FAQ

FAQ

Explore the extensive list of frequently asked questions about perchlorate below, separated by issue area.

Perchlorate Basics

• What is perchlorate?
• Is it true that perchlorate was used as a medicine?
• What are perchlorate's other uses?
• Is perchlorate also found naturally in fertilizer?

About Perchlorate in Water

• Where is perchlorate being found and why are we just now responding to it?
• How can citizens find out if there is perchlorate in their own drinking water supplies?

Perchlorate and Health

• What has been learned about perchlorate in the past few years?
• How does perchlorate affect human health?
• What does it take to cause an adverse health effect?
• Does perchlorate stay in the body?
• Why isn't it an adverse health effect when perchlorate inhibits the thyroid gland's ability to absorb iodide?
• Are the effects of perchlorate on the body permanent?
• Has perchlorate been shown to cause cancer in humans?
• Are newborns and children more sensitive than adults to perchlorate?
• Are there other studies that explore how perchlorate might affect newborns?
• Should pregnant women or mothers of infants take any special precautions? Where can they find further information?
• Much of the research available on perchlorate appears to have been funded by industry. Is this information credible?
• Are there other substances that we consume that have the same effects as perchlorate?
• How can perchlorate be removed from water?

Credible Science Should Lead The Way on the Regulation of Perchlorate

• What are California's proposed "safe" exposure levels and how were they derived?
• Are the federal 24.5 ppb Drinking Water Equivalent Level (DWEL) and California's PHG "final" standards?
• What are the next steps in U.S. EPA's regulatory process for perchlorate?
• What are the next steps in California's regulatory process for perchlorate?
• What are the impacts of unnecessarily restrictive standards?
• What is being done now to address perchlorate in drinking water supplies?

What the NAS Committee Report Says about Perchlorate And Where it Fits into the Regulatory Process

• What are the next steps in EPA's regulatory process for perchlorate?
• The EPA and the NAS Committee recommended a reference dose. What is a reference dose?
• What level is safe for pregnant women? What level is safe for children? Why not be extra protective?
• How does EPA derive an RfD, and how did the NAS Committee derive one in the case of perchlorate?
• What is a NOEL?
• What are "uncertainty" or "safety" factors?
• Is it appropriate to apply a safety factor to a NOEL? Is there a precedent for this? Are there scientific arguments against it?
• What is the ppb level in drinking water that equates to the NOEL as defined by the NAS Committee?
• Are all the sources of perchlorate additive in the body?
• What body weight should be used to calculate a safe drinking water concentration using the NAS Committee's recommended reference dose?
• Who decides whether and how the additional studies should be conducted?
• The NAS Committee says perchlorate is "unlikely" to cause cancer. What studies did the Committee review in order to reach this conclusion?
• What is a simple definition of "point of departure?"

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Perchlorate Basics

Q: What is perchlorate?
A: Perchlorate is a simple salt-like substance made up of chlorine and oxygen. It is found in nature and can be man-made.

Q: Is it true that perchlorate was used as a medicine?
A: Yes, in the 1950s perchlorate was approved by the U.S. Food and Drug Administration as a safe and effective medication to treat people with overactive thyroid glands. While it has been replaced in the U.S. with newer medications (partly because it took enormously high doses to have any effect, and these doses had to be given frequently because perchlorate is so rapidly eliminated from the body ). [1] Perchlorate still is used as a medicine in other parts of the world. Because of its long-standing use as a medicine, we know much today about how perchlorate works in the body.

Q: What are perchlorate's other uses?
A: Perchlorate is widely used today by the military, NASA and the commercial space industry as an ingredient in solid rocket fuel and explosives. The large amounts of oxygen in perchlorate make it an optimal oxidizer to help solid rocket fuel burn. Perchlorate also is used as an oxidizing component in safety flares, fireworks, auto air bag inflators, lubricating oils and aluminum refining. Perchlorate is naturally present in some fertilizers typically used in organic farming.

Q: Is perchlorate also found naturally in fertilizer?
A: Yes, since the early 20th century Chilean nitrate fertilizer containing naturally-occurring perchlorate has been widely used in American agriculture. Current amounts of Chilean nitrate fertilizer products being shipped and used in the United States are substantial. According to the Foreign Trade Division, U.S. Census Bureau, the amounts of sodium nitrate imported from Chile into U.S. ports in 2001 was 88,150 metric tons. Specific to California, Chilean nitrate fertilizer containing perchlorate has been widely used since 1923; and between 1923 and 1998, the reported usage of sodium nitrate in California was 477,061 metric tons. Though the quantities used today are smaller than the amounts applied earlier in the century, the use of Chilean nitrate fertilizer in California remains substantial. Most recent data (2000 U.S. Department of Census) indicates more than 6,600 tons of Chilean nitrate fertilizer was imported to California that year.

