Investigative Immunotoxicology

Immunotoxicology is the study of immune system dysfunction that can result from occupational, inadvertent, or therapeutic exposure to a variety of chemical or biologic agents that alter the immune system and affect human health. Immunotoxicology can manifest in a variety of ways, with one of the most prominent effects being immunosuppression. Immunosuppression can be defined as a reduced ability of the immune system to respond to a challenge from a level considered normal, regardless of whether clinical disease results. Although immunosuppression can lead to an increased incidence and severity of infectious and neoplastic disease, interpreting data from experimental immunotoxicology studies, or even epidemiologic studies, for quantitative risk assessment has been a persistent challenge. Decades of research has resulted in the development of specific assays and the identification of sensitive endpoints that measure effects on the immune response, from which many regulatory agencies have developed specific immunotoxicity testing guidelines. However, establishing a direct link between exposure and disease manifestations for immunosuppression in humans is an ongoing challenge due to inherent limitations of epidemiological studies to draw causal conclusions. Efforts have been made to examine the relationships between laboratory measures of immune response and disease resistance in experimental animal models and also in human studies. The identification of sensitive endpoints and the development of experimental assays to identify suspect immunotoxicants are a primary focus of the field of immunotoxicology. This chapter is organized around sections discussing the impact and scientific basis of immunotoxicity testing, predictive immunotoxicity testing strategies, examples of immunotoxicity testing, and key considerations and recent developments related to effective testing strategies for health risk reduction.