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Developmental Immunotoxicity
Citation:
LUEBKE, R. W. Developmental Immunotoxicity. Presented at Toxicology and Risk Assessment Conference, West Chester, OH, April 15 - 16, 2008.
Impact/Purpose:
Animal models suggest that the immature immune system is more susceptible to xenobiotics than the fully mature system, and sequelae of developmental immunotoxicant exposure may be persistent well into adulthood.
Description:
Animal models suggest that the immature immune system is more susceptible to xenobiotics than the fully mature system, and sequelae of developmental immunotoxicant exposure may be persistent well into adulthood. Immune maturation may be delayed by xenobiotic exposure and recover over time or produce life-long defects in immune function. Defects include immunosuppression or possibly dysregulation of the immune system, resulting in decreased resistance to infection or failure to switch from the “allergic” phenotype of newborns to the adult phenotype that efficiently combats infections. Proposed testing protocols include exposure from gestation until parturition, weaning, or until pups reach sexual maturity. Although certain immune responses can be elicited in newborn rodents, maturation of the immune response continues after birth, attaining adult levels at about the time of sexual maturation in humans and rodents; thus most developmental immunotoxicity studies evaluate function in offspring once the animals reach immunologic maturity. Fewer studies have addressed the effects of developmental exposure on allergy or autoimmunity because fewer assays are available and suppression has long been considered the most likely outcome of developmental exposure. It has yet to be established whether conducting screening tests only in adults is sufficient to detect chemicals that may be developmental immunotoxicants. Although most of the compounds that cause immunosuppression following developmental exposure also affect function in adults at some dose, effective doses and persistence of effects vary significantly depending on when exposure occurs.