Reproductive toxicity of tricresyl phosphate in a continuous breeding protocol in Swiss (CD-1) mice

The effects of a mixture of tricresyl phosphate isomers on reproductive performance in Swiss (CD-1) mice were evaluated using a continuous breeding protocol. Tricresyl phosphate (TCP) was mixed into the feed at 0, 0.05, 0.1, and 0.2% by weight. Although the fertility index was not changed in the animals consuming the high-concentration feed, the number of litters per pair decreased in a dose-related fashion, and the proportion of pups born alive, and their weight, was significantly decreased in the high-dose group. A crossover mating trial found impaired fertility in both males and females exposed to 0.2% TCP, with a greater effect in females. Histopathology of the F0 pairs revealed dose-related seminiferous tubule atrophy, and decreased testis and epididymal weights in the high-dose males, while the female reproductive tract showed no histopathologic changes. There were dose-related changes in the adrenals of both sexes, and body weight was depressed in both sexes at the highest concentration. The last litter born in the 98-day breeding phase was reared to age 74 days and then mated within the control and two of the treatment groups (0.0, 0.05, and 0.1% TCP; there were too few offspring in the 0.2% group). There was a decrease in the fertility index in the 0.1% TCP group, and a decreased proportion of liveborn and number of liveborn pups per litter. In the F1 males at necropsy, sperm concentration and morphology were normal at termination, although motility was decreased in both the 0.05% and the 0.1% groups compared to controls. These data show that TCP impaired fertility in both sexes of mice in the F0 generation and affected sperm motility at even the lowest dose in F1 males.