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Immunotoxicology and Its Application in Risk Assessment
Citation:
Rooney, A. A., R. W. LUEBKE, M. SELGRADE, AND D. R. Germolec. Immunotoxicology and Its Application in Risk Assessment. Chapter 3, Environmental Toxicology, in the series Molecular, Clinical and Environmental Toxicology. Springer, New York, NY, 101:251-288, (2012).
Impact/Purpose:
This is an Invited book chapter. The chapter provides an overview of immunotoxicology, and emphasizes the importance of adequate testing to provide data suitable for risk assessment. The chapter presents a harmonized approach to immunotox testing that incorporates suppression and enhancement of normal immune functions, allergic hypersensitivity and autoimmune disease. Although the Agency mandates testing new pesticides for potential immunosuppressive activity, it has yet to provide formal guidance on interpreting data from the required tests, or the use of the data for risk assessment.
Description:
Immunotoxicology is the study of undesired modulation of the immune system by extrinsic factors. Toxicological assessments have demonstrated that the immune system is a target following exposure to a diverse group of xenobiotics including ultraviolet radiation, chemical pollutants, therapeutics, and recreational drugs. There is a well established cause and effect relationship between suppression of the immune response and reduced resistance to infections and certain types of neoplasia. In humans, mild to moderate suppression of the immune response is linked to reduced resistance to common, community-acquired infections, whereas opportunistic infections, which are very rare in the general population, are common in individuals with severe suppression. Xenobiotic exposure may also result in unintended stimulation of immune function. Although a cause and effect relationship between unintended stimulation of the immune response and adverse consequences has yet to be established, evidence does suggest that hypersensitivity, autoimmunity, and pathological inflammation may be exacerbated in susceptible populations exposed to certain xenobiotics. Xenobiotics can act as allergens and elicit hypersensitivity responses, or they can modulate hypersensitivity responses to other allergens such as pollen or dust mite by acting as adjuvants, enhancing the development or expression of hypersensitivity. Allergic contact dermatitis, allergic rhinitis, and asthma are the most commonly encountered types of hypersensitivity reactions resulting from chemical exposure. The immunologic effectors and mechanisms involved in autoimmune reactions are the same as those associated with responses to foreign antigens; however, the reactions are directed against the host's own cells. Thus, chemicals that induce immune suppression, non-specific immunostimulation or hypersensitivity may also impact autoimmunity. Risk assessment for immunotoxicity should be performed using the same approaches and principals for other non-cancer effects. However, since xenobiotics may have effects on more than one aspect of immune function, immunotoxicity data should be evaluated separately for evidence of suppression, stimulation, hypersensitivity, and autoimmunity. The findings and conclusions in this report represent the opinions of the authors and do not represent, and should not be construed to represent, statements, opinions or conclusions of the National Toxicology Program, NIEHS, NIH, the Environmental Protection Agency or the United States government
