Generic Pharmacokinetic Models for Mother-to-Offspring Transfer of Chemicals

Our speaker is Dustin Kapraun, PhD, physical scientist with the Center for Public Health and Environmental Assessment (CPHEA) in the Office of Research and Development (ORD) at the U.S. Environmental Protection Agency (EPA).

In developing human health risk assessments, it is important to consider pregnant women, developing fetuses, and nursing children because chemical exposures experienced by these groups can lead to special types of adverse health outcomes (e.g., developmental effects) that do not typically arise in non-pregnant adults that experience similar exposures. Dr. Kapraun will educate us on two distinct pharmacokinetic (PK) models that include mother-to-offspring transfer that can help determine chemical risk exposure for these sensitive groups.

What you’ll learn: 

• A PK model that allows for simulations that quantify bioaccumulation of lipophilic persistent environmental chemicals (LPECs) in rats, mice, and humans, as well as transplacental and lactational transfer from mothers to their offspring.
• The second PK model is a physiologically based pharmacokinetic (PBPK) model that describes ADME in a pregnant human mother and her developing fetus during gestation.
• The steps taken to develop and evaluate these models and an explanation of their potential uses and their limitations.

Watch the Recording

Dustin Kapraun is a Physical Scientist with the Center for Public Health and Environmental Assessment (CPHEA) in the Office of Research and Development (ORD) at the U.S. Environmental Protection Agency (EPA). He holds degrees in mathematics (B.S., 1998), physics (M.S., 2002), and applied mathematics (Ph.D., 2014) and has worked in industry (as a computer programmer), academia (as a professor and department chair), and government (as a staff scientist and researcher). After finishing his Ph.D., he completed two postdoctoral research appointments at the EPA National Center for Computational Toxicology, during which he developed PBPK models for human pregnancy and data mining methods for identifying prevalent combinations of chemicals in humans. In 2017, Dr. Kapraun joined the EPA National Center for Environmental Assessment as a staff scientist specializing in PBPK modeling for chemical risk assessment applications. He now works at EPA’s CPHEA, where he continues to develop and apply PBPK models and other mathematical and statistical models to support chemical risk assessments. He also serves as Co-Chair of the CPHEA Pharmacokinetics Workgroup (PKWG) and is an Adjunct Associate Professor in the Department of Mathematics at North Carolina State University. Dr. Kapraun enjoys teaching and continues to find opportunities to do so through mentoring postdoctoral researchers, graduate students, and undergraduate students in quantitative risk assessment methods and leading workshops and training sessions on PBPK modeling and related topics.

Abstract:

In developing human health risk assessments, it is important to consider pregnant women, developing fetuses, and nursing children because chemical exposures experienced by these groups can lead to special types of adverse health outcomes (e.g., developmental effects) that do not typically arise in non-pregnant adults that experience similar exposures. Pharmacokinetic (PK) models, which are frequently used in chemical risk assessments, provide a means for estimating internal dose metrics from applied doses or environmental exposures based on mathematical descriptions of absorption, distribution, metabolism, and excretion (ADME). In addition to the ADME mechanisms commonly represented in adult PK models, PK models for pregnancy (and gestation) and the early postnatal period may include mathematical descriptions of transplacental and lactational transfer of chemicals from mothers to their offspring. We recently published two articles describing two distinct PK models that include mother-to-offspring transfer. The first model allows for simulations that quantify bioaccumulation of lipophilic persistent environmental chemicals (LPECs) in rats, mice, and humans, as well as transplacental and lactational transfer from mothers to their offspring. The second is a physiologically based pharmacokinetic (PBPK) model that describes ADME in a pregnant human mother and her developing fetus during gestation. Both models are generic in the sense that they can be parameterized for many chemicals. In this presentation, we will provide details of the two generic PK models for mother-to-offspring transfer of chemicals, including a description of steps we took to develop and evaluate these models and an explanation of their potential uses and their limitations.

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. A spin-off of the former The CIIT and The Hammer 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.