N-Oxidation of Certain Aromatic Amines, Acetamides, and Nitro Compounds by Monkeys and Dogs2

Abstract

N-hydroxylation occurs in monkeys given 2-naphthylamine and results in the excretion of N-hydroxy-2-naphthylamine in the urine as it does in the dog. Monkeys and dogs given 4-aminobiphenyl excreted N-hydroxy-4-aminobiphenyl. Excretion of acetylated N-hydroxy metabolites occurred in the monkeys, but not in dogs given these amines. Dogs given 2-acetylaminonaphthalene, a noncarcinogen, excreted N-hydroxy-2-acetylaminonaphthalene, but no N-hydroxy-2-naphthylamine or 2-nitrosonaphthalene, These observations are consistent with the hypothesis that the nonacetylated N-hydroxy metabolites of the aromatic amines are the active urinary carcinogens. The relatively weak bladder carcinogen, 4-nitrobiphenyl, was metabolized to small amounts of N-hydroxy-4-aminobiphenyl and 4-nitrosobiphenyl in both monkeys and dogs. Comparable N-oxidation products were found in the urine of monkeys, but not in that of dogs given 2-nitronaphthalene.