CDC′s Perchlorate Biomonitoring Activities and Study Results

Committee on Energy and Commerce Subcommittee on Environment and Hazardous Materials, United States House of Representatives

Wednesday, April 25, 2007

Statement of:
James Pirkle, M.D., Ph.D.
Deputy Director for Science
National Center for Environment Health
Centers for Disease Control and Prevention
U.S. Department of Health and Human Services

Good morning Mr. Chairman and Members of the Subcommittee:

My name is Dr. James Pirkle, Deputy Director for Science in the Division of Laboratory Sciences of the National Center for Environmental Health at the Centers for Disease Control and Prevention (CDC).

I am pleased to appear here today before the Subcommittee to discuss results of two studies conducted by CDC researchers investigating exposure to perchlorate in the U.S. population and the relationship between exposure to perchlorate and thyroid hormone levels.

In my presentation, I will first provide a brief background on CDC′s National Biomonitoring Program and efforts to measure perchlorate, then discuss results of our study examining perchlorate exposure in the U.S. population, and finally, discuss findings from our study that focused on the relationship between exposure to perchlorate and hormone levels.

Briefly, perchlorate is a chemical compound used in solid rocket propellant, explosives, pyrotechnics, flares, and a few other products. It also can form naturally in the atmosphere, producing trace levels in precipitation. Perchlorate in irrigation water can contaminate crops. High doses of perchlorate are known to reduce the amount of thyroid hormone produced; in the past, perchlorate was one medical treatment used to reduce the excessive amount of thyroid hormone produced in people with hyperthyroidism. Therapeutic doses of perchlorate used in the 1950s and 1960s to treat hyperthyroidism were much higher than levels that people are exposed to in the environment.

The Division of Laboratory Sciences at CDC′s National Center for Environmental Health conducts the National Biomonitoring Program, which measures environmental chemicals, such as perchlorate, in blood and/or urine to assess the exposure of the U.S. population and exposure of selected population groups. Our laboratory has been conducting work in biomonitoring for 32 years and currently can measure more than 400 chemicals in human blood or urine. Biomonitoring measurements are reported in the scientific literature and, since 2001, in CDC′s National Report on Human Exposure to Environmental Chemicals. As part of this National Biomonitoring Program, CDC researchers developed a method to measure perchlorate in urine and published that method in the peer–reviewed literature in 2005. This method has an excellent ability to measure perchlorate even at low levels and to distinguish perchlorate from other chemicals.

Using this new method, our laboratory measured perchlorate in the urine of participants in CDC′s National Health and Nutrition Examination Survey (NHANES) for the years 2001–2002. The NHANES survey is designed to provide a unique assessment of the health and nutritional status of the civilian non–institutionalized U.S. population. The survey has been conducted multiple times since the early 1970s. For the survey years 2001–2002, NHANES also measured serum levels of two thyroid hormones in survey participants. These hormones are total thyroxine, also called total T4, and thyroid stimulating hormone, commonly referred to as TSH. In the future, NHANES will evaluate additional measures of thyroid function.

From their analysis of the results, CDC researchers published two papers, the first describing levels of urinary perchlorate in people aged 6 years and older, and the second examining the relationship between levels of urinary perchlorate and thyroid hormone levels in people aged 12 years and older.

In the first paper, which described perchlorate exposure in people aged 6 years and older in the U.S. population, the researchers found measurable levels of perchlorate in the urine of all 2820 survey participants, indicating widespread human exposure to this chemical in the United States. The researchers also found that levels of perchlorate in children were higher than levels found in adolescents and adults, and this difference was statistically significant.

