Immunotoxicity chemicals

Germolec, D.R. et al., The accuracy of extended histopathology to detect immunotoxic chemicals, Toxicol. Sci., 82, 504, 2004b. 

In contrast to profound immunosuppression, such as that which occurs in patients with HIV/AIDS or primary immunodeficiency diseases, exposure to immunotoxic chemicals or drugs is believed to be more likely to cause mild-to-moderate levels of immunosuppression (e.g., a 20% decrease in white blood cell counts). This review attempts to address, both qualitatively and quantitatively, the potential adverse health effects of moderate levels of immunosuppression. The following general conclusions can be surmised. 

NEWGENERIS (Newborns and genotoxic exposure risks) Using 300,000 mother-child birth cohorts and stored specimens from biobanks, study will develop and apply biomarkers of dietary exposure to genotoxic and immunotoxic chemicals and biomarkers of early effects (European Commission 2006). Researchers will analyze blood samples from biobanks in Norway, Denmark, the United Kingdom, Spain, and Greece (European Union 2006). 

Immunotoxicity Occupational workers are exposed to a variety of chemicals in work conditions. The assessment of immunotoxicity in humans exposed to potentially immunotoxic chemicals is a complex task. An immune response in fully immunologically competent individuals will provide protection against several infectious agents and environmental hazards. The immune system is a... 

Immunity The ability of an organism or animal to combat infections by parasites Immunologic toxicity The occurrence of adverse effects on the immune system that may result from exposure to enviromnental agents such as chemicals Immunotoxic Chemical substances that cause adverse health effects to the immune... 

Table 25.1 Representative List of Immunotoxic Chemicals (Continued)...

Immunotoxic chemicals can interfere with the body s ability to ward off disease, can induce and exacerbate allergic responses, and contribute to autoimmune diseases. The complexity of the immune system and its interaction with other body systems makes it particularly vulnerable to attack by xenobiotics. Studies that have been carried out, however, have demonstrated that a wide variety of chemicals are immunotoxic and that chemical mixtures such as those contained in air polluted with the products of combustion, industrial emissions, and tobacco smoke is immunotoxic. Such polluted air can induce immunostimulative responses and bring on allergic reactions in previously sensitized individuals. 

Lang DS, Meier KL, Luster MI. Comparative effects of immunotoxic chemicals on in vitro proliferative responses of human and rodent lymphocytes. Toxicol Sci 1993 21(4) 535-45. 

Since the limited information available on the effects of dermally administered endosulfan suggests that this chemical behaves similarly across both routes of exposure and that adverse effects on immune function end points have also been observed in vitro, there is no reason to suspect that the immunotoxic effects observed following oral exposure are route-specific. Tests of immunologic function in exposed human populations would provide information as to whether immunosuppression also occurs in humans... 

Vos JG, Krajnc El, Beekhof PK, et al. 1982. Methods for testing immune effects of toxic chemicals Evaluation of the immunotoxicity of various pesticides in the rat. In Miyamoto J, Kearney PC, eds. Pesticide chemistry Human welfare and the environment. Oxford, England Pergamon Press, 497-504. 

Toxic equivalency factors (TEFs) are estimated relative to 2,3,7,8-TCDD, which is assigned a value of 1. They are measures of the toxicity of individual compounds relative to that of 2,3,7,8-TCDD. A variety of toxic indices, measured in vivo or in vitro, have been used to estimate TEFs, including reproductive effects (e.g., embryo toxicity in birds), immunotoxicity, and effects on organ weights. The degree of induction of P450 lAl is another measure from which estimations of TEF values have been made. The usual approach is to compare a dose-response curve for a test compound with that of the reference compound, 2,3,7,8-TCDD, and thereby establish the concentrations (or doses) that are required to elicit a standard response. The ratio of concentration of 2,3,7,8-TCDD to concentration of test chemical when both compounds produce the same degree of response is the TEF. Once determined, a TEF can be used to convert a concentration of a dioxin-like chemical found in an environmental sample to a toxic equivalent (TEQ). 

Several studies have suggested that some critical adverse effects like peroxisome proliferation, hepatotoxicity, immunotoxicity, and developmental toxicity may be associated with chemical exposure to PFCs, particularly to PFOS (perfluorooctane sulfonate) and PFOA (perfluorooctanoic acid), two ubiquitous persistent organic pollutants with possible environmental and human health risks. 

Although the effects of chronic exposure of humans to low levels of POPs are difficult to predict, some biological effects have been described. For example, exposure of children to PCBs and PCDD/Fs may be linked to an elevated risk for infectious diseases. Exposure of pregnant women to PCDD/Fs may cause lower fertility in their male offspring. The adverse effects to human health of acute and chronic exposure of high concentrations of POPs, especially among industrial workers exposed to daily intakes of chemicals, are more evident. Elevated concentrations of DDE and TCDD have been associated with the development of cancers such as breast cancer, leukaemia and thyroid cancer. Dioxin exposure may also be associated with immunotoxicity, reproductive diseases and neurotoxicity. Extreme exposure to chlorinated compounds has resulted in death [101]. 

The majority of early publications that can be reasonably identified as comprising immunotoxicology reported altered resistance to infection in animals exposed to various environmental or industrial chemicals. Authors logically concluded that xenobiotic exposure suppressed immune function since the immune system is ultimately responsible for this resistance to infection. Subsequent studies demonstrated that suppression of various cellular and functional endpoints accompanied or preceded increased sensitivity to infection, and that administration of known immunosuppressants likewise decreased host resistance. The human health implications of these studies, that chemical exposure reduced resistance to infection, drove the initial focus of many immunotoxicologists on functional suppression, and provided the theoretical and practical underpinnings of immunotoxicity testing. 

Chemicals that do not fall under the testing requirements for pesticides may have immunotoxic potential. However, submitting all industrial chemicals for immunotoxicity... 

Luster, M.I., Blank, I. A. and Dean, J.H., Molecular and cellular basis of chemically induced immunotoxicity, Annu. Rev. Pharmacol. Toxicol., 27, 23, 1987. 

Luster, M.I. et al., Development of a testing battery to assess chemical-induced immunotoxicity National Toxicology Program s guidelines for immunotoxicity evaluation in mice, Fund. Appl. Toxicol., 10, 2, 1988. 

Krzystyniak, K., Tryphonas, H. and Fournier, M., Approaches to the evaluation of chemical-induced immunotoxicity, Environ. Health Perspect., 103 Suppl. 9, 17, 1995. 

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