Perinatal Immunotoxicity: Why Adult Exposure-Assessment Fails To Predict
Rodney R. Dietert and Michael S. Piepenbrink
Recent research has pointed to the developing immune system as a remarkably sensitive toxicological target for environmental chemicals and drugs. In fact, the perinatal period prior to and just after birth is replete with dynamic immune changes, many of which do not occur in adults. These include not only the basic maturation and distribution of immune cell types and selection against autoreactive lymphocytes but also changes designed specifically to protect the pregnancy against immune-mediated miscarriage. The newborn is then faced with critical immune maturational adjustments to achieve an immune balance necessary to combat the myriad of childhood and later life diseases.
All of these processes set the fetus and neonate completely apart from the adult when it comes to immunotoxicologic risk. Yet for decades, safety evaluation has relied almost exclusively upon exposure of the adult immune system to predict perinatal immune risk.
Recent workshops and forums have suggested a benefit in employing alternative exposures that include exposure throughout early life stages. However, issues remain as to when and where such applications might be required.
The present review details the reasons why immunotoxic assessment is important for current childhood diseases and why adult exposure assessment cannot predict the impact of xenobiotics on the developing immune system. It also provides examples of developmental immunotoxicants where age-based risk appears to differ. Finally, it stresses the need to replace adult exposure assessment for immune evaluation with protocols that can protect the developing immune system.
Table 2: Examples of Perinatal-Induced Immune Outcomes not Predicted by
Standard Adult-Exposure Assessment
Nature of Age-Based Difference: Dose sensitivity
Reference: Havarinasab et al. 2004; Hultman and Hansson-Georgiadis 1999; Silva et al. 2005"
The entire 47 page study: