Reproductive toxicity assessment by continuous breeding in Sprague-Dawley rats: a comparison of two study designs.

The protocol for Reproductive Assessment by Continuous Breeding (RACB) studies was originally designed to use mice as the test species. However, rats are commonly used for reproductive toxicity research and could be used in the basic RACB design. One of the studies reported below evaluated a standard murine RACB design using rats, which rears the fifth litter to test second generation fertility. The second design tested the logistics and feasibility of rearing the second litter for second generation fertility testing. The standard fifth litter design (L5) was modified slightly for rats by increasing the time allowed for gestation and delivery. Compared to rats rearing their second litter (L2), rats in this L5 design had more litters per pair during continuous breeding and maintained this fertility better over time, as evidenced by producing more pups per litter during the crossover mating segment. Both L2 and L5 rats gave sufficient pups to conduct the second generation fertility evaluation. In addition, the L5 design was easier to conduct and produced pups from gametes exposed to chemical throughout spermatogenesis, making it the preferred design for using rats in Continuous Breeding studies.