The excretion of chlorophenylmercapturic acid, chlorophenols and a guanine adduct in the urine of chlorobenzene-treated rats after phenobarbital pretreatment.
Chlorobenzene (CB) was administered to male Wistar rats. Twenty-four-hour urine samples were collected over a period of 7 days. p-Chlorophenylmercapturic acid, chlorophenols and a guanine adduct were determined by chromatographic methods. The excretion pattern of p-chlorophenyl-mercapturic acid did not seem to be significantly affected by phenobarbital. To analyze for the chlorophenols and guanine adducts, diluted urine was subjected to cation exchange chromatography using UV-detection. Fractions were found containing chlorophenols and a compound showing chromatographic properties similar to those of the synthetic N7-phenylguanine. The results of the HPLC analyses suggested the presence of a guanine adduct excreted on days 1 and 2 and between days 4 and 6 post-administration. There were no compounds detected which were identical with p-, m- or o-isomers of N7-chlorophenylguanine. The excretion of p- and m-chlorophenols by phenobarbital-pretreated animals was twice as high as that in untreated rats. A 4-fold increase was detected for o-chlorophenol. It is assumed that it is mainly direct hydroxylation that can be induced by phenobarbital. Dehalogenated phenolic metabolites may be capable of covalent binding to DNA.
Krewet
E
E
Institute of Hygiene and Occupational Medicine, University of Essen, F.R.G.
Müller
G
G
Norpoth
K
K
D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000652:urine; D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D002722:Chlorobenzenes / Q000633:toxicity*; D002733:Chlorophenols / Q000652:urine*; D002849:Chromatography, Gas; D002852:Chromatography, Ion Exchange; D006147:Guanine / Q000378:metabolism* / Q000652:urine; D008297:Male; D013058:Mass Spectrometry; D010634:Phenobarbital / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D013056:Spectrophotometry, Ultraviolet
D002722:Chlorobenzenes; D002733:Chlorophenols; D006147:Guanine; C040133:4-chlorophenylmercapturic acid; C031294:chlorobenzene; D000111:Acetylcysteine; D010634:Phenobarbital