Reprieve for perchlorate: effects not a significant concern. (Science Selections).

Although perchlorate has pharmaceutical uses in the treatment of thyroid disorders, it is most commonly used as an oxygen source in rocket propulsion systems. This latter use is believed to be the source of perchlorate found in drinking water supplies throughout the U.S. Southwest at concentrations ranging from 5 to 20 parts per billion (ppb). But the millions of people drinking this perchlorate-laced water need not be concerned for their health, according to research by Monte Greer, the late head of the Endocrinology Section at Oregon Health & Science University, and colleagues [EHP 110:927-937].

Perchlorate inhibits the uptake of iodine, which is used by the thyroid to produce thyroid hormone. If iodine uptake is inhibited by too much for too long, the result could be hypothyroidism, a condition in which blood levels of thyroid hormone are abnormally low and those of the pituitary hormone thyrotropin (TSH) are abnormally high. Because maternal thyroid hormone level plays a vital role in fetal brain development, the authors say it is important to protect against even mild hypothyroidism in pregnant women.

The research team wanted to establish the extent to which thyroidal iodine uptake is diminished in people given one of four daily perchlorate doses. In particular, they wanted to measure the no-effect level, the highest daily perchlorate dose a person can ingest without experiencing any inhibition of iodine uptake.

To do this, the team enrolled 37 volunteers between the ages of 18 and 57 to drink a fixed volume of perchlorate solution 4 times a day for 14 days. To evaluate thyroidal iodine uptake, they administered a trace amount of radioiodine and then measured the accumulated radioiodine uptake (RAIU) over the thyroid at 8 and 24 hours. To establish the baseline uptake, the researchers performed an initial measurement of the RAIU before the volunteers ingested any perchlorate. The RAIU was also measured 15 days after stopping exposure.

The RAIU measurements performed during perchlorate exposure revealed a strong dose-response relationship, with the RAIU relative to baseline decreasing uniformly from the lowest to highest doses. The researchers also found that at 15 days postexposure the RAIU did not differ from baseline in any dose group. Based on the overall dose-response relationship they found, the researchers estimate the no-effect level for perchlorate inhibition of thyroidal iodine uptake to be at least 5.2 [micro]g/kg-day, the approximate adult dose from a drinking water supply containing 180 ppb perchlorate. Further, based on the observed variability among the study volunteers, the team calculates a 95% probability that uptake will be inhibited by less than 9.5% in persons exposed to perchlorate at this dose. They call this amount of inhibition "physiologically insignificant" for groups (such as the U.S. population) with sufficient iodine intake.

The researchers measured thyroid hormone and TSH levels in serum prepared from blood drawn throughout the study. The only change observed was a slight downward trend in TSH in the high-dose group during the exposure period, with a return to baseline by 15 days postexposure. This finding was unexpected, say the authors, because if iodine uptake is inhibited to the point that thyroid hormone levels are depressed, this should lead to an increase in TSH secretion, not a decrease. The observed effect was thus the opposite of any expected change, and the authors have no explanation for it.

The team also measured the amount of iodine excreted into the urine; they will describe those results in a separate report and evaluate the extent to which iodine nutrition affects the inhibitory response at a given dose of perchlorate. The authors did not estimate a safe level of perchlorate exposure for iodine-insufficient populations. However, they say that iodine supplementation should be provided to iodine-insufficient persons or populations regardless of whether there are known exposures to perchlorate, other inhibitors of iodine uptake such as nitrate or thiocyanate, or foods that naturally contain such inhibitory compounds or their precursors.