Dephenylation of N-phenyl-2-naphthylamine in dogs and its possible oncogenic implications

Abstract

N-Dephenylation of N-phenyl-2-naphthylamine (PBNA) is strictly limited in dogs, and a 5 mg/kg dose gives 0-10 microng of urinary 2-naphthylamine (BNA), which does not appear to undergo further metabolism. Neither 2-naphthylhydroxylamine (BNHA) nor 2-amino-1-naphthylsulphate were detected in the urine of treated animals. Urinary output of BNA varies markedly between dogs, and at different times in the same animal. The extent of PBNA N-dephenylation is unaltered by chronic administration. Calculations based on Druckery and Küpfmüller's equation (1948) and present data indicate that, for dogs to form BNA tumours through exposure to a relatively high dose-level of PBNA, the period of daily dosing would occupy, or even exceed, the normal life-span. The carcinogenic risk of PBNA to human subjects is discussed.