Dose– and time–response studies of sodium o-phenylphenate urinary bladder carcinogenicity in rats

Dose– and time–response studies of urinary bladder carcinogenesis due to orally administered sodium o-phenylphenate (OPP-Na) were performed using 5-week-old male Fischer 344 rats given diets containing 0 (control), 2500, 5000, 10,000, 15,000 or 20,000 ppm OPP-Na for 104 weeks and fed basal diets until 112 weeks (experiment 1). In addition, rats received diets containing 20,000 ppm OPP-Na for 0 (control), 12, 24, 52 or 104 weeks and were killed at week 112 (experiment 2). In experiment 1, the transitional cell carcinoma (TCC) was the major tumor type in the urinary bladder, and the dose–response curve was steep with many tumors occurring at the high doses of 15,000 and 20,000 ppm. The virtually safe dose at a risk level of 10−6 for TCCs and papillomas was estimated to be 144 ppm by the Weibull model, a high value similar to that for sodium saccharin. In experiment 2, a few TCCs developed after 24 weeks of treatment, but the time–response curve was also steep with the majority of lesions occurring after longer exposure periods. Based on the observed steepness in dose– and time–responses, any implied cancer risk of OPP-Na at the low doses of interest to man must be considered to be very small.