IMMUNOTOXIC EFFECTS OF TCDD AND TOXIC EQUIVALENCY FACTORS

This paper first summarizes the studies indicating that the immunotoxi c effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), notably atrop hy of the thymus and suppression of the thymus-dependent immunity, are mediated by binding to a soluble cytosolic protein, the aryl hydrocar bon (Ah) or TCDD receptor, present in the thymus in the epithelial cel ls. On the basis of a common receptor-mediated mechanism of toxic acti on, the relative (immuno)toxicity of individual PCDDs and PCDFs can be expressed relative to TCDD (i.e., toxic equivalents). Next, studies o n TCDD-induced immunosuppression and impaired host resistance, and low est observed effects levels of TCDD resulting in immune alterations, a re summarized. Immune investigations performed in man are discussed an d 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 s ensitivity of the human thymus to TCDD is investigated in so-called se vere 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. (C) 1998 Wil ey-Liss, Inc.