Percutaneous absorption, biotransformation, retention and excretion of 1,3-diaminobenzene in the rat.
Groups of seven male Wistar rats were dermally exposed for 24 hr to 556 mumol [14C]meta-phenylenediamine (MPD; 1,3-diaminobenzene) in either aqueous solution (Group 2) or 4% hydrogen peroxide (Group 3). The percutaneous absorption and the amount of non-excreted radioactivity were significantly higher in Group 2 rats. Radioactivity associated with DNA purified from the liver and kidneys was demonstrated. Urine was the principal route of excretion, especially in Group 2 rats. Rats in Group 3 excreted significantly more MPD in the faeces than did Group 2 rats. Urinary excretion of material that constituted two of the peaks in the high-performance liquid chromatogram demonstrated first-order elimination kinetics. Three N-acetylated metabolites (N-acetyl-1,3-diaminobenzene, N,N'-diacetyl-2,4-diaminophenol and N,N'-diacetyl-1,3-diaminobenzene) accounted for 49 and 37% of the urinary excretion of group 2 and 3 rats, respectively, indicating that such metabolites represent important pathways in the metabolism of MPD. Minor excretion of at least one highly hydrophilic, unidentified metabolite of MPD was demonstrated. High-performance liquid chromatographic analysis of urine indicated that the XAD-2 purification procedure, which is usually used before mutagenicity testing in vitro, resulted in some of the radioactive materials being discarded. The percutaneous absorption of MPD in vivo was compared with the permeability of isolated epidermal membranes in vitro. These studies showed that such in vitro studies might be used to predict the dermal absorption by rats, in vivo, of MPD and similar, topically applied compounds.
Lam
H R
HR
Institute of Toxicology, National Food Agency, Søborg, Denmark.
Bisgaard
H C
HC
D000818:Animals; D001711:Biotransformation; D015197:Carcinogenicity Tests; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000032:analysis; D006868:Hydrolysis; D008297:Male; D009152:Mutagenicity Tests; D010655:Phenylenediamines / Q000493:pharmacokinetics / Q000633:toxicity* / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains; D012869:Skin Absorption; D013056:Spectrophotometry, Ultraviolet
D010655:Phenylenediamines; D004247:DNA; C008381:3-phenylenediamine