Vol. 26, Issue 3, 197-202, March 1998

Dermal Absorption and Pharmacokinetics of Isopropanol in the Male and Female F-344 Rat

Rodney J. Boatman, Louise G. Perry, Laurie A. Fiorica, J. Caroline English, Robert W. Kapp, Jr., Christopher Bevan, Tipton R. Tyler, Marcy I. Banton, and Gary A. Wright

Health and Environment Laboratories, Eastman Kodak Company (R.J.B., L.G.P, L.A.F., J.C.E.); BioTox (R.W.K.); Exxon Biomedical Sciences, Inc. (C.B.); Union Carbide Corp. (T.R.T.); Shell Chemical Co. (M.I.B.); and ARCO Chemical Co. (G.A.W.).

Isopropanol (IPA), as a 70% aqueous solution, was applied under occluded conditions to the shaved backs of male and female Fischer F-344 rats for a period of 4 hr. Maximum analyzed blood concentrations of IPA were attained at 4 hr and decreased steadily following removal of the test material. Blood concentrations were below the limit of quantification 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). ACE blood concentrations were below the limit of quantification at 24 hr. Basic pharmacokinetic parameters were similar for male and female rats 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 administration of [¹⁴C]IPA, 50-55% of the dose was eliminated as ¹⁴CO₂ with lesser amounts recovered as expired volatiles or in urine. Total recoveries following iv administration were 83% for both males and females. Following a 4-hr dermal exposure to [¹⁴C]IPA (70% aqueous solution), 84-86% of the dose was recovered from the application site. Dermal absorption rates were calculated by two independent methods. The values obtained were 0.78 ± 0.03 and 0.85 ± 0.04 mg/cm²/hr for males and 0.77 ± 0.13 and 0.78 ± 0.16 mg/cm²/hr for females. Calculated permeability coefficients of 1.37 to 1.50 x 10^-3 cm/hr for males and 1.35 to 1.37 x 10^-3 cm/hr for females indicate that in the rat, IPA is rapidly absorbed dermally when applied under occluded conditions.