Consensus on the Key Characteristics of Immunotoxic Agents as a Basis for Hazard Identification.

Autor: Germolec DR; Division of the National Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA., Lebrec H; Translational Safety & Bioanalytical Sciences, Amgen Research, South San Francisco, California, USA., Anderson SE; Allergy and Clinical Immunology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, West Virginia, USA., Burleson GR; Burleson Research Technologies, Inc., Morrisville, North Carolina, USA., Cardenas A; Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, Berkeley, California, USA., Corsini E; Laboratory of Toxicology, Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy., Elmore SE; Office of Environmental Health Hazard Assessment, California Environmental Protection Agency, Oakland, California, USA., Kaplan BLF; Department of Comparative Biomedical Sciences, Center for Environmental Health Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, Mississippi, USA., Lawrence BP; Department of Environmental Medicine, University of Rochester School of Medicine & Dentistry, Rochester, New York, USA.; Department of Microbiology & Immunology, University of Rochester School of Medicine & Dentistry, Rochester, New York, USA., Lehmann GM; Center for Public Health and Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA., Maier CC; In Vitro In Vivo Translation, Research and Development, GlaxoSmithKline, Collegeville, Pennsylvania, USA., McHale CM; Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, Berkeley, California, USA., Myers LP; Division of Pharm/Tox, Office of Infectious Diseases, Office of New Drugs, Center for Drug Evaluation and Research, U.S. Federal Food and Drug Administration, Silver Spring, Maryland, USA., Pallardy M; Inserm, Inflammation microbiome immunosurveillance, Université Paris-Saclay, Châtenay-Malabry, France., Rooney AA; Division of the National Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA., Zeise L; Office of Environmental Health Hazard Assessment, California Environmental Protection Agency, Oakland, California, USA., Zhang L; Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, Berkeley, California, USA., Smith MT; Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, Berkeley, California, USA.
Jazyk: angličtina
Zdroj: Environmental health perspectives [Environ Health Perspect] 2022 Oct; Vol. 130 (10), pp. 105001. Date of Electronic Publication: 2022 Oct 06.
DOI: 10.1289/EHP10800
Abstrakt: Background: Key characteristics (KCs), properties of agents or exposures that confer potential hazard, have been developed for carcinogens and other toxicant classes. KCs have been used in the systematic assessment of hazards and to identify assay and data gaps that limit screening and risk assessment. Many of the mechanisms through which pharmaceuticals and occupational or environmental agents modulate immune function are well recognized. Thus KCs could be identified for immunoactive substances and applied to improve hazard assessment of immunodulatory agents.
Objectives: The goal was to generate a consensus-based synthesis of scientific evidence describing the KCs of agents known to cause immunotoxicity and potential applications, such as assays to measure the KCs.
Methods: A committee of 18 experts with diverse specialties identified 10 KCs of immunotoxic agents, namely, 1) covalently binds to proteins to form novel antigens, 2) affects antigen processing and presentation, 3) alters immune cell signaling, 4) alters immune cell proliferation, 5) modifies cellular differentiation, 6) alters immune cell-cell communication, 7) alters effector function of specific cell types, 8) alters immune cell trafficking, 9) alters cell death processes, and 10) breaks down immune tolerance. The group considered how these KCs could influence immune processes and contribute to hypersensitivity, inappropriate enhancement, immunosuppression, or autoimmunity.
Discussion: KCs can be used to improve efforts to identify agents that cause immunotoxicity via one or more mechanisms, to develop better testing and biomarker approaches to evaluate immunotoxicity, and to enable a more comprehensive and mechanistic understanding of adverse effects of exposures on the immune system. https://doi.org/10.1289/EHP10800.
Databáze: MEDLINE
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