Relationship Between Dosing Regimens And Immune System Development

The time required for full development of the immune system varies from species to species. For the human, the various elements of the immune system are fully formed early in the second trimester (around 13 to 20 weeks of gestation) (reviewed in: Barnett 1995; Holladay and Smialowicz 2000, chap. 1). It is generally accepted that exposure to xenobiotics during the formative stages of immune development, i.e., prior to 20 weeks gestation in humans, could lead to either a more detrimental or permanent result. Although there is firm evidence to support this conclusion in experimental animal studies, it is difficult to obtain definitive data to support this conclusion for humans because of the large number of uncontrollable variables inherent in human studies. All of the reported developmental immunotoxicological studies on chlordane were performed using the mouse model. As the obvious reason for conducting experimental immunotoxicological studies is to determine an approximate risk assessment for humans, it is important to note the numerous differences between humans and mice in the timing of immune system development. Mice do not complete their immune system development until shortly after birth and do not transfer hematopoiesis from the fetal liver to the bone marrow until much later in gestation, i.e., approximately 1 to 3 days before birth. In contrast, humans transfer hematopoiesis from the fetal liver to the bone marrow at about 15 to 20 weeks of gestation. Thus, to be certain that all stages of immune system development were exposed to chlordane, for the studies reported herein, all animals were treated with chlordane from post-coital day (pcd) 1 through pcd 18.

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