Evaluation of rodent sperm, vaginal cytology, and reproductive organ weight data from National Toxicology Program 13-week studies.

Sperm morphology and vaginal cytology examinations (SMVCEs), which include evaluations of motility, concentration and head morphology of sperm from the cauda epididymis, and male reproductive organ weight data, were developed by the National Toxicology Program as a screening system for reproductive toxicants. An analysis was conducted of SMVCE studies carried out at the end of fifty 13-week studies (25 for rats, 25 for mice) over a 3-year period. Statistically significant changes in these studies were summarized, as were control data for each male endpoint (mean, SD, 95% confidence limits around the mean, median, and statistical power). Reproductive organ weights (testis, epididymis, cauda epididymis) and sperm motility were the most statistically powerful endpoints evaluated; sperm head morphology may also be a sensitive endpoint for detecting reproductive toxicants. For 24 chemicals tested in both rats and mice, the concordance of results [i.e., no adverse effect in either species, or at least one SMVCE endpoint (not necessarily the same one) adversely affected in both species] was 58%. These data suggest that detection of potential reproductive toxicants might be best when both species are used. Types of sperm head abnormalities and their relative proportion of the total did not differ among control and treatment groups. Estrous cycle data were obtained in the final week of forty-six 13-week studies (23 for mice, 23 for rats). Only 3 chemicals caused an increase in mean cycle length compared with the control group. More data from breeding studies in which female estrous cycle length is measured are needed to assess fully the association of cycle length with reproductive outcome; stages of the estrous cycle are so variable that they may not be useful in assessing potential toxicity. Interlaboratory variability in SMVCE values for many endpoints was documented. Very few of the chemicals that form the basis of this report have been evaluated in definitive reproductive toxicology protocols; a companion paper compares changes in SMVCE endpoints with the outcome of continuous breeding reproduction studies.