Where is the Chemical?: The In Vitro Disposition of Tox21 Chemicals

David M. Crizer Postdoctoral Fellow, National Toxicology Program

Understanding the in vitro disposition of chemicals evaluated in alternative models would enable better translation of in vitro bioactivity to the human dose context. In an effort to extrapolate in vitro media concentrations to in vivo exposures, toxicokinetic models can be used to estimate human oral exposures that would result in blood concentrations equivalent to the nominal media concentrations. One assumption in these models is that the ratio of the chemical concentration in media to cells is equivalent to the ratio of blood to tissue. Another assumption is the static nature of the cell culture exposure compared to the kinetic processes occurring in vivo. In contrast, human exposure is a dynamic process in which absorption, distribution, metabolism and elimination influence blood and tissue chemical concentrations.