The nephrotoxicity of
diphenylamine, the parent compound of the mefenamate family of nonsteroidal anti-inflammatory drugs, was evaluated in male Syrian hamsters, male Sprague-Dawley rats, and male Mongolian gerbils. Total renal papillary
necrosis was observed in four of ten, seven of ten, and six of ten male Syrian hamsters orally treated with
diphenylamine at respective doses of 400 mg/kg
body weight/day, 600 mg/kg
body weight/day, and 800 mg/kg
body weight/day. Total renal papillary
necrosis was also observed in five of ten and four of ten male Syrian hamsters intraperitoneally treated with
diphenylamine at respective doses of 600 mg/kg
body weight/day and 800 mg/kg
body weight/day. Focal intermediate renal papillary
necrosis was induced in two hamsters orally given
diphenylamine at 600 mg/kg
body weight/day and in two of ten hamsters intraperitoneally given
diphenylamine at 800 mg/kg
body weight/day. Apex-limited
necrosis of the medullary interstitial cells and vasa recta and degeneration of the renal interstitial matrix occurred in two Sprague-Dawley rats orally administered
diphenylamine at 800 mg/kg
body weight/day. Degeneration and
necrosis of the pars recta was induced in seven of ten hamsters intraperitoneally given
diphenylamine at 400 mg/kg
body weight/day. Gross and microscopic renal lesions were not observed in any Mongolian gerbils. It was concluded that the Syrian hamster is more susceptible to the papillotoxic effects of
diphenylamine than the Sprague-Dawley rat and the Mongolian gerbil. Renal papillary
necrosis in the Syrian hamster treated orally with
diphenylamine is reproducible, is of short onset, and is induced in a high proportion of the hamsters (70-90%).(ABSTRACT TRUNCATED AT 250 WORDS)