Immunotoxicity guidelines

Ruehl-Fehlert, C. et al., Harmonization of immunotoxicity guidelines in the ICH process—pathology considerations from the guideline Committee of the European Society of Toxicological Pathology (ESTP), Exp. Toxicol. Pathol., 57, 1, 2005. 

In an immunotoxicity guideline (FDA 2006), plasma total globulin measurements and ratios of albumin to globulin are listed, with the suggestion that alterations of total globulin concentrations could be followed by measurement of plasma immunoglobulins (see Chapter 8). 

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. 

Biochemicals Test Guidelines OPPTS 880.3550 Immunotoxicity. United States Environmental Protection Agency, February 1996. 

Follow-on studies are also recommended as needed. These include determination of potential test article effects on blood or tissue immunophenotypes (by flow cytometry or immunohistochemistry), natural killer cell, macrophage, or neutrophil function, host resistance to infection or tumors, and cell-mediated immunity. The important issue in all of these guidelines is this do not ignore signs of immunotoxicity, and assess these findings when observed. 

ICH Harmonised Tripartite Guideline, Immunotoxicity Studies for Human Pharmaceuticals (S8) (http //www.ich.org/, 2005). 

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. 

U.S. Environmental Protection Agency. OPPTS 870-7800, Immunotoxicity, Health Effects Test Guidelines. EPA 712-C98-351, 1999. 

If we consider both the specific immunotoxicity assays surveyed earlier in this chapter and the arrays of endpoints evaluated in traditional toxicology studies, which may be indicative of an immune system effect, these guidelines leave many potential questions unanswered. As additional data on individual endpoints indicative of... 

Hinton, D.M. (1992). Testing guidelines for evaluation of the immunotoxic potential of direct food additives. Critical Rev. in Food Sci. Nutrition 32 173-190. 

Luster, M.L., Munson, A.E., Thomas, P.T., Holsapple, M.P., Fenters, J.D., White, K.L., Jr., Lauer, L.D., Germolec, D.R., Rosenthal, G.J. and Dean, J.H. (1988). Development of a testing battery to assess chemical-induced immunotoxicity National Toxicology Program s Guidelines for Immunotoxicity Evaluation in Mice. Fund. Appl. Toxicol. 10 2-19. 

The standard repeated dose toxicity guidehne studies include a number of parameters relevant for the evaluation of a substance s immunotoxic potential. While some information on potential immunotoxic effects may be obtained from the evaluation of hematology, lymphoid organ weights, and histopathology in these studies, there are data which demonstrate that these endpoints alone are not sufficient to predict immunotoxicity. In addition to these standard studies, the US-EPA has developed a specific test guideline for immunotoxicity testing in rodents (OPPTS 870.7800). This... 

The immunotoxicity study will provide information on suppression of the immune system, which might occur as a result of repeated exposure to a test chemical. The protocol for the US-EPA OPPTS test guideline is intended to be used along with data from routine toxicity testing, to provide more accurate information on risk to the immune system. See also Section 4.7.6. 

The US-EPA OPPTS test guideline on immunotoxicity (OPPTS 870.7800) provides the following definition Immunotoxicity refers to the ability of a test substance to suppress immune responses that could enhance the risk of infectious or neoplastic disease, or to induce inappropriate stimulation of the immune system, thus contributing to allergic or autoimmune disease. ... 

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