The committee aims to address key needs related to physiologically based pharmacokinetic (PBPK) modeling practices and applications that could facilitate use of PBPK models more consistently within the risk assessment context.
This work was focused on the development of a general reporting template derived from a consensus among modelers and risk assessors, which expands on an FDA template and will recommend additional elements necessary for submission of PBPK analyses to public health agencies.
This group is developing a framework to inform the minimum set of in vivo, in vitro, or in silico absorption, distribution, metabolism, or excretion (ADME) data required for various extrapolation applications; manuscript in preparation.
The purpose of this group is to evaluate and address commonly raised technical and scientific issues related to the use of KMD as an approach to select doses in toxicology testing studies or to interpret dose-response study results. Examples of these issues include the appropriate use of PK data to determine dose non-linearity, the possibility of human exposure levels close to KMD, the determination of KMD from sparse blood or tissue concentration data, the use of in silico models to predict systemic dose and key ADME parameters, and the use of KMD to set the top dose in toxicity studies. This group aims to:
This initiative is a joint collaborative project between the HESI PBPK and TEA Committees that is aimed at evaluating the utility of the 90d dog study (OECD TG 409, OPPTS 870.3150) for agrochemical safety evaluation. The project builds on recent international work in this space and strives to identify under what conditions this study is needed to inform human health risk assessment of agrochemicals, with the ultimate goal of identifying conditions where the test can be safely waived within a weight of evidence approach.
Deputy Director
Director, Center for Environmental and Ecological Health (CEEH)
membry@hesiglobal.orgMichelle Embry received her PhD in Toxicology in 2004 and her BS in Biology and Environmental Science and Policy in 1998 from Duke University. She is currently the Deputy Director of Environmental Science at HESI, where she provides leadership, technical direction, and guidance to varied, multi-stakeholder, collaborative committees on topics related to risk assessment and environmental protection worldwide.
Prior to joining HESI in 2006, Dr. Embry worked as an Ecological Risk Assessor at the US EPA’s Office of Pesticide Programs. She has expertise in both human health and ecotoxicology, with an emphasis on integrated approaches and alternative methods. Her current project portfolio includes the Animal Alternatives in Environmental Risk Assessment Committee and the Development of Methods for a Tiered Approach to Assess Bioaccumulation of Chemicals Committee, two of HESI’s projects aimed at improving ecological risk assessment. Dr. Embry’s work also includes the Risk Assessment in the 21st Century (RISK21) Committee, which developed a scientific, transparent, and efficient approach for human health risk assessment, including a web-based tool that has led to outreach and training activities on risk assessment approaches worldwide. In addition, she works with HESI staff and partners on project development related to chemical risk assessment issues.
Dr. Embry is an elected member of the SETAC North America Board of Directors (2014 to present), chair of the SETAC Global Partners Advisory Committee, and a member of the SETAC Bioaccumulation and Animal Alternatives Advisory Group Steering Teams. She is a full member of the Society of Toxicology (SOT) and a member of the SOT Risk Assessment and Mixtures Specialty Sections. She was a member of the ECETOC Task Force on Information to be Considered in a Weight-of-Evidence-Based PBT/vPvB Assessment of Chemicals (Annex XIII of REACH) in 2013 to 2014 and was a steering team member of the SETAC Adverse Outcome Pathway (AOP) Pellston Workshop (Spring 2017). Dr. Embry is also one of the founding partners on the “eco data hub” initiative, started in Fall 2016.
Dr. Claire O’Brien holds a PhD in Pharmacology and Toxicology from the University of California, Davis, and an MPH in Environmental Health from San Diego State University. She comes to HESI with experience a Regulatory Specialist at a biotech company where she helped to develop a regulatory strategy for bringing innovative infant nutrition products to market. She also has experience in safety assessment and toxicology of dietary supplements, educational outreach on environmental health topics within a community setting, and as a lead clinical trials coordinator for a major research study. Dr. O’Brien will work on the Cardiac Safety Committee, PBPK Committee, and the PATB program. She will start with HESI at the end of June.
Sumitomo Chemical Co., Ltd.
Australian Pesticides and Veterinary Medicines Authority
Corteva Agriscience
US Environmental Protection Agency
ExxonMobil
Barton Systems Pharmacology and Toxicology
Bayer CropScience
Liverpool John Moores University
Toxicology and Applied Pharmacology, 2022
A physiologically based pharmacokinetic (PBPK) modeling approach can be a valuable tool used in the early stages of a chemical safety assessment program to optimize the design of longer-term animal toxicity studies or to interpret study results.
Regulatory Toxicology and Pharmacology, 2021
Human health risks from chronic exposures to environmental chemicals are typically estimated from potential human exposure estimates and dose-response data obtained from repeated-dose animal toxicity studies. Various criteria are available for selecting the top (highest) dose used in these animal studies. For example, ...
Regulatory Toxicology and Pharmacology, 2021
Top dose selection for repeated dose animal studies has generally focused on identification of apical endpoints, use of the limit dose, or determination of a maximum tolerated dose (MTD). The intent is to optimize the ability of toxicity tests performed in a small number of animals to detect effects for hazard identification. An ...
Regulatory Toxicology and Pharmacology, 2020
Physiologically-based pharmacokinetic (PBPK) modeling analysis does not stand on its own for regulatory purposes but is a robust tool to support drug/chemical safety assessment. While the development of PBPK models have grown steadily since their emergence, only a handful of models have been accepted to support regulatory ...
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