Two‐year Study of Carcinogenicity and Chronic Toxicity of Biphenyl in Rats

Abstract

Two‐year Study of Carcinogenicity and Chronic Toxicity of Biphenyl in Rats: Yumi Umeda, et al. Japan Bioassay Research Center, Japan Industrial Safety and Health Association— Carcinogenicity and chronic toxicity of biphenyl were examined in 50 male and 50 female F344 rats exposed to 0, 500, 1,500 or 4,500 ppm biphenyl in the diet for 105 weeks. Bladder tumors were found in the 4,500 ppm males, as evidenced by significantly increased incidence of carcinoma (24/50) and papilloma (10/50) of the transitional cells as well as one rarely observed case both of carcinoma and papilloma of the squamous cells. The survival rate of the 4500 ppm males significantly decreased, due to the bladder tumors and the hematuria accompanied by bladder calculi. The bladder calculi were found in 43 males in the 4,500 ppm group, but in only 8 females. Urinary pH significantly increased in the males, and occult blood was observed both in males and females in the 4,500 ppm group. The pre‐neoplastic lesions were hyperplasia of transitional epithelium (simple, nodular and papillary hyperplasia) in the bladder of the 4,500 ppm males. Incidences of calculus formation and transitional cell hyperplasia in the renal pelvis also significantly increased in the 4,500 ppm males and females. On the other hand, the incidences of the transitional cell hyperplasia and the calculus formation in the bladder and the renal pelvis were far lower in females than in males, and no bladder tumors were observed in the females. Causative factors of the bladder tumors and their male predominance were discussed with reference to the findings reported in the literature and the previous study of biphenyl metabolism.