Chronic Nephropathy and Renal Carcinogenicity of o-Benzyl-p-chlorophenol in F344/N Rats and B6C3F1 Mice

o-Benzyl-p-chlorophenol, an aryl halide biocide, was evaluatedin male and female F344/N rats and B6C3F₁ mice in a series ofsubchronic and 2-year toxicity and carcinogenicity studies.Kidney was the primary target of toxicity in the 13-week gavagestudies in rats and mice, with increased nephropathy noted aslow as 240 mg/kg in male rats. Considering the nephropathy tobe dose-limiting, the chronic (2-year) study was conducted atlower 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 mg/kg;in corn oil; n=50/group). Survival and body weights of dosedrats were similar to controls in the 2-year study. Survivalof high-dose male and female mice, and body weights of all dosedmale and mid- and high-dose female mice, were lower than controls.The incidence and severity of nephropathy increased with doseand length of treatment in both rats and mice. There was anincreased incidence of renal tubule adenomas or carcinomas inboth the mid- and high-dose male mice. Despite similar evidenceof nephropathy, however, there were no increased incidencesof neoplasms in female mice or in male or female rats. Thisstudy suggests therefore that while nephrotoxicity may havebeen a necessary component, factors other than the marked nephrotoxicityof o-benzyl-p-chloro-phenol were critical to the developmentof renal carcinogenesis induced in only male mice.