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Monte A. Greer,¹ Gay Goodman,² Richard C. Pleus,² and Susan E. Greer¹

¹Oregon Health & Science University, Portland, Oregon, USA; ²Intertox, Inc., Seattle, Washington, USA

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 ¹²³I 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 µg/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 µg/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. Key words: clinical, human, iodine, perchlorate, risk assessment, sodium-iodide symporter, thyroid. Environ Health Perspect 110:927-937 (2002) . [Online 14 August 2002]

http://ehpnet1.niehs.nih.gov/docs/2002/110p927-937greer/ abstract.html

Address correspondence to G. Goodman, Intertox, Inc., 2819 Elliott Ave., Suite 201, Seattle, WA 98121 USA. Telephone: (206) 284-4820. Fax: (206) 284-8425. E-mail: ggoodman@hhrr.com

We are indebted to the General Clinical Research Center, Nuclear Medicine staff, and L. Bradley of OHSU for their generous support and to C. Crump, D. Lurie, and E. Crouch for consultation on statistical analyses. M.A.G. was the principal investigator, G.G. was the co-investigator, and S.E.G. was the study coordinator. The protocol was developed by G.G., M.A.G., and R.C.P. with the substantial contribution of D. Mattie and J. Fisher of the Air Force Research Laboratory and A. Jarabek of the U.S. Environmental Protection Agency, National Center for Environmental Assessment. M. Greer died in a traffic accident on 24 March 2002. We mourn deeply the loss of this gentle, brilliant man: colleague, mentor, and father.

This work was supported by the Perchlorate Study Group and by NIH grant MO1 RR 00334.

Received 26 July 2001 ; accepted 12 February 2002.

Figure 6 was corrected on 12 September, 2002.