Metabolism of some ω-halogenoalkylbenzenes and related alcohols in the rabbit

Abstract

The metabolism of [omega]-halogenoalkylbenzenes and 5 related alcohols has been studied in the rabbit. The chief metabolic products excreted after administration of benzyl chloride, p-chloro- and p-nitro-benzyl chloride were the corresponding mercapturic acids, hippuric acids and benzoic acids; little or no conjugation with glucuronic and sulfuric acids occurred. The corresponding alcohols yielded the same metabolites except that no significant amounts of mercapturic acid were excreted; 14% of the dose of benzyl alcohol was excreted conjugated with glucuronic acid. p-Chloromethylbenzyl chloride and benzyl bromide caused such severe anorexia that satisfactory quantitative results could not be obtained. Both compounds yielded mercapturic acids. p-Methoxybenzyl chloride was too unstable to give satisfactory results. p-Methoxybenzyl alcohol was excreted as ester-type glucosiduronic acid (50% of dose), p-methoxyhippuric acid and p-methoxybenzoic acid. With phen-ethyl bromide, 3-bromopropylbenzene and 4-bromobutylbenzene the proportion of a dose excreted as mercapturic acid decreased as the chain length increased. The two higher members, but not phenethyl bromide, yielded 20-30% of the dose as glycine conjugates. All 3 were excreted to a considerable extent as ether-type glucosiduronic acid and ethereal sulfate and there is evidence that w -bromoalkylphenols may be major metabolites of these compounds.