Cross-species coherence in effects and modes of action in support of causality determinations in the U.S. Environmental Protection Agency's Integrated Science Assessment for Lead. (1st April 2015)

• Record Type: Journal Article
• Authors: Lassiter, Meredith Gooding; Owens, Elizabeth Oesterling; Patel, Molini M.; Kirrane, Ellen; Madden, Meagan; Richmond-Bryant, Jennifer; Hines, Erin Pias; Davis, J. Allen; Vinikoor-Imler, Lisa; Dubois, Jean-Jacques
• Is Part Of: Toxicology. Volume 330(2015)
• Page Start: 19
• Page End: 40
• Publication Date: 2015-04-01
• Subjects: δ-ALA delta aminolevulinic acid -- ALAD aminolevulinic acid dehydratase -- AOP adverse outcome pathway -- BW body weight -- CASAC Clean Air Scientific Advisory Committee -- DNA deoxyribonucleic acid -- EPA Environmental Protection Agency -- FSH follicle stimulating hormone -- GABA gamma aminobutyric acid -- GnRH gonadotropin releasing hormone -- Hb hemoglobin -- HERO Health and Environmental Research Online -- HPG hypothalamic–pituitary–gonadal -- IGF-1 insulin-like growth factor -- ISA Integrated Science Assessment -- LH luteinizing hormone -- MOA(s) mode(s) of action -- NAAQS National Ambient Air Quality Standards -- Pb lead -- ROS reactive oxygen species -- U.S. United States -- ZPP zinc–protoporphyrin production; Cross-species -- Mode of action -- Lead -- Biological plausibility -- Causality -- Coherence; Toxicology -- Periodicals; Chemicals -- Physiological effect -- Periodicals; 615.9005
• DOI: 10.1016/j.tox.2015.01.015
• Languages: English
• ISSNs: 0300-483X

Abstract

Abstract: 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 (U.S.) Environmental Protection Agency (EPA) applied a cross-species approach in the 2013 Integrated Science Assessment (ISA) for Lead for evaluating the causality of relationships between Pb exposure and specific endpoints that are shared by humans, laboratory animals, and ecological receptors (i.e., hematological effects, reproductive and developmental effects, and nervous system effects). Other effects of Pb (i.e., cardiovascular, renal, and inflammatory responses) are less commonly assessed in aquatic and terrestrial wildlife limiting the application of cross-species comparisons. 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. As illustrated for effects of Pb where evidence across species exists, the integration of coherent effects and common underlying modes of action can serve as a means to substantiate conclusions regarding the causal nature of the health and ecological effects of environmental toxicants.