Dermal absorption and pharmacokinetics of isopropanol in the male and female F-344 rat.
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.
Boatman
R J
RJ
Health and Environment Laboratories, Eastman Kodak Company, Rochester, NY 14652-6272, USA.
Perry
L G
LG
Fiorica
L A
LA
English
J C
JC
Kapp
R W
RW
Bevan
C
C
Tyler
T R
TR
Banton
M I
MI
Wright
G A
GA
D019840:2-Propanol / Q000097:blood / Q000493:pharmacokinetics*; D000042:Absorption / Q000502:physiology; D000096:Acetone / Q000097:blood / Q000493:pharmacokinetics; D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism; D002250:Carbon Radioisotopes / Q000378:metabolism; D005260:Female; D007275:Injections, Intravenous; D008297:Male; D010539:Permeability; D051381:Rats; D011916:Rats, Inbred F344; D012869:Skin Absorption / Q000502:physiology*
D002250:Carbon Radioisotopes; D000096:Acetone; D002245:Carbon Dioxide; D019840:2-Propanol