolution of the Discipline of Developmental Immunotoxicology
Leigh Ann Burns Naas, PhD, DABT, ATS, ERT, Magnolia Toxicology Consulting, LLC

Comparative Developmental Immunology and Implications for Testing and Data Interpretation
Hollie Skaggs, PhD, Horizon Therapeutics

The Role of the Metagenome and Microbiome During Pregnancy and Lactation on the Risk of Immune-Related Disease
Kjersti M. Aagaard, MD, PhD, FACOG, Baylor College of Medicine

Prenatal Immunity Represents a Functionally Distinct Hematopoietic Lineage
Eliver Ghosn, PhD, Emory University School of Medicine

Paving the Road toward the Development and Acceptance of Alternative (In Vitro) Methods to Assess Developmental Immunotoxicity
Fenna Sille, PhD, Johns Hopkins Bloomberg School of Public Health

Roundtable Discussion and Conclusion
Moderator: Patrick Crittenden, PhD, US FDA CFSAN
All speakers

SOT FDA Colloquium Organizing Committee

Stephen W. Edwards, PhD, 2022-2023 Colloquium Series Chair, RTI International, Chapel Hill, NC
David C. Dorman, DVM, PhD, DABT, DABVT, ATS, 2022–2023 Colloquium Series Co-chair, North Carolina State University, Raleigh, NC
Jason R. Richardson, PhD, DABT, ATS, 2023-2024 Colloquium Series Co-chair, Florida International University, Miami Beach, FL
Udayan M. Apte, PhD, DABT, University of Kansas Medical Center, Kansas City, KS
Jason L. Aungst, PhD, FDA Liaison, US FDA, College Park, MD
Omari Bandele, PhD, US FDA, Rockville, MD
Suzanne C. Fitzpatrick, PhD, DABT, US FDA, College Park, MD
Esther M. Haugabrooks, PhD, The Coca-Cola Company, Atlanta, GA
Rayetta Henderson, PhD, ToxStrategies Inc., Katy, TX
Willie McKinney, PhD, DABT, McKinney Regulatory Science Advisors, LLC, Henrico, VA
Jason R. Richardson, PhD, DABT, ATS, Florida International University, Miami Beach, FL
Jeffrey J. Yourick, PhD, DABT, ATS, US FDA, Laurel, MD
Christine Perdan Curran, PhD, Council Contact, Northern Kentucky University, Highland Heights, KY
Chidozie Amuzie, Johnson and Johnson, Toronto, Canada, 2023-2024 Council Contact
Betty Eidemiller, PhD, SOT Staff Liaison, Reston, VA

Co-Chairs: Steven J. Hermansky, Pharm D, PhD, DABT, FDA CFSAN; and Paul Hanlon, PhD, DABT, Abbott Nutrition

Overview

Compounds such as acrylamide, 4-MEI, furan, PAH, and 3-MCPD created during food processing including cooking at home have been identified as constituents of food. Hundreds of such process-formed compounds have been identified in food, and improvements in analytical methodology are likely to lead to identification of more in the future. While the discovery of these compounds in food has been relatively recent, it is recognized that most have been a component of food for centuries. Never-the-less, there is increasing interest to understand the potential human health risk associated with these compounds and using risk-based prioritization, developing techniques to reduce or eliminate compounds from the diet that could be expected to pose risk to consumers. Experience with acrylamide and other process-formed compounds demonstrate that the resources expended for traditional toxicology studies are not practical for the high number of these compounds known to exist in food. Furthermore, when compounds such as these are found unexpectedly in the diet, there can be a need for a rapid risk assessment that would benefit from methods that can be executed faster than traditional in vivo methods. Thus, these compounds represent an interesting test case to leverage New Approach Methods (NAMS) to help risk assessors and regulators better understand the biological effects of these compounds and prioritize them for additional investigation. This colloquium brings together researchers, risk assessors, and regulators to discuss opportunities to leverage a mixture of traditional testing and NAMS to help solve real-world, complex toxicology problems.

Colloquium Materials

Toxicogenomics and Its Relevance to Support Hazard Assessment—May 4, 2022

Presentation Slides

Welcome and Introduction of Topic and Speakers
Kristi Muldoon Jacobs, Current Director, US FDA Office of Food Safety; and
Dori Germolec, SOT Vice President, NIEHS-NTP, Durham, NC
Steven Hermansky, Pharm D, PhD, DABT, US FDA CFSAN, College Park, MD

Analytical Challenges Related to the Analysis of Processing Contaminants in Foods and Impacts on Risk Assessment
Jessica Beekman, PhD, US FDA CFSAN, College Park, MD

Next Generation Systemic Toolbox
Matthew Dent, PhD, IDT, Unilever, Sharnbrook, UK

Codex Alimentarius: Guidelines for Rapid Risk Analysis Following Instances of Detection of Contaminants in Food Where There Is No Regulatory Level
Lauren Robin, PhD, US FDA CFSAN, College Park, MD

The Challenge of Assessing Minor Constituents: An Example from the Flavor Industry
Sean Taylor, PhD, Verto Solutions, Washington, DC

Summary and Current Challenges of New Approach Methods for Industry
Paul Hanlon, PhD, DABT, Abbott Nutrition, Columbus, OH

Roundtable Discussion and Conclusion
Moderator: Paul Hanlon, PhD, DABT, Abbott Nutrition, Columbus, OH
Panelists: Speakers and Suzanne Fitzpatrick, PhD, US FDA CFSAN, College Park, MD

SOT FDA Colloquium Organizing Committee

Stephen W. Edwards, PhD, 2022–2023 Colloquium Series Chair, RTI International, Chapel Hill, NC
David C. Dorman, DVM, PhD, DABT, DABVT, ATS, 2022–2023 Colloquium Series Co-chair, North Carolina State University, Raleigh, NC
Udayan M. Apte, PhD, DABT, University of Kansas Medical Center, Kansas City, KS
Jason L. Aungst, PhD, FDA Liaison, US FDA, College Park, MD
Omari Bandele, PhD, US FDA, Rockville, MD
Suzanne C. Fitzpatrick, PhD, DABT, US FDA, College Park, MD
Willie McKinney, PhD, DABT, McKinney Regulatory Science Advisors, LLC, Henrico, VA
Jason R. Richardson, PhD, DABT, ATS, Florida International University, Miami Beach, FL
Jeffrey J. Yourick, PhD, DABT, ATS, US FDA, Laurel, MD
Christine Perdan Curran, PhD, Council Contact, Northern Kentucky University, Highland Heights, KY
Betty Eidemiller, PhD, SOT Staff Liaison, Reston, VA

Co-Chairs: Stephen Edwards, RTI International; and Xiugong Gao, US FDA CFSAN

Overview

Toxicogenomics uses genomic technologies to gain mechanistic understanding of biological effects induced by exposure to chemicals and may provide more sensitive biomarkers for the prediction and assessment of their toxicity, thus contributing significantly to toxicology. With recent technological innovations such as next generation sequencing (NGS), toxicogenomics now provides an unprecedented opportunity for improved, animal-free risk assessment of chemicals. Nonetheless, challenges remain in many aspects of toxicogenomics to meet regulatory needs. This colloquium will present the state of the science in toxicogenomics and its relevance to support hazard assessment of chemicals. Recent technological innovations in toxicogenomics are covered, and case studies of toxicogenomics application in risk assessment and toxicity prediction of chemicals related to food and cosmetics are highlighted. The colloquium will also discuss current challenges facing regulatory application and provide perspectives on future directions of toxicogenomics.

Colloquium Materials

Agenda | Event Captions | Video Presentation | Speaker Biographies

Presentation Slides

Welcome, Overview, and Speaker Introductions
Steven M. Musser, PhD, Deputy Director of Scientific Operations, CFSAN, US FDA
Michael Aschner, PhD, SOT President
Steven Edwards, PhD, Colloquium Co-chair, RTI International

Overview of Toxicogenomics and Its Contribution to Toxicological Science
Carole L. Yauk, PhD, University of Ottawa/Health Canada, Ottawa, Canada

High-Throughput Transcriptomics for Chemical Bioactivity Screening and Tiered Hazard Evaluation
Joshua A. Harrill, PhD, US EPA, Research Triangle Park, NC

Toxicogenomics to Support Hazard
Russell Thomas, PhD, US EPA, Research Triangle Park, NC

Application of Toxicogenomics in Toxicity Assessment of Chemicals in Food and Cosmetics
Jorge Naciff, PhD, Procter & Gamble Company, Mason, OH

Roundtable Discussion and Concluding Slides
Moderator: Jason Aungst, PhD, CFSAN, US FDA
Discussion: Co-Chairs and all speakers

SOT FDA Colloquium Organizing Committee

Udayan M. Apte, PhD, DABT, 2021-2022 Colloquium Series Chair, University of Kansas Medical Center, Kansas City, KS
Stephen W. Edwards, PhD, 2022-2023 Colloquium Series Chair, RTI International, Chapel Hill, NC
David C. Dorman, DVM, PhD, DABT, DABVT, ATS, 2022-2023 Colloquium Series Co-chair, North Carolina State University, Raleigh, NC
Jason L. Aungst, PhD, FDA Liaison, US FDA, College Park, MD
Omari Bandele, PhD, US FDA, Rockville, MD
Suzanne C. Fitzpatrick, PhD, DABT, US FDA, College Park, MD
A. Wallace Hayes, PhD, DABT, ERT, ATS, FRSB, FACFE, University of South Florida and Michigan State University, Temple Terrace, FL
Willie McKinney, PhD, DABT, McKinney Regulatory Science Advisors, LLC, Henrico, VA
Jason R. Richardson, PhD, DABT, ATS, Florida International University, Miami Beach, FL
Jeffrey J. Yourick, PhD, DABT, ATS, US FDA, Laurel, MD
Xiugong Gao, PhD, Colloquium Co-chair, US FDA, College Park, MD
Christine Perdan Curran, PhD, Council Contact, Northern Kentucky University, Highland Heights, KY
Betty Eidemiller, PhD, SOT Staff, Reston, VA

Arsenic and Children’s Health—December 1, 2021

Co-Chairs: Aaron Barchowsky, University of Pittsburgh; and Brenna Flannery, US FDA CFSAN

Overview

Arsenic is a naturally occurring element found in low concentrations in foods worldwide, including those commonly consumed by young children and pregnant women. Because arsenic occurs naturally, it is not possible to completely remove it from the food supply, which results in arsenic exposure. Arsenic exposure in-utero and/or in childhood is associated with harmful effects including adverse birth outcomes, developmental delay, decreased cognitive function, impaired lung function, perturbations in the immune and cardiovascular systems and leaves children at greater risk for future adult diseases. Therefore, it is essential for children’s health to understand the impact of arsenic exposure on child development. This colloquium will present the latest science in the area of arsenic toxicity and children’s development from both toxicology and epidemiology perspectives with specific focus on developmental arsenic exposure and the role of nutrition in arsenic toxicity. This colloquium will also explore the framework of ongoing risk assessments related to arsenic exposure and children’s health outcomes and discuss efforts related to arsenic mitigation in food to reduce children’s arsenic exposure.

