Immunotoxicity detection

As was the case with tier testing, developmental immunotoxicology has been driven by expert workshops to reach consensus on the most important issues three workshops were held in 2001 [79-81], and another in 2003 [82], These workshops contributed to the development of a proposed testing framework to detect developmental immunotoxicity, which is described in detail in chapter 21. 

Kuper, C.F. et al., Histopathologic approaches to detect changes indicative of immunotoxicity, Toxicol. Pathol., 28,454, 2000a. 

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

Ringerike, T. et al., Detection of immunotoxicity using T-cell based cytokine reporter cell lines ( Cell Chip ), Toxicology, 206, 257, 2005. 

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... 

Immunotoxicity. No data were located regarding immunological effects in humans after inhalation, oral, or dermal exposure to chloroform. The data obtained from animal studies are limited to one inhalation study in mice and three oral studies in rats and mice (Aranyi et al. 1986 Chu et al. 1982b Munson et al. 1982). Depressed humoral and cell-mediated immunity were detected however, the chloroform-induced changes were more serious in the acute exposure study than in the intermediate-duration study, indicating that the changes may be transient. Studies regarding skin sensitization with chloroform were not performed. A battery of immune function tests has not been performed in humans or in animals, but would provide helpful information to support or refute the limited evidence for chloroform immunotoxicity. 

De Jong, W.H., Kroese, E.D., Vos, J.G. and Van Loveren, H. (1999) Detection of immunotoxicity of benzo[a]pyrene in a subacute toxicity study after oral exposure in rats. Toxicological Sciences, 50, 214-220. 

The resulting epitope density may depend on the number of lysine groups in the particular protein, and this will in turn affect the immunogenicity of the antigen. Trifluoroacyl adducts have been detected on the outer surface of hepatocytes, presumably as a result of the hapten-complex processing and delivery by MHC I, which is described above. The fact that the production of the trifluoroacetyl chloride is part of the major metabolic pathway and that the majority of patients produce trifluoroacylated proteins suggests that it is differences in the immune surveillance system or immune responsiveness, which determine which patients will succumb to the immunotoxic effect. 

Various standards and procedures exist for the evaluation of the biological and immunotoxicity response of an implant [81] from the point of view of biocompatibility. Acute toxicity screening and in vivo implantation tests are fundamental in this respect. Cytotoxicity testing to detect the biological activity of the material on a mammalian cell monolayer is often the first step in assessing biocompatibility of a device. An international standard on the biological evaluation... 

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