The Facts About Perchlorate and Cancer

Why Claims of a Cancer Risk from Perchlorate are Based on Assumptions, and Upon Exposure Levels Impossible to Obtain in the Environment

The issue of whether perchlorate poses a cancer risk is a critical one, but one in which the science has been quite clear. The National Academy of Sciences panel on perchlorate recently concluded - as stated several times in its report - that perchlorate is unlikely to cause cancer. 1

  • "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 (between humans and rats) in thyroid function." (p 7)
  • "The committee notes, however, that on the basis of its understanding of the biology of human and rodent thyroid tumors, it is unlikely that perchlorate poses a risk of thyroid cancer in humans." (p 73)
  • "It is unlikely that perchlorate poses a risk of cancer in humans." (p 95)
  • "Specifically, the development of thyroid tumors as an ultimate result of perchlorate exposures is an unlikely outcome in humans." (p 109)

A peer review document produced for the University of California stated "no data are presented that show perchlorate, by itself, is a carcinogen2." Likewise, California's Office of Environmental Health Hazards Assessment stated "perchlorate does not pose a known cancer risk to the public."3

Perchlorate's effects are limited to the thyroid gland. While the U.S. Environmental Protection Agency (EPA) does state "to date, no chemical has been identified as being carcinogenic to the human thyroid,"4 EPA, to provide an abundance of precaution, has written in its risk assessment that perchlorate "may" pose a cancer risk to humans. EPA bases this possibility on a single study in rats, and EPA's Policy for Assessment of Thyroid Follicular Tumors requires it to make this assumption. This has led some organizations to raise alarms, which, unfortunately, have no backing in science.

The full story on this debate is somewhat complex, but it is important to understand all the facts to avoid misrepresenting the science. This document shows why claims of a cancer risk from perchlorate are based on presumptions at best, and upon exposure levels which are impossible to obtain at levels present in the environment.

1. WHY EPA SAYS PERCHLORATE MAY CAUSE CANCER:

In 1998, Argus Labs conducted a study for EPA known as the "Two Generation Reproduction Study of Ammonium Perchlorate in Rats." In the study, perchlorate was given in various doses to different groups of pregnant rats. The two generations of offspring of those rats were assessed to determine whether perchlorate has any reproductive effects. For the highest dose group, the data show that there were three "adenomas of the thyroid gland" in two of the male offspring (out of a pool of 60 total offspring). The scientists that conducted the study did not report increases of any type of cancer in these offspring.

What everyone should know about this finding:

  • The dose of perchlorate given to the mothers of the rats in which the thyroid adenomas were detected was 30 mg/kg-day, the highest dose tested. In humans, this dosage would equate to a concentration in water of 1,050,000 parts-per-billion.5 At average levels, a person would have to drink at least 20,000 gallons of water per day just to have an equal exposure.
  • Other than one benign tumor in one of the control rats (the rats that were not given any perchlorate), no adenomas, which are classified as benign tumors that may or may not become cancerous, were found in any of the other animals.

2. IODINE, PERCHLORATE AND THYROID HORMONES

Iodine is used by the thyroid to make thyroid hormones. If perchlorate is consumed at high levels (above 245 ppb) it may reduce the thyroid's ability to absorb iodide from the bloodstream. While this is labeled as "thyroid disruption," it is in fact a harmless and reversible event, and actually occurs naturally every day in humans as a result of diet and other factors. Also, it is usually compensated for by a large store of iodine in the thyroid gland itself.

If production of thyroid hormones is reduced, the pituitary gland in the rat or human responds by increasing production of what's known as Thyroid Stimulating Hormone (TSH). TSH is, simply, a hormone that tells the thyroid that it needs to make more thyroid hormones. This feedback is a normal process that occurs naturally throughout the day to maintain optimal thyroid hormone levels.

