OpenTox Summer School 2023

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.