Immunotoxic effects of TCDD and toxic equivalency factors

This paper first summarizes the studies indicating that the immunotoxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), notably atrophy of the thymus and suppression of the thymus-dependent immunity, are mediated by binding to a soluble cytosolic protein, the aryl hydrocarbon (Ah) or TCDD receptor, present in the thymus in the epithelial cells. On the basis of a common receptor-mediated mechanism of toxic action, the relative (immuno)toxicity of individual PCDDs and PCDFs can be expressed relative to TCDD (i.e., toxic equivalents). Next, studies on TCDD-induced immunosuppression and impaired host resistance, and lowest observed effects levels of TCDD resulting in immune alterations, are summarized. Immune investigations performed in man are discussed and it is concluded that, for risk assessment purposes, further studies are necessary to determine the sensitivity of the human immune system to TCDD. For this purpose, a recent study is summarized in which the sensitivity of the human thymus to TCDD is investigated in so-called severe combined immunodeficient (SCID) mice in which human thymus grafts were transplanted. This study indicates that the human thymus and the Wistar rat thymus display a similar sensitivity to TCDD.