title: Percutaneous penetration and genotoxicity of 4,4'-methylenedianiline through rat and human skin in vitro.
abstract: 4,4'-Methylenedianiline (MDA) is a primary aromatic amine used in the plastics industry and is classified by the International Agency for Research on Cancer as an animal carcinogen and possible human carcinogen. In order to estimate human exposure it is useful to determine percutaneous penetration. Previous studies have suggested that both rat and human skin were permeable to MDA, with greater penetration being seen through human skin. In this study no significant difference was seen between the percutaneous penetration of MDA through human or rat skin for three different treatment levels: 0.01, 0.1 and 1mg per skin membrane (0.32 cm(2)). The apparent dermal flux was calculated as 0.7 +/- 0.3 and 10.1 +/- 2.0 microg/cm(2)/h for the 0.01 and 0.1mg treatments, respectively. The permeability constant K(p) was estimated at 1.8 x 10(-3) cm/h and the lag time at 3.5 +/- 0.5 h. MDA absorbed into the skin was found to be bioavailable. Experiments also showed that after application of 0.1mg MDA, 4% penetrated through latex and nitrile gloves, respectively. The potential genotoxicity of MDA in human skin was assessed by DNA (32)P-postlabelling; levels of DNA adducts were detected, following the treatment and penetration of 1mg MDA.
authors.affiliation: Biological Chemistry, Faculty of Medicine, Sir Alexander Fleming Building, South Kensington Campus, Imperial College London, London SW7 2AZ, UK.
authors.forename: Susan H
authors.initials: SH
authors.lastname: Kenyon
authors.forename: Joya
authors.initials: J
authors.lastname: Bhattacharyya
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Benson
authors.forename: Paul L
authors.initials: PL
authors.lastname: Carmichael
mesh_terms: D000814:Aniline Compounds / Q000493:pharmacokinetics* / Q000633:toxicity*; D000818:Animals; D004247:DNA / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification; D018736:DNA Adducts / Q000187:drug effects; D015194:Diffusion Chambers, Culture; D006801:Humans; D066298:In Vitro Techniques; D007840:Latex; D008297:Male; D009153:Mutagens / Q000493:pharmacokinetics* / Q000633:toxicity*; D009570:Nitriles; D010539:Permeability; D010544:Peroxidases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012869:Skin Absorption; D001559:Benzhydryl Compounds
chemical_list: D000814:Aniline Compounds; D004247:DNA; D018736:DNA Adducts; D007840:Latex; D009153:Mutagens; D009570:Nitriles; D010544:Peroxidases; C009505:4,4'-diaminodiphenylmethane; D001559:Benzhydryl Compounds