The Disruption of Thyroid Gland Homeostasis by the Lead and Polychlorinated-Biphenyls Mixture in Rats.

Humans are continuously exposed to a complex mixture of chemicals. While the composition of these mixtures is perpetually changing, most of the risk evaluation is based upon single-component studies. Because both lead (Pb) and polychlorinated biphenyls (PCBs) are ubiquitous chemicals, we investigated whether the environmentally relevant mixture of these chemicals has any effects on thyroid homeostasis and are these changes are dose dependent. Doses of 0.1, 0.5, and 1 mg Pb/kg/day and 0.25, 0.5, and 1 mg PCBs/kg/day were administered to male albino Wistar rats using a 3 × 3 dose design for 28 days. At the end of the mixture treatment period, the measurements of the serum levels of thyroid hormones and thyroid-stimulating hormone (TSH) were performed. In the thyroid gland tissue, oxidative stress parameters were analyzed. The obtained results were used to create the dose-response models in PROAST. An increase in the level of free thyroxine (FT4), total and free triiodothyronine, TSH, total oxidative status (TOS), and sulfhydryl groups was documented. In contrast, a significant decrease in relative thyroid weight (TW) and total antioxidative status (TAS) was observed, while the significant differences in total thyroxine, rat body weight, and albumin serum levels were not confirmed between the control and the exposed groups. The most sensitive parameter was the decrease in the TAS in thyroid gland tissue, while the benchmark dose's lower confidence limit (BMDL) calculated for the FT4 parameter can be used as a reference point. The presented study and available literature suggest that Pb and PCBs in the mixture can act through their toxicological mechanisms on different levels of the hypothalamic-pituitary-thyroid gland axis, including the disruption of oxidative-antioxidative status.