About Perchlorate in Water

Q: Where is perchlorate being found?
A: Until recently, perchlorate was detected only in a few places where it was either manufactured or used in large quantities. In 1997, new techniques were developed that made it possible to detect perchlorate in water at very low levels - about 4 parts per billion (ppb). Because of these advancements, low levels of perchlorate have been detected in more places. Once perchlorate was detected at these low levels, industry and government began a unique partnership to review and study the health effects of perchlorate, resulting in several new studies that showed these low levels have no measurable effect on human health. Treatment technologies have been developed and put in place to address perchlorate contamination. Learn more about perchlorate removal technologies »

Q: How can citizens find out if there is perchlorate in their own drinking water supplies?
A: The easiest way to obtain this information is to call their local water company. Or, if their water service is provided by a municipal utility, citizens can contact the customer service center (usually listed on their utility bill) and get information on who their water purveyor is and how to contact them. They can also visit the water supplier's Web site and look for either the water quality report or the Consumer Confidence Report. If a district has detected perchlorate it must be listed.
Many of these reports are also available on the EPA website »

Perchlorate and Health

Q: What has been learned about perchlorate in the past few years?
A: A great deal is known about perchlorate, in part because of its longstanding use as a medicine. Substantial research has been conducted since the mid-1990s to improve scientific and medical understanding of perchlorate's health effects. These studies, particularly one by Greer, et al. show there are no measurable effects on human beings at levels many times higher than the minute amounts being found in some drinking water supplies.
Read the abstract of the Greer study »

Q: How does perchlorate affect human health?
A: Credible studies show perchlorate's direct effects on human health are limited to the thyroid. High levels of perchlorate can prevent the thyroid gland from absorbing iodide (which it needs to make hormones) from the bloodstream. This in itself is not dangerous however, because the body automatically compensates for this. Further, according to the U.S. Food and Drug Administration, Perchlorate-induced changes to thyroid function have not been demonstrated in studies of humans exposed to perchlorate.

Q: What does it take to cause an adverse health effect?
A: A sequence of three events is required for perchlorate to have any adverse effect on health, each requiring higher doses of perchlorate.

First: Perchlorate exposure must be high enough to prevent the thyroid from getting its usual amount of iodide. This may begin to happen at around 245 ppb of perchlorate in drinking water, AND

Second: Exposure must be high enough to overwhelm the body's normal adaptive process, thereby lowering the amount of thyroid hormones in the body (scientific research indicates this does not occur at levels below 14,000 ppb), AND

Third: Exposure must be high enough, and sustained long enough, to reduce thyroid hormone levels for a long period of time. An adverse health effect would require daily consumption of more than 14,000 ppb in drinking water. This would require an adult to drink 500 gallons of water per day with 20 ppb perchlorate.

Q: Does perchlorate stay in the body?
A: Perchlorate is not stored anywhere in the body.

Q: Why isn't it an adverse health effect when perchlorate inhibits the thyroid gland's ability to absorb iodide?
A: "Inhibition of iodide uptake," as this effect is called, is a routine occurrence, caused by a number of factors in our diet and environment. The body naturally compensates if the thyroid can't absorb its normal amount of iodide from the bloodstream. The thyroid itself has an enormous iodide reserve. It also can open additional "channels" to let more iodide in. It's important to note that most Americans eat a diet that provides more than twice the daily need of iodide.

Q: Are the effects of perchlorate on the body permanent?
A: Although there are no measurable effects when perchlorate is in the body at low levels, any effects of perchlorate on the body's ability to produce hormones are fully reversible once exposure to high levels declines or stops.

Q: Has perchlorate been shown to cause cancer in humans?
A: No. The National Academy of Sciences has confirmed it is unlikely perchlorate causes cancer, and numerous other credible studies have shown NO evidence that perchlorate causes cancer in humans, even when consumed at levels far higher than any found in drinking water. The state of California has also stated that perchlorate does not pose a known cancer risk to the public.

