Immunotoxicity tests

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. 

Germolec, D.R. et al., Extended histopathology in immunotoxicity testing interlaboratory validation Studies, Toxicol. Set., 78, 107, 2004a. 

Hinton, D.M., US FDA Redbook II immunotoxicity testing guidelines and research in immunotoxicity evaluations of food chemicals and new food proteins, Toxicol. Pathol., 28, 467, 2000. 

Organisation for Economic Cooperation and Development, Immunotoxicity Testing Possible Future Work, ENV/MC/CHEM/TG(98)6, Paris, 1998. 

Germolec, D.R., Selectivity and predictivity in immunotoxicity testing Immune endpoints and disease resistance, Toxicol. Letters, 149, 109, 2004. 

Immunotoxicity Testing Committee, Application of flow cytometry to immunotoxicity testing summary of a workshop report, ILSI/HESI, Washington D.C., 1999. 

Langezaal, I. et al., Evaluation and prevalidation of an immunotoxicity test based on human whole-blood cytokine release, Altern. LabAnim., 30, 581, 2002. 

Selgrade, M.K., Daniels, M.J. and Dean, J.H., Correlation between chemical suppression of natural killer cell activity in mice and susceptibility to cytomegalovirus rationale for applying murine cytomegalovirus as a host resistance model and for interpreting immunotoxicity testing in terms of risk of disease, J. Toxicol. Environ. Flealth, 37, 123, 1992. 

Burchiel, S.W., et al., Uses and future applications of flow cytometry in immunotoxicity testing, Methods, 19, 28, 1999. 

Immune Function Assays Used in Developmental Immunotoxicity Testing..334... 

A recent workshop18 and forum19 addressed issues of the appropriate immune function methods and rodent species for evaluating developmental immunotoxicity. In both meetings the rat was identified as the preferred animal model for developmental immunotoxicity testing. This chapter will review evidence which implicates certain chemicals and drugs as being developmental immunotoxicants in rodents. 

IMMUNE FUNCTION ASSAYS EMPLOYED IN DEVELOPMENTAL IMMUNOTOXICITY TESTING... 

Immunotoxicity testing in rodents exposed to industrial and/or environmental chemicals, has been recognized as an important toxicological concern for over 25 years. Early immunotoxicity testing relied primarily on the mouse, due to the plethora of immune structure and function research performed by immunologists to better understand the human immune system. As such, the mouse has been the most employed rodent for immunotoxicity testing. Immune system function assays employed in screening for immunotoxicity were developed in adult mice. These same immune function assays have served to help identify toxicant induced immunosuppression in the rat. 

Koeter, H. International harmonization of immunotoxicity testing. Human Experimental Toxicology, 14(1), 151-154, 1995. 

Holsapple, M.P. Developmental immunotoxicity testing A review. Toxicology, 185, 193, 2003. 

Induced models are often used to the study the pathogenesis of, and therapeutic venues for relevant autoimmune diseases. Some of these models, in particular EAE and AA models, have also been proposed as means to evaluate the immunomodulatory effects of chemicals on established autoimmune diseases in the Tiered Approach of immunotoxicity testing. 

TABLE 7.7. FDA Draft Recommendation for Type I Immunotoxicity Test That Can Be Included in Repeated Dose Toxicity Studies... 

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