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.
The primary objective of this initiative is to provide clear recommendations on utilizing physiologically-based pharmacokinetic (PBPK) models for conducting critical extrapolations needed in human health risk assessments. These extrapolations cover inter-species, route-to-route, age-related, and intra-species absorption models.
Two specialized groups have successfully collected and categorized data from hundreds of PBPK studies focusing on oral absorption and brain distribution models from the published literature.
The ongoing work aims to develop this data into two manuscripts that will:
In collaboration with the HESI TEA Committee, this project aims to create a science-based waiver framework for 90-day dog studies in agrochemical assessment. We are contributing to USEPA’s ongoing review of these studies, assisting their data analysis, and connecting with international efforts. Expect increased activity in this area by early 2025, sparked by USEPA’s findings.
A paper on “New Approach Methodologies for Repeat-Dose Study Design and Interpretation: Weight of Evidence to Determine Dose Dependent Transitions” is in progress.
Launched in 2024, this project addresses training gaps in PBPK by gathering input through surveys and developing a WebHub to connect training resources and tools. The immediate goal is to outline plans for this resource hub.
Kinetically Derived Maximum Dose (KMD): 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:
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.
SLR Consulting
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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