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RISK ASSESSMENT OF THYROID HORMONE DISRUPTION AND MIXTURES IN MARINE BIOTA
Citation:
DEVITO, M. J. RISK ASSESSMENT OF THYROID HORMONE DISRUPTION AND MIXTURES IN MARINE BIOTA. Presented at Korean Society of Toxicology Meeting, Daegu, SOUTH KOREA, May 09 - 11, 2006.
Description:
Varieties of chemicals alter thyroid hormones (THs) in vertabrates. The importance of THs during neurodevelopment, suggest that these chemicals would likely be developmental neurotoxicants. A number of epidemiological studies have demonstrated associations between exposure to polychlorinated hydrocarbons, such as PCBs and dioxins, and alterations in thyroid homeostasis and neurodevelopmental delays. Ecological studies have also observed associations between environmental pollutants and thyroid hormone disruption in mammals, birds, and fish. However, the effect of thyroid disruption on population levels in ecological systems is uncertain. Several levels of uncertainty affect our understanding of the point of departure, mode-of-action, and mechanism-of-action of xenobiotics that alter THs. One uncertainty is the impact of species differences in the pharmacokinetics of THs. In rodents, the serum half-life of T4 is approximately hours whereas in humans it is 4-7 days. In humans, serum is a major storage pool for thyroid hormones. In rodents, the major storage pool is the thyroid gland. In rats, glucuronidation is a major deactivation pathway while in humans, deiodination and sulfation are more important. These differences may result in altered sensitivity to environmental chemicals. Another uncertainty is species differences is due to altered sensitivity to the mechanisms of action of xenobiotics; e.g., induction of UDPGT, which increases elimination of THs, are mediated in part by CAR and PXR pathways. There are species differences in the structure activity relationship for activation of these pathways that could lead to altered species sensitivity to xenobiotics. Another uncertainty is the effects of exposure to multiple thyroid hormone disruptors. Recent studies in rodents demonstrate that exposure to mixtures of thyroid hormone disruptors has the potential for synergism at high exposures. Future studies aimed at examining mixtures of thyroid hormone disrupters in multiple species would aid in our understanding of the potential adverse health and ecological effects of thyroid hormone disruptors. (This abstract does not reflect USEPA policy)