A mixture of ammonium perchlorate and sodium chlorate enhances alterations of the pituitary-thyroid axis caused by the individual chemicals in adult male F344 rats.
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 T(4) (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 T(4) levels were significantly (p < 0.05) reduced in rats following exposure to the mixtures, but not after exposure to the individual chemicals. Serum T(3) (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.
Khan
Moazzam A
MA
National Research Council, Environmental Carcinogenesis Divisions, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA.
Fenton
Suzanne E
SE
Swank
Adam E
AE
Hester
Susan D
SD
Williams
A
A
Wolf
Douglas C
DC
D000818:Animals; D002704:Chlorates / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D006706:Homeostasis / Q000187:drug effects; D008297:Male; D010472:Perchlorates / Q000633:toxicity*; D010902:Pituitary Gland / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000644:Quaternary Ammonium Compounds / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D013961:Thyroid Gland / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
D002704:Chlorates; D010472:Perchlorates; D000644:Quaternary Ammonium Compounds; D014284:Triiodothyronine; D013972:Thyrotropin; D013974:Thyroxine; C032706:sodium chlorate; C053506:ammonium perchlorate