Subchronic Sodium Chlorate Exposure in Drinking Water Results in a Concentration-Dependent Increase in Rat Thyroid Follicular Cell Hyperplasia

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Abstract
Chlorine dioxide (ClO 2) is an effective drinking water disinfectant, but sodium chlorate (NaClO3) has been identified as a potentially harmful disinfection by-product. Studies were performed to describe the development of thyroid lesions in animals exposed to NaClO3 in the drinking water. Male and female F344 rats and B6C3F1 mice were exposed to 0, 0.125, 0.25, 0.5, 1.0, or 2.0 g/L NaClO3 for 21 days. Additional male F344 rats were exposed to 0, 0.001, 0.01, 0.1, 1.0, or 2.0 g/L NaClO 3 for 90 days. Female F344 rats were exposed to 0, 0.5, 1.0, 2.0, 4.0, or 6.0 g/L of NaClO3 for 105 days. Thyroid tissues were processed by routine methods for light microscopic examination, and follicular cell hyperplasia was diagnosed using a novel method. Thyroid hormone levels were altered significantly after 4 and 21 days. NaClO3 treatment induced a concentration-dependen t increase in the incidence and severity of thyroid follicular cell hyperplasia. Male rats are more sensitive to the effects of NaClO3 treatment than females. Follicular cell hyperplasi a was not present in male or female B6C3F1 mice. These data can be used to estimate the human health risk that would be associated with using ClO 2, rather than chlorine, to disinfect drinking water.