#57 Perchlorate dosage on thyroid – laboratory confirmation of occupational epidemiology findings

PURPOSE: Perchlorate is known to affect the thyroid by blocking the uptake of iodine at the sodium-iodide symporter (NIS) receptor site of the basolateral membrane of the thyroidal cell in a dose-response manner. A previous occupational study of employees at a plant where perchlorate was manufactured examined for the level at which iodine uptake inhibition in chronically-exposed workers was sufficient to cause a reduction in the free thyroxine index (FTI). The data analysis predicted a 10% inhibition at an exposure of about 45 mg/day and demonstrated no effect on FTI at occupational exposures of about 35, 11, 4, and 1 mg/day. METHODS: The occupational exposures were a mixture of inhalation, ingestion, and possibly dermal routes. The dosages had been modeled based on urine perchlorate levels across one work shift with airborne exposures measured. The laboratory studies were conducted using measured oral dosages in drinking water for a two-week period with determination of radio-active iodine uptake before, during, and following exposure period. Thyroid function tests and urine and serum concentrations of perchlorate and iodine were also determined. RESULTS: Laboratory studies demonstrated a significant 38% inhibition of iodine uptake at 10 mg/day and a non-significant 10% inhibition at 3 mg/day (Lawrence 2000, 2000b). Another laboratory conducted studies at doses of about 35, 7, 1.4, and 0.5 mg/day and found iodine inhibition rates of 67%, 45%, 16%, and 2% (not significant) (Greer et al., 2002). Neither free thyroxine index nor free thyroxine levels were affected at any laboratory exposure level. Log-linear extrapolation of the data indicated that an exposure level slightly below 0.5 mg/day perchlorate would be below the threshold level for iodine uptake inhibition in these populations. CONCLUSION: An occupational health study found no adverse effect on thyroid hormone (FTI) at exposures of about 1, 4, 11, and 35 mg/day perchlorate, a chemical known to inhibit iodine uptake. Measurement of iodine uptake inhibition at similar levels showed that the uptake inhibition threshold was just below 0.5 mg/day and that adverse effects on thyroid hormone (FTI) were not seen with exposures equivalent to 67% inhibition. Thus, a range of iodine uptake inhibition at which thyroxine level appears not to be adversely affected is indicated.