Immunotoxicology: A brief history, current status and strategies for future immunotoxicity assessment

The discipline of immunotoxicology had its origins in the early 1970s, following the recognition of altered immune function and increased sensitivity to infections and cancers after exposure to environmental chemicals and therapeutic drugs. Reduced resistance to infectious disease was a well-documented consequence of primary and acquired immunodeficiencies, but a novel finding following xenobiotic exposure. The awareness of the consequences of altered immune function was likely heightened by the HIV epidemic, leading some to inappropriately characterize xenobiotic-induced immunosuppression as “chemical AIDS”, although it is now clear that mild to moderate suppression is the most likely outcome of inadvertent exposure. The human health implications of studies in which chemical exposure reduced resistance to infection, drove an early focus on immunosuppression within the toxicology community. Allergic hypersensitivity was well known to clinicians and symptoms were readily apparent, and therefore was not the initial focus of the developing toxicology subspecialty of immunotoxicology. The first review in the field of immunotoxicology was published by Vos in 1977, and, as research expanded during the years that followed, many of the assays, methodologies and approaches that are currently used to identify potential immunotoxicants were developed. Over the years, advances in our understanding of basic immunology have made it clear that allergy, immunosuppression and, in some cases, autoimmunity, are a matter of polarization of the immune response by immunotoxicants, rather than independent outcomes of chemical exposure. •The discipline of immunotoxicology had its origins in the early 1970s, following the recognition of alterations in immune function and disease resistance after exposure to environmental chemicals and therapeutic drugs.•As methods to evaluate immunotoxicity became standardized, tiered approaches became a potentially useful tool to evaluate specialized toxicity to the immune system.•Numerous in vitro techniques have become routine in assessments of immunotoxicity.•In 2012, a Guidance for Immunotoxicity Risk Assessment of Chemicals was published by the IPCS, which uses a weight of evidence approach to evaluate the spectrum of available immunotoxicology data.