You are here:
MIXTURES OF THYROID DISRUPTING CHEMICALS: TESTING ADDITIVITY OF HEPATIC INDUCERS AND THYROID PEROXIDASE INHIBITORS.
Citation:
FLIPPIN, J. L., K. M. CROFTON, G. A. LEBLANC, J. M. HEDGE, AND M. J. DEVITO. MIXTURES OF THYROID DISRUPTING CHEMICALS: TESTING ADDITIVITY OF HEPATIC INDUCERS AND THYROID PEROXIDASE INHIBITORS. Presented at Society of Toxicology Annual Meeting, Charlotte, NC, March 25 - 29, 2007.
Description:
Humans are exposed to chemical mixtures via diet, occupation, and the environment. Previous data demonstrated that low doses of polycyclic halogenated aromatic hydrocarbons (PHAHs) acting through similar mechanisms result in an additive reduction of thyroxine (T4). If xenobiotics acting through the same mechanism are able to disrupt thyroid hormone homeostasis, it is reasonable to expect that chemical mixtures acting through different mechanisms but targeting the same endpoint (i.e. serum thyroid hormone levels) would exert additive effects on T4. Along with PHAHs, which induce T4-eliminating hepatic enzymes, certain pesticides are shown to decrease production of T4 by inhibiting thyroid peroxidase in the thyroid gland. Female Long-Evans rats, 28 days of age, were dosed with a mixture of 18 PHAHs (2 dioxins, 4 dibenzofurans, and 12 PCBs, including dioxin-like and non-dioxin like PCBs) and a mixture of 3 pesticides (thiram, pronamide, and mancozeb) for 4 consecutive days. Stock solutions were prepared with concentrations of the PHAH mixture and each individual pesticide that individually produce a 20% decrease in circulating T4 levels. Six serial dilutions (66, 33, 10, 6.6, 3.3, and 1%) and a control were administered in the 4-day bioassay. Tissues were collected 24 hours after the last dose and serum total T4 was quantified via radioimmunoassay. Animals exposed to the four highest doses resulted in serum T4 decreases between 3 and 45% compared to control animals; the two lowest doses showed a slight increase in circulating T4. Dose and response addition models fit to the data suggest that the combination of UGT-inducers and TPO inhibitors are antagonistic. The results of this research suggest that environmentally complex chemical mixtures interact in a complicated fashion to disrupt thyroid hormone homeostasis. (Funded by the EPA NHEERL/NCSU Cooperative Training Program in Environmental Sciences Research, CT826512010. This abstract does not represent USEPA policy).