Toxicokinetics and metabolism of aniline and 4-chloroaniline in medaka (Oryzias latipes).

The in vivo toxicokinetics and in vitro hepatic microsomal metabolism of [14C]aniline and [14C]4-chloroaniline in medaka (Oryzias latipes) were investigated to provide a basis upon which to interpret the toxicological responses of small aquarium fish to aniline derivatives. During static aqueous exposures of up to 320 min, parent equivalents failed to reach steady state and results from depuration studies clearly demonstrated biphasic elimination. Due to low elimination rates, 40 to 20% of absorbed aniline and 4-chloroaniline doses, respectively, remained within the fish through 330 min postexposure. Based on an analysis of excreted metabolites, N-acetylation was the dominant route of in vivo metabolism for 4-chloroaniline, with no indication of ring hydroxylation, while the evidence suggested that polar conjugates were the dominant in vivo aniline metabolites. The toxicokinetics and in vivo metabolism of both aniline and 4-chloroaniline were best described by a two-compartment model that was consistent with the assumption that metabolites of the parent amines were accumulating in the fish. In partial support of the hypothesis that these amines are being metabolically activated in medaka, N-hydroxylation of aniline and 4-chloraniline to phenylhydroxylamine and 4-chlorophenylhydroxylamine were quantified in hepatic microsomal preparations.