Colloquium Materials

Agenda | Event Captions | Video Presentation | Speaker Biographies

Presentation Slides

Welcome, Overview, and Speaker Introductions
Conrad Choiniere, PhD, Office of Analytics and Outreach Office Director, US FDA, CFSAN, College Park, MD
Aaron Barchowsky PhD, University of Pittsburgh, Pittsburgh, PA

Current Understanding of Mechanisms Underlying Arsenic-Induced Developmental Toxicity
Rebecca Fry, PhD, University of North Carolina, Chapel Hill, NC

Nutritional Manipulation of One-Carbon Metabolism: Effects on Arsenic Methylation and Toxicity
Mary Gamble, PhD, Columbia University, New York, NY

Systematic Review Framework and Dose-Response Methods for Identifying Reference Doses for Inorganic Arsenic
Alexandra Larsen, PhD, US Environmental Protection Agency, Research Triangle Park, NC
References

Arsenic Mitigation in Foods and Ingredients
Cheryl Callen, MS, Nestle USA, Arlington, VA

Summary, Roundtable Discussion, and Concluding Slides
Brenna Flannery, PhD, US FDA, College Park, MD
Roundtable Discussion Moderators: Co-Chairs
Discussion: All speakers
Additional Panelist: Jeffrey Gift, PhD, US EPA, Research Triangle Park, NC

SOT FDA Colloquium Organizing Committee

Udayan M. Apte, PhD, DABT, Colloquium Series Chair, University of Kansas Medical Center, Kansas City, KS
Stephen W. Edwards, PhD, Colloquium Series Co-chair, RTI International, Chapel Hill, NC
Jason L. Aungst, PhD, FDA Liaison, US FDA, College Park, MD
Omari J. Bandele, PhD, FDA Co-Liaison, US FDA, College Park, MD
Suzanne Compton Fitzpatrick, PhD, DABT, US FDA, College Park, MD
Wallace Hayes, PhD, DABT, ERT, ATS, FRSB, FACFE, University of South Florida and Michigan State University, Temple Terrace, FL
Willie McKinney, PhD, DABT, McKinney Regulatory Science Advisors, LLC, Henrico, VA
Aaron Barchowsky, PhD, Colloquium Co-chair, University of Pittsburgh, Pittsburgh, PA
Brenna Flannery, PhD, Colloquium Co-chair, US FDA, College Park, MD
Christine Perdan Curran, PhD, Council Contact, Northern Kentucky University, Highland Heights, KY
Betty Eidemiller, PhD, SOT Staff, Reston, VA

The Toxicology of Nanoparticles—April 8, 2021

Chair: Richard Canady, NeutralScience
Co-Chair: Kapal Dewan, US FDA CFSAN

Overview

One of the most challenging aspects of safety assessment for nanomaterial use in consumer products is deriving an estimate of dose from use of a product that can be compared to doses delivered in a toxicology assay. What is the status of this critical translation between use and testing today? This SOT FDA Colloquium explored issues of problem formulation for toxicology and exposure assessment in safety assessment of nanomaterial use in consumer products.

Colloquium Materials

Agenda | Event Captions | Event Captions | Video Presentation | Speaker Biographies

Presentation Slides

Welcome and Speaker Introductions
George Daston, PhD, SOT President, Procter & Gamble, Mason, OH
Richard Canady, Colloquium Chair, NeutralScience LC#, Camano Island, WA

Lessons Learned from Nanomaterial Characterization: Critical Quality Attributes that Influence Biological Properties
Anil Patri, PhD, NCTR, Jefferson, AK

Standard Dose Measurement for Nanomaterials: What to Include in Exposure and Toxicity so That We Can Bound Dose Estimates for Safety?
Christie Sayes, PhD, Baylor University, Waco, TX

Dosing-Related Challenges in Toxicity Studies and Risk Assessment of Titanium Dioxide in Food
Walter Brand, PhD, ERT, RIVM, Bilthoven, The Netherlands

Practical Application to Regulatory Toxicology: Issues Faced in Consideration of Developing Health Guideline Values
Lynne Haber, PhD, DABT, University of Cincinnati Risk Science Center, Cincinnati, OH

Concluding Slides
Roundtable Discussion
Moderator: Richard Canady
All Speakers
Additional Panelists:
Timothy Duncan, PhD, US FDA, Bedford, IL
Agnes Oomen, PhD, RIVM, Bilthoven, Netherlands

SOT FDA Colloquium Organizing Committee

Jia-Sheng Wang, MD, PhD, Colloquium Series Chair, University of Georgia, Athens, GA
Udayan M. Apte, PhD, DABT, Colloquium Series Co-chair, University of Kansas Medical Center, Kansas City, KS
Jason L. Aungst, PhD, FDA Liaison, US FDA, College Park, MD
Stephen W. Edwards, PhD, RTI International, Chapel Hill, NC
Suzanne Compton Fitzpatrick, PhD, DABT, US FDA, College Park, MD
A. Wallace Hayes, PhD, DABT, ERT, ATS, FRSB, FACFE, University of South Florida and Michigan State University, Temple Terrace, FL
Stephen M. Roberts, PhD, University of Florida, Gainesville, FL
Jason Dietz, MS, Colloquium Chair, US FDA CFSAN, College Park, MD
Alison Harrill, PhD, Council Contact, National Toxicology Program, Durham, NC
Betty Eidemiller, PhD, SOT Staff, Reston, VA

New Plant-Based Foods and Proteins from Novel Sources—December 3, 2020

Chair: Jason Dietz, US FDA CFSAN

Overview

Plant-based foods and proteins from novel sources are gaining interest from food manufacturers and consumers. Consumers may see these products in the grocery store in the form of foods like plant-based burgers and sausages, egg substitutes and non-dairy frozen desserts, with more products reported to be under development. This colloquium will provide topical information about plant-based foods and the food use of proteins from novel sources. Topics examined will include the historical food use of proteins from novel sources and current trends regarding plant-based foods. The colloquium will explore why firms and consumers are interested in plant proteins and proteins from novel sources, the function of these proteins in food, and any food safety considerations associated with the use of these proteins. The future application of modern molecular techniques to produce proteins with desired food characteristics will also be discussed.

Colloquium Materials

Agenda | Event Captions | Video Presentation | Speaker Biographies

Presentation Slides

Welcome and Speaker Introductions
Dennis Keefe, OFAS Office Director, US FDA, CFSAN, College Park, MD
Jason Dietz, Colloquium Chair, US FDA CFSAN, College Park, MD

Proteins in Our Diet from Novel Sources
Jeremiah Fasano, US FDA CFSAN, College Park, MD

Functions and Appeal of Plant-Based Proteins and Novel Proteins
Baraem (Pam) Ismail, University of Minnesota, Minneapolis, MN

Future Developments in Plant-Based Foods
Michael Leonard, Motif FoodWorks, Boston, MA

Safety Assessment Considerations for Proteins from Novel Sources
Supratim Choudhuri, US FDA CFSAN, College Park, MD

Concluding Slides
Roundtable Discussion
Moderator: Jason Dietz
All speakers

SOT FDA Colloquium Organizing Committee

Jia-Sheng Wang, MD, PhD, Colloquium Series Chair, University of Georgia, Athens, GA
Udayan M. Apte, PhD, DABT, Colloquium Series Co-chair, University of Kansas Medical Center, Kansas City, KS
Jason L. Aungst, PhD, FDA Liaison, US FDA, College Park, MD
Stephen W. Edwards, PhD, RTI International, Chapel Hill, NC
Suzanne Compton Fitzpatrick, PhD, DABT, US FDA, College Park, MD
A. Wallace Hayes, PhD, DABT, ERT, ATS, FRSB, FACFE, University of South Florida and Michigan State University, Temple Terrace, FL
Jieun Lee, PhD, DABT, CJ Foods, Inc., La Palma, CA
Stephen M. Roberts, PhD, University of Florida, Gainesville, FL
Jason Dietz, MS, Colloquium Chair, US FDA CFSAN, College Park, MD
Alison Harrill, PhD, Council Contact, National Toxicology Program, Durham, NC
Betty Eidemiller, PhD, SOT Staff, Reston, VA

Integrated Approaches to Testing and Assessment (IATA)—The Future of Predictive Toxicology—May 28, 2020

Chair: Lidia Ceriani, Humane Society International
Co-chair: Suzanne C. Fitzpatrick, US FDA CFSAN

Overview

This colloquium will feature an emerging flexible approach to evaluating and generating information to meet different regulatory purposes by means of Integrated Approaches to Testing and Assessment (IATA). IATAs are pragmatic, science-based frameworks for chemical hazard or risk characterization, which follow an iterative, integrative approach to answer a defined question with the required certainty in a specific regulatory context. Development of an IATA begins with problem formulation: the context of the decision and taking into account the overall risk management goals. Different types of information from existing sources, new testing (e.g., in chemico, in vitro, and in vivo), and non-testing (e.g., in silico), can be considered as needed, potentially using Integrated or Sequential Testing Strategies (ITS/STS) and evaluated using Weight of Evidence in an iterative process. IATA can be supported by Adverse Outcome Pathways (AOPs) that can inform hypothesis generation, weight of evidence analysis, and choice of assays for integrated assessment.

This session will introduce the concept, process, and components that comprise an IATA and present several case studies demonstrating different applications of this decision tool. Issues, challenges, and prospects of adopting IATAs in regulatory risk assessment will be discussed.

Colloquium Materials

Agenda | Event Captions | Video Presentation | Speaker Biographies

Presentation Slides

Welcome and Speaker Introductions
Suzanne Fitzpatrick, Colloquium Co-chair, US FDA CFSAN, College Park, MD
Lidia Ceriani, Humane Society International, Brussels, Belgium

Integrated Approaches to Testing and Assessment (IATA)—An Introduction
Lidia Ceriani, Humane Society International, Brussels, Belgium

Learnings and Recommendations from Four EU-ToxRisk Case Studies on Applying New Approach Methodologies Data to Support Read-Across
Susanne Hougaard Bennekou, Technical University of Denmark, Copenhagen, Denmark

Uncertainty Characterization in IATA for Chemical Safety Assessment: Overview of Available Guidance
Andrea-Nicole Richarz, ECHA, Helsinki, Finland

IATA as an Opportunity for Next-Generation Risk Assessment: The Propylparaben Case Study
Gladys Ouédraogo, L’Oréal, Paris, France

Global Harmonization Efforts for Skin Sensitization IATA
Nicole Kleinstreuer, NICEATM, Durham, NC

Applications of New Multi-Organ-Chip Tools for Toxicity Assessment
Reyk Horland, TissUse GmbH, Berlin, Germany

Concluding Slides
Roundtable Discussion
Moderator: Lidia Ceriani
All speakers

SOT FDA Colloquium Organizing Committee

Allen Rudman, PhD, 2019–2020 Colloquium Series Chair, College Park, MD
Jia-Sheng Wang, MD, PhD, 2020–2021 Colloquium Series Chair, University of Georgia, Athens, GA
Udayan M. Apte, PhD, DABT, University of Kansas Medical Center, Kansas City, KS
Jason L. Aungst, PhD, FDA Liaison, US FDA, College Park, MD
Stephen W. Edwards, PhD, RTI International, Chapel Hill, NC
Suzanne Compton Fitzpatrick, PhD, DABT, US FDA, College Park, MD
A. Wallace Hayes, PhD, DABT, ERT, ATS, FRSB, FACFE, University of South Florida and Michigan State University, Temple Terrace, FL
Jieun Lee, PhD, DABT, CJ Foods, Inc., La Palma, CA
Stephen M. Roberts, PhD, University of Florida, Gainesville, FL
Jeffrey J. Yourick, PhD, DABT, ATS, US FDA, Laurel, MD
Anne Chappelle, PhD, DABT, 2019-2020 Council Contact, Chadd’s Ford, PA
Alison Harrill, PhD, 2020-2021 Council Contact, National Toxicology Program, Durham, NC
Betty Eidemiller, PhD, SOT Staff, Reston, VA

Artificial Intelligence Applications in Food and Cosmetic Safety—April 29, 2020

Chair: Jim E. Riviere, 1DATA Consortium, Institute of Computational Comparative Medicine
Co-chair: Ernest K. Kwegyir-Afful, US FDA CFSAN

Overview

Artificial Intelligence (AI) is defined as the science and engineering of making intelligent machines. Machine learning is a subset of Artificial Intelligence in which analytical model building is automated and not explicitly programmed. It is based on the idea that systems can learn from data, identify patterns, and make decisions with minimal human intervention. As more data are generated in various scientific disciplines, AI promises to provide an analytical tool with more precision than existing standard methods. Advances in computational toxicology have benefited public health by reducing reliance on animal studies and reducing the cost of performing such experiments. Machine learning methods can extend the capacity of computational toxicology methods such as read across, QSAR, and kinetic models. In fact, natural language processing and deep learning methods are being used to develop predictive toxicology models to outperform the traditional QSAR and read across models.