Q: Are newborns and children more sensitive than adults to perchlorate?
A: The best scientific and medical research shows that newborns and children are not affected by perchlorate at the low levels found in drinking water. Most recently, two studies conducted by Dr. Elizabeth Pearce and colleagues in 2010 and 2011 have added to the scientific database of research confirming this conclusion. These studies examined thousands of pregnant women in Cardiff (Wales), Turin (Italy), Cordoba (Argentinae) and Los Angeles (USA) and both had the same finding: low level perchlorate exposure is ubiquitous in the population, however it is not associated with alterations in thyroid function during the critical first trimester of pregnancy.

Q: Are there other studies that explore how perchlorate might affect newborns?
A: One study (Li et al.) looked at the thyroid function of newborns in Las Vegas, Nevada, where low levels of perchlorate exist in the water, and in Reno, Nevada, where there is no perchlorate in the water. In comparing the results of standard tests of newborns in the two areas, scientists found no difference between the newborns in terms of thyroid function. A separate study (Lamm and Doemland) comparing counties in California and Nevada, some with trace amounts of perchlorate in the water and some without, had similar results. Another study by Tellez et al. found no impacts from perchlorate on pregnant women during the critical period between the late first and early second trimesters, and no effect on fetal development or thyroid levels in newborns. The study examined pregnant women and babies from three cities in Chile, where perchlorate levels range from non-detectable to 110 ppb, and daily intake of dietary iodide is equivalent with the U.S. Yet another study (by Kelsh et al.) evaluated whether newborns had higher rates of primary congenital hypothyroidism (PCH) or elevated concentrations of thyroid-stimulating hormones in a community where perchlorate was detected in groundwater wells. The findings, according to the Journal of Occupational and Environmental Medicine, suggest that residence in a community with potential perchlorate exposure has not impacted PCH rates or newborn thyroid function. Other studies show there are no measurable effects on human beings at doses up to 245 ppb.

Q: Should pregnant women or mothers of infants take any special precautions? Where can they find further information?
A: As with all questions of health relating to pregnancy, prospective mothers can obtain the best possible information for informed decision making by speaking directly with their doctor. Information may also be obtained from the American Thyroid Association.

Q: Much of the research available on perchlorate appears to have been funded by industry. Is this information credible?
A: This is an important issue that must be well understood. On the one hand, some people believe that industry - rather than taxpayers - should fund this kind of research. At the same time, it's important that safeguards be in place to guarantee the validity and credibility of the research findings. With respect to the perchlorate research referred to here, several of these safeguards are in place:

1. The scientific research has been conducted entirely independent of the funding organizations.
2. The research findings have been peer-reviewed by independent, neutral and respected scientists to verify the research was done correctly and the results are valid.
3. These studies have also been published in internationally respected scientific journals.

This critical review ensures the studies conducted can be replicated by other scientists, now and in the future. Taken together, all these factors can give the public confidence in the accuracy, validity and credibility of the research.

Q: Are there other substances that we consume that have the same effects as perchlorate?
A: A variety of substances found in everyday foods and drinking water can affect the body in essentially the same way as perchlorate. Specifically, nitrates and thiocyanates, which occur naturally in several kinds of vegetables that are considered essential to a healthy diet, have the same thyroid effect as perchlorate.

Q: How can perchlorate be removed from water?
A: There are currently two major technologies in use for treating large volumes of water that contain perchlorate. Ion Exchange Technology uses of a resin to absorb perchlorate and remove it from water, affording the opportunity for safe and appropriate disposal of the perchlorate. Biological treatment is a process that uses microorganisms to break down perchlorate into other components. In this process, water can be treated in a tank or in the ground. The primary resulting component is chloride, which is part of common table salt. Other technologies are currently under development.

Credible Science Should Lead The Way on the Regulation of Perchlorate

Q: What are California's proposed "safe" exposure levels and how were they derived?
A: In 2007, The State of California - accounting for perchlorate exposure from water, farm products and cow's milk - enacted a Maximum Contaminant Level (MCL) for perchlorate in drinking water of 6 ppb. This is an exceptionally conservative approach considering:

• Studies that show perchlorate begins to affect the thyroid at approximately 245 ppb, and below this level there is no measurable effect. (Studies show levels below 14,000 ppb do inhibit the body's ability to absorb iodine, but even this is not an adverse health effect.)
• Cal/EPA requested a peer review by a panel of scientists convened by the University of California (UC) to review its own risk assessment on perchlorate;
• Three UC researchers conducted the review and each disagreed with Cal/ EPA's Office of Environmental Health Hazard Assessment, and one another, on how the state should proceed.

