CHRONIC NEPHROPATHY AND RENAL CARCINOGENICITY OF O-BENZYL-P-CHLOROPHENOL IN F344 N RATS AND B6C3F(1) MICE/

o-Benzyl-p-chlorophenol, an aryl halide biocide, was evaluated in male and female F344/N rats and B6C3F(1) mice in a series of subchronic an d 2-year toxicity and carcinogenicity studies. Kidney was the primary target of toxicity in the 13-week gavage studies in rats and mice, wit h increased nephropathy noted as low as 240 mg/kg in male rats. Consid ering the nephropathy to be dose-limiting, the chronic (2-year) study was conducted at lower doses (male rats: 30, 60, or 120 mg/kg; female rats: 60, 120, or 240 mg/ kg; male and female mice: 120, 240, or 480 m g/kg; in corn oil; n = 50/group). Survival and body weights of dosed f ats were similar to controls in the 2-year study. Survival of high-dos e male and female mice, and body weights of all dosed male and mid- an d high-dose female mice, were lower than controls. The incidence and s everity of nephropathy increased with dose and length of treatment in both rats and mice. There was an increased incidence of renal tubule a denomas or carcinomas in both the mid- and high-dose male mice. Despit e similar evidence of nephropathy, however, there were no increased in cidences of neoplasms in female mice or in male or female rats. This s tudy suggests therefore that while nephrotoxicity may have been a nece ssary component, factors other than the marked nephrotoxicity of o-ben zyl-p-chlorophenol were critical to the development of renal carcinoge nesis induced in only male mice. (C) 1995 Society of Toxicology