title: Percutaneous absorption of nicotinic acid, phenol, benzoic acid and triclopyr butoxyethyl ester through rat and human skin in vitro: further validation of an in vitro model by comparison with in vivo data.
abstract: The in vitro percutaneous absorption of three model compounds, nicotinic acid, phenol and benzoic acid, and the herbicide triclopyr butoxyethyl ester (triclopyr BEE) has been investigated in flow-through diffusion cells using skin from male Fischer 344 rats and humans. After the application of the four chemicals to the epidermal surface of unoccluded full-thickness rat skin, the absorption of each compound across the skin and into the receptor fluid at 72 hr reached 3.7 +/- 0.3, 5.7 +/- 0.6, 26.7 +/- 3.7 and 48.3 +/- 1.2% (mean +/- SD, n = 2-7) of the applied dose for triclopyr BEE, nicotinic acid, phenol and benzoic acid, respectively. After the application of the four chemicals to the epidermal surface of unoccluded full-thickness human skin, the absorption of each compound across the skin and into the receptor fluid at 72 hr was significantly (P < 0.05) less than through rat skin, reaching 0.7 +/- 0.1, 0.7 +/- 0.2, 18.8 +/- 1.3 and 37.8 +/- 6.9% (mean +/- SD, n = 2-7) of the applied dose for triclopyr BEE, nicotinic acid, phenol and benzoic acid, respectively. Occlusion of the skin surface with teflon caps often significantly (P < 0.05) enhanced the percutaneous absorption of the model compounds, although this effect was not uniform, varying with the compound under study and the skin (rat or human) used. When rat skin was occluded with teflon caps, the extent of absorption at 72 hr reached 8.6 +/- 0.8, 36.2 +/- 1.7 and 51.8 +/- 3.3% (mean +/- SD, n = 3-4) for nicotinic acid, phenol and benzoic acid, respectively. Corresponding values for human skin occluded with teflon caps were 3.3 +/- 1.6, 47.1 +/- 0.5 and 65.5 +/- 7.1% (mean +/- SD, n = 3-4). The experiments on the absorption of each model compound through rat and human skin were repeated and there was generally good agreement between the results from the two sets of experiments. The in vitro data reported compare favourably with data obtained by other workers using both in vitro and in vivo methodologies. The in vitro: in vivo correlation supports the use of the flow-through diffusion cell system as a model for the prediction of percutaneous absorption in vivo in the rat and in humans.
authors.affiliation: Department of Pharmacology and Toxicology, St Mary's Hospital Medical School, Imperial College of Science, Technology and Medicine, London, UK.
authors.forename: S A
authors.initials: SA
authors.lastname: Hotchkiss
authors.forename: P
authors.initials: P
authors.lastname: Hewitt
authors.forename: J
authors.initials: J
authors.lastname: Caldwell
authors.forename: W L
authors.initials: WL
authors.lastname: Chen
authors.forename: R R
authors.initials: RR
authors.lastname: Rowe
mesh_terms: D000042:Absorption; D000818:Animals; D001565:Benzoates / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019817:Benzoic Acid; D004305:Dose-Response Relationship, Drug; D006016:Glycolates / Q000493:pharmacokinetics*; D006801:Humans; D007700:Kinetics; D008297:Male; D009525:Niacin / Q000493:pharmacokinetics*; D019800:Phenol; D010636:Phenols / Q000493:pharmacokinetics*; D051381:Rats; D011916:Rats, Inbred F344; D012867:Skin / Q000378:metabolism*
chemical_list: D001565:Benzoates; D006016:Glycolates; D010636:Phenols; D009525:Niacin; D019800:Phenol; D019817:Benzoic Acid; C032742:triclopyr