Q: Are the federal 24.5 ppb Drinking Water Equivalent Level (DWEL) and California's PHG "final" standards?
A: California's MCL is "fFinal" in that it is currently enforceable, but is under review by regulatory authorities as part of a five-year review process required by state law. At the federal level, U.S. EPA has determined that it will move forward to set a national drinking water standard for perchlorate, but there is no indication of what standard EPA may propose.

Q: What are the next steps in U.S. EPA's regulatory process for perchlorate?
A: EPA's 24.5 ppb RFD Reference Dose (the maximum dose without any risk, abbreviated RfD) may be used by officials throughout the agency to make site-specific cleanup or interim drinking water standard decisions involving perchlorate. States and private parties also may look to EPA's RfD and Drinking Water Equivalent Level (DWEL) as they make similar decisions.

In February 2011, despite evidence in the scientific record - and despite the fact that perchlorate does not meet the requirements for regulation under the federal Safe Drinking Water Act - EPA made a determination to move forward in setting a drinking water standard for perchlorate. EPA’s determination begins a multi-year process that will involve several opportunities for public comment. Barring any decision by EPA to pause or stop the process, a draft standard must be issued for public comment in February 2013.

At this juncture, EPA must decide whether to promulgate a Federal drinking water standard (MCL) for perchlorate. EPA will only proceed with a standard if it determines that perchlorate adversely affects human health, is known or likely to substantially occur in public water systems at frequencies and levels that would cause adverse health effects, and that setting a Federal standard for perchlorate presents a meaningful opportunity to reduce the risk from perchlorate exposure.

Q: What are the next steps in California’s regulatory process for perchlorate?
A: Following a mandatory five-year review mandated by state law, California proposed revising its Public Health Goal (PHG) for perchlorate from 6 parts per billion (ppb) to 1 ppb. Because the state’s rationale for the change is based on questionable scientific assumptions, the proposal is currently undergoing scientific peer review. It is unclear what the state’s obligations are if the peer review does not support the conclusions. If California decides to move forward in any case, there will be a regulatory process wherein the state must decide whether to change the Maximum Contaminant Level (MCL) for perchlorate. The MCL is synonymous with the state standard. Revising and establishing a new MCL would require a public process expected to last 18 months to three years.

Q: What are the impacts of unnecessarily restrictive standards?
A: The costs of an overly restrictive (i.e., more restrictive than what credible science says is necessary to protect public health) drinking water standard for perchlorate are potentially staggering. California, Nevada and Arizona could be the states most impacted. Overly strict standards would in effect create a "problem" where one does not really exist, - forcing citizens, industry and government to incur significant expenses for new treatment plants, retrofitting existing treatment plants, purchasing additional water supplies, lowering reservoir levels and pumping more groundwater from existing sources. This could not only be a substantial expense of resources that could lead to no public health benefit, it could also contribute to a significant water shortage crisis as water supplies are closed because they do not meet the new standards.

Read more »

Q: What is being done now to address perchlorate in drinking water supplies?
A: Perchlorate is being contained, removed and treated at sites where it has been used in the past for manufacturing. New state-of-the-art technologies for removing perchlorate from water have been developed and put into use. Others are being developed or refined. In addition, key members of the aerospace and defense industries, along with the U.S. EPA, the U.S. Department of Defense, and the U.S. Air Force, formed the Perchlorate Information Bureau in 1993 to fund scientific research so policies could be established to protect public health based on credible science.

What the NAS Committee Report Says about Perchlorate and Where it Fits into the Regulatory Process

Q: What are the next steps in U.S. EPA's regulatory process for perchlorate?
A: EPA's 24.5 ppb Reference Dose (the maximum dose without any risk, abbreviated RfD) RFD may be used by officials throughout the agency to make site-specific cleanup or interim drinking water standard decisions involving perchlorate. States and private parties also may look to EPA's RfD and Drinking Water Equivalent Level (DWEL) as they make similar decisions.

In February 2011, despite evidence in the scientific record - and despite the fact that perchlorate does not meet the requirements for regulation under the federal Safe Drinking Water Act - EPA made a determination to move forward in setting a drinking water standard for perchlorate. EPA’s determination begins a multi-year process that will involve several opportunities for public comment.

