Year: 2021
Type: article
Abstract: BACKGROUND: The concept of chemical agents having properties that confer potential hazard called key characteristics (KCs) was first developed to identify carcinogenic hazards. Identification of KCs of cardiovascular (CV) toxicants could facilitate the systematic assessment of CV hazards and understanding of assay and data gaps associated with current approaches. OBJECTIVES: We sought to develop a consensus-based synthesis of scientific evidence on the KCs of chemical and nonchemical agents known to cause CV toxicity along with methods to measure them. METHODS: An expert working group was convened to discuss mechanisms associated with CV toxicity. RESULTS: The group identified 12 KCs of CV toxicants, defined as exogenous agents that adversely interfere with function of the CV system. The KCs were organized into those primarily affecting cardiac tissue (numbers 1-4 below), the vascular system (5-7), or both (8-12), as follows: 1) impairs regulation of cardiac excitability, 2) impairs cardiac contractility and relaxation, 3) induces cardiomyocyte injury and death, 4) induces proliferation of valve stroma, 5) impacts endothelial and vascular function, 6) alters hemostasis, 7) causes dyslipidemia, 8) impairs mitochondrial function, 9) modifies autonomic nervous system activity, 10) induces oxidative stress, 11) causes inflammation, and 12) alters hormone signaling. DISCUSSION: )] air pollution, arsenic, anthracycline drugs, and other exogenous chemicals possess one or more of the described KCs. In conclusion, the KCs could be used to identify potential CV toxicants and to define a set of test methods to evaluate CV toxicity in a more comprehensive and standardized manner than current approaches. https://doi.org/10.1289/EHP9321.
DOI: 10.1289/ehp9321
Authors: Lars Lind, Jesus A. Araujo, Aaron Barchowsky, Scott Belcher, Brian R. Berridge, Nipavan Chiamvimonvat, Weihsueh A. Chiu, Vincent J. Cogliano, Sarah Elmore, Aimen K. Farraj, Aldrin V. Gomes, Cliona M. McHale, Kathleen B. Meyer-Tamaki, Nikki Gillum Posnack, Hugo M. Vargas, Xi Yang, Lauren Zeise, Changcheng Zhou, Martyn T. Smith
Institutions: Uppsala University, University of California, Los Angeles, University of Pittsburgh, North Carolina State University, National Institutes of Health, National Institute of Environmental Health Sciences, University of California, Davis, Texas A&M University, California Environmental Protection Agency, Environmental Protection Agency, University of California, Berkeley, Sangamo BioSciences (United States), Children's National, Sheikh Zayed Institute for Pediatric Surgical Innovation, Amgen (United States), United States Food and Drug Administration, Center for Drug Evaluation and Research, University of California, Riverside
Language: English
Subfield: Health, Toxicology and Mutagenesis
Field: Environmental Science
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $5,000
Awards: G1618561042, Endocrine disruptor mediated activation of PXR causes dyslipidemia and atherosclerosis, G1819655924, G2018540114, G2366971526, A novel mechanism for ART-associated dyslipidemia and atherosclerosis, G462392413, G4857922553, G5070689718, G5291971774, G57603413, G5841330901, G6039722132, G6563211918, G7299864457, G7711462637, G7862069436, G9000053967, G9000062136, G9000071690, G9000116430, G9000117304, G9000159506, G9000183856, G9000225865, G9000324781, G99573168
OpenAlex ID: W3201417477