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Cross-Species Coherence in Effects and Modes of Action in Support of Causality Determinations in the EPA’s Integrated Science Assessment (ISA) for Lead
Citation:
Lassiter, Meredith, B. Owens, M. Patel, E. Kirrane, M. Madden, J. Richmond-Bryant, E. Hines, Allen Davis, L. Vinikoor-Imler, AND J. dubois. Cross-Species Coherence in Effects and Modes of Action in Support of Causality Determinations in the EPA’s Integrated Science Assessment (ISA) for Lead. TOXICOLOGY. Elsevier Science Ltd, New York, NY, 330:19-40, (2015).
Impact/Purpose:
Our manuscript describes a novel approach applied by the U.S. EPA to support conclusions regarding causality of relationships of lead exposure with health and ecological effects. Evaluation of the coherence of the effects of lead across humans, laboratory animals and ecological receptors is described, as well as key events in mode of actions (MOA)s across multiple disciplines and species that are elements of a larger causal framework. Specifically, the integration of effects of lead and the MOAs common to human and ecological receptors (i.e. hematological effects, reproductive and developmental effects, nervous system effects) strengthened the overall weight of evidence relating to biological plausibility and coherence across disciplines and species. This approach could be applied in other regulatory settings to identify possible effects of common exposures between humans and biota.
Description:
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.
URLs/Downloads:
http://www.sciencedirect.com/science/article/pii/S0300483X150002
LASSITER.PDF (PDF, NA pp, 308 KB, about PDF)