Bioassay of parathion for possible carcinogenicity.
A bioassay for possible carcinogenicity of technical-grade parathion was conducted by administering the test chemical in the diet to Osborne-Mendel rats and B6C3F1 mice. Groups of 50 rats of each sex were administered parathion at one of two doses for 80 weeks, then observed for 32 or 33 weeks. Time-weighted average doses for males were 32 or 63 ppm; for females, they were 23 or 45 ppm. All surviving rats were killed at 112 or 113 weeks. Groups of 50 mice of each sex were administered parathion at one of two doses, either 80 or 160 ppm. The low-dose males were administered parathion for 71 weeks; the high-dose males for 62 weeks; and the low- and high-dose females for 80 weeks. The animals were then maintained for observation and all surviving mice were killed at 89 or 90 weeks. Matched controls consisted of groups of 10 untreated rats or mice of each sex; pooled controls of rats or mice taken from similar bioassays of other test chemicals were also used. Mean body weights of high-dose male and female rats and of high- and low-dose male mice were generally lower than those of the matched controls during the period of administration of the chemical. Mean body weights of the other groups of dosed rats and mice did not differ appreciably from those of the matched controls. Since body weights and survival of the female mice were not affected, female mice may have been able to tolerate a higher dose. Sufficient numbers of male and female animals of both species were at risk for the development of late-appearing tumors. In both male and female rats, the incidences of cortical adenomas or carcinomas of the adrenal showed dose-related trends (P<0.001) using pooled controls and, in direct comparisons, were higher in the high-dose groups (P<0.001) than in the pooled controls (males: pooled controls 3/80, matched controls 0/9, low-dose 7/49, high-dose 11/46; females: pooled controls 4/78, matched controls 1/10, low-dose 6/47, high-dose 13/42). Most of the tumors were adenomas. When the matched controls were used, dose-related trends in incidences of the adrenal tumors were significant (males, P=0.048; females, P=0.028); in direct comparisons, however, the incidences of the tumors in the individual groups did not differ significantly from those in corresponding matched controls. The incidences of the tumors in the dosed male and female rats were higher than those in corresponding historical controls (males 8/148, females 5/180). In mice, no tumors occurred in either sex at incidences that were significantly higher in the dosed groups than in the corresponding control groups. It is concluded that under the conditions of this bioassay, parathion was not carcinogenic to B6C3F1 mice. In the male and female Osborne-Mendel rats receiving parathion in their diet, there was a higher incidence of cortical tumors of the adrenal than in pooled or historical controls, suggesting that parathion is carcinogenic to this strain of rat.