Bioassay of phosphamidon for possible carcinogenicity.

Abstract

A bioassay of technical-grade phosphamidon for possible carcinogenicity was conducted using Osborne-Mendel rats and B6C3F1 mice. The test material was administered in feed to 50 rats and 50 mice of each sex at one of two doses, either 80 or 160 ppm. The rats were fed the test chemical for 80 weeks, then observed without compound administration for 30 or 31 weeks; the low-dose male mice were fed for 71 weeks, then observed for 19 weeks; the high-dose male mice were fed for 62 weeks, then observed for 28 weeks; and the low- and high-dose female mice were fed for 80 weeks, then observed for 10 or 11 weeks. Matched controls consisted of groups of 10 untreated rats or 10 untreated mice of each sex; pooled controls consisted of the matched controls combined with 85 male and 85 female untreated rats or 80 male and 80 female untreated mice from similar bioassays of eight other test chemicals. All surviving rats were killed at 110 or 111 weeks; all surviving mice were killed at 90 or 91 weeks. Hyperexcitability and tremors, both indications of phosphamidon toxicity, were observed in dosed rats and mice. However, sufficient numbers of all groups of both species were at risk for the development of late-appearing tumors. In male rats, the combined incidence of hemangiomas and hemangiosarcomas in the spleen showed a statistically significant (P=0.012) dose-related trend. However, the comparison with matched controls was not significant, and the historical records of this laboratory on untreated males of this strain show a tumor incidence of 6/240 (3%) with incidences in individual control groups as high as 3/9 (33%)and 2/9 (22%), compared with 5/49 (10%) seen in the high-dose group in this study. No hemangiomas or hemangiosarcomas were found in the females. In female rats, the Cochran-Armitage test for dose-related trend was significant (P=0.003) for C-cell adenomas and carcinomas of the thyroid when pooled controls were compared with the dosed groups. The incidences of these tumors were also significant when low-dose females (P=0.003) and high-dose females (P=0.004) were compared directly with pooled controls. However, the historical records of this laboratory show a tumor incidence of 16/235 (7%) in untreated female rats of this strain of female rats, with incidences in individual control groups as high as 3/9 (33%) and 3/10 (30%); these data are therefore considered marginal and insufficient to establish an association between the tumors and administration of the chemical. In males, the incidence of these tumors was not statistically significant. In mice, no tumor occurred at a higher incidence in dosed animals than in controls. It is concluded that under the conditions of this bioassay, technical-grade phosphamidon was not carcinogenic for B6C3F1 mice. The data obtained in this bioassay with Osborne-Mendel rats are insufficient to allow the interpretation that technical-grade phosphamidon is carcinogenic in this species.