These developments in science and technology show great potential in further advancing the safety of our food and cosmetic production. In the broader food production and food safety space, AI technologies are being developed to enhance the growth of foods by monitoring and modifying growth parameters, managing supply chains, cleaning processing equipment, identifying plant diseases, developing new products, and enforcing employee personal hygiene procedures during food processing. In the cosmetic space, AI technologies are being used to augment data from in vitro studies and predict dermal absorption and toxicity in the absence of animal tests. As these technologies mature, we must start thinking about how to standardize procedures for safety assessments derived from AI generated data and how to best leverage these technologies to advance food and cosmetic safety.

Colloquium Materials

Agenda | Event Captions | Video Presentation | Speaker Biographies

Presentation Slides

Welcome
Amy P. Abernethy, Principal Deputy Commissioner, Acting Chief Information Officer, US FDA, College Park, MD

Overview and Speaker Introductions
Ernest K. Kwegyir-Afful, US FDA CFSAN, College Park, MD

From Artificial to Real: AI Stories in Government
Steve Bennett, SAS Institute, Cary, NC

Artificial Intelligence in Food and Cosmetic Safety Overview
Jim Riviere, 1DATA Consortium, Institute of Computational Comparative Medicine, Raleigh, NC

AI Technologies for Future Factory Cleaning V
Nicholas Watson, University of Nottingham, Nottingham, UK

Using AI to Extend QSAR Models
Chaoyang (Joe) Zhang, University of Southern Mississippi, Hattiesburg, MS

Using Machine Learning for Cosmetics and Cosmetic Ingredients
Tim Allen, University of Cambridge, Cambridge, UK

Concluding Slides
Roundtable Discussion
Moderator: Jim Riviere, 1DATA Consortium
All speakers
Additional Panelist: Ernest K. Kwegyir-Afful, US FDA CFSAN, College Park, MD

SOT FDA Colloquium Organizing Committee

Allen Rudman, PhD, Colloquium Series Chair, College Park, MD
Jia-Sheng Wang, MD, PhD, Colloquium Series Co-Chair, University of Georgia, Athens, GA
Jason L. Aungst, PhD, FDA Liaison, US FDA, College Park, MD
Suzanne Compton Fitzpatrick, PhD, DABT, US FDA, College Park, MD
Wallace Hayes, PhD, DABT, ERT, ATS, FRSB, FACFE, University of South Florida and Michigan State University, Temple Terrace, FL
Jieun Lee, PhD, DABT, CJ Foods, Inc., La Palma, CA
Stephen M. Roberts, PhD, University of Florida, Gainesville, FL
Jeffrey J. Yourick, PhD, DABT, ATS, US FDA, Laurel, MD
Anne Chappelle, PhD, DABT, Council Contact, Chadd’s Ford, PA
Betty Eidemiller, PhD, SOT Staff, Reston, VA

Route-to-Route Extrapolation in the 21st Century—February 19, 2020

Chair: Harvey J. Clewell, III, Ramboll
Co-Chair: Jeffrey Fisher, NCTR

Overview

The toxicity and pharmacokinetic profiles of substances may vary with the exposure route. If appropriately-conducted studies are available for a relevant route of exposure, generally the point of departure (POD) is calculated based on the data from the studies. However, if adequate data based on the relevant route of exposure are not available, a route-to-route extrapolation methodology may be employed to predict toxicity and estimate POD for risk assessment. This methodology evaluates data from studies based on other non-relevant routes of exposure, provided that the observed toxicity or biomarkers of toxicity are systemic and not related to portal of entry. Route-to-route extrapolation-based approaches utilize equivalent internal dose rather than external dose for predicting effects. Physiologically-based pharmacokinetic (PBPK) models enable route-to-route extrapolations of pharmacokinetics and systemic toxicity by normalizing internal dosimetrics for different routes of exposure. Given that route-to-route extrapolations do not incorporate differences in modes of action between exposure routes, there could be a certain degree of uncertainty associated with the model. However, extrapolation uncertainty reduces with the incorporation of additional data or assumptions (such as 100% absorption, in vitro, or QSAR-based predictions), when sufficient information is available to support the changes to the model. Although route-to-route extrapolation-based approaches are being explored for predicting effects and estimating POD, there are some inconsistencies in methods used by different organizations, which may introduce variability. This session will present considerations for conducting route-to-route extrapolations and discuss the possibility of developing consistent methods for utilizing such extrapolations for risk assessment.

Colloquium Materials

Agenda| Event Captions | Video Presentation | Speaker Biographies

Presentation Slides

Welcome, Overview, and Speaker Introductions
Jeffery Yourick, US FDA, College Park, MD
Harvey J. Clewell, III, Ramboll, Research Triangle Park, NC

Introduction to Route-to-Route Exposure
Harvey J. Clewell, III, Ramboll, Research Triangle Park, NC

OECD Guidance on the Characterisation, Validation, and Reporting of Physiologically Based Kinetic (PBK) Models
Alicia Paini, European Commission’s Joint Research Centre, Ispra, Italy

In Vitro to In Vivo Extrapolation of Metabolism Data to Support Physiologically-Based Modeling for Route-to-Route Extrapolation
John C. Lipscomb, Center for Toxicology & Environmental Health, Little Rock, AR

Determination of an Internal Margin of Exposure Between Rodent Oral and Human Dermal Exposures to Phenoxyethanol Using Physiologically-Based Modeling
John Troutman, Procter and Gamble, Cincinnati, OH

Examples of Route-to-Route Extrapolation Conducted at the FDA Center for Food Safety and Nutrition
Shruti K. Kabadi, US FDA, College Park, MD

Concluding Slides
Roundtable Discussion
Moderators: Harvey J. Clewell
All Speakers: Jeffrey Fisher

SOT FDA Colloquium Organizing Committee

Allen Rudman, PhD, Colloquium Series Chair, College Park, MD
Jia-Sheng Wang, MD, PhD, Colloquium Series Co-Chair, University of Georgia, Athens, GA
Jason L. Aungst, PhD, FDA Liaison, US FDA, College Park, MD
Suzanne Compton Fitzpatrick, PhD, DABT, Member, US FDA, College Park, MD
Wallace Hayes, PhD, DABT, ERT, ATS, FRSB, FACFE, University of South Florida and Michigan State University, Temple Terrace, FL
Jieun Lee, PhD, DABT, CJ Foods, Inc., La Palma, CA
Stephen M. Roberts, PhD, University of Florida, Gainesville, FL
Jeffrey J. Yourick, PhD, DABT, ATS, US FDA, Laurel, MD
Anne Chappelle, Council Contact, Chadds Ford, PA
Betty Eidemiller, PhD, SOT Staff, Reston, VA

Dermal Absorption and Toxicity: Concepts for Application to Safety Assessment—December 12, 2019

Chair: Nancy Monteiro-Riviere, North Carolina State University and Kansas State University
Co-Chair: Jeffrey Yourick, US FDA

Overview

Dermal absorption information is needed to conduct a realistic exposure assessment for a chemical that is directly applied to skin or otherwise comes in contact with skin. If a potentially hazardous chemical/ingredient has been identified that contacts skin, then the next step in the process of safety evaluation is to estimate human exposure. Systemic exposure resulting from skin contact is a function of many different properties including the amount of chemical applied to the skin, the duration of skin contact, area of body contact, chemical physio-chemical properties and the extent of dermal absorption. If no data are available for specific exposure conditions for a chemical, then reasonable estimates of these parameters must be used. This colloquium will explore how different factors can affect the extent of dermal absorption such as skin structure, dermal absorption measurement techniques (in vivo and in vitro), skin metabolism, use of skin absorption kinetic modeling techniques, physio-chemical properties, mixtures, formulations and some case-study examples. A reasonable estimate of human exposure to a topically applied chemical can be calculated if the extent of skin absorption is realistically determined.

Colloquium Materials

Agenda | Event Captions | Video Presentation | Speaker Biographies

Presentation Slides

Welcome, Overview, and Speaker Introductions
Jeffery Yourick, US FDA, College Park, MD

Introduction to the Comparative Anatomical Factors Affecting Topical Skin Delivery
Nancy Monteiro-Riviere, North Carolina State University, Raleigh, NC and Kansas State University, Manhattan, KS

Simulation and Modeling of Dermal Absorption Kinetics: What Level of Detail is Needed?
Gerald Kasting, University of Cincinnati, Cincinnati, OH

Assessing Mixture and Formulation Influence on Skin Absorption
Ronald Baynes, North Carolina State University, Raleigh, NC

Cutaneous Metabolism and Its Importance for Skin Permeation and Toxicity
Simon Charles Wilkinson, Newcastle University, Newcastle upon Tyne, United Kingdom

Practical Considerations for Incorporating Skin Penetration Data into a Risk Assessment for a Consumer Product Launch
Tim McCarthy, Johnson and Johnson, Skillman, NJ

Concluding Slides
Roundtable Discussion
Moderators: Nancy Monteiro-Riviere
All Speakers: Nakissa Sadrieh, US FDA, College Park, MD

Organizing Committee

Allen Rudman, PhD, Colloquium Series Chair, US FDA, College Park, MD
Jia-Sheng Wang, MD, PhD, Colloquium Series Co-Chair University of Georgia, Athens, GA
Jason L. Aungst, PhD, FDA Liaison, US FDA, College Park, MD
Suzanne Compton Fitzpatrick, PhD, DABT, Member, Colloquium Chair, US FDA, College Park, MD
Wallace Hayes, PhD, DABT, ERT, ATS, FRSB, FACFE, University of South Florida and Michigan State University, Temple Terrace, FL
Jieun Lee, PhD, DABT, CJ Foods, Inc., La Palma, CA
Stephen M. Roberts, PhD, University of Florida, Gainesville, FL
Jeffrey J. Yourick, PhD, DABT, ATS, US FDA, Laurel, MD
Anne Chappelle, Council Contact, Chadds Ford, PA
Betty Eidemiller, PhD, SOT Staff, Reston, VA

In Silico Methods for Food Ingredient, Dietary Supplement, and Cosmetic Safety—May 15, 2019

Chair: Kirk Arvidson, US FDA, College Park, MD
Co-Chair: Chihae Yang, MN AM, Nurnberg, Germany

Overview

This colloquium will feature the science behind new international trends in the in silico safety assessment of chemical exposure. Two common themes shared by international regulatory bodies are the critical issues involved in alternative methods to animal testing and the rigorous treatment of uncertainties to obtain reproducible and transparent weight-of-evidence approaches to decision making. For alternative methods to repeated-dose toxicity, toxicokinetics and metabolism are emphasized to understand chemical exposure and bioavailability. Biokinetics is further being applied to data-waiving methods such as the Threshold of Toxicological Concerns (TTC). Internal TTC is a TTC concept for situations of low internal exposure, where this value is more relevant than the external exposure. Development of internal TTCs requires a significant amount of data and computational tools (e.g., PBPK modeling) to convert the chemical specific external doses (i.e., NOAELs) in the TTC databases into an estimate of the internal exposure. The common concerns related to the relevance of in silico chemical safety assessment that may hinder its adoption if not properly addressed will be discussed.

