title: 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.
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.
authors: National Center for Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA. Electronic address: lassiter.meredith@epa.gov.
authors: Meredith Gooding
authors: MG
authors: Lassiter
authors: National Center for Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA. Electronic address: owens.beth@epa.gov.
authors: Elizabeth Oesterling
authors: EO
authors: Owens
authors: National Center for Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA. Electronic address: patel.molini@epa.gov.
authors: Molini M
authors: MM
authors: Patel
authors: National Center for Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA. Electronic address: kirrane.ellen@epa.gov.
authors: Ellen
authors: E
authors: Kirrane
authors: Oak Ridge Institute for Science and Education Research Participation Program, National Center for Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA. Electronic address: meagankmadden@gmail.com.
authors: Meagan
authors: M
authors: Madden
authors: National Center for Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA. Electronic address: richmond-bryant.jennifer@epa.gov.
authors: Jennifer
authors: J
authors: Richmond-Bryant
authors: National Center for Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA. Electronic address: hines.erin@epa.gov.
authors: Erin Pias
authors: EP
authors: Hines
authors: National Center for Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA. Electronic address: davis.allen@epa.gov.
authors: J Allen
authors: JA
authors: Davis
authors: National Center for Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA. Electronic address: vinikoor-imler.lisa@epa.gov.
authors: Lisa
authors: L
authors: Vinikoor-Imler
authors: Southern Region Integrated Pest Management Center, North Carolina State University, 1730 Varsity Drive, Suite 110, Raleigh, NC 27606, USA. Electronic address: jbdubois@ncsu.edu.
authors: Jean-Jacques
authors: JJ
authors: Dubois
mesh_terms: D000818:Animals; D004785:Environmental Pollutants / Q000378:metabolism / Q000633:toxicity*; D006402:Hematologic Diseases / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007854:Lead / Q000378:metabolism / Q000633:toxicity*; D013045:Species Specificity; D014481:United States; D014484:United States Environmental Protection Agency / Q000639:trends*
chemical_list: D004785:Environmental Pollutants; D007854:Lead
keywords: Biological plausibility; Causality; Coherence; Cross-species; Lead; Mode of action