Trimethylphosphate is an alkylating agent which has been used as a gasoline additive, a methylating agent, an intermediate for the production of polymethyl phosphates, and a flame retardant in polymers.
A bioassay of trimethylphosphate for possible carcinogenicity was conducted by administering the compound by gavage to Fischer 344 rats and B6C3F1 mice.
Groups of 50 rats and 50 mice of each sex were administered trimethylphosphate in distilled water three times per week at one of two doses, either 50 or 100 mg/kg body weight for the rats and either 250 or 500 mg/kg body weight for the mice. Vehicle controls consisted of groups of 20 rats and 20 mice of each sex. The rats were dosed for 104 weeks and the mice for 103 weeks. All surviving rats were killed at week 105 and all surviving mice at week 103.
Mean body weights of dosed male and female rats and female mice were slightly lower than those of the corresponding vehicle controls throughout the study; mean body weights of the male mice were comparable to those of the vehicle controls. Survival rates of both rats and mice were high, and adequate numbers of animals were at risk for the development of late-appearing tumors.
In male rats, the incidence of fibromas of the subcutaneous tissue was higher (P=0.036) in the high-dose group than in the vehicle controls (control 0/20, low-dose 2/50, high-dose 9/49), and there was a dose-related trend (P=0.006) in the incidences of these fibromas. In the female rats, no tumors occurred in the dosed groups at significantly increased incidences, compared with corresponding controls.
In the male mice, no tumors occurred in the dosed groups at significantly increased incidences, compared with controls. In the female mice, the incidence of adenocarcinomas of the endometrium was higher (P=0.004) in the high-dose group than in the vehicle controls (controls 0/16, low-dose 7/40, high-dose 13/37), and there was a significant dose-related trend (P=0.003) in the incidences of these adenocarcinomas.
It is concluded that under conditions of this bioassay, trimethylphosphate was carcinogenic in female B6C3F1 mice, inducing adenocarcinomas of the uterus/endometrium. Trimethylphosphate was associated with the induction of benign fibromas of the subcutaneous tissue in male Fischer 344 rats. No evidence of carcinogenicity of the compound was obtained in female rats or in male mice.