OpenTox Summer School 2022
Theory, Practice, and Exercises in Toxicokinetics
When you are exposed to a chemical, you may wonder: How much of it gets into your body? Where does it go in your body? How long does it stay in your body? Is that enough to cause any kind of health effect? Or you may wonder the reverse: If studies have shown that some health effect occurs at a certain blood level of a chemical, what exposure would it take to reach that blood level? These questions can be answered using toxicokinetics (TK): the study of how the body absorbs, distributes, metabolizes, and excretes chemicals. This session will first introduce some basic concepts of toxicokinetic modeling: mathematical structure and parameters of TK models; one- and two-compartment models; physiologically-based TK models; metrics of internal exposure; and applications of TK models (extrapolating between species, between routes, between internal and external exposures, and between in vitro and in vivo contexts). Then, the session will introduce high-throughput toxicokinetics (HTTK): TK models that can be rapidly parameterized and applied to make predictions for thousands of chemicals. We have developed a free, open-source software package (for the statistical software environment R) that implements HTTK, including simulation of population variability in TK. The session will introduce the “httk” R package to participants, with a hands-on activity that will give participants practical experience in using this software tool to answer questions relevant to chemical prioritization.
OpenTox 2022 Virtual Conference
Monte Carlo for uncertainty and variability simulation in high-throughput toxicokinetic modeling
When using high-throughout toxicokinetics (HTTK) for risk-based chemical prioritization, it is important to quantify both uncertainty and inter-individual variability in HTTK model predictions. In our open-source R package “httk”, uncertainty and variability quantification are accomplished using a Monte Carlo approach. This presentation will provide an overview of Monte Carlo for uncertainty and variability simulation, including the following topics:
Uncertainty vs. Variability in HTTK models
Key uncertainties in TK parameters and how they are quantified
Simulating human TK variability: HTTK-Pop
Simulating sensitive subpopulations using HTTK-Pop
Relative contributions of uncertainty and variability to HTTK model predictions
The views expressed in this abstract and presentation are those of the author(s) and do not necessarily reflect the views or policies of the U.S. EPA.