June 22, 2004

Rocket Fuel in Cows' Milk - Perchlorate: Health Risks

Women of child-bearing age and infants are the most important population to consider when assessing the risks of perchlorate consumption because the developing fetus and infant are much more susceptible to injury from perchlorate exposure than adults. Perchlorate interferes with normal thyroid function by blocking iodide uptake, a necessary building block of thyroid hormones, and can lead to hypothyroidism. In adults, hypothyroidism is associated with a variety of adverse symptoms such as fatigue, depression, anxiety, unexplained weight gain, hair loss and low libido. [9]

Although these symptoms can be serious, especially if left untreated, the consequences of depressed thyroid hormone levels on developing fetuses and infants can be devastating: In a developing fetus or infant, even temporary disruption of thyroid hormones can lead to permanent defects in the developing organism. [1] Numerous studies on laboratory animals have shown that perchlorate affects the developing fetus at much lower levels than it affects exposed adults. [19, 20] Unlike adults, infants and fetuses do not have large stores of thyroid hormones, which would enable them to buffer changes in iodide availability and thyroid hormone levels in the body. [21]

Moreover, recent research has shown how remarkably sensitive the developing fetus can be to small disturbances in thyroid hormone level. One study found that women whose levels of a particular thyroid hormone measured in the lowest 10 percent of the population during the first trimester of pregnancy were more than 2.5 times as likely to have a child with an IQ of less than 85 and five times as likely to have a child with an IQ of less than 70. This was true whether or not these women were clinically hypothyroid, and many women in this group had thyroid hormone levels considered to be in the normal range. [22] This is important because it means that perchlorate does not have to alter women's thyroid hormone levels dramatically to have critical effects.

There is also evidence to suggest that perchlorate can have effects even at low doses. An epidemiological study of newborns in Arizona, for example, found that babies born to mothers who drank contaminated Colorado River water during pregnancy had significantly different thyroid hormone levels than infants of mothers who drank uncontaminated water. [23] An epidemiological study of thousands of California infants born in 1996 had similar findings, with significant differences in infant thyroid hormone levels of infants whose mothers drank water contaminated with perchlorate levels at just 1 to 2 ppb. [24]

Regulators are faced with a wide array of scientific decisions when developing risk assessments for a given chemical: Should they use a "weight of the evidence" approach that considers multiple studies, or base the assessment on a single "critical" study? What should they choose for the value of the "uncertainty factors" which account for remaining scientific uncertainties and variability within the population? How appropriate is each given human or animal study for the purpose of risk assessment? The three regulatory bodies that have so far published risk assessments for perchlorate — the US Environmental Protection Agency (EPA), California EPA (Cal-EPA), and the Massachusetts Department of Environmental Protection (MADEP) — have all come up with somewhat different answers to these recurring questions. But all three have agreed that perchlorate poses a health risk to the population at low doses.

Cal-EPA's Office of Environmental Health Hazard Assessment (OEHHA) relied on a single human study, known as the Greer study, to derive a perchlorate PHG of 6 ppb. [12] The Greer study involved dosing a small number of healthy adults (7 to 10 per dose group) with perchlorate for two weeks and examining how the toxin affected iodide uptake by the thyroid. [25] Although the study provided some valuable information, it also "has a number of inherent limitations" that make it difficult to extrapolate the results "to long-term exposures of infants and other susceptible people to perchlorate," as the MADEP noted in a recent report. [3]

Because of these limitations, both Massachusetts and the EPA chose to use a "weight of the evidence" approach in their toxicological risk assessments, looking not only at the Greer study but also the many animal studies that showed perchlorate-related effects on the developing fetus and nursing neonates. [1, 3] Looking at these earlier life stages is critical since studies dating back to the 1950s have clearly shown that perchlorate affects young animals at much lower doses than it does adults. But notably, after reviewing the process by which OEHHA arrived at its PHG, MADEP concluded that "the Greer study results themselves support a lower interim guidance value for sensitive individuals than adopted by CA EPA." [3]

Aside from its choice of studies to include, California also differed considerably from Massachusetts and the EPA in how it accounted for scientific uncertainty in its perchlorate risk assessment. While OEHHA used a single uncertainty factor of 10 (or just 3 for its calculations for infants) to account for differences between children and adults, variability between individual sensitivities within the general population and remaining scientific data gaps, both Massachusetts and EPA determined that a much higher uncertainty factor (UF) was needed to adequately protect sensitive populations. [1, 2, 12] In fact, when MADEP evaluated the California PHG it concluded that, using Cal-EPA's approach, a total "UF of at least 30 is clearly justified and values from 100 - 300 can be supported," resulting in a PHG "from approximately 1 ppb to the sub-ppb range." [3] The EPA's proposed and Massachusetts' final perchlorate reference doses are both equivalent to 1 ppb in drinking water. The MADEP, however, has stated that although it chose a "guidance level" of 1 ppb, a lower level "can be supported on the basis of the toxicity data" and noted that a driving factor in their decision was that current testing methodologies can not reliably detect perchlorate below 1 ppb. [3]

The EPA's RfD has been highly contentious, no doubt because the Department of Defense, perchlorate manufacturers, and major defense contractors face liable for millions of dollars in clean-up costs. Perchlorate contamination has now been detected at eight DOD sites around the country so far, and most have not even been tested. The National Academy of Sciences (NAS) has been called into review the EPA's proposed standard, but the objectivity of this body is in question: As California Sens. Barbara Boxer and Dianne Feinstein charged in a recent letter to NAS president Bruce Alberts, at least two members of the review panel have documented financial ties to polluters, raising "serious issues about NAS review of conflict of interest, bias and balance." [10] The NAS review was originally scheduled to be released in August of 2004, but has now been delayed until at least December, if not later.