Abstract for TR-103

Fenthion, the O,O-dimethyl ester of O-(4-(methylthio)-m-tolylphosphorothioic acid, is one of the organophosphate pesticides. It was developed by G. Schrader and E. Schegk and first marketed by Farbenfabriken Bayer A.G. as an insecticide in 1957.

A bioassay of fenthion for possible carcinogenicity was conducted by administering the test chemical in feed to F344 rats and B6C3F1 mice.

Groups of 50 rats of each sex and 50 mice of each sex were administered fenthion in the diet at one of two doses, either 10 or 20 ppm, for 103 weeks and then observed for 0 to 2 additional weeks. Matched controls consisted of groups of 25 untreated animals of each species and sex. All surviving animals were killed at 103 to 105 weeks.

The mean body weights and the survival of the dosed animals were essentially unaffected by administration of the test chemical with the exception of the survival of the low-dose male mice, which was significantly lower than that of the corresponding matched control. Thus, most of the animals may have been able to tolerate higher doses. Sufficient numbers of animals in all groups of rats and mice were at risk for development of late-appearing tumors.

In the male and female rats and the female mice, no tumors occurred at incidences that were significantly higher in dosed groups than in control groups.

In the male mice, sarcomas, fibrosarcomas, or rhabdomyosarcomas of the integumentary system occurred at incidences that were dose related (P=0.043). In direct comparisons of the incidences of these tumors in the dosed groups with the incidence in the control group, the P values of 0.048 and 0.028 for the low- and high-dose groups, respectively, did not meet the Bonferroni criterion of P=0.025 for significance when multiple comparisons are made (controls 0/25, low-dose 7/49 or 14%, high-dose 8/48 or 17%). However, the incidence of sarcomas and fibrosarcomas in historical-control male B6C3F1 mice used in bioassays of other chemicals tested at this laboratory was 7/435 (1.6%), and no rhabdomyosarcomas occurred in the historical-control male mice.

It is concluded that under the conditions of this bioassay, fenthion was not carcinogenic for male or female F344 rats or for female B6C3F1 mice. The increased incidence of sarcomas, fibrosarcomas, and especially rhabdomyosarcomas of the integumentary system in the male B6C3F1 mice suggested that the test chemical was carcinogenic in these animals.