Key characteristics of cardiovascular Toxicants

Lars Lind, Jesus A. Araujo, Aaron Barehowsky, Scott Belcher, Brian R. Berridge, Nipavan Chiamvimonvat, Weihsueh A. Chiu, Vincent J. Cogliano, Sarah Elmore, Aimen K. Farraj, Aldrin V. Gomes, Cliona M. McIiale, Kathleen B. Meyer-Tamaki, Nikki Gillum Posnack, Hugo M. Vargas, Xi Yang, Lauren Zeise, Changcheng Zhou, Martyn T. Smith

Research output: Contribution to journalArticlepeer-review

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: These 12 KCs can be used to help identify pharmaceuticals and environmental pollutants as CV toxicants, as well as to better understand the mechanistic underpinnings of their toxicity. For example, evidence exists that fine particulate matter [PM ≤ 2.5 }.im in aerodynamic diameter (PM2.5)] 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.

Original languageEnglish (US)
Article number095001
JournalEnvironmental health perspectives
Volume129
Issue number9
DOIs
StatePublished - Sep 2021

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Health, Toxicology and Mutagenesis

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