Fundamentals of physiologically-based toxicokinetic models

Environmental toxicants enter the body via inhalation, ingestion, and/or dermal absorption, The exposure scenario and physical properties of a compound largely determine the actual uptake route(s). Once a xenobiotic enters the body, it is transported by blood to the organs and tissues where it can be stored in lipids and fatty tissue or eliminated through exhalation, excretion, and/or metabolism. Physiologically-based toxicokinetic (PBTK) models mathematically represent the biological, physiological, and metabolic processes in the body affecting the disposition of a xenobiotic. This paper describes the processes involved in the uptake, distribution and elimination of xenobiotics with an emphasis on endocrine disrupting compounds. It provides references to several data sources and discusses the issues of uncertainty and variability.