Toxicokinetic

Toxicokinetics is the study of how a toxic substance is absorbed, distributed, metabolized, and excreted by an organism, and how these processes shape the time course of internal exposure. It focuses on the relationship between external dose and internal dose, often described by pharmacokinetic principles applied to harmful agents.

Key processes include absorption, distribution to tissues, metabolism (often to more polar, excretable forms), and elimination through renal, biliary, or other excretory routes. The combined effect is described by models such as compartment models or physiologically based pharmacokinetic (PBPK) models, yielding parameters like clearance, volume of distribution, bioavailability, half-life, and the area under the concentration-time curve (AUC).

Variability arises from route of exposure, dose, species, age, sex, genetics, disease, and interactions with other chemicals. Kinetic processes can be nonlinear at high doses due to saturable metabolism or transport, and enzyme induction or inhibition can change clearance over time.

Applications include risk assessment, interspecies and route-to-route extrapolation, and biomonitoring. Toxicokinetic data support in vitro–in vivo extrapolation (IVIVE) to predict internal doses from external exposures and help interpret biomarker measurements. It is distinguished from toxicodynamics, which describes the biological effects once target tissues are reached.