More than just perchlorate?
Other chemicals found in food may have thyroid-inhibiting effects similar to those of perchlorate.
The presence of perchlorate in foods has attracted widespread attention because of the chemical’s ability to interfere with iodide uptake by the thyroid. But other chemicals found in food can also inhibit the uptake of iodide, an essential component of the thyroid hormones that direct brain development. Researchers are now looking beyond perchlorate at other iodide blockers, including thiocyanate and nitrate, to determine whether they are cause for concern.
“The question of the impact of multiple sources of perchlorate and multiple iodine blockers is not known,” says Gregory Brent, a medical professor at the University of California, Los Angeles. Chief among these other iodide blockers are thiocyanate and nitrate, says John Gibbs, medical director at former perchlorate manufacturer Kerr-McGee.
To get a better handle on overall iodide availability, Benjamin Blount and colleagues at the U.S. Centers for Disease Control and Prevention recently published a new method for quantifying iodide and its blockers, perchlorate, thiocyanate, and nitrate, in human amniotic fluid. “We know that you need perchlorate and iodide exposure data to get a good picture of iodide to the thyroid—that’s critical,” says Blount. “These other chemicals may also affect the picture,” he adds.
In developed countries, the main source of exposure to thiocyanate is cyanide in tobacco smoke, which is metabolized in the body to thiocyanate, a relatively potent iodide uptake inhibitor. “Smoking has been shown to reduce the amount of iodide in breast milk because thiocyanate interferes with iodide uptake,” says University of California, Los Angeles, medical center endocrinologist Jerome Hershman. Cruciferous vegetables such as broccoli, cabbage, and Brussels sprouts are also a source of thiocyanate. Unless properly processed, cassava, eaten as a starch in tropical regions, can contain large amounts of cyanogens, which are metabolized in the body to thiocyanate.
Nitrate is present in many common foods, often at much higher levels than perchlorate. In leafy vegetables, nitrate levels are ~10,000× greater than perchlorate levels.
In 2004, Gibbs and colleagues published a paper on in vitro experiments to evaluate the relative potency of thiocyanate and nitrate. They exposed Chinese hamster ovary cells expressing the human protein that controls iodine uptake to individual inhibitors at various doses and to combinations of inhibitors. Perchlorate is 250× more potent than nitrate and 15× more effective than thiocyanate. “We confirmed previous work on the relative potency and showed that over a wide range of exposures the effect of the three is additive,” says Gibbs.
Most leafy vegetables have relatively high nitrate values, says Charles Sanchez, a soil scientist at the University of Arizona’s Yuma Agricultural Research Center. Using Gibbs’s potency factors to convert nitrate to perchlorate equivalents, Sanchez and colleagues found that, in most green leafy vegetables, nitrate has >100× the iodide-inhibiting effect of perchlorate. Sanchez has also measured thiocyanate in broccoli and found 15,000 µg/kg. This would be equivalent to 30,000 µg/kg perchlorate, if Gibbs’s potency factors are correct.
Gibbs’s potency factors are a good first step, says Herschman, but they can’t really be applied to food. “To determine whether particular foods and chemicals in them alter human thyroid hormone production, the steps necessary are cell studies, animal studies, and then carefully controlled human studies,” he says.
One of the few investigations of nitrate’s ability to block iodide uptake in humans, a 2000 study conducted at the Netherlands National Institute for Public Health and the Environment, suggests that nitrate is not likely to significantly inhibit iodide uptake. The scientists gave 10 healthy human volunteers 15 mg NaNO3/kg body weight for 28 d. At the end of the exposure period, no change had occurred in the iodide uptake of the volunteers, even though the volunteers were on an iodine-restricted diet. The researchers also found no effect on thyroid hormone levels in the volunteers’ blood.
Regulators in California and Massachusetts, states that have established some regulatory standards for perchlorate, acknowledge that nitrate and other iodide inhibitors may play a role in determining the risk of perchlorate exposure. They qualitatively allow for this possibility in their uncertainty estimates and in their assumptions for the amount of perchlorate that comes from food as opposed to drinking water.
To reduce that uncertainty, “We will need to have epidemiologic studies that integrate all forms of exposures with thyroid function to determine the cumulative effects,” says Brent.
