Using existing assessments for problem formulation in the IRIS Program: Case example for the reassessment of uranium-induced toxicity
The IRIS Program is currently undertaking a reassessment of the noncancer health effects of uranium via oral exposure and is relying on the literature review and scientific analysis contained in ATSDR’s 2013 Toxicological Profile (TR). The ATSDR derived Minimal Risk Levels (MRLs) for oral exposure to uranium compounds are based on uranium-induced renal, developmental, and reproductive toxicity, and the IRIS assessment will examine whether newly available data indicate a need to revise the conclusions for these and all other potential hazards. A systematic evidence map (SEM) of the uranium evidence base from 2011 to early 2022 was generated by conducting a literature search and then screening of studies to identify those consistent with data considered relevant to the defined Populations, Exposure, Comparators and Outcomes (PECO) criteria. Epidemiological and toxicological endpoints were reviewed and analyzed to determine whether newly available data indicate a need to update evidence conclusions and toxicity values for principal health outcomes from the ATSDR Toxicological profile. For identified outcomes with new data, EPA will synthesize evidence across the new studies and the studies cited in ATSDR 2013. This approach leverages existing assessments to develop a literature search strategy and analysis that is focused on outcomes for which there is new relevant evidence that can inform hazard evaluation and dose-response.