Toxicologist's Report on Metabolism and Pharmacokinetics of Radiolabeled TBA 534 Tertiary Butyl, Alcohol with Cover Letter dated 03/24/94

摘要

Data on the metabolism and pharmacokinetics of radiolabeled terti- ary butyl alcohol TBA3 collected by Midwest Research Institute (MRI), Kansas City, have been reviewed, analyzed and summarized in this report. While studies were not completed by MRI, much Lapor- tant information bearing on the interpretation of TBA toxicity tests was obtained. From available data, it is evident that: TBA is rapidly absorbed and distributed after oral administration. The half-life of TBA and its metabolites in blood at several dose levels and by both oral and inhalation exposure routes is about 9 hours. Oral dosing of 1500 mg/kg exceeded the capacity of rats to eliminate TBA and its metabolites. Comparable blood levels of TBA and its metabolites are found after either oral dosing of 350 mq/kg or by inhalation of 2000 ppm. Nearly all the radioactivity which is recovered from the urine (at least 25% of the administered dose) is one or more polare volatile metabolites. There are no obvious differences in the pharmacokinetics of TBA following gavage vs following inhalation exposure. Levels above 1500 ppm (by inhalation) or 1500 mq/kg (oral) cannot be used in teratology/reproduction studies because rats are heavily sedated.