Consensus on the Key Characteristics of Immunotoxic Agents as a Basis for Hazard Identification
ORCID
Kaplan: 0000-0002-1992-4145
MSU Affiliation
College of Veterinary Medicine; Department of Comparative Biomedical Sciences; Center for Environmental Health Sciences
Creation Date
2026-03-30
Abstract
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.
Publication Date
10-1-2022
Publication Title
Environmental Health Perspectives
Publisher
National Institute of Environmental Health Sciences
First Page
105001
Recommended Citation
Germolec, D. R., Lebrec, H., Anderson, S. E., Burleson, G. R., Cardenas, A., Corsini, E., Elmore, S. E., Kaplan, B. L. F., Lawrence, B. P., Lehmann, G. M., Maier, C. C., McHale, C. M., Myers, L. P., Pallardy, M., Rooney, A. A., Zeise, L., Zhang, L., & Smith, M. T. (2022). Consensus on the Key Characteristics of Immunotoxic Agents as a Basis for Hazard Identification. Environmental health perspectives, 130(10), 105001. https://doi.org/10.1289/EHP10800
