DERMAL ABSORPTION AND PHARMACOKINETICS OF ISOPROPANOL IN THE MALE ANDFEMALE F344 RAT

Isopropanol (IPA), as a 70% aqueous solution, was applied under occlud ed conditions to the shaved backs of male and female Fischer F-344 rat s for a period of 4 hr. Maximum analyzed blood concentrations of IPA w ere attained at 4 hr and decreased steadily following removal of the t est material. Blood concentrations were below the limit of quantificat ion at 8 hr. Acetone (ACE) blood levels rose steadily during the 4-hr exposures and continued to rise following removal of the test material , reaching Peak analyzed levels at 4.5 hr (male) and 5 hr (females). A CE blood concentrations were below the limit of quantification at 24 h r. Basic pharmacokinetic parameters were similar for male and female r ats with mean, first-order elimination half-lives for IPA and ACE of 0 .8 to 0.9 hr and 2.1 to 2.2 hr, respectively. Following iv administrat ion of [C-14]IPA, 5055% of the dose was eliminated as (CO2)-C-14, with lesser amounts recovered as expired volatiles or in urine. Total reco veries following iv administration were 83% for both males and females . Following a 4-hr dermal exposure to [C-14]IPA (70% aqueous solution) , 84-86% of the dose was recovered from the application site. Dermal a bsorption rates were calculated by two independent methods. The values obtained were 0.78 +/- 0.03 and 0.85 +/- 0.04 mg/cm(2)/hr for males a nd 0.77 +/- 0.13 and 0.78 +/- 0.16 mg/cm(2)/hr for females. Calculated permeability coefficients of 1.37 to 1.50 x 10(-3) cm/hr for males an d 1.35 to 1.37 x 10(-3) cm/hr for females indicate that in the rat, IP A is rapidly absorbed dermally when applied under occluded conditions.