Mixtures and Combined Exposures in Immunotoxicology

Humans are rarely exposed to a single chemical in isolation. In real-world settings, exposure occurs simultaneously or sequentially to complex mixtures of pollutants, pharmaceuticals, food contaminants, consumer product chemicals, and agrochemicals together with endogenous or environmental co-stressors. Chemical spill sites, heavy metal contamination, chemical manufacturing and formulation, and purpose-driven use of combinatorial chemicals present a risk of mixtures exposure to workers and the general public. In addition, many products in use today should be considered mixtures in their final intended use formulations, including agrochemicals and cosmetics. Even when formulations contain a single active ingredient, excipients, cofactors, activators, carriers, and other normally innocuous ingredients can have a profound impact on toxicology. Despite this reality, most immunotoxicological research intended for regulatory decision making continues to rely on single-substance evaluations, leaving a gap in understanding how combined exposures affect immune function, host defense, and disease susceptibility.The immune system is a particularly sensitive and integrative target for combined chemical action. Interactions between substances, whether additive, synergistic, or antagonistic, can alter immune cell development, signaling, and regulatory balance in ways that may not be adequately predictable from modeling single-agent data alone. These effects may manifest in unpredictable outcomes, including immunosuppression, hypersensitivity, autoimmunity, or altered susceptibility to infection and cancer, with implications across the life course, including heightened vulnerability during early development and aging. This Research Topic aims to bring together current research addressing the immunotoxicological consequences of mixtures and combined exposures, spanning experimental, mechanistic, computational, and regulatory perspectives. It will advance understanding of how chemical mixtures interact to influence immune outcomes and promote new approaches for predicting and assessing mixture immunotoxicity. Themes of interest include, but are not limited to:• Mechanistic studies on immunotoxic interactions between chemicals, including additive, synergistic, and antagonistic effects.• Combined exposures to environmental pollutants, pesticides, per- and polyfluoroalkyl substances (PFAS), heavy metals, and microplastics.• New approach methodologies (NAMs), including in vitro, in silico, and organ-on-chip models for mixture immunotoxicity testing.• Comparative assessment of mixture immunotoxicity relative to predictive modeling based on the immunotoxicity of individual components.• Cumulative and aggregate risk assessment frameworks for immune endpoints generated from mixture exposures.• Omics and systems biology approaches to characterize immune responses to complex exposures.• Developmental and early-life immunotoxicology in the context of combined exposures.• Case studies linking real-world mixture exposures to immune-mediated disease outcomes.• Regulatory and policy perspectives on incorporating mixture effects into chemical safety assessment.We encourage submissions of Original Research, Review, Perspective, and Methods articles that advance the science of mixture immunotoxicology and support more realistic, human-relevant exposure and risk assessment strategies. Topic editors: Victor J Johnson, Randle Gallucci, Drake Phelps Source: https://www.frontiersin.org/research-topics/86251/mixtures-and-combined-exposures-in-immunotoxicology