Immunotoxicity assessment

Vos, J.G., Immunotoxicity assessment Screening and function studies, Arch. Toxicol., S4, 95, 1980. 

SOT sunset session Developmental toxicology Issues with including neurotox and immunotox assessments in reproductive toxicology studies. New Orleans, LA March, 2005... 

Bunn, T.L., Ladies, G.S., Holsapple, M.P., and Dietert, R.R. Developmental immunotoxicity assessment in the rat Age, gender, and strain comparisons after exposure to lead. Toxicol. Methods, 11,41, 2001. 

Inclusion of additional nonroutine parameters for immunotoxicity assessment in subsequent (longer-term) toxicity assays. Can also include additional satellite groups for functional tests that may require coadministration of... 

AN INTEGRATED APPROACH TO PRECLINICAL AND CLINICAL IMMUNOTOXICITY ASSESSMENTS... 

INTEGRATED APPROACH TO PRECLINICAL CLINICAL IMMUNOTOXICITY ASSESSMENTS 325... 

Cavagnaro J. Immunotoxicity assessment of biotechnology products a regulatory point of view. Toxicology 1995 105 1-6. 

Buse E, Habermann G, Osterburg I, Korte R, Weinbauer GF. Reproductive/devel-opmental toxicity and immunotoxicity assessment In the nonhuman primate model. Toxicology 2003 185 221-7. 

Because bone marrow evaluation is a critical part of immunotoxicity assessment, it is important that appropriate techniques be employed. The site of bone marrow collection, consistency in the collection, processing and evaluation of marrow, and expertise of the individual(s) evaluating each component of the assessment are important. 

Figure 3.3.1-2 Application of the TDAR assay in immunotoxicity assessment. When evaluating unintended immunosuppression, the TDAR assay may be conducted when evidence of immunotoxicity is seen in repeated-dose toxicity studies. In these instances, the assay should be conducted prior to Phase 3 or earlier, depending on factors such as the severity of the findings and the intended patient population. The TDAR assay also could be used early in the drug development process to screen for immunotoxicity potential. This approach may be useful particularly to help de-risk unintended off-target immunomodulation or when a novel target/mechanisms may alter immune function.

Zhu Y, Herlaar E, Masuda ES, Burleson GR, Nelson AJ, Grossbard EB, Clemens GR. Immunotoxicity assessment for the novel spleen tyrosine kinase inhibitor R406. Toxicol Appl Pharmacol 2007 221 268-277. 

As is noted in subsequent sections describing recently published age-based comparisons of rodent immunotoxicity (Luebke et al, 2006), the adult immune system appears to be relatively insensitive for immunotoxicity compared with that of earlier life stages. Based on these recent conclusions, use of an adult immunotoxicity indicator as a trigger for developmental immunotoxicity assessment is likely to be ineffective (Dietert and Piepenbrink, 2006a). 

End Points for Nonhuman Primate Developmental Immunotoxicity Assessment... 

Vos, J. G. 1980. Immunotoxicity assessment Screening and function. Archives of Toxicology 4 (SuppL) 95-108. 

Vollmuth, T.A., J.D. Heck, H.V. Ratajczak, and P.T. Thomas. 1989. Immunotoxicity assessment of flavoring ingredients using a rapid and economical screen. Toxicologist 9 206. 

Some examples of in vitro assays for immunotoxicity assessment follow (Table 13.1), but this list is not intended to be comprehensive. It should be borne in mind that this is a rapidly growing area of research, and many of the assays employed in immunotoxicity or immunosafety evaluation of pharmaceuticals are fit-for-purpose assays based on mechanism or target and are beyond the scope of this chapter. Evaluation of effects on individual cell types and mechanisms (e.g., neutrophil, macrophage, cytotoxic T lymphocyte, and NK function) will not be discussed, as these are rarely employed unless driven by STS findings or intended mechanism of action. 

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