Reproductive Toxicity of Tricresyl Phosphate in a Continuous Breeding Protocol in Swiss (CD-1) Mice

Reproductive Toxicity of Tricresyl Phosphate in a ContinuousBreeding Protocol in Swiss (CD-I) Mice. CHAPIN, R. E., GEORGE,J. D., AND LAMB, J. C. IV. (1988). Fundam. Appl. Toxi-col. 10,344-354. The effects of a mixture of tricresyl phosphate isomerson reproductive performance in Swiss (CD-I) mice were evaluatedusing 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 animalsconsuming the high-concentration feed, the number of littersper pair decreased in a dose-related fashion, and the proportionof pups born alive, and their weight, was significantly decreasedin the high-dose group. A crossover mating trial found impairedfertility in both males and females exposed to 0.2% TCP, witha greater effect in females. Histopathology of the Fo pairsrevealed dose-related seminiferous tubule atrophy, and decreasedtestis and epididymal weights in the high-dose males, whilethe 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 rearedto age 74 days and then mated within the control and two ofthe treatment groups (0.0,0.05, and 0.1 % TCP; there were toofew offspring in the 0.2% group). There was a decrease in thefertility index in the 0.1% TCP group, and a decreased proportionof liveborn and number of liveborn pups per litter. In the F,males at necropsy, sperm concentration and morphology were normalat termination, although motility was decreased in both the0.05% and the 0.1% groups compared to controls. These data showthat TCP impaired fertility in both sexes of mice in the Fogeneration and affected sperm motility at even the lowest dosein F, males.