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.

Abstract

The aim of this study was to determine the effects of subchronic exposure to complex mixtures of polyhalogenated aromatic hydrocarbons (PHAHs) on the thyroid hormone and retinoid status in female Sprague-Dawley rats and to investigate the predictability of these effects by the toxic equivalency factor (TEF) concept. In the first experiment, the focus was on a complex dioxin-like PHAH mixture, which covered > 90% of the total toxic equivalents (TEQ) present in Baltic herring. In the second experiment, the contribution of non-dioxin-like polychlorinated biphenyls (PCBs) was investigated by testing the commercial PCB mixture Aroclor 1260, its 0-1 ortho and 2-4 ortho fractions and the reconstituted 0-4 ortho fraction. Hepatic retinoid levels were severely decreased ( approximately 70%) after treatment with the dioxin-like PHAH mixture, similar to the effect of a TEQ equivalent dose of 1 microg 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 PHAH mixture, whereas an increase (21%) was found after treatment with TCDD. A more severe decrease of total thyroid hormone in plasma was observed after exposure to the PHAH mixture compared to treatment with TCDD ( approximately 60% vs. 38%). The discrepancy found between the predicted and observed effects for plasma retinol and thyroid hormone is possibly due to an additional effect of hydroxylated PCBs, formed from metabolizable PCBs present in the PHAH mixture. Aroclor 1260 and its fractions did not significantly alter the retinoid and thyroid hormone status at the dose levels tested, indicating 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 retinoid and thyroid hormone status.