Effects of subchronic exposure to complex mixtures of dioxin-like and non-dioxin-like polyhalogenated aromatic compounds on thyroid hormone and vitamin A levels in female Sprague-Dawley rats

The aim of this study was to determine the effects of subchronic exposure t o complex mixtures of polyhalogenated aromatic hydrocarbons (PHAHs) on the thyroid hormone and retinoid status in female Sprague-Dawley rats and to in vestigate the predictability of these effects by the toxic equivalency fact or (TEF) concept. In the first experiment, the focus was on a complex dioxi n-like PHAH mixture, which covered > 90% of the total toxic equivalents (TE Q) present in Baltic herring. In the second experiment, the contribution of non-dioxin-like polychlorinated biphenyls (PCBs) was investigated by testi ng the commercial PCB mixture Aroclor 1260, its 0-1 ortho and 2-4 ortho fra ctions and the reconstituted 0-4 ortho fraction. Hepatic retinoid levels we re severely decreased (similar to 70%) after treatment with the dioxin-like PHAH mixture, similar to the effect of a TEQ equivalent dose of 1 mug 2,3, 7,8-TCDD/kg bw/week. However, the TEF concept failed to predict the effect on plasma retinol; a decrease (21%) was observed after treatment with the P HAH mixture, whereas an increase (21%) was found after treatment with TCDD. A more severe decrease of total thyroid hormone in plasma was observed aft er exposure to the PHAH mixture compared to treatment with TCDD (similar to 60% vs. 38%). The discrepancy found between the predicted and observed eff ects for plasma retinol and thyroid hormone is possibly due to an additiona l effect of hydroxylated PCBs, formed from metabolizable PCBs present in th e PHAH mixture. Aroclor 1260 and its fractions did not significantly alter the retinoid and thyroid hormone status at the dose levels tested, indicati ng that in case of exposure to complex PCB mixtures at environmental levels , no effects, or at best, only marginal effects can be expected on the reti noid and thyroid hormone status.