The value of multiple endpoint data in male reproductive toxicology: revelations in the rat.

To explore the relationship between sperm measures and reproductive success in the laboratory rat, a review has been conducted of results of several male reproductive toxicology studies containing both fertility and multiple endpoint data. Comparisons are made between subchronic and acute exposure studies, emphasizing for each approach the value of multiple endpoint data. Further, the choice of endpoints in male reproductive toxicology is discussed with select examples of endpoints for which an understanding is evolving. We conclude that sperm measures are far more sensitive indicators of reproductive organ impairment than is the measurement of fertility, and that evaluation of multiple endpoints in acute studies is a key step in determining mechanisms of toxicant action that are critical for accurate interspecies risk extrapolation.