The underestimated value of OECD 421 and 422 repro screening studies: putting it in the right perspective.

To assess the efficacy of reproduction/developmental screening studies (OECD 421 and 422), a retrospective evaluation of 134 studies was performed. The major findings were: (1) for up to half of the studies with developmental and reproductive toxicity, these effects would have been missed in other types of studies, which underscores that reproduction/developmental screening studies should not be waived by default based on negative 28-day and/or prenatal developmental data, (2) the required number of animals as stated in the guidelines, is appropriate for detecting developmental and reproductive toxicity, and (3) adding measurements like anogenital distance, internal sex determination and nipple retention, plus extending the postnatal period would add predictive value. Overall, the current reproduction/developmental screening studies are effective in providing unique data, especially considering the limited number of animals used. Some simple additions would enrich its value in risk assessment even further.