The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program. The findings were not evaluated in accordance with the levels of evidence for reproductive or developmental criteria established by NTP in March 2009. The findings and conclusions for this study should not be construed to represent the views of NTP or the U.S. Government.
Trans-diethylstilbestrol (DES) was evaluated as a model compound in a reproductive toxicology testing scheme which has been designated "Reproductive Assessment by Continuous Breeding".
In the present DES study, Task 1 (dose range-finding) was not performed since sufficient data were available in the literature to select dose levels for Task 2 (continuous breeding). Dietary levels of 1, 10 and 50 ppb DES (~99% pure) were employed in Task 2. Continuous exposure of breeding pairs to dietary DES led to rapid onset of infertility in the 50 ppb DES group, whereas fertility was unaffected in the 0, 1, and 10 ppb DES groups. In addition, the 50 ppb DES pairs produced fewer litters and had fewer live pups per litter and a lower proportion of pups born alive per litter than did the pairs in the other treatment groups. Therefore a crossover mating trial was conducted to determine which sex was adversely affected (Task 3).
In the crossover mating trial the proportion of detected matings did not differ significantly among treatment groups, but fertility and the number of live pups per litter and the proportion of pups born alive were significantly reduced (p<0.05),in the control male x 50 ppb DES female group versus the control male x control female group. The proportion of fertile pairs in the 50 ppb DES male x control female group did not differ significantly from either of the above two groups. Hence, exposure to 50 ppb DES in the diet primarily affected fertility in female mice. The sex of pups born alive and the live pups weights, however, did not differ significantly among the three groups.
Thus, these data support the conclusion that, under the conditions of this reproductive toxicity study, DES was a reproductive toxicant in female CD-l mice as evidenced by a decreased fertility index, decreased number of litters, decreased number of live pups per litter and a lower proportion of pups born alive per litter.