Correlation of mechanistic data and histopathology in the evaluation of selected toxic endpoints of the endocrine system

The objective of this review is to correlate endocrinologic data from mecha nistic studies with quantitative histopathology in selected examples of tox ic endpoints of the endocrine system in laboratory animals. Mechanistic dat a can aid in the interpretation of animal toxicology findings and help clar ify their significance in risk assessment. Endocrine organs of rodents freq uently undergo proliferative changes with advancing age and following chron ic exposure to large doses of xenobiotic chemicals, and the sensitivity of rodent endocrine tissues appears to be increasing. Many xenobiotic chemical s in large doses disrupt thyroid function in rodents either by a direct eff ect on the thyroid influencing synthesis of thyroid hormones or by adversel y influencing their peripheral metabolism. A number of chemicals disrupt th yroid function by inhibiting the important enzyme, thyroperoxidase (TPO). A contemporary example of a chemical acting as TPO-inhibitor is sulfamethazi ne. In short-term mechanistic studies in rats there was a log-dose response relationship in circulating levels of thyroid and pituitary hormones plus a similar non-linear dose-response in morphologic changes in thyroid follic ular cells. Endocrinologic data from mechanistic studies and histopathologi c/ultrastructural findings will also be presented for the effects of the fo od color, FDC Red No. 3 (Erythrosine), on the thyroid gland in rats and par athyroid hormone-related protein (a major causative factor in cancer-associ ated hypercalcemia) on parathyroid chief cells in mice. (C) 1998 Elsevier S cience Ireland Ltd. All rights reserved.