Q: The EPA and the NAS Committee recommended a reference dose. What is a reference dose?
A: A reference dose (RfD) is defined by EPA as, "an estimate estimate of a daily oral exposure to the human population, including sensitive subgroups such as children, that is not likely to cause harmful effects during a lifetime."
See the definition of reference dose on the EPA website »

The definition is based on the assumption that exposure could occur throughout the lifetime and takes into account all stages of life. Also, the definition takes into account "sensitive subgroups," such as pregnant women, infants and children, and fetuses.

It is sometimes misunderstood to mean that doses above the RfD are unsafe. This is not correct. Because the RfD incorporates a number of safety factors to ensure that the value is health-protective, when a dose exceeds an RfD value, it does not mean that an adverse effect will occur.
Learn more about safe water from the EPA »

The RfD is not a regulatory standard - it is one of the building blocks assembled into a regulatory standard, and should not be misinterpreted as serving the purposes of a regulatory standard.

Q: What level is safe for pregnant women? What level is safe for children? Why not be extra protective?
A: To derive their recommended reference dose, the National Academies of Science (NAS) Committee selected as its starting point the No Observed Effect Level (NOEL) dose of 0.007 milligrams per kilogram per day. This level is the lowest dose used in a clinical study of adults by Greer et al. (2002). At this dose, there was no difference in the amount of iodide uptake inhibition by the thyroid between people exposed to perchlorate and those not exposed to perchlorate. The Committee indicated that this effect, inhibition of iodide uptake by the thyroid, is the first effect that must occur before any other effects of exposure can occur. However, the Committee is clear that iodide uptake inhibition is not an adverse effect. (See the NAS report, "Health Implications of Perchlorate Ingestion.") Using standard default EPA conversion practices, the reference dose of 0.007 milligrams per kilogram per day is equivalent to 245 ppb in drinking water.

The Committee then divided this dose by a safety factor of 10 to account for sensitive populations. They identified the most sensitive population to be fetuses; particularly those of pregnant women who have hypothyroidism or iodide deficiency. (See Page 172 of the NAS report, "Health Implications of Perchlorate Ingestion.") The Committee's resulting recommended reference dose (0.0007 milligrams per kilogram of body weight per day) would be equivalent to 24.5 ppb in drinking water.

The NAS Committee acknowledges that they used an unconventional approach to develop their reference dose and used as its starting point a dose that causes no effects at all. This dose is already 57 times lower than the dose that the NAS Committee identified as the minimum dose before any adverse effects of perchlorate exposure could occur (14,000 ppb). Any level of exposure below the Committee's reference dose of 245 ppb is clearly safe, since no adverse effect can occur to anybody, including pregnant women, their fetuses, infants, and children, at levels of exposure that are below the highest dose at which no effects at all occur. No public health benefit is gained by reducing exposures any further below this level, a fact confirmed by two studies in 2010 and 2011 by6 Pearce, et al.

Q: How does EPA derive an RfD, and how did the NAS Committee derive one in the case of perchlorate?
A: Typically, EPA derives an RfD by starting with the highest dose at which no adverse effects can be observed (the No Observed Adverse Effect Level, or NOAEL).
Learn more from the U.S. EPA about how that agency sets reference doses  

It is unprecedented to use the level at which no effect at all, even a mundane, biochemical effect, is observed (the No Observed Effect Level, or NOEL); however, this is the starting point that the NAS Committee used in the case of perchlorate. The Committee defined a NOEL as "the highest dose at which there are no statistically or biologically significant increases in the frequency or severity of any effect between the exposed populations and its appropriate control." (See page 168 of the NAS report, "Health Implications of Perchlorate Ingestion.")

Where a NOAEL is used, uncertainty factors are then customarily applied to this starting dose to account for scientific uncertainty and to ensure that the RfD protects public health. For example, to account for sensitive populations such as pregnant women, children, infants and fetuses, the EPA typically divides the NOAEL by an uncertainty factor of 3 or 10.

The NOEL dose that the Committee selected as its starting point was 0.007 milligrams per kilogram per day. The Committee then divided this dose by a safety factor of 10 to account for sensitive populations. Given their departure from standard practice in their selection of a NOEL as the starting point for their reference dose, it is puzzling that the NAS felt they needed to apply an additional ten-fold safety factor. As the Committee itself states, below the level that has no effect, "all other proposed effects of perchlorate exposure would be avoided." (See page 178 of the NAS report, "Health Implications of Perchlorate Ingestion.") There is no apparent precedent for this level of conservatism.

