Assays for reproductive toxicity have heretofore been long and cumbersome, necessitating months of dosing to assure sufficient exposure of potential germ cell targets. However, the number of chemicals for which no reproductive or teratologic data exist is large, and growing larger. What is needed is a test that would help prioritize chemicals for complete reproductive testing. This design uses one group of 10 male mice, which are mated before treatment to a group of 10 females/dose group. These females are dosed during gestational days 8-14, are allowed to give birth, and nurse the young until day 4. The males are then dosed with the test compound, and mated, after 4 days, with another group of females for 5 days. Both males and females are dosed during mating and up until sacrifice. These females are sacrificed on g.d. 10-15, and uterine contents assessed. The males are sacrificed after 19 days of exposure, and subject to a thorough reproductive necropsy (epididymal sperm evaluations, organ weights, and histology). Because this design evaluates many aspects of reproductive and development both functionally (sperm motility, fertilizing capability, ovulation, implantation, development and nursing) and structurally (detailed histopath on potential target organs), it is expected to identify those compounds that possess significant reproductive and/or teratologic activity. Tests are currently underway to assess the sensitivity of this design, using chemicals of known potency (generated from previous Continuous Breeding studies).
