Comparison of immunotoxicity among tetrachloro-, pentachloro-, tetrabromo- and pentabromo-dibenzo-p-dioxins in mice

Abstract

There is concern about the growing environmental levels of brominated dioxins. Brominated dioxins are known to bind and activate the transcription factor aryl hydrocarbon receptor (AhR), as their chlorinated congeners do. However, data on the potency of brominated dioxins for immunotoxicity in vivo is largely lacking, even though the immune system is a vulnerable target for dioxins. In this study, we investigated the immunotoxic effects on mice of the brominated dioxins, 2,3,7,8-tetrabromodibenzo-p-dioxin (TBDD) and 1,2,3,7,8-pentabromodibenzo-p-dioxin (PeBDD), in comparison with those of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and 1,2,3,7,8-pentachlorodibenzo-p-dioxin (PeCDD), the two most toxic chlorinated dioxins, to gain insight into the potency of brominated dioxins for immunotoxicity. C57BL/6 mice were dosed with the dioxins and immunized with ovalbumin (OVA), and several endpoints that sensitively detect immunotoxicity were investigated, including IL-5 production by the splenocytes. The results of the present study demonstrated that TCDD and TBDD show identical effects on a per weight basis at 1.0-10mug/kg for all the endpoints examined. PeCDD also showed effects similar to those of TCDD. On the other hand, PeBDD showed somewhat dose-independent effects and was more potent at a lower dose and less potent at a higher dose than PeCDD. Dose-dependent linearity of PeBDD-induced induction of CYP1A1, an AhR target gene, was also less clear in the spleen than in the liver. These results have provided valuable data for estimating the potency of brominated dioxins for immunotoxicity.