The Committee identified the NOAEL for perchlorate as 0.4 milligrams per kilogram body weight per day, stating that, in adults, "sustained exposure" (i.e., several months or longer) to more than 0.4 milligrams per kilogram of perchlorate per day is likely required before any harm could occur.

If, alternatively, an uncertainty factor of 3 or 10 for sensitive populations was applied to the NOAEL identified by the NAS Committee, the resulting dose would be 0.04 to 0.13 milligrams per kilogram per day. Applying standard default EPA exposure assumptions about how much a typical person weighs and how much water they drink makes this dose equivalent to 1,400 to 4,655 ppb in drinking water.

Q: What is a NOEL?
A: The NAS Committee defines a NOEL as "the highest dose at which there are no statistically or biologically significant increases in the frequency or severity of any effect between the exposed populations and its appropriate control." (See page 168 of the NAS report, "Health Implications of Perchlorate Ingestion.")

The Committee states that a dose of 0.007 milligrams per kilogram of body weight per day is the NOEL. (See page 169) Using standard default EPA conversion practices, this is equivalent to 245 ppb in drinking water.

Q: What are "uncertainty" or "safety" factors?
A: As with most issues in life, health and safety decisions must be made absent absolute certainty. "Uncertainty" or "safety" factors are incorporated into the process to account for a lack of scientific data or to address possible variability in population sensitivity when deriving a safe dose level.
Learn more about EPA's definition of uncertainty factors  

Q: Is it appropriate to apply a safety factor to a NOEL? Is there a precedent for this? Are there scientific arguments against it?
A: Applying a safety factor to a NOEL is unusual and no precedent has been identified wherein EPA has applied safety factors to an analogous endpoint to derive an RfD.

The NAS Committee acknowledges that its recommendation "differs from the traditional approach." (See page 15) Moreover, the Committee does not provide any supporting precedent to justify applying a safety factor to this kind of dose.

In this instance, the Committee recommends a reference dose that is more than 570 times lower than the dose it concludes does not cause adverse effects in humans. No additional health protection is gained by setting a reference dose below the threshold dose.

Q: What is the ppb level in drinking water that equates to the NOEL as defined by the NAS Committee?
A: EPA uses standard default conversion factors for body weight (70 kilograms) and tap water consumption (2 liters per day) to translate RfDs to drinking water equivalents in ppb. For most people in a population, these assumptions are conservative since most people do not drink this much water each day (i.e., 2 liters per day is the 84th percentile of the adult drinking water rate, meaning 84 percent of the population drinks less than this amount each day). The following ppb equivalents correspond to various perchlorate doses:

PPB-EQUIVALENTS FOR VARIOUS DOSES

No Observed Adverse Effect Level (NOAEL) [0.4 mg/kg per day]	14,000 ppb
No Observed Effect Level (NOEL) [0.007 mg/kg per day]	245 ppb
NAS Committee recommended reference dose [0.0007 mg/kg per day]	24.5 ppb

The Committee based its reference dose on the NOEL instead of the NOAEL, and applied an additional 10-fold safety factor to account for sensitive populations.

Q: Are all the sources of perchlorate additive in the body?
A: The effect of perchlorate in the body at doses above 0.007 milligrams per kilogram per day (equivalent to 245 ppb in drinking water using EPA default assumptions) will be the same, regardless of whether its source is from drinking water or food. Perchlorate is not absorbed through the skin.

To calculate the total dose from all sources, however, it is not correct to simply add the concentrations found in water, milk and various other foods. This is because when calculating a total dose, the amounts of water, milk and other foods that a person ingests also must be considered.
Learn more about perchlorate and food from the U.S. EPA Q&A on perchlorate »

Q: What body weight should be used to calculate a safe drinking water concentration using the NAS Committee's recommended reference dose?
A: By definition, a reference dose assumes exposure over a lifetime and takes into account the special considerations of sensitive populations such as pregnant women, children, infants and the developing fetus.
Read the U.S. EPA’s definition of a reference dose on their website »

The NAS Committee calculated a reference dose by starting with a NOEL and applying a 10-fold safety factor to ensure protection of potentially sensitive populations. If this value was used to calculate a safe drinking water concentration, any additional adjustment to account for sensitive populations, such as using body weights and drinking water consumption rates for the sensitive population, would be unnecessary and in essence "double counting."

