Bioassay of Endrin for Possible Carcinogenicity (CAS No. 72-20-8)

Endrin is an organochlorine pesticide having a structural characteristic of the cyclodiene group, which includes aldrin (CAS No. 309-00-2), dieldrin (CAS No. 60-57-1), chlordane (CAS No. 57-74-9), heptachlor (CAS No. 76-44-8), and endosulfan (CAS No. 115-29-7). It is the most acutely toxic compound in the cyclodiene group but is less persistent in the environment than DDT or dieldrin. As an insecticide, it is currently used for small grains, sugarcane, and cotton; as an avicide, for forest seed and perch applications; and as a rodenticide, for forest seed and orchard soil applications. A bioassay of technical-grade endrin for possible carcinogenicity was conducted by administering the test chemical in feed to Osborne-Mendel rats and B6C3F1 mice. Groups of 50 rats of each sex were administered one of two doses of endrin for 80 weeks, then observed for 31 or 34 weeks. The doses used for the male rats were 2.5 or 5 ppm. The initial doses of 5 or 10 ppm used for the females were not well tolerated and were reduced during the study. The time-weighted average doses used for the females were 3 or 6 ppm. Matched controls consisted of groups of 10 rats of each sex; pooled controls, used for statistical evaluation, consisted of the matched-control groups combined with 40 untreated male and 40 untreated female rats from similar bioassays of other test chemicals. All surviving rats were killed at 110 to 114 weeks. Groups of 50 mice of each sex were administered endrin at one of two doses for 80 weeks, then observed for 10 or 11 weeks. Initial doses of 2.5 or 5 ppm used for the males were not well tolerated and were reduced during the study. The time-weighted average doses used for the males were 1.6 or 3.2 ppm; the doses used for the females were 2.5 or 5 ppm. Matched controls consisted of groups of 10 mice of each sex; pooled controls, used for statistical evaluation, consisted of the matched-control groups combined with 50 untreated male and 50 untreated female mice from similar bioassays of other test chemicals. All surviving mice were killed at 90 or 91 weeks. The clinical signs observed in both rats and mice indicated that the doses of endrin used were near the maximum tolerated doses. In mice these signs includedhyperexcitability, a manifestation of toxicity of the organochlorine pesticides. However, mean body weights of the rats and mice were not affected by administration of endrin. Although the survival of the high-dose male mice at the end of the study was markedly lower than that of the controls, the survivals of the low- and high-dose female mice and male and female rats were unaffected by the endrin. The survival of the low-dose male mice could not be evaluated, due to the accidental administration of excessive quantities of endrin to this group during week 66. However, a substantial portion of all groups of rats and mice survived to an age at which tumors could be expected to occur. In rats, the combination of adenomas and carcinomas of the adrenal occurred at the following incidences -- males: pooled controls 2/44, matched controls 2/9, low-dose 4/46, high-dose 8/44; females: pooled controls 4/46, matched controls 3/9, low-dose 16/49, high-dose 7/47. These incidences did not show consistent statistical significance. Furthermore, the incidences of the tumors in the matched controls of either sex were higher than those of the corresponding pooled controls, and the incidences in the matched controls equaled or exceeded those in any of the respective dosed groups. Thus, these tumors cannot be clearly related to administration of the test chemical. In mice, no tumors occurred in dosed groups at incidences that were significantly higher than those in pooled or matched controls. It is concluded that under the conditions of this bioassay, endrin was not carcinogenic for Osborne-Mendel rats or for B6C3F1 mice.