Developmental immunotoxicity testing exposure

Developmental immunotoxicity testing has gained increasing attention with the recognition that for most drugs compared to date, when immunomodulatory effects are observed, the developing immune system is more sensitive than that of the adult. Therefore, safety limits for exposure of non-adults can be difficult to predict in the absence of age-relevant exposure assessment. 

Short- to medium-term exposure has shown neurotoxicity, developmental toxicity, immunotoxicity, and endocrine disruption to be relevant end-points. Table 24 summarizes the critical studies for each compound and identifies NOAELs or LOAELs. The degree of each of the toxic end-points differs across the group as a whole. For example, tributyltin is well established as an aromatase inhibitor, and dibutyltin appears to have some potency also (exact characterization of the endocrine disrupting capacity of dibutyltin alone is difficult because of the presence of tributyltin as an impurity). Monobutyltin and mono- and dioctyltins have no aromatase inhibiting capacity in in vitro tests. No data are available for this end-point for the methyltins. 

While gender-based differences in immunotoxic responses following adult exposures have been reported, the incidence of sex-specific outcomes for developmental immunotoxicants is unexpectedly high. In fact, sex-specific outcomes have been reported for a majority of developmental immunotoxicants examined in rodents where both sexes have been tested. Such sex-based skewing of responses might be expected for endocrine-disrupting compounds. However, sex-based differences in DIT have been reported for a variety of toxicants many of which are not presently classified as endocrine disruptors. 

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