Colloquium Materials

Agenda | Event Captions (not available) | Video Presentation

Presentation Slides

Welcome and Overview
Suzanne Fitzpatrick, US FDA, CFSAN, College Park, MD
Speaker Introductions
Kirk Arvidson, US FDA, College Park, MD

Drivers for the Application and Acceptance ofIn Silico Safety Assessment Based on Chemical Exposure
Mark Cronin, Liverpool John Moores University, Liverpool, UK

Current Issues of Uncertainty in In Silico Methods
James F. Rathman, The Ohio State University, Columbus, OH

A Case Study on PBPK and Biologically Based Dose-Response Modeling for Safety Assessment Considerations: Utility and Challenges
Annie Lumen, NCTR, Jefferson, AR

Transformation of Threshold of Toxicological Concerns (TTC) to Internal TTC: Why Internal Exposure Matters and How We Will Get There
Corie Ellison, Procter and Gamble, West Chester, OH

Concluding Slides
Roundtable Discussion
Moderators: Kirk Arvidson, US FDA, College Park, MD, and Chihae Yang, MN AM, Nurnberg, Germany
All Speakers

Organizing Committee

Allen Rudman, PhD, Colloquium Series Chair, US FDA, College Park, MD
Jia-Sheng Wang, MD, PhD, Colloquium Series Co-Chair University of Georgia, Athens, GA
Jason L. Aungst, PhD, US FDA, College Park, MD
Suzanne Compton Fitzpatrick, PhD, DABT, Member, Colloquium Chair, US FDA, College Park, MD
Wallace Hayes, PhD, DABT, ERT, ATS, FRSB, FACFE, University of South Florida and Michigan State University, Temple Terrace, FL
Jieun Lee, PhD, DABT, Kellogg, Battle Creek, MI
Stephen M. Roberts, PhD, University of Florida, Gainesville, FL
Jeffrey J. Yourick, PhD, DABT, ATS, US FDA, Laurel, MD
Anne Chappelle, Council Contact, Chadds Ford, PA
Betty Eidemiller, PhD, SOT Staff, Reston, VA

Alternative Methods for Predictive Safety Testing: 3D Bioprinted Tissue Models—April 9, 2019

Chair: Edward L. LeCluyse, LifeNet Health, Research Triangle Park, NC
Co-Chair: Margaret Kraeling, US FDA, Laurel, MD

Overview

Bioprinting of 3D human tissues is a newly developing field that is currently being pursued by private industry, academia, and government. Human 3D bioprinted tissues represent a valuable in vitro approach for chemical, personal care product, cosmetic, and preclinical toxicity/safety testing. Bioprinting applications are appealing alternative methods for cosmetics testing especially given the current regulatory situation in the European Union that bans animal testing on new cosmetic products. Bioprinting of skin, liver, and kidney is already appearing in toxicity testing applications for chemical exposures and disease modeling. The use of 3D bioprinted tissues and organs may provide future alternative approaches for testing that may more closely resemble and simulate intact human tissues to more accurately predict human responses to chemical and drug exposures.

Colloquium Materials

Redesigning the Rodent Bioassay for the 21st Century—February 20, 2019

Presentation Slides

Welcome and Overview
Mary Torrence, US FDA Director of the Office of Applied Research and Safety Assessment, Laurel, MD
Speaker Introductions
Margaret Kraeling, US FDA, Laurel, MD

Overview and Challenges of Bioprinting
Sharon Presnell, Amnion Foundation, Winston-Salem, NC

Putting 3D Bioprinting to the Use of Tissue Model Fabrication
Y. Shrike Zhang, Brigham and Women’s Hospital, Harvard Medical School and Harvard-MIT Division of Health Sciences and Technology, Boston, MA

Uses of Bioprinted Liver Tissue in Drug Development
Jean-Louis Klein, GlaxoSmithKline, Collegeville, PA

Biofabrication of 3D Tissue Models for Disease Modeling and Chemical Screening
Marc Ferrer, National Center for Advancing Translational Sciences, NIH, Rockville, MD

Concluding Slides
Roundtable Discussion
Moderator: Edward LeCluyse, LifeNet Health, Research Triangle Park, NC
Margaret Kraeling, US FDA, Laurel, MD
All speakers

Organizing Committee

Bryan Delaney, PhD, DABT, ATS, Colloquium Series Chair, Johnston, IA
Allen Rudman, PhD, Colloquium Series Co-chair, US FDA, College Park, MD
Jason L. Aungst, PhD, US FDA, College Park, MD
Suzanne Compton Fitzpatrick, PhD, DABT, Member, Colloquium Chair, US FDA, College Park, MD
Jieun Lee, PhD, DABT, Kellogg, Battle Creek, MI
Stephen M. Roberts, PhD, University of Florida, Gainesville, FL
Jia-Sheng Wang, MD, PhD, University of Georgia, Athens, GA
Jeffrey J. Yourick, PhD, DABT, ATS, US FDA, Laurel, MD
Patricia Ganey, Council Contact, Michigan State University, East Lansing, MI
Betty Eidemiller, PhD, SOT Staff, Reston, VAe Park

Chair: Suzanne Fitzpatrick, US FDA, College Park, MD
Co-Chair: Warren M. Casey, NTP/NIEHS, Research Triangle Park, NC

Overview

The Society of Toxicology in conjunction with the US FDA Center for Food Safety and Applied Nutrition CFSAN) have partnered to provide this colloquia series. The series presents scientific information that is high-quality, cutting-edge, future-oriented toxicological science to provide a well-grounded foundation to inform the work of US FDA employees. These sessions are open to the public to attend in person or via webcast. These events are not a public forum for discussion of toxicology regulatory issues.

Today, toxicological evaluation of chemicals is beginning to take advantage of the on-going revolution in biology and biotechnology. This revolution is making it increasingly possible to study the effects of chemicals using cells, cellular components, and tissues—preferably of human origin—rather than whole animals. In carrying out its mission to protect and promote public health, FDA must use the best scientific and technological information available to make decisions on the products it regulates. Regulators must assure their toxicology toolbox keeps pace with advances in science and technology. This workshop will discuss at how one important toxicology tool, the rodent chronic bioassay, should be redesigned to meet the needs of 21st century risk assessment.

FDA envisions that this workshop will be the beginning of an ongoing dialogue between stakeholders on the utility of the chronic rodent bioassay for regulatory risk assessment.

Colloquium Materials

The Big 8: Advances in Food Allergy Risk Assessment and Management—October 11, 2018

Presentation Slides

Welcome and Introductions
Admiral Denise Hinton, FDA Chief Scientist
Suzanne Fitzpatrick, US FDA, College Park, MD

The Chronic Cancer Bioassay Is Frequently Conducted for Pesticides When It Is Not Always Needed to Protect Human Health
Doug Wolf, Syngenta Crop Protection Inc., Research Triangle Park, NC

Threshold-based Risk Assessment is the Same for Cancer and Non-cancer Endpoints for Non-DNA Reactive Carcinogens
Samuel Monroe Cohen, University of Nebraska Medical Center, Omaha, NE

Is the 2 Year Rodent Bioassay Needed to Address Carcinogenic Risk for Human Pharmaceuticals?
Frank D. Sistare, Merck & Co Inc., West Point, PA

A Weight of Evidence Approach to Cancer Assessment
Alan R. Boobis, Imperial College, London, UK

Concluding Slides
Roundtable Discussion: How can the Rodent Bioassay Evolve to Meets the Need of Predictive Toxicology?
Moderator: A. Wallace Hayes, University of South Florida and Michigan State University, Temple Terrace, FL
Panelists: Todd Bourcier, US FDA, Silver Spring, MD; and Janet Zang, US FDA, College Park, MD
All Speakers

Organizing Committee

Bryan Delaney, PhD, DABT, ATS, Colloquium Series Chair, Johnston, IA
Allen Rudman, PhD, Colloquium Series Co-chair, US FDA, College Park, MD
Jason L. Aungst, PhD, US FDA, College Park, MD
Suzanne Compton Fitzpatrick, PhD, DABT, Member, Colloquium Chair, US FDA, College Park, MD
Jieun Lee, PhD, DABT, Kellogg, Battle Creek, MI
Stephen M. Roberts, PhD, University of Florida, Gainesville, FL
Jia-Sheng Wang, MD, PhD, University of Georgia, Athens, GA
Jeffrey J. Yourick, PhD, DABT, ATS, US FDA, Laurel, MD
Patricia Ganey, Council Contact, Michigan State University, East Lansing, MI
Betty Eidemiller, PhD, SOT Staff, Reston, VA

Chair: Steve Taylor, University of Nebraska, Lincoln, NE
Co-Chair: Stefano Luccioli, US FDA, College Park, MD

Overview

Food allergies are increasing in prevalence and pose a significant public health burden. Major food allergens (The Big 8) are defined in the Food Allergen Labeling and Consumer Protection Act (FALCPA) and are also addressed in the risk-based Preventive Controls for Human Food rule of the FDA Food Safety Modernization Act (FSMA). Yet, presence of incidental and poorly declared levels of allergens in food products continues to present challenges for the food industry, regulators, and consumers and are an important cause of food recalls and accidental allergic reactions. The purpose of this symposium is to explore the latest issues influencing the food allergy risk assessment and management landscape, including 1) identification and characterization of IgE-mediated allergen hazards, 2) clinical prevention and treatment of food allergies, 3) understanding dose thresholds, and 4) implementation of allergen preventive controls and labeling.

Colloquium Materials

Food from Genetically Engineered Plants: What Role for Metabolomics?—June 13, 2018

Presentation Slides

Welcome and Introductions
Susan T. Mayne, CFSAN Director, US FDA, College Park, MD
Bryan Delaney, SOT FDA Colloquium Commitee Chair, Corteva Agriscience™ Agriculture
Division of DownDuPont, Johnston, IA

The Public Health Impacts of Food Allergies
Stefano Luccioli, US FDA, CFSAN, College Park, MD

Clinical Management of Food-Allergic Patients: Prevention and Treatment--Where Do We Stand?
Matthew Greenhawt, Colorado Children's Hospital, Denver, CO

How Much Is Too Much? Threshold Does for Allergenic Foods
Joseph Baumert, University of Nebraska, Lincoln, NE

Food Industry Perspective on Controlling the Risk
Scot Hegenbart, ConAgra Brands, Omaha, NE

Concluding Slides
Roundtable Discussion
Moderator: Stephen Taylor, University of Nebraska, Lincoln, NE
All Speakers

Organizing Committee

Bryan Delaney, PhD, DABT, ATS, Colloquium Series Chair, DuPont Pioneer, Johnston, IA
Allen Rudman, PhD, Colloquium Series Co-chair, US FDA, College Park, MD
Jason L. Aungst, PhD, US FDA, College Park, MD
Suzanne Compton Fitzpatrick, PhD, DABT, US FDA, College Park, MD
Jieun Lee, PhD, DABT, Kellogg, Battle Creek, MI
Stephen M. Roberts, PhD, University of Florida, Gainesville, FL
Jia-Sheng Wang, MD, PhD, University of Georgia, Athens, GA
Jeffrey J. Yourick, PhD, DABT, ATS, US FDA, Laurel, MD
Patricia Ganey, Council Contact, Michigan State University, East Lansing, MI
Steve Taylor, PhD, Colloquium Chair, University of Nebraska, Lincoln, NB
Stefano Luccioli, MD, Colloquium Co-chair, US FDA, College Park, MD
Betty Eidemiller, PhD, SOT Staff, Reston, VA

Chair: Norbert E. Kaminski, Michigan State University, East Lansing, MI
Co-Chair: Jason Dietz, US FDA CFSAN, College Park, MD

Overview

New plant varieties intended for commercial release have routinely been examined for agronomic characteristics and product quality (e.g., taste and suitability for processing) prior to commercialization. Foods from varieties that have passed these premarket analyses have historically been safe. In addition to these analyses, food safety assessments of genetically engineered crops routinely include, among other analyses, a targeted compositional analysis typically comparing the levels of toxicants, anti-nutrients and key nutrients in food from the new variety to those in food historically consumed. The intent of this analysis is to determine whether there have been changes in the levels of key substances in the food that would be important from a nutritional or toxicological perspective. While the methods historically used for this assessment have been reliable, new methods (referred to as metabolic profiling or sometimes metabolomics) provide the ability to produce a molecular profile of new varieties that spans more substances than typically examined in the focused biochemical analysis. Although metabolic profiling may provide more data about the composition of food from a new variety, it is not certain that metabolic profiling would routinely improve predictability of food safety assessments.

Plant composition may be affected by a wide range of factors (e.g., genetics, environment, life stage, etc.) that have not historically precipitated food safety issues in new varieties. Only in notable exceptions has food from new plant varieties contained harmful levels of endogenous substances. This colloquium will describe the premarket safety assessments performed for foods from genetically engineered plants and examine the scientific factors important when considering whether metabolic profiling data would have utility or added value in the safety assessment of food from genetically engineered plants.

Colloquium Materials

Can Alternatives Inform the Risk Assessments of Mixtures in Foods?—March 27, 2018

Presentation Slides

Welcome and Introductions
Welcome from FDA, Conrad J. Choiniere, Director, Office of Analytics and Outreach, CFSAN, US FDA, College Park, MD
Welcome from SOT and Introductions, Norbert E. Kaminski, SOT Past President, Colloquium Chair, Michigan State University, East Lansing, MI

Introduction to the Safety Assessment of Foods from Genetically Engineered Plant Varieties
Jason Dietz, CFSAN US FDA, College Park, MD

Factors Influencing the Composition/Metabolic Profile of Food from Plants
Sherry Flint-Garcia, USDA/ARS, University of Missouri, Columbia, MO

Introduction to Metabolic Profiling
Ann Knolhoff, CFSAN, US FDA, College Park, MD

Composition Testing in the Safety Assessment of Foods from Genetically Modified Crops
Bryan Delaney, Corteva Agriscience™ Agriculture Division of DowDuPont™, Johnston, IA

Concluding Slides
Roundtable Discussion
Moderator: Norbert Kaminski, Michigan State University, East Lansing, MI
All Speakers
Additional Panelist: Supratim Choudhuri, CFSAN, US FDA, College Park, MD

Organizing Committee

Bryan Delaney, PhD, DABT, ATS, Colloquium Series Chair, Corteva Agriscience™ Agriculture Division of DowDuPont™, Johnston, IA
Allen Rudman, PhD, Colloquium Series Co-chair, US FDA, College Park, MD
Jason L. Aungst, PhD, US FDA, College Park, MD
Suzanne Compton Fitzpatrick, PhD, DABT, Member and Colloquium Co-chair, US FDA, College Park, MD
Jieun Lee, PhD, DABT, Kellogg, Battle Creek, MI
Stephen M. Roberts, PhD, University of Florida, Gainesville, FL
Jia-Sheng Wang, MD, PhD, University of Georgia, Athens, GA
Jeffrey J. Yourick, PhD, DABT, ATS, US FDA, Laurel, MD
Patricia Ganey, Council Contact, Michigan State University, East Lansing, MI
Norbert E. Kaminski, PhD, Michigan State University, East Lansing, MI
Jason Dietz, PhD, Colloquium Co-chair, CFSAN, US FDA, College Park, MD
Betty Eidemiller, PhD, SOT Staff, Reston, VA

Chair: A. Wallace Hayes, University of South Florida College of Public Health, Tampa, FL, and Institute for Integrative Toxicology, Michigan State University, East Lansing, MI
Co-Chair: Suzanne Compton Fitzpatrick, US FDA, College Park, MD

Overview

Current risk assessments of chemicals in food do not generally consider exposure to multiple substances but rely instead on the assessment of individual substances in individual food commodities. Humans however are routinely exposed simultaneously to numerous chemicals in food. These mixtures can be variable and constantly changing and defining them presents a challenge. Models could be used independently and in an integrated manner to assess health impacts. This symposium will examine whether new testing approaches such as in vitro, in silico models, and non-mammalian in vivo models could be used to assess the potential health impacts of exposure to chemical mixtures in food.

Colloquium Materials

Presentation Slides

Welcome and Introductions
Welcome from FDA, Conrad J. Choiniere, Director, Office of Analytics and Outreach, CFSAN, US FDA, College Park, MD
Welcome from SOT, Suzanne Fitzpatrick, CFSAN, USFDA, College Park, MD
Speaker Introductions, A. Wallace Hayes, Colloquium Chair, University of South Florida College of Public Health, Tampa, FL, and Institute for Integrative Toxicology, Michigan State University, East Lansing, MI

Why a New Approach Is Needed | Video Presentation (video will advance to this presentation)
A. Wallace Hayes, University of South Florida College of Public Health, Tampa, FL, and Institute for Integrative Toxicology, Michigan State University, East Lansing, MI

Can High Thru-Put Assays/Tox 21 Inform Hazard Assessment? | Video Presentation (video will advance to this presentation)
Michael J. DeVito, NTP, Research Triangle Park, NC

Proposed In Silico Approach for Botanical Mixtures | Video Presentation (video will advance to this presentation)
Catherine Mahony, Procter & Gamble Technical Centres Ltd, Surrey, UK

Non-Mammalian In Vivo Models: C. elegans as a Model System to Inform Hazard | Video Presentation (video will advance to this presentation)
Piper Reid Hunt, US FDA, Laurel, MD

Extrapolating New Approaches into a Tiered Approach to Mixtures Risk | Video Presentation (video will advance to this presentation)
Mike Dourson, Toxicology Excellence for Risk Assessment, Cincinnati, OH

Analysis of In Vitro to In Vivo Concordance Studies for Food Safety Assessment in Humans—October 24, 2017

Organizing Committee

Bryan Delaney, PhD, DABT, ATS, Colloquium Series Chair, DuPont Pioneer, Johnston, IA
Jason L. Aungst, PhD, US FDA, College Park, MD
Suzanne Compton Fitzpatrick, PhD, DABT, Member and Colloquium Co-chair, US FDA, College Park, MD
Norbert E. Kaminski, PhD, Michigan State University, East Lansing, MI
Jieun Lee, PhD, DABT, Kellogg, Battle Creek, MI
Stephen M. Roberts, PhD, University of Florida, Gainesville, FL
Allen Rudman, PhD, US FDA, College Park, MD
Jeffrey J. Yourick, PhD, DABT, ATS, US FDA, Laurel, MD
John B. Morris, SOT Council Contact, University of Connecticut, Storrs, CT
A. Wallace Hayes, PhD, Colloquium Chair, Harvard T.H. Chan School of Public Health, Temple Terrace, FL
Betty Eidemiller, PhD, SOT Staff, Reston, VA

Chair: Bryan Delaney, PhD, DABT, ATS, DuPont Pioneer, Johnston, IA
Co-Chair: Paddy Wiesenfeld, PhD, CFSAN, US FDA, Laurel, MD

Overview

Concordance in safety assessment generally refers to the accuracy of in vitro test results to correctly predict an in vivo response in humans. For food additive ingredients in vivo, animal studies in various targeted areas (e.g., carcinogenicity, neurological disorders, developmental delays and deficits, and reproductive disorders) are typically used. Dietary supplements and cosmetic ingredients, which do not require pre-market approval, still must be safe for consumer use and require safety assessments. Toxicological reviews for safety assessments typically consider in vitro data as one facet of their evaluation but there is increasing emphasis to increase their use and to replace some aspects of in vivo testing. Many challenges remain to be addressed (e.g., metabolic activation of agents in in vitro systems) and there are limitations to the interpretation of the data (e.g., the mechanistic relationship between rapid in vitro responses and more chronic in vivo responses), however, there also are benefits to using in vitro studies to assess safety (e.g., cost, speed of the assay, ability to use high-throughput, and high-output methods to address a large range of potential toxic substances). New and innovative in vitro technologies (e.g., high-throughput sequencing methods for quantifying gene expression, microRNA expression and proteomics) are emerging that may also increase concordance to tissue, organ, and the whole organism effects. However, there is still a need to improve scientific confidence in the utilization of these in vitro tests to replace in vivo testing in safety assessment. The invited speakers to this colloquium will review the state-of-the-art in using in vitro technologies for safety assessment and how they are being utilized.

Colloquium Materials

Presentation Slides

Welcome and Introductions
Welcome from FDA, Steven Musser, PhD, Deputy Director of Scientific Operations for CFSAN, CFSAN, US FDA, College Park, MD
Welcome from SOT and Speaker Introductions, Bryan Delaney, PhD, DABT, ATS, DuPont Pioneer, Johnston, IA

’Omic Biomarkers for Assessing Cellular Toxicity: Integration of In Vivo and In Vitro Data — Why It Is Important | Video Presentation (video will advance to this presentation)
Bruce Fowler, PhD, ATS, Toxicology and Risk Assessment Consulting Services, LLC, Rockville, MD

Establishing an Integrated Ex Vivo Female Reproductive Tract in the Microfluidic Platform: Screening of Reproductive Toxic Chemicals | Video Presentation (video will advance to this presentation)
Shuo Xiao, PhD, University of South Carolina, Columbia, SC

Investigation of an In Vitro Method for Protein Hazard Characterization | Video Presentation (video will advance to this presentation)
Bryan Delaney, PhD, DABT, ATS, DuPont Pioneer, Johnston, IA

Analysis of In Vitro to In Vivo Concordance Studies for Food Safety Assessment in Humans | Video Presentation (video will advance to this presentation)
Miriam E. Mossoba, PhD, US FDA, Laurel, MD

Safety Assessment of Food Packaging and Other Food Contact Substances—May 23, 2017

Organizing Committee

Bryan Delaney, PhD, DABT, ATS, Colloquium Chair, Colloquium Series Chair, DuPont Pioneer, Johnston, IA
Jason L. Aungst, PhD, US FDA, College Park, MD
Suzanne Compton Fitzpatrick, PhD, DABT, US FDA, College Park, MD
Norbert E. Kaminski, PhD, Michigan State University, East Lansing, MI
Jieun Lee, PhD, DABT, Kellogg, Battle Creek, MI
Stephen M. Roberts, PhD, University of Florida, Gainesville, FL
Allen Rudman, PhD, US FDA, College Park, MD
Jeffrey J. Yourick, PhD, DABT, ATS, US FDA, Laurel, MD
John B. Morris, Council Contact, University of Connecticut, Storrs, CT
Paddy Wiesenfeld, PhD, Colloquium Co-Chair, CFSAN, US FDA, Laurel, MD
Clarissa Russell, SOT Staff, Reston, VA

Chair: Charles Barton, PhD, DABT, Valspar Corporation, Sewickley, PA
Co-Chair: Jason L. Aungst, PhD, US FDA, College Park, MD

Overview

A large majority of the public thinks of food safety primarily in terms of either the food or food additives shown on the labels in which they are packaged. However, materials that come in contact with food are also subject to regulation as food additives because the components of these packaging and contact materials may migrate into the food. As the distribution and product protection of food has expanded over a period of decades, highly engineered packaging has evolved to protect foods from contamination and spoilage. This colloquium focused on various types of packaging (e.g., coatings, plastics/polymer), manufacturing processes, and safety and exposure assessments.

The first presentation reviewed the regulatory science framework for assessing the safety of food packaging materials and how it is evolving. The second presentation provided an overview of the materials in key packaging types, such as the plastics and polymers used in bottles, and how they are made and processed. The third presentation discussed safety considerations and communication. The fourth presentation illuminated migration estimates, i.e., the transfer of chemicals from packaging to the food, and estimation of dietary exposure. The fifth presentation discussed the latest innovations and materials used in food packaging.

Colloquium Materials

Presentation Slides

Welcome and Introductions
Welcome from FDA, Michael Adams, US FDA, College Park, MD
Welcome from SOT and Overview, Peter L. Goering, SOT Past President, US FDA, Silver Spring, MD
Introduction of Chair, Jason Aungst, US FDA, College Park, MD
Speaker Introductions, Charles Barton, Valspar Corporation, Sewickley, PA

Overview of Regulatory Science of Food Contact Substances
Michael Adams, US FDA, College Park, MD

Overview of Key Food Packaging
Steve Hentges, American Chemistry Council, Washington, DC

Can Coatings, Primer, and Safety Assessment: Communicating Evidence of Absence
Mark Maier, Sheperian Toxicology, Albuquerque, NM

Migration and Exposure Considerations
Jessica Cooper, US FDA, College Park, MD

Packaging Innovations to Improve Food Safety
Maria Rubino, Michigan State University, East Lansing, MI

Considerations for the Determination of Adversity in Food Chemical Safety Evaluations—March 27, 2017

Organizing Committee

Bryan Delaney, PhD, DABT, ATS, Colloquium Series Chair, DuPont Pioneer, Johnston, IA
Jason L. Aungst, PhD, US FDA, College Park, MD
Suzanne Compton Fitzpatrick, PhD, DABT, US FDA, College Park, MD
Peter L. Goering, PhD, DABT, ATS, US FDA, Silver Spring, MD
Norbert E. Kaminski, PhD, Michigan State University, East Lansing, MI
Jieun Lee, PhD, DABT, Kellogg, Battle Creek, MI
Stephen M. Roberts, PhD, University of Florida, Gainesville, FL
Allen Rudman, PhD, US FDA, College Park, MD
Ivan Rusyn, MD, PhD, Texas A&M University, College Station, TX
Jeffrey J. Yourick, PhD, DABT, ATS, US FDA, Laurel, MD
John B. Morris, SOT Council Contact, University of Connecticut, Storrs, CT
Charles Barton, PhD, DABT, Colloquium Chair, Valspar Corporation, Sewickley, PA
Betty Eidemiller, PhD, SOT staff

Chair: Bernadene Magnuson, Chair, PhD, ATS, Health Science Consultants, Inc., Mississauga, ON, Canada
Co-Chair: Sabine Francke, Co-chair, DVM, PhD, Fellow IATP, CFSAN, US FDA, College Park, MD

Overview

Historically, food safety laws and regulations in the United States were aimed to protect against adulteration and microbial contaminations, but have evolved gradually to also address the safety of food ingredients, food additives, and food contact materials. To prevent adversity, broadly defined as “harm to the biological system” guidelines for conducting chemical and toxicological safety assessments have been established to include the evaluation of food compounds intentionally added to foods (such as food additives or novel ingredients), as well as chemicals that unintentionally may become part of foods (such as food contact materials and environmental contaminants). The resulting food safety frameworks, as well as toxicological assessments driving these frameworks, rely in many cases on extrapolations from animal studies to humans and use endpoint-based no observable adverse effect levels (NOAEL) to derive health-based guidance values such as acceptable daily intake (ADI) and tolerable daily intake (TDI).

