Approaches to evaluating reproductive hazards and risks.

Development of approaches to risk assessment for reproductive toxicity has aided in the critical evaluation of the scientific basis for interpretation of data and the description of assumptions underlying the process. In addition, it has helped to standardize, to the extent possible, the use of qualitative and quantitative data in the hazard identification and dose-response processes and to identify research needed to fill gaps in the available database. The standard study protocols for evaluating reproductive and developmental hazards include developmental toxicity studies and both short-term and longer-term reproductive studies. These study protocols have been in use for several decades, but development of risk assessment approaches has prompted the recommendation of additional end point measures to these protocols. These include evaluation of specific neurologic and behavioral function of offspring following prenatal and postnatal exposure, evaluation of sperm production and quality, reproductive organ weights, and more in-depth testicular histopathology in males, as well as measures of age at vaginal opening, vaginal cytology, oocyte toxicity, time to mating, gestation length, and reproductive organ weights in females. Current approaches to risk assessment in reproductive toxicity involve the determination of a no-observed-adverse-effect level (NOAEL) and the application of uncertainty factors (UFs) to account for differences between the experimental animal species and humans, variability in sensitivity within the human population, and other factors as necessary to derive the reference dose (RfD), or a specified RfD for developmental toxicity to account for the short period of exposure required.(ABSTRACT TRUNCATED AT 250 WORDS)