70 Biochemical Studies of Toxic Agents

Baumann & Preusse (1879) and Jaff6 (1879) showed that the mercapturic acids which they isolated from the urine of dogs dosed with bromobenzene or chlorobenzene were formed by the decomposition of acid-labile compounds in the urine, and they believed that these precursors were derivatives of glucuronic acid. This work has recently been revised and extended as a result of the findings of Boyland, Sims & Solomon (1957) and Knight & Young (1957). From the urine of rabbits dosed with naphthalene, Boyland et al. (1957) and Boyland & Sims (1958) isolated a compound which on acidification yielded 1and 2naphthol as well as 1-naphthylmercapturic acid, and they suggested that the compound is N-acetylS-(2-hydroxy1:2-dihydro 1 naphthyl)-Lcysteine. They also stated that anthracene and bromobenzene appear to give similar metabolites. The present paper contains an account of chromatographic studies which have shown that the administration of benzene, naphthalene, anthracene, fluorobenzene, chlorobenzene, bromobenzene and iodobenzene to rabbits or rats is followed by the excretion of acid-labile precursors of the corresponding mercapturic acids. In a preliminary account of this work (Knight & Young, 1957) the name 'premercapturic acid' was proposed for such precursors. The radiochromatographic examination of urine containing 35S-labelled 1-naphthylpremercapturic acid or p-bromophenylpremercapturic acid has indicated that acid decomposition of a premercapturic acid can lead to the formation of another sulphur-containing compound in addition to the mercapturic acid. Furthermore, by means of isotope-dilution techniques it has been possible to show that the amount of l-naphthylmercapturic acid which can be liberated by mineral acid in the urine of rats dosed with naphthalene depends on the pH at which the 1-naphthylpremercapturic acid breaks down. Not all the mercapturic acids isolated from urine are derived from the decomposition of premercapturic acids, for chromatographic studies and tracer-isotope experiments have led to the conclusion that the urine of rats dosed with benzyl chloride does not contain an acid-labile precursor of benzylmercapturic acid. * Part 10: Marsden & Young (1958). CHROMATOGRAPHIC STUDIES