This colloquium will begin by introducing current concepts underlying determinations of adversity from food compounds utilizing chemical characterization, in vitro or in silico assays, as well as animal and human toxicology studies. Second, the definitions of adversity (harm) will be considered in the context of the laws and regulations that apply to foods and food ingredients. Third, a case study on low calorie sweeteners will be provided to illustrate determinations of adversity by describing what data were used in the assessment of safety. Fourth, alternatives to the current frameworks for adversity determinations will be discussed in terms of their strengths and weaknesses considering a toxicological, decision-making and public perspective. Finally, the colloquium will conclude with a panel discussion addressing the key issues brought up by the speakers and questions from participants.

Colloquium Materials

Presentation Slides

Welcome and Introductions
Welcome from US FDA and Overview
Suzanne Fitzpatrick, PhD, DABT, CFSAN, US FDA, College Park, MD

Welcome from SOT and Introductions
Peter Goering, PhD, SOT Past President, US FDA, Silver Spring, MD Speaker Introductions
Bernadene Magnuson, PhD, ATS, Health Science Consultants, Inc., Mississauga, ON, Canada

Sabine Francke, DVM, PhD, Fellow IATP
CFSAN, US FDA, College Park, MD

Adversity in Regulatory Science: Historical Perspective and Future Challenges
Nigel J. Walker, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC

When is Adversity Legally Cognizable?
Ricardo Carvajal, Hyman, Phelps & McNamara, P.C., Washington, DC

No Observed Adverse Effect Level: Sucralose as a Case Study
Bernadene Magnuson, Health Science Consultants, Inc., Mississauga, ON, Canada

New Approaches to Adversity Assessment in Food Safety Evaluation
Daniel Krewski, University of Ottawa, Ottawa, Ontario, Canada

Application of In Vitro to In Vivo Extrapolation in Safety Assessment—December 1, 2016

Organizing Committee

Ivan Rusyn, MD, PhD, Colloquia Series Chair, Texas A&M University, College Station, TX
Jason L. Aungst, PhD, US FDA/CFSAN, College Park, MD
Bryan Delaney, PhD, DABT, ATS, DuPont Pioneer, Johnston, IA
Suzanne Compton Fitzpatrick, PhD, DABT, US FDA/CFSAN, College Park, MD
Norbert E. Kaminski, PhD, Michigan State University, East Lansing, MI
Jieun Lee, PhD, DABT, Kellogg, Battle Creek, MI
Allen Rudman, PhD, US FDA/CFSAN, College Park, MD, Chair of this colloquium
Peter Goering, PhD, DABT, ATS, SOT Council Contact, US FDA/CDRH, Silver Spring, MD
Bernadene Magnuson, PhD, ATS, Colloquium Chair, Health Science Consulting, Inc, Mississauga, ON, Canada
Sabine Francke, DVM, PhD, Colloquium Co-chair, US FDA/ CFSAN, College Park, MD, USA
Marguerite Leishman, SOT Staff, Reston, VA

Chair: Richard A. Becker, PhD, DABT, American Chemistry Council, Washington, DC
Co-Chair: Lisa M. Sweeney, PhD, DABT, Naval Medical Research Unit Dayton, Dayton, OH

Overview

The development and use of in vitro methods to examine potential effects of consumer product chemicals, commodity substances, food additives and ingredients is accelerating. Compared to traditional animal toxicity studies, advanced high throughput screening methods (HTS) and high content cellular based omics hold considerable promise to more efficiently define biological activity profiles of chemicals. However, methods are needed to extrapolate the concentrations found to elicit effects in vitro to equivalent doses and relevance in humans. This is accomplished with In Vitro to In Vivo Extrapolation (IVIVE), a technique that uses knowledge (or measurements) of chemical specific distribution parameters and physiologically-based pharmacokinetic modeling to calculate oral equivalent doses (or internal circulating/target organ concentrations) in humans. Such IVIVE-derived doses can then be compared to modeled or measured human intakes or exposures to better understand margins of exposure.

The colloquium started with an overview of IVIVE and a discussion of the principles underpinning the development of the methodology and highlight key elements to think through when considering applying IVIVE. Second, technical details and data needed for IVIVE were discussed. Third, examples of IVIVE applications in chemical assessment (including substances relevant to food safety) were presented. Fourth, the opportunities and challenges for using IVIVE in safety evaluations were discussed. Finally, the colloquium concluded with a panel discussion addressing the key issues brought up by the speakers and questions from participants.

Colloquium Materials

Presentation Slides

Welcome and Introductions
US FDA Welcome and Overview, Mary D. Ditto, PhD, US FDA/CFSAN, College Park, MD
Welcome from SOT and Introductions, Peter Goering, PhD, SOT Past President, US FDA, Silver Spring, MD Speaker Introductions, Richard A. Becker, American Chemistry Council, Washington, DC

Overview and Principles Underpinning In Vitro to In Vivo Extrapolation
Lisa M. Sweeney, Naval Medical Research Unit Dayton, Dayton, OH

Data Requirements for Developing IVIVE Models
Nynke Kramer, Utrecht University, Netherlands

Examples Illustrating Potential Applications of IVIVE in Chemical Assessment
Miyoung Yoon, ScitoVation, Research Triangle Park, NC

Opportunities and Challenges for Using IVIVE to Improve Decision Making
Weihsueh Chiu, Texas A&M University, College Station, TX

State of the Science in Developmental Neurotoxicology—October 12, 2016

Organizing Committee

Ivan Rusyn, MD, PhD, Colloquia Series Chair, Texas A&M University, College Station, TX
Jason L. Aungst, PhD, US FDA/CFSAN, College Park, MD
Bryan Delaney, PhD, DABT, ATS, DuPont Pioneer, Johnston, IA
Suzanne Compton Fitzpatrick, PhD, DABT, US FDA/CFSAN, College Park, MD
Norbert E. Kaminski, PhD, Michigan State University, East Lansing, MI
Jieun Lee, PhD, DABT, Kellogg, Battle Creek, MI
Allen Rudman, PhD, US FDA/CFSAN, College Park, MD, Chair of this colloquium
Peter Goering, PhD, DABT, ATS, SOT Council Contact, US FDA/CDRH, Silver Spring, MD
Richard A. Becker, PhD, Colloquium Chair, American Chemistry Council, Washington, DC
Betty Eidemiller, PhD, SOT Staff, Reston, VA

Chair: Timothy J. Shafer, Chair, US EPA, Research Triangle Park, NC
Co-Chair: Jeffrey J. Yourick, Co-Chair, US FDA, Laurel, MD

Overview

Development of the nervous system is a complex process that is critically important for normal function and it is vulnerable to both endogenous and exogenous factors. There is increasing awareness among scientists and regulators that neurodevelopment is a critical window of susceptibility for childhood and adult-onset diseases. A growing concern among the general public is that exposures to some environmental factors, dietary components or consumer products may contribute to neurodevelopmental decrements. Novel experimental approaches and scientific concepts are being developed to address the need for more informative and comprehensive testing for the potential developmental neurotoxicity effects of chemicals.

The colloquium will begin with an overview of neurodevelopment and discuss the current state-of-the-art in developmental neurotoxicity assessment. Second, advances in the use of whole-animal alternative models, such as zebrafish, in evaluating developmental neurotoxicity will be discussed. Third, an overview of in vitro alternative models and screening batteries to assess developmental neurotoxicity will be presented. Fourth, the framework of adverse outcome pathways will be used to demonstrate the utility of novel data streams from alternative species and in vitro assays to improve mechanistic understanding of how chemicals elicit developmental neurotoxicity. Finally, the colloquium will conclude with a panel discussion addressing the key issues brought up by the speakers and questions from participants.

Colloquium Materials

Agenda | Event Captions| | Video Presentation

Presentation Slides

Welcome and Introductions
US FDA Welcome and Overview, Mickey Parish, PhD, Acting Director of the Senior Science Advisor Staff, CFSAN, US FDA, College Park, MD
Welcome from SOT and Introductions, Peter Goering, PhD, SOT President, US FDA, Silver Spring, MD
Speaker Introductions, Timothy Shafer, Chair, US EPA, Research Triangle Park, NC

Developmental Neurotoxicity Testing: An Introduction to the State of the Science and Opportunities for Improvement
Charles V. Vorhees, Cincinnati Children’s Hospital Research Foundation, Cincinnati, OH

Zebrafish as an Alternative Species for Developmental Neurotoxicity Testing that can Provide Hazard Identification and Mechanistic Information
Randall T. Peterson, Harvard University, Boston, MA

Video file for page 20

Video file for page 25

In Vitro Approaches to Screening Compounds for Developmental Neurotoxicity Hazard
Ellen Fritsche, University of Düsseldorf, Düsseldorf, Germany

Adverse Outcome Pathways for Developmental Neurotoxicity
Anna K. Price, ECVAM, Ispra, Italy

Safety Assessment Approaches in Young Children—May 20, 2016

Organizing Committee

Ivan Rusyn, MD, PhD, Colloquium Organizing Committee Chair, Texas A&M University, College Station, TX
Jason L. Aungst, PhD, US FDA, CFSAN, College Park, MD
Bryan Delaney, PhD, DABT, ATS, DuPont Pioneer, Johnston, IA
Suzanne Compton Fitzpatrick, PhD, DABT, US FDA, CFSAN, College Park, MD
Norbert E. Kaminski, PhD, Michigan State University, East Lansing, MI
Jieun Lee, PhD, DABT, Kellogg, Battle Creek, MI
Allen Rudman, PhD, US FDA, OFAS, CFSAN, College Park, MD
Jeffrey J. Yourick, PhD, DABT, ATS, US FDA, CFSAN, Toxicology Branch, Laurel, MD
Peter Goering, PhD, DABT, ATS, SOT Council Contact, US FDA, CDRH, Silver Spring, MD
Timothy J. Shafer, PhD, Colloquium Chair, US EPA, Research Triangle Park, NC
Yen-Ching Wu, BA, PhD, for this colloquium, US FDA, CSFAN, OFAS DFCN, College Park, MD
Betty Eidemiller, PhD, SOT Staff, Reston, VA

Chair: Allen Rudman, Chair, US FDA, CFSAN, College Park, MD
Co-Chair: Elaine Faustman, Co-Chair, University of Washington, Seattle, WA

Overview

For over a decade we have recognized that children and infants are not simply little adults (WHO Training Report, 2008) and many initiatives and research during life stage have supported this concept. The implications of this statement have had many manifestations. In this colloquium we will focus on early childhood (from birth to 5 years of age) to examine what those general differences are, provide examples of the differences in this age group, and discuss safety assessment approaches that are being used and proposed.

