Use of the NIH shift to determine the relative contribution of competing pathways of aniline metabolism in the rat.

The retention of tritium in urinary p-aminophenol and p-hydroxyacetanilide was determined following the administration of p-3H-aniline or p-3H-acetanilide to rats. When p-3H-aniline (1.5 mmol/kg, ip) was given to rats, the retention of tritium in urinary p-aminophenol and p-hydroxyacetanilide was 15% and 38%, respectively. Similar results were obtained following the administration of p-3H-acetanilide (1.5 mmol/kg). However, when p-3H-acetanilide was given to rats which had been pretreated with bis-(p-nitrophenyl)phosphate to block the deacetylation capacity, urinary 3H-p-hydroxyacetanilide was recovered with 53% retention of tritium. The data indicate that, at the doses studied: the primary route of aniline metabolism is via sequential acetylation and hydroxylation, and deacetylation plays a significant role in the disposition of acetanilide.