Applications of PBPK Modeling in Pesticide Risk Assessment

Thanks to all who joined us on Tuesday, Mar. 30, for a special review of how PBPK modeling can be successfully applied to pesticide risk assessment, presented by Dr. Cecilia Tan, of the US EPA Office of Pesticide Programs. If you missed it, you may view the recording.

The webinar had over 200 attendees, and was a great success! Stay tuned for next webinar, to be announced soon!

Abstract

Since the 1970s, the development and application of PBPK models for environmental chemicals, including pesticides, have grown steadily. However, only a handful of models have been accepted to support regulatory risk assessment due to challenges such as the difficulty to recruit reviewers with both modeling expertise and risk assessment experience, or the lack of transferability across modeling platforms. Despite these challenges, the number of PBPK models for pesticides submitted to regulatory agencies has risen in recent years. These models have been applied to estimate data-derived extrapolation factors (DDEFs) in lieu of default uncertainty factors when conducting inter-species and/or intra-species extrapolations. In other cases, PBPK models have been used to estimate human points of departure that are specific to exposure routes, durations and frequencies, and life-stages; assess mechanisms of biological responses based on their relationship with dose metrics by linking to a pharmacodynamic model; or investigate the major determinants of pharmacokinetic behaviors for pesticides within the same class. In this webinar, a short introduction on pesticide risk assessment will be introduced, followed by examples of PBPK applications to replace default uncertainty factors. Lessons learned from reviewing PBPK model submission will also be shared to encourage the modeling community to overcome these challenges so that PBPK modeling can be used more frequently as a quantitative tool in regulatory risk assessment for pesticides. 

About Dr. Cecilia Tan

Dr. Cecilia Tan received a MS in Environmental Health Sciences from the Harvard School of Public Health and a Ph.D. in Environmental Engineering and Sciences from the University of North Carolina, Chapel Hill. She also received an MBA from North Carolina State University. She was a postdoctoral fellow at CIIT and became a research scientist to continue her research on computational modeling approaches to refine chemical risk assessment. She later became the Associate Director in the Center for Human Health Assessment to manage contracts and lead several research projects. In 2009, Dr. Tan was recruited to be a research scientist in the Office of Research & Development (ORD) at the U.S. Environmental Protection Agency. While in ORD, Dr. Tan’s research focused on using biomarker data to assess potential health risk, and improving the understanding of the quantitative relationship among external exposures, internal doses, and adverse outcomes. In 2018, Dr. Tan transferred to the OPP as a senior scientist in the Health Effects Division to further support the OPP’s weight of evidence approach to integrate quantitative and qualitative data for improved risk assessment of pesticides, including the use of physiologically based pharmacokinetic (PBPK) models to replace the use of default uncertainty factors. As part of her outreach, she led the development of a reporting template for PBPK modeling analysis with a Health and Environmental Sciences Institute (HESI) working group; co-chaired with Joint Research Centre (JRC) to develop an OECD guidance on characterizing and validating PBPK models that are developed using non-animal methods; initiated a project to explore the opportunities for applying the kinetically derived maximum dose approach in risk assessment. Dr. Tan has authored more than 60 scientific publications. She frequently provides lectures and courses in pharmacokinetic modeling. 

About ScitoVation

ScitoVation helps clients assess chemical compound safety using innovative science, next-generation technology, and professional expertise. ScitoVation is known for partnership, flexibility, and proven success in its work to develop safer and more effective pharmaceuticals, food ingredients, agricultural chemicals, commodity chemicals, and consumer products.

As a spin-off of former The CIIT and The Hamner Institutes for Chemical & Drug Safety Sciences, ScitoVation is an industry leader of New Approach Methods (NAMS) for chemical/drug discovery & development in the rapidly evolving global regulatory landscape.