A dietary oncogenicity study of tributyl phosphate in the CD-1 mouse

Tri-n-butyl phosphate (TBP), an industrial chemical, was administered in the diet at concentrations of 0, 150, 1000 or 3500 ppm to groups of 50 male and 50 female CD-1 mice for 18 months. Survival, clinical signs and hematology parameters were unaffected by treatment at any concentration. Initial weight losses and significant decreases in body weight gain occurred in males and females receiving the high dose (3500 ppm) of TBP in diet. A significant dose-related increase in absolute and relative liver weights was seen in male and female mice which received the two highest dietary concentrations of TBP (1000 and 3500 ppm). The incidence of hepatocellular adenomas was significantly increased in male mice treated with 3500 ppm TBP in diet. No other tumors were associated with TBP administration in this study. The NOEL for chronic toxicity was 150 ppm, or 28.9 mg/kg/day for females and 24.1 mg/kg/day for males. Although rats treated chronically with TBP have exhibited urinary bladder hyperplasia and urinary bladder papillomas and transitional cell carcinomas, no urinary bladder alterations attributed to TBP administration occurred in this study.