LACK OF ACTIVITY OF ESTRADIOL IN RODENT BONE-MARROW MICRONUCLEUS ASSAYS

Estradiol has been evaluated in five independent rodent bone marrow mi cronucleus assays and has been found to be inactive. The dose-range ev aluated extended from three daily doses of 20 mu g/kg to the rat, a re gimen that elicited a potent uterotrophic response from the animals, t o single doses of between 10-150 mg/kg to the mouse. The mouse assays simulated and extended the conditions of test employed by earlier inve stigators who had found estradiol, and three structurally-related synt hetic estrogens, to be active in mouse micronucleus assays over the do se range 1-10 mg/kg. It is concluded that estradiol is not genotoxic t o the bone marrow of rodents. The top dose-level used in the present m icronucleus assays (150 mg/kg) represented similar to 150000 times the minimum estrogenic dose of this chemical to rodents, and that was con sidered to be above the dose at which useful genetic toxicity data wou ld be generated for this potent estrogen. The maximum tolerated dose ( MTD) of estradiol to rodents remains to be established. (C) 1997 Elsev ier Science B.V.