The first presentation will lay the groundwork for this concept and provide an introduction to example case studies that illustrate the importance of safety assessment approaches in early childhood. The second talk will focus on pharmacokinetic considerations that provide a mechanistic basis for our assessments. Critical drug metabolism differences underlie many of the measureable differences for children during early childhood. The speaker will share these new observations and resources to find out information about age dependent metabolism differences. Discussion will include examples from the neonatal, post birth surge in metabolism capabilities as well as slower trajectory of some metabolism capabilities before reaching adult activities. The third talk will provide insight from industry including new models for predicting and modeling responses in early childhood. The current regulatory science behind food safety assessments to protect children during this critical window of susceptibility will be the focus of the concluding presentation. Case studies will be provided and a panel discussion will enhance interaction with the attendees.

Colloquium Materials

State of the Art in the Cramer Classification Scheme and Threshold of Toxicological Concern—March 29, 2016

Presentation Slides

Welcome and Introductions
US FDA Welcome and Overview, Suzanne Fitzpatrick, PhD, ATS, CFSAN, US FDA, College Park, MD;
Welcome from SOT, Peter Goering, PhD, DABT, ATS, SOT President, US FDA, Silver Spring, MD

Speaker Introductions, Allen Rudman, PhD, CFSAN, US FDA, College Park, MD

Children Matter: Using a Lifecourse Approach to Understanding Safety Assessment Needs for Children
Elaine Faustman, University of Washington, Seattle, WA

Early Life Development of Pharmacokinetic Pathways: Framework and Case Examples with Implications for Safety Assessment
Gary Ginsberg, Connecticut Department of Public Health, Hartford, CT

Ensuring Safety for Early Life Exposures: Adequacy of Current Methods and Opportunities to Advance the Science
Susan Felter, Procter & Gamble Company, Mason, OH

Toxicology Challenges in Lifestage-Specific Safety Assessments
April Neal-Kluever, US FDA, College Park, MD

Organizing Committee

Ivan Rusyn, MD, PhD, Colloquia Series Chair, Texas A&M University, College Station, TX
Jason L. Aungst, PhD, US FDA, CFSAN, College Park, MD
Ronald Chanderbhan, PhD, US FDA, CFSAN, College Park, MD
Bryan Delaney, PhD, DABT, ATS, DuPont Pioneer, Johnston, IA
Suzanne Compton Fitzpatrick, PhD, DABT, US FDA, CFSAN, College Park, MD
Kristi Muldoon Jacobs, PhD, US FDA, CFSAN, College Park, MD
Norbert E. Kaminski, PhD, Michigan State University, East Lansing, MI
Jieun Lee, PhD, DABT, Kellogg, Battle Creek, MI
James J. Pestka, PhD, Michigan State University, East Lansing, MI
Allen Rudman, PhD, US FDA, CFSAN, College Park, MD, Chair of this colloquium
Catherine Whiteside, PhD, US FDA, CFSAN, College Park, MD
Peter Goering, PhD, DABT, ATS, SOT Council Contact, US FDA, CDRH, Silver Spring, MD
April Neal-Kluever, US FDA, CFSAN, College Park, MD, Ad hoc member for this colloquium
Betty Eidemiller, PhD, SOT Staff, Reston, VA

Chair: Ivan Rusyn, Chair, Texas A&M, College Station, TX
Co-Chair: Timothy Adams, Co-Chair, US FDA, College Park, MD

Overview

The Threshold of Toxicological Concern (TTC) is a risk assessment approach aimed at deriving a level of human intake or exposure to a chemical that is perceived to be of negligible risk, despite the absence of chemical-specific toxicity data. The original Cramer Decision Tree was proposed in 1978 for the classification of chemical substances of concern and was the basis for the subsequent adoption of the TTC approach. TTC has been originally developed to qualitatively assess the risk of low-level substances in the diet, but is now used frequently to determine whether a comprehensive risk assessment is required for a broad range of chemicals. It also has been a major advance in the prioritization and evaluation of food substances with low exposure scenarios. The application of the TTC approach to a broader universe of chemicals and routes of exposure has been the main focus of recent research, along with a number of proposals for the revision of the Cramer Decision Tree. However, an updated Cramer Decision Tree would require collection and integration of a database of information on species- and sex-specific toxicology, chemistry, dose-dependent metabolism, pharmacokinetics, and mechanism of action for a chemical space related to food exposure.

The objectives of this colloquium include a review of the evolution of the Cramer Decision Tree and TTC approach, presentation of possible revisions to the original Cramer Decision Tree and its impact on TTC levels for other routes of exposure, and a discussion of the possible expansion of the Cramer Decision Tree or other computational approaches to more diverse chemicals, multiple structural classes, and the chemical specificity of questions.

Colloquium Materials

Role of Mode of Action in Dose-Response Assessment for Carcinogens—January 25, 2016

Presentation Slides

Welcome and Introductions
US FDA Welcome and Overview, Mary Torrence, Director, Office of Applied Research and Safety Assessment Laboratories (OARSA), US FDA, College Park, MD; and Welcome from SOT and Introductions, Peter Goering, PhD, SOT President, US FDA, Silver Spring, MD

Threshold of Toxicological Concern Approach in Regulatory Decision-Making: The Past, Present, and Future
Grace Patlewicz (Tier), US EPA, Research Triangle Park, NC

Advancements in Food Ingredient Safety Prioritization: An Expanded Cramer Decision Tree Schema
Timothy Adams, US FDA, College Park, MD

In Silico Methods for Threshold of Toxicological Concern Assessment
Andrew Worth, European Commission, Joint Research Centre, Ispra, Italy

Quantitative Prediction of Continuous Toxicity Values using Chemical Structure Information
Jessica Wignall, ICF International, Arlington, VA

Organizing Committee

Ivan Rusyn, MD, PhD, Colloquium Organizing Committee Chair, Texas A&M University, College Station, TX
Jason L. Aungst, PhD, US FDA CFSAN, College Park, MD
Ronald Chanderbhan, PhD, US FDA, CFSAN, College Park, MD
Bryan Delaney, PhD, DABT, ATS, DuPont Pioneer, Johnston, IA
Suzanne Compton Fitzpatrick, PhD, DABT, US FDA, CFSAN, College Park, MD
Kristi Muldoon Jacobs, PhD, US FDA, CFSAN, College Park, MD
Jieun Lee, PhD, DABT, Kellogg, Battle Creek, MI
James J. Pestka, PhD, Michigan State University, East Lansing, MI
Allen Rudman, PhD, US FDA, Office of Food Additive Safety, CFSAN, College Park, MD
Catherine Whiteside, PhD, US FDA, CFSAN/OFVM/CFSAN, College Park, MD
Timothy Adams, PhD, US FDA, CFSAN/OFVM/CFSAN, College Park, MD
Norbert E. Kaminski, PhD, SOT Council Contact, Michigan State University, East Lansing, MI
Betty Eidemiller, PhD, SOT Staff, Reston, VA

Suzanne Fitzpatrick, Chair, US FDA, College Park, MD
Co-Jieun Lee, Co-Chair, Kellogg, Battle Creek, MI

Overview

Among the primary goals of a risk assessment are 1) determination of the presence or absence of a cause-effect relationship and 2) quantifying the risk through dose-response analysis. Dose-response data may be derived from in vivo studies in animals or humans, which usually provide the basis for risk characterization, and in vitro studies, which are often related to investigations of mode of action (MOA). MOA information describes key events and processes that would explain the overall process of development of a toxic effect. MOA can also be relevant in considering susceptibility factors within populations and in considering the cumulative effects of exposure to more than a single agent. Over the last several years, advances in our understanding of the ways that chemicals interact with biological systems have yielded several frameworks for evaluating toxicity datasets to determine biologically plausible modes of action and relevance to humans. These frameworks can be used to consider the weight of evidence of hypothesized modes of action in animals and their potential human relevance for both cancer and non-cancer effects. This could result in a move away from defaults to adopt modern knowledge on MOA to improve risk assessments, including the choices for dose-response assessment.

This symposium will include an overview talk about dose-response, including recommendations from the NRC Silver Book; a discussion of mode of action including definition, differences from mechanism of action, and some framework key events; a case study of the choices in dose-response analysis for a mutagenic mode of action; and recommendations from the Risk21 project on the role of key events in deciding on the dose-response analysis.

Colloquium Materials

A Path Forward for Using Computational and In Vitro Methods for Food Ingredient Assessments—October 13, 2015

Presentation Slides

Welcome and Introductions
Betty Eidemiller, Society of Toxicology, Reston, Virginia, and Elaine Faustman, University of Washington, Seattle, WA

The Role of Mode of Action in Dose-Response Assessments: Recommendations from the 2009 NRC Report “Science and Decisions”
Lauren Zeise, NRC Committee Member, Berkeley, CA

Mode of Action, Distinguishing between Mode and Mechanism of Action, and Some Key Events for MOA
Michael Dourson, TERA, Cincinnati, OH

The Mutagenic Mode of Action and the Choices for the Dose-Response Analysis
Rita Schoeny, US EPA (retired), Washington, DC

Risk21 Quantitative Key Events Dose-Response Framework
J. Craig Rowlands, Dow Chemical Company, Midlands, MI

Roundtable Discussion and Conclusion
Elaine Faustman, University of Washington, Seattle, WA, Moderator

Organizing Committee

Ivan Rusyn, MD, PhD, Colloquium Organizing Committee Chair, Texas A&M University, College Station, TX
Jason L. Aungst, PhD, US FDA CFSAN, College Park, MD
Ronald Chanderbhan, PhD, US FDA, CFSAN, College Park, MD
Bryan Delaney, PhD, DABT, ATS, DuPont Pioneer, Johnston, IA
Suzanne Compton Fitzpatrick, PhD, DABT, US FDA, CFSAN, College Park, MD
Kristi Muldoon Jacobs, PhD, US FDA, CFSAN, College Park, MD
Ji-Eun Lee, PhD, DABT, Kellogg, Battle Creek, MI
James J. Pestka, PhD, Michigan State University, East Lansing, MI
Allen Rudman, PhD, US FDA, Office of Food Additive Safety, CFSAN, College Park, MD
Catherine Whiteside, PhD, US FDA, CFSAN/OFVM/CFSAN, College Park, MD
Dan Levy, PhD, US FDA, CFSAN/OFVM/CFSAN, College Park, MD, for this colloquium
Norbert E. Kaminski, PhD, SOT Council Contact, Michigan State University, East Lansing, MI
Betty Eidemiller, PhD, SOT Staff, Reston, VA

Overview

New data types, primarily from in vitro tests, and an ever-increasing plethora of computational tools for in silico modeling have ushered in the era of “big data” in investigative toxicology. Practitioners in the field of human health assessments are transitioning rapidly away from lamenting a lack of data to drowning in a deluge of information. There is a clear opportunity for a paradigm shift toward high-throughput risk assessment and non-traditional data-based regulatory decision-making; however, only very recently has the information from rapid screening, in silico modeling, and prioritization efforts begun to make inroads into human health decisions. This colloquium is following up on the “Contemporary Issues in Risk Assessment” (June 17, 2015) colloquium and extends the discussion to the use of new computational and in vitro science, approaches, and technologies for risk assessment and regulatory decision-making.

Specifically, this session will cover (1) an overview of risk- and hazard-based decision contexts at the US FDA; (2) a case study of replacement of an animal test with a battery of in vitro tests; (3) examples of how in vitro and in silico data aid in developing category and analogue read-across; and (4) the use of in vitro data to fill in data gaps in a traditional cancer hazard assessment. Overall, the learning objective for this session is to demonstrate recent examples of the implementation of the novel information streams from computational and in vitro methods into the practice of risk assessment across a wide array of decision contexts.

