Health effects assessment for environmental perchlorate contamination: the dose response for inhibition of thyroidal radioiodine uptake in humans.

Abstract

Application of a sensitive new detection method has revealed widespread perchlorate contamination of groundwater in the southwestern United States, typically at 0.005-0.020 mg/L (5-20 ppb). Perchlorate is a competitive inhibitor of the process by which iodide is actively transported from the bloodstream into the thyroid. This inhibitory action of perchlorate is the basis of its pharmaceutical use (in the treatment of hyperthyroidism) as well as its potential toxicity. To establish the dose response in humans for perchlorate inhibition of thyroidal iodide uptake and any short-term effects on thyroid hormones, we gave perchlorate in drinking water at 0.007, 0.02, 0.1, or 0.5 mg/kg-day to 37 male and female volunteers for 14 days. In 24 subjects we performed 8- and 24-hr measurements of thyroidal (123)I uptake (RAIU) before exposure, on exposure days 2 (E2) and 14 (E14), and 15 days postexposure (P15). In another 13 subjects we omitted both E2 studies and the 8-hr P15 study. We observed a strong correlation between the 8- and 24-hr RAIU over all dose groups and measurement days. We found no difference between E2 and E14 in the inhibition of RAIU produced by a given perchlorate dose. We also found no sex difference. On both E2 and E14, the dose response was a negative linear function of the logarithm of dose. Based on the dose response for inhibition of the 8- and 24-hr RAIU on E14 in all subjects, we derived estimates of the true no-effect level: 5.2 and 6.4 micro g/kg-day, respectively. Given default body weight and exposure assumptions, these doses would be ingested by an adult if the drinking-water supply contained perchlorate at concentrations of approximately 180 and 220 micro g/L (ppb), respectively. On P15, RAIU was not significantly different from baseline. In 24 subjects we measured serum levels of thyroxine (total and free), triiodothyronine, and thyrotropin in blood sampled 16 times throughout the study. Only the 0.5 mg/kg-day dose group showed any effect on serum hormones: a slight downward trend in thyrotropin levels in morning blood draws during perchlorate exposure, with recovery by P15.

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).…”

“…Environmental perchlorate exposure is of possible health concern because much larger doses of perchlorate have been shown to competitively inhibit iodide uptake by the thyroid gland (Wyngaarden et al, 1953;Greer et al, 2002); sustained inhibition of iodide uptake could potentially lead to hypothyroidism. The thyroid plays a crucial role in energy homeostasis and neurological development.…”

“…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.…”

Immobilization, Trapping, and Anion Exchange of Perrhenate Ion Using Copper-Based Tripodal Complexes

“…[1][2][3][4][5][6][7][8] Because anions regulate a variety of physiological processes, they are potential toxins. As examples, perchlorate ion can adversely affect human health by interfering with iodide uptake into the thyroid, [9][10][11] and chromate (CrO 4 2-) is toxic, mutagenic, and a human carcinogen. 12,13 As a result, many oxo-hydroxo anionic forms of metals and p-block elements are listed as U. S. EPA priority pollutants.…”

Perchlorate exposure from food crops produced in the lower Colorado River region

“…A reference dose (RfD) of 0.7 mg/kg per day has been established by the US Environmental Protection Agency (USEPA, 2005). This action followed review of a human dose-response study (Greer et al, 2002) and a recommendation by the National Academy of Science (NAS, 2005) that inhibition of iodine uptake by the thyroid in humans was a key biochemical event that preceded any health effects caused by perchlorate. One epidemiological study examined perchlorate exposure in Chilean women and found no changes in thyroid hormone levels despite exposure doses estimated to be higher than the RfD (Tellez et al, 2005).…”