An ad hoc committee under the auspices of the National Research Council (NRC) will develop a strategy for evaluating evidence of low-dose adverse human effects that act through an endocrine-mediated pathway. The study will include a scientific workshop to support the conduct of systematic reviews of human and animal toxicology data for two or more chemicals that affect the estrogen, androgen, or perhaps other endocrine systems. The workshop will seek to identify examples of relevant chemicals, populations/model systems, and end points of interest for further study using systematic-review methods. Systematic reviews for these chemicals/populations/end points for human and animal data streams will be performed under the direction of the committee. The committee will evaluate the results of the systematic reviews, demonstrate how human and animal data streams can be integrated, determine whether the evidence supports a likely causal association, and evaluate the nature and relevance of the dose-response relationship(s). The committee will consider how to use adverse outcome pathway (AOP) or other mechanistic data, including high-throughput data and pharmacokinetic information, to elucidate under what circumstances human and animal data may be concordant or discordant. The results of the committee’s evaluation of low-dose toxicity can be used to inform EPA on the adequacy of its current regulatory toxicity-testing practices.