© 1994 Oxford University Press
research-article |
Disposition and Pharmacokinetics of Isopropanol in F-344 Rats and B6C3F1 Mice1,2
*International Research and Development Corporation Mattawan, Michigan 49071
Research Triangle Institute, Research Triangle Park North Carolina
Exxon Biomedicai Sciences East Millstone, New Jersey
ARCO Chemical Co., Newton Square Pennsylvania
|| Shell Oil Co., Houston, Texas
¶ BP America, Cleveland, Ohio
** Union Carbide Corp, Danbury, Connecticut
Received February 18, 1993; accepted December 27, 1993
The absorption, metabolism, disposition, and excretion of isopropanol (IPA) were studied in male and female rats and mice. Animals were exposed by iv (300 mg/kg) and inhalation (500 and 5000 ppm for 6 hr) routes; additionally, IPA was given by gavage to rats only in single and multiple 300 and 3000 mg/ kg doses. In the rat approximately 81–89% of the administered dose was exhaled (as acetone, CO2, and unmetabolized IPA); approximately 76% of the dose in mice was exhaled after iv bolus but 92% was exhaled following inhalation. Approximately 3–8% of the administered dose was excreted in urine as IPA, acetone, and a metabolite tentatively identified as isopropyl glucuronic acid. Small amounts of radiolabel were found in feces and in the carcass. There were no major differences in the rates or routes of excretion observed either between sexes or between routes of administration. Additionally, repeated exposure had no effect on excretion. However, both the route of administration and the exposure or dose level influenced the form in which material was exhaled. Following exposure to 5000 ppm, a greater percentage of unmetabolized IPA was recovered in the expired air than following exposure to 500 ppm, implying saturation of metabolism.