Rodent models immunotoxicity testing

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. 

Immunotoxicity testing of biopharmaceuticals can be very challenging, since rarely can the clinical drug candidate be tested in the standard rodent models. These assays are either conducted (when appropriate) in NHPs or in a rodent with a surrogate molecule, or in a rodent with the target knocked-out or overexpressed. All of these options have their own issues and caveats which pres-... 

One advantage of rodents, beyond the exceptionally well-characterized immune system and availability of reagents, is the fact that DIT assessment may be able to be dovetailed into existing developmental and reproductive assessments. Certainly DIT testing using other mammalian species may be appropriate under some circumstances, but the opportunity to examine developmental immunotoxicity, developmental neurotoxicity, and reproductive toxicity using a common model suggests that the rodent is likely to remain the standard model of choice. This conclusion was also reached by various consensus panels (Holsapple et al., 2005). 

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