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AN ADDITIVE EFFECT OF A MIXTURE OF AMMONIUM PERCHLORATE AND SODIUM CHLORATE ON PITUTARY-THYROID AXIS IN MALE F-344 RATS
Citation:
Khan, M A., A E. Swank, G W. Knapp, S D. Hester, S E. Fenton, AND D C. Wolf. AN ADDITIVE EFFECT OF A MIXTURE OF AMMONIUM PERCHLORATE AND SODIUM CHLORATE ON PITUTARY-THYROID AXIS IN MALE F-344 RATS. Presented at Society of Toxicology, BALTIMORE, MD, March 21-25, 2004.
Description:
An Additive Effect of a Mixture of Ammonium Perchlorate
and Sodium Chlorate on Pitutary-Thyroid Axis in Male F-344 Rats
Moazzam A. Khan 1,2,, 3Suzanne E. Fenton. 2Adam E. Swank, ZGeremy W. Knapp, 2Susan D.
Hester, and 2Douglas C. Wolf. 1NRC, 2Environmental Carcinogenesis and 3Reproductive
Toxicology Divisions, NHEERL, ORD. USEPA, RTP, NC 27711
Abstract: Humans are exposed to mixtures of chemicals through drinking water. Ammonium perchlorate (AP) and Sodium chlorate (SC) have been detected in public drinking water supplies in many parts of the U.S. AP is widely used as an oxidizer in solid rocket propellants, munitions, fireworks, and air bag inflators. SC not only originates as a drinking water disinfection byproduct of chlorine dioxide, it is also used as an oxidizing agent in many industrial processes. Numerous studies conducted in rodents have shown that exposure to either of these chemicals causes perturbations in the pituitary-thyroid homeostasis. AP and SC competitively inhibit iodide uptake preventing the synthesis of thyroglobulin, thus reducing circulating T4. Persistent long-term exposure to either of these chemicals can result in persistent stimulation of the pituitary-thyroid axis resulting in thyroid tumor development in rats. The present study was designed to describe the potential of an additive effect in rats following short-term exposure to both chemicals. Adult male F-344 rats were exposed to AP (0.1, 1.0, 10 mg/L) or SC (10, 100, 1000 mg/L) or their mixtures through the drinking water for 7 days. Serum and tissues were collected for biochemical, histological, and molecular endpoints. Serum T4 was decreased (p < 0.05) in rats exposed to the mixtures, but not to the individual chemicals. Serum T3 levels were unaffected by each treatment and TSH was only elevated in the high dose chlorate group. Histological examination of the thyroid gland showed, colloid depletion and significant (p < 0.05) hypertrophy of follicular epithelial cells in all the single chemical and mixture treated animals while hyperplasia was observed only in AP 10 + SC 10, AP 0.1 + SC 1000, and AP 10 + SC 1000 mg/L mixture groups. The data suggest that the combined exposure to chlorate and perchlorate results in an additive effect on the rat thyroid.
(This abstract does not reflect the policies and opinions of the USEPA).