Distribution and DNA adduct formation of radiolabeled methylenediphenyl-4,4'-diisocyanate (MDI) in the rat after topical treatment.
Female Wistar rats were treated topically with [14C]methylenediphenyl-4,4'-diisocyanate (MDI) in acetone on the back. Fecal excretion of radioactivity amounted to 20% of the administered radioactivity within 24 h. Urinary excretion was below 1%. About 10% of the radioactivity was retained at the site of application. Epidermal nuclear protein exhibited very high specific radioactivities; 32P-postlabeling analysis did not reveal isocyanate-DNA adducts. In liver, lung and kidney, nuclear protein radioactivity was much lower than in the epidermis. DNA radioactivity in liver was at the limit of detection. Conversion to the units of the Covalent Binding Index, CBI = (micromol adduct/mol DNA nucleotide) per (mmol chemical administered/kg body weight) resulted in a value of < 0.1. In comparison with genotoxic carcinogens, this upper bound value is indicative of a very weak maximum possible systemic genotoxic potency of topically administered MDI.
Vock
E H
EH
Department of Toxicology, University of Würzburg, Germany.
Lutz
W K
WK
D000287:Administration, Topical; D000818:Animals; D001665:Binding Sites; D002250:Carbon Radioisotopes; D004247:DNA / Q000378:metabolism*; D018736:DNA Adducts / Q000096:biosynthesis*; D005260:Female; D017953:Isocyanates / Q000493:pharmacokinetics*; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000187:drug effects / Q000378:metabolism*; D014018:Tissue Distribution; D001559:Benzhydryl Compounds
D002250:Carbon Radioisotopes; D004247:DNA; D018736:DNA Adducts; D017953:Isocyanates; D009687:Nuclear Proteins; C005969:4,4'-diphenylmethane diisocyanate; D001559:Benzhydryl Compounds