Cross-Species Coherence in Effects and Modes of Action in Support of Causality Determinations in the EPA’s Integrated Science Assessment (ISA) for Lead
The peer-reviewed literature on the health and ecological effects of lead (Pb) indicates common effects and underlying modes of action across multiple organisms for several endpoints. Based on such observations, the United States Environmental Protection Agency (EPA) applied a cross-species approach in the 2013 Integrated Science Assessment (ISA) for Lead for evaluating the causality of some relationships between Pb exposure and specific endpoints shared by humans, laboratory animals, and ecological receptors (i.e. hematological effects, reproductive and developmental effects, and nervous system effects). Determinations of causality in ISAs are guided by a framework for classifying the weight of evidence across scientific disciplines and across related effects by considering aspects such as biological plausibility and coherence. The integration of coherent effects and common underlying modes of action across species added to the weight of evidence and substantiated conclusions regarding the causal nature of some of the health and ecological effects of Pb exposure.