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 microg/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.

Perchlorate Exposure of the US Population, 2001–2002

“…Other previously published studies did not report measurable background levels of perchlorate, likely due to inadequate analytical sensitivity (Lawrence et al, 2000;Greer et al, 2002;Gibbs et al, 2004;Braverman et al, 2005); therefore, application of these methods resulted in reported urinary background values of less than method detection limits of 500 mg/l (Lawrence et al, 2000), 20 mg/l (Greer et al, 2002;Merrill et al, 2005) and 5 mg/l (Gibbs et al, 2004;Braverman et al, 2005). Significantly higher levels of urinary perchlorate were found in populations in northern Chile consuming tap water with perchlorate levels as high as 114 mg/l (Tellez et al, 2005).…”

“…NonHispanic white males had higher adjusted urinary perchlorate levels than non-Hispanic white females (P ¼ 0.01) and nonHispanic black males (Po0.001). Fasting for 8 or more hours was associated with decreased urinary perchlorate (Po0.001), likely due to a lack of dietary intake and the relatively short physiological half life of perchlorate in the human body (Anbar et al, 1959;Lawrence et al, 2000).…”

“…Urine is the principal route by which non-lactating humans excrete perchlorate (Anbar et al, 1959;Lawrence et al, 2000). During lactation human mammary tissue expresses the sodium iodide symporter (Wolff, 1998), and thus significant transfer of perchlorate into human milk is likely.…”

“…Also, we assumed that 100% of perchlorate intake is absorbed and excreted unmetabolized in the urine (Anbar et al, 1959;Lawrence et al, 2000). This assumption leads to underestimation of perchlorate dose in lactating women because perchlorate is secreted in human milk (Capuco et al, 2005;Kirk et al, 2005) as well as urine.…”

“…Urinary perchlorate provides a reasonable measure of human exposure because 70-95% of a perchlorate dose is excreted unchanged in the urine with a half-life of B8 h (Anbar et al, 1959;Lawrence et al, 2000;Greer et al, 2002). Sensitive and selective methods are needed to quantify perchlorate anion in urine in the presence of much higher levels of chloride, sulfate and phosphate anions.…”