Thyroid Follicular Cell Carcinogenesis: Mechanistic and Science Policy Considerations (Sab Review Draft)
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A Technical Panel of EPA's Risk Assessment Forum investigated the potential mechanisms of action of agents that cause thyroid follicular tumors in animals and potentially in humans in an effort to develop a scientifically plausible approach for assessing risk due to exposure to these agents. Based on its review of relevant scientific information, the Technical Panel concluded that:
(1) thyroid follicular cell tumors may arise from long-term disturbances in thyroid-pituitary hormonal feedback under conditions of reduced circulating thyroid hormone and elevated thyroid stimulating hormone (TSH);
(2) the steps leading to these tumors are expected to show thresholds, such that the risks of tumor development are minimal when thyroid-pituitary homeostasis exists; and
(3) models that assume thresholds may be used to assess the risks of certain thyroid follicular cell tumors where there is evidence of thyroid-pituitary imbalance.
The policy set out in this report provides guidance on determining whether it is reasonable to presume that the observed thyroid follicular tumors are the result of thyroid-pituitary imbalance, and on selecting appropriate procedures to use in estimating the risks related to these tumors.