The National Academies of Sciences, Engineering, and Medicine is undertaking a study to provide the Environmental Protection Agency (EPA) with a review of the variability and relevance of existing laboratory mammalian toxicity tests for human health risk assessment to inform the development of approaches for validation and establishing scientific confidence in using New Approach Methods (NAMs), and recommendations on expectations associated with NAMs when they cannot be compared with human studies. The work of the study committee will be informed by an initial public workshop, by a literature review that addresses the variability and human relevance of current laboratory mammalian toxicity tests and approaches to validation and establishing scientific confidence in using NAMs, and by public information gathering meetings organized by the study committee.