Immunotoxicity assays

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... 

Generally accepted 28 consecutive daily doses in rodents. Adaptations of immunotoxicity assays have been described using non-rodent species. The species, strain, dose, duration, and route of administration used in immune function assays should be consistent, where possible, with the non-clinical toxicology study in which an adverse immune effect was observed. 

A very interesting opportunity is the fact that the very same test can be performed ex vivo after immunomodulatory treatment or intoxications [68-70]. The example of the whole blood immunotoxicity assay shows that with the relatively easy access to human primary cells, the field is predestined for using cells from the target species of interest. Noteworthy, protocols for other immune function assays using whole blood incubations available affording similar advantages [71, 72],... 

Rodgers KE, Leung N, Imamura T, et al. 1986. Rapid in vitro screening assay for immunotoxic effects of organophosphorus and carbamate insecticides on the generation of cytotoxic T lymphocyte responses. Pestic Biochem Physiol 26 292-301. 

The toxicology of PCBs is complex and not fully understood. Coplanar PCBs interact with the Ah-receptor, with consequent induction of cytochrome P4501A1/2 and Ah-receptor-mediated toxicity. Induction of P4501A1 provides the basis of valuable biomarker assays, including bioassays such as CALUX. Certain PCBs, for example, 3,3, 4,4 -TCB, are converted to monohydroxymetabolites, which act as thyroxine antagonists. PCBs can also cause immunotoxicity (e.g., in seals). 

Goven, A.J., S.C. Chen, L.C. Fitzpatrick, and B.J. Venables. 1994. Lysozyme activity in earthworm (Lumbricus terrestris) coelomic fluid and coelomocytes enzyme assay for immunotoxicity of xenobiotics. Environ. Toxicol. Chem. 13 607-613. 

The functional capacity of the immune system should be established before concluding that a given compound is immunotoxic. Many functional assays have been developed... 

It is recommended that a flow chart/decision tree approach be used to evaluate whether or not a compound is immunotoxic (initial screening). Detection of compounds as potential immunotoxicants can then be followed up by more detailed in vitro mechanistic assays... 

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

IMMUNE FUNCTION ASSAYS EMPLOYED IN DEVELOPMENTAL IMMUNOTOXICITY TESTING... 

More recently, the National Institute of Environmental Health Sciences and the National Institute for Occupational Safety and Health convened a workshop in which experts in the field of developmental immunotoxicology developed a tiered approach for assaying the developmental immunotoxicity of chemicals.18 The recommended assays were separated into three groups (1) an initial set of screening assays, (2) assays for validation of a correlation between the assay end point and functional outcomes in humans, and (3) assays for research development.18 The initial screening assays included analysis of the primary antibody response to a T-dependent antigen, the delayed type... 

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. 

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