New Developments in the Assessment of Developmental Immunotoxicology

Recent progress has been made in directly comparing the risk of immunotoxicity following exposure to various drugs and environmental chemicals during different stages of life. With the availability of an increased developmental immunotoxicology database, new concepts of effective immunotoxicological risk assessment have emerged. From the standpoint of risk assessment, recent results suggest that there is greater value obtained from exposure-assessment of non-adults than can be derived solely from adult-exposure-outcome data. This is hardly surprising given the fact that, for the vast majority of known immunotoxicants compared across age groups, the non-adult stages are more sensitive than adults for risk of clinically important immunomodulation. Therefore, if immunotoxicity testing is to identify risk for the more susceptible subpopulations, the adult is not the informative model. This brief review, based on the Immuntoxicology III conference presentation, describes the data supporting age-based differences in sensitivity to immunotoxicants, differences in immunotoxic outcomes, and the potential benefits of utilizing non-adult exposures and life-stage-relevant immune assessment. In essence, the issue is whether historic adult immunotoxicity testing strategies can continue to ensure adequate protection of the most vulnerable subpopulations in the face of recent developmental immunotoxicological data. The review describes the possible benefits of substituting non-adult exposures for adult exposures in future assessment protocols.