Integrated approaches for immunotoxicity risk assessment: challenges and future directions

The integration of immunotoxicity data into chemical risk assessment paradigms is essential for comprehensively evaluating the potential health hazards posed by chemical exposures. This review provides a comprehensive overview of the methodologies, challenges, and future directions for integrating immunotoxicity data into risk assessment frameworks. It discusses the fundamental principles of immunotoxicology and its relevance to chemical risk assessment, highlighting the critical roles of the immune system in health and defense against harmful agents. Next, we explore traditional chemical risk assessment frameworks, including exposure assessment, hazard identification, dose–response assessment, and risk characterization, highlighting the need for incorporating immunotoxicity endpoints to enhance hazard characterization and risk estimation. Subsequently, we delve into dose–response modelling for immunotoxicity, elucidating principles, methods, and case studies illustrating dose–response relationships and extrapolation of data from animal studies to humans. Furthermore, we discuss hazard characterization of immunotoxicity, focusing on the identification of immunotoxic hazards, evaluation of immunotoxicity endpoints, and utilization of immunological biomarkers in risk assessment. We then examine cumulative risk assessment strategies, presenting a conceptual framework for assessing cumulative risks of immunotoxicity from multiple chemical exposures and methods for integrating exposure and hazard data from different chemicals. Lastly, we explore emerging trends and future directions in immunotoxicity risk assessment, including high-throughput screening assays, omics technologies, computational modelling, and alternative testing methods, along with potential regulatory implications and future research needs. This review provides valuable insights for researchers, regulators, and stakeholders involved in chemical risk assessment and public health protection, facilitating the development of evidence-based strategies for safeguarding human health from immunotoxic risks associated with chemical exposures.