Studies in detoxication. 66. The metabolism of halogenobenzenes. 1:2:3-, 1:2:4- and 1:3:5-trichlorobenzenes

Abstract

A study was made of the fate in the rabbit of oral doses (0.5 g/kg) of the 3 isomeric trichlorobenzenes. The l:2:3-isomer is the most rapidly metabolized isomer. It is nevertheless slowly metabolized, 62% of the dose appearing, during 5 days after dosing, as conjugates of glucuronic (50%) and sulfuric acids (12%); maximum excretion occurred on the first day after dosing. The major metabolite was 2:3:4-trichlorophenol, but small amounts of 3:4:5-trichlorphenol and traces of 3:4:5-trichloro-catechol were also formed. Small quantities (0.3%) of mercapturic acid were formed and identified as 2:3:4-trichlorophenylmercapturic acid. The l:2:4-isomer was more slowly metabolized and O2 conjugates accounted for 38% of the dose in 5 days, the maximum occurring on the 2nd day after dosing. Two major phenols, 2:4:5- and 2:3:5-tri-chlorophenol, were excreted, together with small amounts of 3:4:6-tri-chlorocatechol. Small amounts (0.3%) of two mercapturic acids, 2:3:5- and 2:4:5-trichlorphenylmercapturic acid, were excreted. 1:3:5-Trichlorobenzene was the least rapidly metabolized of the isomers; about 23% of the dose was excreted as O2 conjugates in 5 days. Practically no ethereal sulfate or mercapturic acid was formed and the only phenol detected was 2:4:6-trichlorophenol. Unchanged l:3:5-trichlorobenzene was found in the feces. The paper chromato-graphic behavior and color reactions of 11 trichlorophenols were recorded, together with the UV spectra of some of them. Five isomeric hexachlorodiphenyl disulfides were synthesized as reference compounds for the identification of trichlorophenylmercapturic acids. The orientations of the phenolic metabolites found were discussed in the light of current theories of metabolic hydroxylation.