Q: Who decides whether and how the additional studies should be conducted?
A: The NAS Committee made several recommendations for future research, although noting that sufficient data now exist to move forward with the regulatory process. Since the NAS report multiple studies have since filled the few data gaps identified by NAS and have confirmed the NAS conclusions.

Q: The NAS Committee says perchlorate is "unlikely" to cause cancer. What studies did the Committee review in order to reach this conclusion?
A: The NAS Committee stated "it is unlikely that perchlorate poses a risk of cancer in humans." (See page 145 of the NAS report, "Health Implications of Perchlorate Ingestion.")

"There are no reports of the appearance of a new thyroid disorder, thyroid nodules, or thyroid carcinoma in any patient treated with potassium perchlorate for hyperthyroidism. Iodide deficiency in the thyroid gland, a possible consequence of perchlorate administration or exposure, is not associated with an increase in thyroid cancer ... In hyperthyroid patients treated with antithyroid drugs, there was no increase in thyroid cancer mortality" (See page 62 of the NAS report, "Health Implications of Perchlorate Ingestion.")

"The committee concludes that the thyroid tumors in the (rat) offspring were most likely treatment related but that thyroid cancer in humans resulting from perchlorate exposure is unlikely because of the hormonally mediated mode of action and species differences in thyroid function." (see page 12)

"In addition, EPA's science policy document on the assessment of thyroid follicular-cell tumors notes that although there may be some qualitative similarities, there is evidence that "humans may not be as sensitive quantitatively to thyroid cancer development of thyroid-pituitary disruption as are rodents" . The increased sensitivity may be due to marked species differences in the physiology of the thyroid gland . The EPA and IARC documents provide guidance for the evaluation of thyroid follicular-cell tumors based on mode of action (for example, tumors secondary to hormone imbalance)." (see page 145)

One of the animal studies of perchlorate looked at two-generations of rats that were exposed to perchlorate in drinking water. A certain type of thyroid tumor known as a follicular cell tumor was identified in two of the rats given perchlorate. On page 145 of the report, the NAS Committee indicates that these types of tumors are not unexpected in rats when they are exposed to agents that affect the thyroid because "spontaneous thyroid follicular-cell adenomas can occasionally be observed in control rats of this strain and age." In other words, thyroid tumors occur often in rats (especially Sprague Dawley rats as were studied here) even when they are not exposed to anything. The Committee also notes that, in this regard, rats are much different than humans, stating "humans may not be as sensitive quantitatively to thyroid cancer development of thyroid-pituitary disruption as are rodents...The increased sensitivity may be due to marked species differences in the physiology of the thyroid gland."

Rats are known to respond much more rapidly and to a greater extent to agents that affect their thyroid than do humans because of many physiological differences. When a rat is exposed to an agent that affects the thyroid, more thyroid stimulating hormone (TSH) is produced than in a human at a comparable dose, which causes a much more rapid production of thyroid cells. When cells multiply rapidly, the likelihood that cellular mutations will occur increases, which can lead to tumors. Since TSH levels are not affected in humans at equivalent doses, stimulation of the thyroid to produce more cells does not occur. The NAS states that these agents "can be assumed not to be carcinogenic in humans in concentrations that do not lead to alterations in thyroid hormone homeostasis." (See page 145 of the NAS report, "Health Implications of Perchlorate Ingestion.")

Q: What is a simple definition of "point of departure?"
A: In risk assessment, the "point of departure" is the dose selected as the starting point to which uncertainty or safety factors are applied to derive a "safe" dose.
See the EPA’s definition of "point of departure" on their website »

Historically, this starting point is either the NOAEL or the LOAEL. The use of a NOEL is a dramatic departure from current policy and constitutes a much more conservative starting point than has been used for any other regulated chemical.

[1] - In the early 1960s there was a concern that perchlorate might have an association with aplastic anemia. Seven patients who were being treated with perchlorate developed the disease. There were several possible reasons why, ranging from misdiagnosis of hypothyroidism to environmental concerns (the cases were clustered in two specific areas). No evidence of a connection between perchlorate and aplastic anemia has been shown. What is known is that in the four decades since, perchlorate has continued to be used, and no cases of aplastic anemia have arisen among any of these patients.