Colloquium Materials

Contemporary Issues in Risk Assessment—June 17, 2015

Presentation Slides

US FDA and SOT Welcome and Overview
Suzanne Fitzpatrick, US FDA/CFSAN, College Park, MD
Peter Goering, PhD, SOT President, US FDA, Silver Spring, MD

Development of In Silico Tools at OFAS CFSAN FDA
Patra Volarath, US FDA/CFSAN, College Park, MD

Gaining Confidence in Replacing Animal Tests: A Case Study of the Endocrine Disruption Program at the US EPA
Richard Judson, US EPA/NCCT, Research Triangle Park, NC

Read-Across with Computational and In Vitro Data
Elisabet Berggren (by webinar), Joint Research Centre, European Commission, Ispra, Italy

Use of Computational and In Vitro Data in Cancer Hazard Assessment of Data Rich Chemicals: Examples of IARC Monographs
Ivan Rusyn, Texas A&M University, College Station, TX

Organizing Committee

Ivan Rusyn, MD, PhD, Colloquium Organizing Committee Chair, Colloquium Chair, Texas A&M University, College Station, TX
Jason L. Aungst, PhD, US FDA CFSAN, College Park, MD
Ronald Chanderbhan, PhD, US FDA, CFSAN, College Park, MD
Bryan Delaney, PhD, DABT, ATS, DuPont Pioneer, Johnston, IA
Suzanne Compton Fitzpatrick, PhD, DABT, US FDA, CFSAN, College Park, MD
Kristi Muldoon Jacobs, PhD, US FDA, CFSAN, College Park, MD
Ji-Eun Lee, PhD, DABT, Kellogg, Battle Creek, MI
James J. Pestka, PhD, Michigan State University, East Lansing, MI
Allen Rudman, PhD, US FDA, Office of Food Additive Safety, CFSAN, College Park, MD
Catherine Whiteside, PhD, US FDA, CFSAN/OFVM/CFSAN, College Park, MD
Norbert E. Kaminski, PhD, SOT Council Contact, Michigan State University, East Lansing, MI
Betty Eidemiller, PhD, SOT Staff, Reston, VA

Overview

The National Academies of Sciences committee that produced a report “Science and Decisions: Advancing Risk Assessment” (NRC, 2009) recommended that “risk assessment should be viewed as a method for evaluating the relative merits of various options for managing risk rather than an end in itself.” How can the federal government best accomplish this goal? This session will focus on recent improvements in the practice of human health assessments. Exciting advances in the methods and best practices, consistent with the advice from the National Academies, have been made in the recent years and implemented by a number of stakeholders. Specifically, this session will cover the lessons learned from (1) problem formulation and protocol development in chemical-specific human health assessments; (2) evidence identification and transparent criteria for inclusion and exclusion of the individual studies in the assessment; (3) harmonization of the cancer and non-cancer dose-response assessments; and (4) the use of the mechanistic data in support of human health assessments. Overall, the learning objective for this session is to demonstrate tangible examples of the implementation of the best practices in risk assessment to illustrate how the field is evolving to meet the needs of various stakeholders.

Colloquium Materials

The Use of the Mechanistic Evidence in Human Health Assessments

Presentation Slides

Welcome, Overview, and Speaker Introduction
Suzanne Fitzpatrick, Colloquium Chair, US FDA Center for Food Safety and Applied Nutrition, College Park, MD
Peter L. Goering, SOT President, FDA, Silver Spring, MD
Ivan Rusyn, Organizing Committee Chair, Texas A&M, College Park, MD

Problem Formulation and Scoping for Human Health Assessments
Juleen Lam, University of California San Francisco, San Francisco, CA

Identification and Selection of the Evidence Base for Human Health Assessments
Kathryn Guyton, International Agency for Research on Cancer Monographs Programme, Lyon, France

Harmonizing Dose-Response Assessment for Cancer and Non-Cancer Endpoints in Human Health Assessments
Weihsueh Chiu, Texas A&M University, College Station, TX

The following Excel® files were used to conduct the case study examples discussed in this presentation, and are provided to help users better familiarize themselves with the approaches described. Specifically, the “BMDS Wizard” files are used to conduct benchmark dose modeling based on US EPA Benchmark Dose Software (BMDS), and the “APROBA” files are used to conduct probabilistic dose-response assessment based on a framework and approach developed by the WHO/IPCS. Execution of the macros in the BMDS wizard files requires that the computer have US EPA BMDS installed.

Deoxynivalenol Case Study—BMDS Wizard file
Deoxynivalenol Case Study—APROBA file
Methyleugenol Case Study using 10% extra risk—BMDS Wizard file
Methyleugenol Case Study using 10% extra risk—APROBA file
Methyleugenol Case Study using 1% extra risk – BMDS Wizard file
Methyleugenol Case Study using 1% extra risk—APROBA file

Note: Case studies using BMDS wizard requires that the computer running the BMDS wizard has BMDS installed.

J. Vincent Cogliano (by webinar), US EPA, Crystal City, VA

Organizing Committee

Ivan Rusyn, MD, PhD, Colloquium Organizing Committee Chair, Texas A&M University, College Station, TX
Suzanne Compton Fitzpatrick, Colloquium Chair, PhD, DABT, US FDA, CFSAN, College Park, MD
Ronald Chanderbhan, PhD, US FDA, CFSAN, College Park, MD
Bryan Delaney, PhD, DABT, ATS, DuPont Pioneer, Johnston, IA
Kristi Muldoon Jacobs, PhD, US FDA, CFSAN, College Park, MD
Ji-Eun Lee, PhD, DABT, Kellogg, Battle Creek, MI
James J. Pestka, PhD, Michigan State University, East Lansing, MI
Allen Rudman, PhD, US FDA, Office of Food Additive Safety, CFSAN, College Park, MD
Catherine Whiteside, PhD, US FDA, CFSAN/OFVM/CFSAN, College Park, MD
Norbert E. Kaminski, PhD, SOT Council Contact, Michigan State University, East Lansing, MI
Betty Eidemiller, PhD, SOT Staff, Reston, VA

Immunotoxicology in Food and Ingredient Safety Assessment: Approaches and Case Studies—April 14, 2015

Overview

The focus of this colloquium is on the methods used in safety assessment of substances present in foods that may target the immune system. The immune system is a complex set of cellular, chemical, and soluble mediators that protects the body against foreign substances. Immunotoxicology is the subdiscipline of toxicology that focuses on unintended modulation of the immune system following exposure to environmental chemicals or therapeutics. Adverse effects may include immunosuppression, immunostimulation, allergic hypersensitivity, or autoimmunity, and may result in outcomes such as increased incidences of infectious diseases or neoplastic diseases, allergy/asthma, or autoimmune diseases, respectively. The majority of immunotoxicity testing efforts to date have focused on the potential for xenobiotics to suppress immune function or induce dermal sensitization. With the increased use and development of immune-based or immune-targeted therapeutic proteins, unintended stimulation of the immune system has also become an area of concern. The colloquium will begin with a brief overview of the cells and soluble mediators critical to immune function and the tiered testing strategies used to identify substances that may target immune effectors. Following this introduction, experts will provide a state of the art review of methodological approaches using case studies to elucidate how immunotoxicology data can be used in assessing the safety of ingested materials.

Colloquium Materials

Application of ADME/PK Studies to Improve Safety Assessments for Foods and Cosmetics—February 23, 2015

Presentation Slides

Welcome and Overview
Susan Mayne, PhD, Director, US FDA Center for Food Safety and Applied Nutrition
Peter L. Goering, PhD, SOT Vice President, US FDA

Introduction to Immunology and Immunotoxicology
Dori R. Germolec, PhD, Immunology Discipline Leader, Toxicology Branch, National Toxicology Program, National Institute for Environmental Health Sciences

Immunomodulatory Effects of Perfluoroalkyl Substances in Rodents and Humans
Jamie DeWitt, PhD, Assistant Professor, Department of Pharmacology & Toxicology, Brody School of Medicine, East Carolina University

Toxicology and Food Allergy: Case Study of tBHQ
Cheryl Rockwell, Assistant Professor, Department of Pharmacology & Toxicology, Michigan State University

Dietary Supplement Modulation of Autoimmune Disease
Prakash Nagarkatti, PhD, Vice President for Research, University of South Carolina

Organizing Committee

James J. Pestka, PhD, Colloquia Series Chair, Michigan State University, East Lansing, MI
Ronald Chanderbhan, PhD, US FDA, CFSAN, College Park, MD
Bryan Delaney, PhD, DABT, ATS, DuPont Pioneer, Johnston, IA
Suzanne Compton Fitzpatrick, PhD, DABT, US FDA, CFSAN, College Park, MD
Kristi Muldoon Jacobs, PhD, US FDA, CFSAN, College Park, MD
Ji-Eun Lee, PhD, DABT, Kellogg, Battle Creek, MI
Allen Rudman, PhD, US FDA, Office of Food Additive Safety, CFSAN, College Park, MD
Ivan Rusyn, MD, PhD, Texas A&M University, College Station, TX
Catherine Whiteside, PhD, US FDA, CFSAN/OFVM/CFSAN, College Park, MD
Dori Germolec, PhD, NIEHS, Research Triangle Park, NC (Chair, Colloquium 3)
Betty Eidemiller, PhD, SOT, Reston, VA

Overview

The focus of this colloquium is on the application of ADME/PK studies to improve safety assessments for foods and cosmetics. Pharmacokinetic data on the time-course of a chemical in the body can be used to support the key extrapolations that are typically necessary for chemical risk assessments. In the past, the primary concern has been to extrapolate the doses in animal studies showing effects to equivalent doses in the human. With the recent emphasis on in vitro-based risk assessment, pharmacokinetic information is now being used to support the extrapolation from media concentrations associated with effects in vitro to the equivalent in vivo dose. This colloquium will provide a synopsis of the current state of the art for the application of pharmacokinetic data and modeling to risk assessments for foods, food contaminants and cosmetic ingredients. Three case studies will be provided illustrating the process of incorporating pharmacokinetic data in risk assessments based either on traditional or emerging toxicity study approaches. A panel discussion will enhance interaction with the attendees.

Colloquium Materials

Complexities in Evaluating Human Clinical and Observational Data for Ingredient Safety Assessment: Partially Hydrogenated Oils As a Case Study—November 7, 2014

Presentation Slides

US FDA Welcome
Dennis Keefe, PhD, Director, Office of Food Additive Safety Center for Food Safety and Nutrition

Overview: Value of ADME/PK Studies in Safety Assessment
Harvey J. Clewell, PhD, DABT, FATS, Director , Center for Human Health Assessment The Hamner Institutes for Health Sciences

The Importance of ADME/PK to Inform Human Safety Assessments Based on Animal Studies: Example with Furan
Gregory L. Kedderis, PhD, Independent Consultant

The Role of ADME/PK in the Extrapolation of In Vitro Toxicity Results to Equivalent In Vivo Exposures: Where It Started with the Acrylamide Example and Where We Are Now
Bas Blaauboer, Institute for Risk Assessment Sciences, Utrecht University

Consideration of ADME/PK in Safety Assessments for Engineered
William Boyes, PhD, USEPA/NHEERL

Organizing Committee

James J. Pestka, PhD, Colloquia Series Chair, Michigan State University, East Lansing, MI
Ronald Chanderbhan, PhD, US FDA, CFSAN, College Park, MD
Bryan Delaney, PhD, DABT, ATS, DuPont Pioneer, Johnston, IA
Suzanne Compton Fitzpatrick, PhD, DABT, US FDA, CFSAN, College Park, MD
Kristi Muldoon Jacobs, PhD, US FDA, CFSAN, College Park, MD
Ji-Eun Lee, PhD, DABT, Kellogg, Battle Creek, MI
Allen Rudman, PhD, US FDA, Office of Food Additive Safety, CFSAN, College Park, MD
Ivan Rusyn, MD, PhD, Texas A&M University, College Station, TX
Catherine Whiteside, PhD, US FDA, CFSAN/OFVM/CFSAN, College Park, MD
Harvey J. Clewell III, PhD, DABT, FATS; The Hamner Institutes for Health Sciences
Research Triangle Park, NC (Chair, Colloquium 2)
William L Roth, PhD, US FDA, College Park, MD (Member for Colloquium 2)
Betty Eidemiller, PhD, SOT, Reston, VA

Overview

Toxicological evidence is important in evaluating the health risks of food components and additives. This colloquium will provide a state-of-the art review of methodological approaches used in toxicology studies, using research related to Partially Hydrogenated Oils as a case study. Traditional controlled studies are difficult to conduct in humans although evidence can be brought together from epidemiological and other clinical studies. In addition, application of data obtained in animal studies has to be carefully evaluated for applicability for humans. Presentations by experts in the field will provide the scientific basis for understanding of current methods and of the science in this area.

Colloquium Materials