Induction of tumours of the urinary system in F344 rats by dietary administration of sodium o-phenylphenate

Abstract

Sodium o-phenylphenate (OPP-Na), a fungicide approved as a food additive in Japan, was given in pellet diets at dietary levels of 0, 0·125, 0·25, 0·5, 1·0, 2·0 or 4·0% to groups of about 10 male and female F344/Du rats for 13 wk and to male F344/Du rats for 91 wk. In the 13-wk study, urinary bladder tumours developed in one out of ten male rats fed 1% OPP-Na, nine out of ten male rats fed 2% OPP-Na, one out of ten male rats fed 4% OPP-Na and two out of ten female rats fed 4% OPP-Na. Five transitional cell carcinomas were observed in male rats fed 2% OPP-Na and one such carcinoma was found in a male rat fed 4% OPP-Na. In the 91-wk study, tumours of the urinary bladder, renal pelvis and renal papilla developed in one out of 21 rats (5%) fed 0·5% OPP-Na, seven out of 21 rats (33%) fed 1% OPP-Na, 20 out of 21 rats (95%) fed 2% OPP-Na and 17 out of 21 rats (85%) fed 4% OPP-Na. These were all transitional cell carcinomas, except for one carcinosarcoma in the 2% group. A dose-related increase in the incidence of non-neoplastic lesions of the kidney were observed in treated rats. In the 13-wk study, slight to moderate pyelonephritis was observed in six out of ten male rats and one out of ten female rats fed 4% OPP-Na. In the 91-wk study, moderate to severe pyelonephritis was observed in four out of 21 rats (19%) fed 2% OPP-Na and in all of 20 rats fed 4% OPP-Na.