Percutaneous absorption of benzyl acetate through rat skin in vitro. 2. Effect of vehicle and occlusion.
The effect of vehicle and occlusion on the in vitro percutaneous absorption of [methylene-14C]-benzyl acetate (1.7-16.6 mg/cm2) has been studied in diffusion cells using full thickness skin from male Fischer 344 rats. Absorption of neat benzyl acetate through rat skin occluded with parafilm was 49.3 +/- 2.0% (mean +/- SD, n = 4) after 48 hr. When benzyl acetate in ethanol was applied to the skin and the skin was occluded with parafilm, the extent of absorption at 48 hr was not significantly different from that after neat application. However at 6 hr, as the ethanol content of the application mixture was increased, the absorption of benzyl acetate through occluded skin was enhanced proportionally (r = 0.999). When phenylethanol was used as a vehicle, the extent of the benzyl acetate absorption through occluded skin at 48 hr was enhanced (P less than 0.05) compared with that after application neat; with 50% (v/v) phenyl-ethanol, absorption at 48 hr was 56.3 +/- 4.9%. However, this enhanced absorption did not correlate with the proportion of phenylethanol in the application mixture. When dimethylsulphoxide was used as a vehicle, the extent of absorption of benzyl acetate through occluded skin at 48 hr was enhanced (P less than 0.05) compared with that after application neat (absorption was 59.3 +/- 3.7% of the applied dose when 50% (v/v) dimethylsulphoxide was used). As the dimethylsulphoxide content of the application mixture was increased, the absorption of benzyl acetate was enhanced proportionally. Occlusion of the skin surface with parafilm often significantly enhanced absorption (P less than 0.05), although the effect varied with time and vehicle. In general, the degree of any enhanced absorption caused by the use of a vehicle or occlusion of the skin was small, and, in most cases, would be unlikely to be toxicologically significant.
Department of Pharmacology and Toxicology, St Mary's Hospital Medical School, Imperial College of Science Technology and Medicine, London, UK.
S A
SA
Hotchkiss
J M
JM
Miller
J
J
Caldwell
D000818:Animals; D001593:Benzyl Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002250:Carbon Radioisotopes; D004121:Dimethyl Sulfoxide / Q000008:administration & dosage; D004337:Drug Carriers; D000431:Ethanol / Q000008:administration & dosage; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D010232:Paraffin; D010626:Phenylethyl Alcohol / Q000008:administration & dosage; D011138:Polytetrafluoroethylene; D051381:Rats; D011916:Rats, Inbred F344; D012869:Skin Absorption
D001593:Benzyl Compounds; D002250:Carbon Radioisotopes; D004337:Drug Carriers; C046412:benzyl acetate; D000431:Ethanol; D010232:Paraffin; D011138:Polytetrafluoroethylene; D010626:Phenylethyl Alcohol; D004121:Dimethyl Sulfoxide