Perchlorate—which sometimes exists as a contaminant present in water, food, and breast milk—has been used as a medication to treat hyperthyroidism for many decades. At high doses—approximately 5-20 g/day—the administration of perchlorate was considered the standard of care in the United States, and it remains the approved pharmacologic intervention for many countries.
Several short-term studies suggest the administration of low-doses of potassium perchlorate (600 mg/day) does not present a health risk among those with Graves’ disease and iodine-induced hyperthyroidism while restoring normal thyroid function. More recent studies among nine ammonium perchlorate production workers with normal thyroid function and iodine intake indicated that administration of 3 or 10 mg/day of perchlorate over a 14-day period did not adversely affect thyroid function, even though radioactive iodine uptake was reduced. The latter observation resolved upon perchlorate withdrawal. These results are consistent with those reported by Greer et al. (2002).
With the advent of radioactive iodine and more-effective anti-thyroid medications, the use of perchlorate as a medication has been discontinued in the United States. A 2005 report from the National Academy of Sciences indicated perchlorate only affects the thyroid gland by blocking iodine uptake. Interestingly, in vitro studies suggest perchlorate can be actively transported into thyroid cells, resulting in iodine uptake inhibition by these cells. This process may be mediated by thyroid-stimulating hormone (TSH), a hormone that is synthesized in and secreted by the anterior pituitary. Importantly, this effect does not inhibit thyroid cell function or cell growth.
Several studies among susceptible populations, such as pregnant women, newborns, and children, indicate the absence of any impact of environmental perchlorate upon fetal development, the incidence of congenital hypothyroidism, or thyroid health of newborns or children. These findings support the American Thyroid Association’s 2004 position that perchlorate may not present clinically adverse events to these vulnerable populations.
Various perchlorate-containing compounds are found in solid-fuel propellants for rockets (ammonium perchlorate), fireworks displays, and Chilean fertilizer. Perchlorate also occurs naturally in many regional soils and groundwater and may be produced in the atmosphere.
Modern analytical technologies can detect perchlorate as low as ppb (μ/L or μ/kg) in drinking water, foods, and dietary supplements. Perchlorate is present in cow’s milk (5–10 ppb), breast milk (1.3–411 ppb), and infant formula (0.2–4.1 ppb), according to Pearce et al. (2007). The researchers noted that while the 1971–1994 National Health and Nutrition Examination Surveys (NHANES) data indicated an adequate iodine intake among women of childbearing age, the urinary iodine values were depressed. These urinary iodine data suggest that nearly 50% of breastfed infants may not receive adequate dietary iodine during the perinatal period. Other investigators noted that serum thyroid hormones, TSH, and thyroid antibodies are critical covariant biomarkers. These biomarkers were not assessed in this dietary survey; thus, it is inappropriate to assume the iodine status of the breastfed infants in the United States was compromised.
Resting primarily upon the Greer study, the Environmental Protection Agency (EPA) established an oral reference dose of perchlorate at 0.7 μg/kg/day, which includes an interspecies uncertainty factor of 10. In recommending this reference dose in its draft report, the EPA considered a non-adverse effect, which is more conservative than a more-traditional adverse effect. This translates to 24.5 ppb in drinking water for a 70 kg person consuming 2 L water/day. This is a typical National Research Council (NRC) approach when recommending specific nutrient intakes for adults. According to the NRC, this oral reference factor is sufficient to protect the health of even the most sensitive groups. The NHANES data indicate that the 95th percentile of the estimated daily perchlorate dose in the adult population is 0.234 μg/kg/day, which is well below the EPA and NAS reference dose.
While several states have established drinking water limits for perchlorate as low as 1 ppb, several studies suggest that—even among the most sensitive populations—drinking water with perchlorate levels at 4–340 ppb does not lead to thyroid dysfunction.
References for the studies mentioned above are available from the authors.
by Roger Clemens, Dr.P.H.,
Contributing Editor
Scientific Advisor, ETHorn, La Mirada, Calif.
[email protected]
by Peter Pressman, M.D.,
Contributing Editor
LCDR, Medical Corps, U.S. Navy
[email protected]