Bioassay of photodieldrin for possible carcinogenicity.
A bioassay of dieldrin-free photodieldrin (synthesized by Gulf South Research Institute) for possible carcinogenicity was conducted by administering the test material in feed to Osborne-Mendel rats and B6C3F1 mice. Groups of 50 rats of each sex were initially administered photodieldrin at one of two doses, either 5 or 10 ppm. Because of neurotoxic signs, doses in the females were reduced after 30 weeks. Total periods of treatment for low- and high-dose males and low-dose females were 80 weeks, followed by periods of 31 or 32 weeks of additional observation; the total period of treatment for the high-dose females was 59 weeks, followed by a period of additional observation of 53 weeks. The time-weighted average doses for the females were 3.4 or 7.5 ppm. Matched controls consisted of 10 untreated rats of each sex; pooled controls, used for statistical evaluation, consisted of the matched controls combined with 65 untreated male and 65 untreated female rats from similarly performed bioassays of six other test chemicals. All surviving rats were killed at 111-112 weeks. Groups of 50 mice of each sex were administered photodieldrin at one of two doses, either 0.32 or 0.64 ppm, for 80 weeks, then observed for an additional 13 weeks. Matched controls consisted of groups of 10 untreated mice of each sex at each dose; pooled controls, used for statistical evaluation, consisted of the matched controls combined with 60 untreated male and 60 untreated female mice from similarly performed bioassays of six other test chemicals. All surviving mice were killed at 93 weeks. Mean body weights attained by low- and high dose male and female rats and mice were essentially unaffected by photodieldrin. Convulsions and hyperactivity were noted in treated male and female rats and in male mice. Mortality rates of either sex or either species were not affected by treatment. In rats, benign tumors (adenoma and fibroadenoma) of the mammary gland in females showed a dose-related trend (P=0.039) compared with matched, but not pooled, controls (8/72 pooled controls, 0/9 matched controls, 5/50 low-dose, 10/49 high-dose). Adenocarcinoma of the mammary gland occurred in two additional low-dose females. The incidences of these tumors in either of the treated groups were not significantly higher than those in the control groups using either matched or pooled controls. Three papillary and follicular-cell adenomas and one papillary adenocarcinoma of the thyroid occurred in the low-dose females, giving a statistically significant increase over the pooled controls (P=0.022), but these thyroid tumors did not occur in the high-dose animals. The dose-related trend was not statistically significant using either pooled or matched controls, and the incidence in the low-dose group is not greater than that in the historical controls. In male rats, the incidence of hemangiomas showed a statistically significant dose-related trend (P=0.021) using pooled controls, but the direct comparison of the three hemangiomas in the high-dose group with the pooled-control group was not statistically significant. Furthermore, three hemangiomas is a small number, and the tumors occurred in more than one anatomic site (two in the spleen, one in subcutaneous tissue). The occurrence of these tumors cannot clearly be associated with treatment. In mice, there were no tumors that were statistically significant in treated groups of either sex. It is concluded that under the conditions of this bioassay, photodieldrin was not carcinogenic for Osborne-Mendel rats or B6C3F1 mice.