The Effect of Short-Term Low-Dose Perchlorate on Various Aspects of Thyroid Function

Abstract

Perchlorate (ClO₄) salts are found in rocket fuel, fireworks, and fertilizer. Because of ground water contamination, ClO₄ has recently been detected in large public water supplies in several states in the 4-18 μg/L (parts per billion [ppb]) range. The potential adverse effect of chronic low level ClO₄ ingestion on thyroid function is of concern to the Environmental Protection Agency (EPA). The daily ingestion of ClO₄ at these levels would be magnitudes below the therapeutic effect level of hundreds of milligrams of ClO₄ used in treating hyperthyroidism. Studies were carried out in nine healthy male volunteers who had normal thyroid function and negative thyroid antibodies to determine whether the ingestion of 10 mg of ClO₄ daily (approximately 300 times the estimated maximum amount of ClO₄ consumed from the affected water supplies) would affect any aspect of thyroid function. They ingested 10 mg of ClO₄ dissolved in a liter of spring water during waking hours for 14 days. Baseline serum thyrotropin (TSH), free thyroxine index (FTI), total triiodothyronine (TT₃), 4-, 8-, and 24-hour thyroid ₁₂₃I uptakes (RAIU), serum and 24-hour urine ClO₄, 24-hour urine iodine, complete blood count (CBC), and chemistry profile were determined. All blood and urine tests were repeated on days 7 and 14 of ClO₄ administration and thyroid RAIU on day 14 of ClO₄ administration. All tests were repeated 14 days after ClO₄ was discontinued. No effect of ClO₄ on serum thyroid hormone or TSH concentrations, urinary iodine excretion, CBC, or blood chemistry was observed. Urine and serum ClO₄ levels were appropriately elevated during the course of ClO₄ ingestion in all subjects, demonstrating compliance. By day 14 of ClO₄ administration, the 4-, 8-, and 24-hour thyroid RAIU values decreased in all nine subjects by a mean value of 38% from baseline and rebounded above baseline values by 25% at 14 days after ClO₄ withdrawal (p < 0.01 analysis of variance (ANOVA) and Tukey). It is well known that the major effect of ClO₄ on the thyroid is a decrease in the thyroid iodide trap by competitive inhibition of the sodium iodide symporter (NIS). The present study demonstrates the sensitivity of the thyroid iodide trap to ClO₄ because a low dose of 10 mg daily significantly decreased the thyroid RAIU without affecting circulating thyroid hormone or TSH concentrations. It is possible, however, that the daily consumption of low levels of ClO₄ in drinking water over a prolonged period of time could adversely affect thyroid function but no evidence of hypothyroidism was observed at 10 mg of ClO₄ daily in this 2-week study. It is now of interest to determine a no effect level for ClO₄ on the inhibition of the thyroid RAIU and to carry out a long-term ClO₄ exposure study.