Reproductive toxicity of 2,2-bis(bromomethyl)-1,3-propanediol in a continuous breeding protocol in Swiss (CD-1) mice

The effect of 2,2-bis(bromomethyl)-1,3-propanediol (BMP) on reproduction in Swiss CD-1 mice was evaluated by use of a continuous breeding protocol. BMP was administered in the feed at 0.1, 0.2, and 0.4% concentrations. Both male and female F0 mice (20 pairs per treatment group, 40 pairs of control animals) were dosed 7 days prior to and during a 98-day cohabitation period. Although the fertility index was unchanged in the high-dose group, BMP exposure significantly decreased the numbers of litters per pair, pups born alive per litter, and pup weight when adjusted for litter size. Crossover mating between treated and control F0 animals indicated a specific effect only on female reproductive capacity. At the highest dose, BMP caused a body weight decrease in the F0 animals of both sexes with no effect on relative organ weights. Sperm concentration, motility, morphology, and estrual cyclicity were unaffected by BMP exposure. Histopathology in the F0 animals revealed specific kidney lesions in both sexes; males were more sensitive than females. The last litter born in the 98-day breeding phase was reared to age 74 days and then mated to nonsiblings of the same treatment group. The effect of high-dose BMP exposure on F1 fertility, body and organ weights, sperm parameters, and estrual cyclicity was the same as that for the F0 animals, with the exception of the lack of renal lesions seen in the F1 females. These data show that BMP impaired fertility in female mice in both generations in the absence of an effect on reproductive organ weights and estrual cyclicity.