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Animal testing is often used to evaluate the potential risks, uses, and environmental impacts of chemicals. New Approach Methodologies (NAMs) are technologies and approaches that can potentially provide the same hazard and risk assessment information without the use of animal testing. To further establish scientific confidence in these approaches, this study will review the variability and relevance of existing mammalian toxicity tests, specifically when it comes to human health risk assessment. The goal of this study is to set data-driven and science-based expectations for NAMs based on the variability and relevance of the traditional toxicity testing models.
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Consensus
·2023
As part of its core mission, the U.S. Environmental Protection Agency (EPA) is tasked with assessing the hazards and risks to human health from exposure to pollutants. While some pollutants are well studied, there are little or no data on the potential health effects for many thousands of chemic...
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Description
An ad hoc committee of the National Academies of Sciences, Engineering, and Medicine will provide the Environmental Protection Agency (EPA) with a review of the variability and relevance of existing laboratory mammalian toxicity tests for human health risk assessment to inform the development of approaches for validation and establishing scientific confidence in using New Approach Methods (NAMs), and recommendations on expectations associated with NAMs when they cannot be compared with human studies. The work of the study committee will be informed by an initial public workshop organized by a subgroup of the committee, by a literature review that addresses the variability and human relevance of current laboratory mammalian toxicity tests and approaches to validation and establishing scientific confidence in using NAMs, and by public information gathering meetings organized by the study committee.
The proposed charge questions are as follows:
1. Does the committee assess the literature review and data provided as reflecting a comprehensive, workable, objective, and transparent process?
2. Given the results of the literature review and workshops, what are the implications of the qualitative and quantitative variability of laboratory mammalian toxicity studies when using them to establish the performance of NAMs?
3. What do the literature review and workshops indicate about concordance between laboratory mammalian models and humans in the adverse effects following chemical exposure and how might this frame expectations of NAMs when they cannot be compared directly with human studies?
4. The Committee shall impart expert advice on addressing the two related issues that were left unresolved in the 2017 NRC report:
a. Evaluation of the validity of assays that are not intended as one-to-one replacements for in vivo toxicity assays; and
b. Assessment of the concordance of data from assays that use cells or proteins of human origin with toxicity data that are virtually all derived from animal models.
5. Based on the conclusions from 1 – 4 above, how may the Committee foresee this information being incorporated into a new or the existing validation paradigm or scientific confidence framework so that EPA can ensure that NAMs are equivalent to or better than the animal tests replaced?
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Committee Membership Roster Comments
Patience Browne, OECD, served on the committee until 9/29/22
Nicole Kleinstreuer, NIEHS, served on the committee until 9/29/22
A. John Bailer, Miami University, and Malcolm Macleod, University of Edinburgh, will be working with the committee as unpaid consultants as of October 2022.
A. John Bailer is emeritus professor of statistics at Miami University. He retired after 34 years at Miami University where he was university distinguished professor and founding chair of the Department of Statistics. He also was an affiliate member of the Departments of Biology, Media, Journalism & Film, and Sociology & Gerontology. His research interests include the design and analysis of environmental and occupational health studies, quantitative risk estimation and communicating statistical concepts in journalism. He is a founder and panelist on the Stats+Stories podcast. Dr. Bailer is a fellow of the American Statistical Association (ASA), a fellow of the Society for Risk Analysis, and a recipient of the ASA Founders Award. He has served on several National Research Council committees, including the Committee on Improving Risk Analysis Approaches Used by the U.S. EPA, the Committee on Spacecraft Exposure Guidelines, the Committee to Review the OMB Risk Assessment Bulletin, and the Committee on Toxicologic Assessment of Low-Level Exposures to Chemical Warfare Agents. He also has served as a member of the Report on Carcinogens Subcommittee and the Technical Reports Review Subcommittee of the Board of Scientific Counselors of the National Toxicology Program. Dr. Bailer received a Ph.D. in biostatistics from the University of North Carolina at Chapel Hill.
Malcolm Macleod has been Professor of Neurology and Translational Neurosciences at the University of Edinburgh since 2012, and Academic Lead for Research Improvement and Research Integrity since 2019. His primary contribution has been in the application of systematic review and meta-analysis to data from in vivo and in vitro laboratory studies, including the development of novel methodologies and automation tools; and he founded the CAMARADES collaboration on 2005. He holds degrees in Pharmacology (BSc, University of Edinburgh, 1987) and Medicine (MBChB, University of Edinburgh, 1991); a PhD (On the Neuroprotective Actions of FK506, University of Edinburgh, 2001); has completed postgraduate training in internal medicine (MRCP, Royal College of Physicians, 1994) and Neurology (Certificate of Completion of Specialist Training, UK JCHMT, 2005); and is a Fellow of the Royal Society of Biology (2016) and the Academy of Medical Sciences (2022). He has authored over 300 peer reviewed publications with an h-index of 92, and his team were awarded the 2021 British Neuroscience Association Credibility in Neuroscience Award. He participated in the March 2013 NAS Weight of Evidence Workshop hosted by the Committee to Review the IRIS process, and the June 2022 National Academies Workshop to Support EPA's Development of Human Health Assessments: Artificial Intelligence and Open Data Practices in Chemical Hazard Assessment.
Sponsors
EPA
Staff
Kathryn Guyton
Lead
Leslie Beauchamp
Natalie Armstrong