If the need for thyroid hormones is great enough and continues for a long enough period of time, the thyroid responds either by increasing the size of cells that produce thyroid hormones or producing more cells that are capable of producing thyroid hormones. This can cause the thyroid gland to enlarge.

For rats, if TSH is significantly elevated for a long time and thyroid cell production is substantially increased, the growth of thyroid cells can become abnormal and when that happens, thyroid cancer has sometimes been reported to develop. This mechanism has been shown to occur only in animals, particularly rodents. U.S. EPA has acknowledged "to date, no chemical has been identified as being carcinogenic to the human thyroid." 6

3. Rats vs. Humans

Many Scientists agree that because the rat is more susceptible to thyroid cancer than humans it is not a good animal model to predict thyroid cancer effects of chemicals.

Despite this, U.S. EPA's Policy for Assessment of Thyroid Follicular Tumors (http://epa.gov/osp/spc/spcthyr.htm) suggests, "in the absence of chemical specific data, humans and rodents are presumed to be equally sensitive to thyroid cancer due to thyroid-pituitary disruption."

However, in this same research document, EPA also states that "rodents show significant increases in cancer with thyroid pituitary disruption; humans show little, if any."

In other words, the rat is more sensitive to thyroid-pituitary disruption than humans. Further, the U.S. Food and Drug Administration has stated:

"The pathogenesis of thyroid tumors in rats and humans is different. There is no evidence for a primary causative role of TSH in thyroid tumor formation in humans; however, TSH at normal levels may play some necessary, but incomplete role in human thyroid tumor development. Accordingly, there are few examples of thyroid carcinogens in humans. X-irradiation and radioactive iodine are the only clearly known human thyroid carcinogens; there are no other chemicals known to induce thyroid tumors in humans."

— Poirer, et al., "An FDA Review of Sulfamethazine toxicity", December 1999.

There are several reasons why this is thought to be true:

  • For one, humans and rodents have different proteins that attach to and carry thyroid hormones to different sites in the body where the thyroid hormones are used.
  • The protein found in humans binds the thyroid hormones more tightly, so that the hormones stay in the body much longer.
  • Because the turnover of thyroid hormones in rodents is much greater compared to the human, the rodent thyroid must produce much more thyroid hormone.
  • To accomplish this, the rodent pituitary produces much more TSH, which in turn has a greater stimulatory effect on the thyroid.

4. A word on "mutagens"

U.S. EPA acknowledges perchlorate is not mutagenic - that is, it does not cause permanent changes in the genetic material of cells that can be passed on when the cell divides. Genetic changes in the cell are often the precursor of cancerous conditions.

 

For more information on this topic, visit:

The National Academy of Sciences

Capen, et al., "Species Differences in Thyroid, Kidney and Urinary Bladder Carcinogenesis, International Agency for Research on Cancer (IARC) Scientific Publications, No. 147 (1999).

McClain, RM, "Mechanistic Considerations for the Relevance of Animal Data on Thyroid Neoplasia to Human Risk Assessment," Mutat Res.333(1-2):131-42 (1995)

Gibbs, J. "Thyroid Neoplasia in Rodents Secondary to Goitrogen Induced Hormone Imbalance Are Not Relevant to Predicting Human Risk of Thyroid Neoplasia."


1National Academy of Sciences report, "Health Implications of Perchlorate Ingestion," January 2005.

2"Three Scientific Peer Reviews of OEHHA's December 2002 Draft Public Health Goal Document on Perchlorate in California Drinking Water, "Peer Review #3," by Jerome M. Hershman, MD, January, 2004.

3OEHHA document, "Frequently Asked Questions About Perchlorate," March 2004.

4 (March 1998).

5The highest dose group received 30 milligrams per kilogram of perchlorate per day. For a 250-gram adult rat, this would be 7.5 milligrams per day. For a 70 kilogram human, this would be 2,100 milligrams per day. This translates to a drinking water concentration of 1,050,000 parts per billion.

6 (March 1998).