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A Mixture of Ammonium Perchlorate and Sodium Chlorate Enhances Alterations of the Pitutary-Thyroid Axis Caused by the Individual Chemicals in Adult Male F344 Rats

¹ National Research Council
² Health Canada, Ottawa, Ontario, Canada
³ Reproductive Toxicology
⁴ Environmental Carcinogenesis Divisions, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA

Correspondence: Address correspondence to: Dr. Douglas C. Wolf, Environmental Carcinogenesis Division (B143-06), U.S. Environmental Protection Agency, 109 T.W. Alexander Dr, RTP, NC 27711, USA; e-mail:wolf.doug{at}epa.gov

Ammonium perchlorate (AP) and sodium chlorate (SC) have been detected in public drinking water supplies in many parts of the United States. These chemicals cause perturbations in pituitary-thyroid homeostasis in animals by competitively inhibiting iodide uptake, thus hindering the synthesis of thyroglobulin and reducing circulating T₄ (thyroxine). Little is known about the short-term exposure effects of mixtures of perchlorate and chlorate. The present study investigated the potential for the response to a mixture of these chemicals on the pituitary-thyroid axis in rats to be greater than that induced by the individual chemicals. Adult male F-344 rats were exposed, via their drinking water, to the nominal concentrations of 0.1, 1.0, 10 mg/L AP or 10, 100, 1000 mg/L SC and their mixtures for 7 days. Serum T₄ levels were significantly (p < 0.05) reduced in rats following exposure to the mixtures, but not after exposure to the individual chemicals. Serum T₃ (triiodothyronine) was not altered by treatment and TSH (thyroid stimulating hormone) was only increased after the high-dose chlorate treatment. Histological examination of the thyroid gland showed colloid depletion and hypertrophy of follicular epithelial cells in high-dose single chemical and all mixture-treated rats, while hyperplasia was observed only in some of the rats treated with mixtures (AP 10 + SC 100, AP 0.1 + SC 1000, and AP 10 + SC 1000 mg/L). These data suggest that short-term exposure to the mixture of AP and SC enhances the effect of either chemical alone on the pituitary-thyroid axis in rats.

Key Words: Ammonium perchlorate • sodium chlorate • thyroid gland • thyroid hormones • environmental contaminants • drinking water

Abbreviations: AP, Ammonium perchlorate • SC, Sodium chlorate • HPT-axis, Hypothalamo-pituitary-thyroid axis • T4, Thyroxine • T3, Triiodothyronine • TSH, Thyroid stimulating hormone

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