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SOT FDA Colloquia

In 2014, SOT and the US FDA Center for Food Safety and Applied Nutrition (CFSAN) began a partnership to present colloquia designed to present high-quality, cutting-edge, future-oriented toxicological science to provide a well-grounded foundation to inform the work of US FDA employees. These colloquia are open at no cost to all who are interested. Recordings and materials are available after the events and can be found below.

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2019–2020

Four topics are now in development for colloquia to be held in 2019-2020.

  • October: Integrated Approaches to Testing and Assessment
  • December: Dermal Absorption Concepts
  • February: Route-Route Extrapolation
  • April: Use of Artificial Intelligence/Big Data in Food Additive, Ingredient, and Cosmetics Evaluation
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 (pending)

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

Agenda | Event Captions | Video Presentation

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

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

Agenda | Event Captions | Video Presentation

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

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

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.

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

Agenda | Event Captions | Video Presentation

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

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

Agenda | Event Captions | Video Presentation

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

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

Agenda | Event Captions | Video Presentation

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

Concluding Slides

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

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

Agenda | Event Captions | Video Presentation

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

Concluding Slides

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

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

Agenda | Event Captions | Video Presentation

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

Concluding Slides

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

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

Agenda | Event Captions | Video Presentation

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

Concluding Slides

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

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

Agenda | Event Captions | Video Presentation

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

Concluding Slides

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

Timothy J. Shafer, Chair, US EPA, Research Triangle Park, NC
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 (Coming Soon) | 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

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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

Concluding Slides

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
Safety Assessment Approaches in Young Children—May 20, 2016

Allen Rudman, Chair, US FDA, CFSAN, College Park, MD
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

Agenda | Event Captions (Coming Soon) | Video Presentation

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

Ivan Rusyn, Chair, Texas A&M, College Station, TX
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

Agenda | Event Captions (Coming Soon) | Video Presentation

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

Suzanne Fitzpatrick, Chair, US FDA, College Park, MD
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

Agenda | Event Captions | Video Presentation

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

 

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

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

Agenda | Event Captions | Video Presentation

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
Contemporary Issues in Risk Assessment—June 17, 2015

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

Agenda | Event Captions | Video Presentation

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.


The Use of the Mechanistic Evidence in Human Health Assessments

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

Agenda | Event Captions | Video Presentation

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

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

Agenda | Event Captions | Video Presentation

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

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

Agenda | Event Captions | Video Presentation

Presentation Slides

Setting the Case Study Framework—An Introduction to PHOs
Martin Ronis, PhD, Professor, Department of Pediatrics, Department of Pharmacology & Toxicology, University of Arkansas for Medical Sciences, Associate Director for Basic Research, Arkansas Children’s Nutrition Cente

Mode of Action and Dose-Response Evaluation of the Effect of Partially
Michael L. Dourson, PhD, DABT, ATS

Dose-Response Assessment Approaches to the Analysis of Non-Cancer Health Effects: Current Practices, Advice from the National Academies, and 2014 WHO/IPCS Guidance
Weihsueh A. Chiu, PhD, Chief, Toxicity Pathways Branch Integrated Risk Information System (IRIS) Division National Center for Environmental Assessment Office of Research and Development US Environmental Protection Agency

Organizing Committee

  • James J. Pestka, PhD, Colloquia Series Chair, Michigan State University, East Lansing, MI
  • Martin Ronis, PhD, Colloquium Chair, University of Arkansas for Medical Sciences, Little Rock, AR
  • 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
  • Jin Young K. Park, US FDA, CFSAN, College Park, MD
  • 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
  • Betty Eidemiller, PhD, SOT, Reston, VA