Toxic responses to environmental chemicals are known to be dependent on exposure route, kinetic behavior, as well as the dosage used in the toxicology study. Therefore the knowledge of the basic kinetic parameters, bioavailability, dose proportional range, and internal dose are indispensible. Such data are vital for the selection of dosages for the toxicology studies, interpretation of toxicology study results, facilitation of interspecies scaling, as well as risk assessment. The toxicokinetics of chlorpyrifos were determined in F344/N rats and B6C3F1 mice. Groups of rodents were dosed with chlorpyrifos intravenously at a dose of 3 mg/kg and orally at 30 mg/kg. Blood samples were collected at a series of time points after dosing and the plasma prepared for analysis of chlorpyrifos and its main metabolite 3,5,6-trichloro-2-pyridinol. All samples were analyzed using a bioanalytical method that was developed for these studies. Results of the analyses showed a relatively rapid elimination of chlorpyrifos (half- life of 15 minutes) and a low bioavailability (3%). Results of the kinetic studies will be useful in helping select dosages for subsequent toxicity studies.
