TOXICOLOGICAL SCIENCES 102(2), 392–412 (2008)

No information exists on reproductive/developmental effects in mice exposed to dietary 17b-estradiol (E2) over multiple generations. Therefore, under OECD Test Guideline 416 with enhancements, CD-1 mice (F0 generation, 25 mice/sex/group) were exposed to dietary E2 at 0, 0.001, 0.005, 0.05, 0.15, or 0.5 ppm (~0, 0.2, 1, 10, 30, or 100 mg E2/kg body weight/day) for 8 weeks prebreed, 2 weeks mating, ~3 weeks gestation, and 3 weeks lactation. At weaning, selected F1 offspring (F1 parents; 25/sex/ group) and extra retained F1 males (one per litter) were exposed to the same dietary concentrations and durations as the F0 generation; study termination occurred at F2 weaning; F1/F2 weanlings (up to three per sex per litter) were necropsied with organs weighed. At 0.5 ppm, effects were increased F1/F2 perinatal loss, prolonged F0/F1 gestational length, reduced numbers of F2 (but not F1) litters/ group, reduced F1/F2 litter sizes, accelerated vaginal patency (VP