The researchers compared the levels found in the population with the Environmental Protection Agency (EPA) reference dose. The EPA reference dose is defined as an estimate of a daily exposure to the human population that is likely to be without an appreciable risk of deleterious effects during a lifetime. The EPA reference dose for perchlorate is 0.7 micrograms per kilogram of body weight per day. The National Academy of Sciences recommended this reference dose in 2005. For adults, equations to estimate dose from urine perchlorate concentrations are available. We calculated dose estimates for each adult in the 2001–2002 survey on the basis of each person′s urine perchlorate level and found that only 11 adults (out of 1532 people) had levels exceeding this reference dose (RfD). The median estimated total daily perchlorate dose for adults was about one–tenth of the RfD, and the 95th percentile was about one–third of the RfD.

The second study examined the relationship between urine perchlorate levels and thyroid hormone levels – specifically total thyroxine and TSH. Thyroxine and TSH measurements were available for people aged 12 years and older. Thyroxine regulates the body′s metabolism and is important for proper development of the brain. TSH is secreted by the pituitary gland and regulates the production of thyroxine by the thyroid gland. When the thyroid is not producing adequate amounts of thyroxine, TSH levels increase in order to stimulate more production. At high doses, perchlorate is known to block iodine uptake into the thyroid, causing decreased production of thyroxine and increased production of TSH. This second study examined perchlorate levels of the U.S. population, levels that are much lower than those previously known to decrease thyroxine and increase TSH.

Among men, the researchers found no relationship between perchlorate levels and levels of the thyroid hormones thyroxine and TSH. After the initial analyses of the results obtained for women, the researchers divided women for further analysis into two groups: those with urinary iodine levels above and below a cut–off of 100 micrograms per liter. This cut–off is based on a World Health Organization finding that the frequency of goiter from hypothyroidism increases in populations that have a median urinary iodine level of less than 100 micrograms per liter. It is reasonable to hypothesize that people with lower urinary iodine levels could be more vulnerable to a perchlorate effect on thyroid function.

The researchers found that, among women who had urinary iodine levels that were less than 100 micrograms per liter, perchlorate levels were associated with both thyroxine and TSH levels. For both thyroxine and TSH, these associations were statistically significant and consistent in direction with those expected from perchlorate inhibition of iodine uptake into the thyroid. That is, higher perchlorate levels were associated with lower levels of thyroxine and higher levels of TSH. However, thyroid hormone levels remained within clinically normal ranges. Thirty–six percent of women in the U.S. population have urinary iodine levels less than 100 micrograms per liter, a percentage that corresponds to about 43 million women.

Among women with urinary iodine levels greater than or equal to 100 micrograms per liter, the researchers found that perchlorate levels showed a statistically significant association with TSH but not with thyroxine. Change in TSH levels is a more sensitive indicator of decreased thyroid function, which may account for this finding in this group of women.

This was the first study to examine the association of perchlorate with thyroid hormone levels in women who had levels of urinary iodine that were less than 100 micrograms per liter. The differences we saw in study findings between men and women merit further research. Other research has shown that women have higher rates of hypothyroidism than men.

The finding of an association between perchlorate exposure and thyroid function in these women was unexpected based on previous research and has prompted further study. CDC researchers are planning a second study to affirm their findings and evaluate additional measures of thyroid function.

Adequate intake of iodine has previously been recognized as important for healthy thyroid function. Our study results would reinforce that recommendation for women.

In summary, these two studies show that low perchlorate exposure is widespread in the U.S. population but generally is below the EPA RfD in our study population of women aged 20 years and older. Among men, perchlorate levels were not associated with hormone levels. Among women with lower levels of iodine in their urine, perchlorate exposure that is common in the U.S. population was associated with small– to–medium–size changes in thyroid hormone levels. Adequate intake of iodine substantially diminishes the association of perchlorate exposure with thyroid hormone levels in women.

Copies of both studies have been provided to the Committee. The publication “Urinary Perchlorate and Thyroid Hormone Levels in Adolescents and Adult Men and Women Living in the United States” is available on line at: http://www.ehponline.org/members/2006/9466/9466.pdf

Mr. Chairman, this concludes my prepared statement. Thank you for giving me the opportunity to speak before the Subcommittee. I would be happy to respond to any questions that you or other Members of the Subcommittee may have.