Critical Aspects of EPA's IRIS Assessment of Inorganic Arsenic: Interim Report (2013)Board on Environmental Studies and Toxicology
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This report reviews critical aspects of the scientific literature on inorganic arsenic and a draft plan by the U.S. Environmental Protection Agency (EPA) that describes how the agency will perform its Integrated Risk Information System (IRIS) assessment of the potential health effects of oral exposure to this chemical. The report finds that EPA's draft plan includes improved approaches for evaluating evidence and conducting analyses but should take greater advantage of the robust database on inorganic arsenic in order to reach the best evidence-based conclusions. Furthermore, the report recommends alternative statistical approaches for developing risk estimates.
- EPA's draft planning documents outline an improved approach to determining the cancer and noncancer effects that may be associated with exposure to inorganic arsenic, and describe how a causal determination framework will be used to categorize evidence on different health end points into five possible categories. The committee supports this five-tier approach, and recommends that judgments are characterized with respect to standard criteria for causality.
- EPA has indicated that several systematic reviews of the scientific literature will be used to support its toxicologic assessment of inorganic arsenic. A statistical technique called meta-analysis could also be used as an evaluation tool to pool evidence from systematic reviews if certain conditions are met. The report provides guidance on how the agency should proceed with conducting systematic reviews and meta-analyses.
- EPA's draft plans outline an evaluation process to organize mechanistic information to inform dose–response modeling with respect to the shape of the curve, particularly in the low dose region of the curve, and the understanding of human variability. The committee supports EPA's plans to perform mode-of-action analyses for health outcomes on which there appears to be a causal or likely to be causal relationship with inorganic arsenic. The report provides further guidance on the approach such analyses could take.
- Multiple factors can affect susceptibility to inorganic arsenic, including life stage, genetic factors, sex, nutritional deficiencies, health status, lifestyle (for example, smoking and alcohol consumption), and coexposures. The committee agrees with EPA's proposal to use probabilistic approaches in considering the uncertainty and variability associated with those factors.
- Epidemiologic data are expected to serve as the basis for the dose-response analyses performed for most health effects. EPA's efforts should be directed at performing dose-response analyses in the range of epidemiologic observations. Should the data in the range of observation be inadequate for developing risk estimates that meet EPA's needs, mode-of-action data should be used to the extent possible to extrapolate below the observed range. The committee concurs with EPA's draft plan that even if a mode of action cannot be determined with reasonable certainty, dose-response analyses should be performed on health end points deemed to have a causal or likely causal relationship with arsenic. In the absence of mode-of-action data, alternative statistical approaches are recommended.