Developmental immunotoxicology: focus on health risks.Chem Res Toxicol 2009; 22(1):17-23CR
Developmental immunotoxicity (DIT) has gained attention with the recognition that many chronic diseases of increasing incidence feature immune dysfunction as a component of the disease. The maturing immune system represents a vulnerable target for toxicants as it progresses through a series of novel prenatal and perinatal events that are critical for later-life host defense against a wide array of diseases. These critical maturational windows display a particular sensitivity to chemical disruption with the outcome usually taking the form of persistent immune dysfunction and/or misregulation. For this reason, health risks are significantly increased following early life vs adult immunotoxic exposure. Additionally, DIT-associated health risks are not readily predicted when based on adult-exposure safety data or via the evaluation of an unchallenged immune system in developmental toxicity testing. The same toxicant [e.g., heavy metals, 2,3,7,8-tetraclorodibenzo-p-dioxin (TCDD)] may disrupt different immune maturational processes depending upon the specific developmental timing of exposure and the target organ dose at a given stage of development. Therefore, a single toxicant may promote different immune-associated diseases that are dependent upon the specific window of early life exposure, the gender of the exposed offspring, and the genetic background of the offspring. This perspective considers the linkage between early life chemical exposure, DIT, and the postnatal immune dysfunctions associated with a variety of childhood and adult diseases. Because DIT is linked to a majority of the most significant childhood chronic diseases, safety testing for DIT is a pivotal issue in the protection of children's health.