Biomonitoring Summary

Perchlorate

CAS No. 7601-90-3

General Information

Perchlorate is an inorganic chemical containing one chlorine and four oxygen atoms. It is normally found and produced as the anion of a sodium, potassium, or ammonium salt. Perchlorate is stable under most environmental and physiological conditions, but has strong oxidant properties in the presence of concentrated acids, certain catalytic metals, and reducing agents. The ammonium salt of the perchlorate ion has been manufactured in the military defense and aerospace industries primarily for use as an oxidizer in solid propellant systems for rockets and missiles. Other manufactured uses include fireworks, matches, and limited applications in pharmaceutics, laboratory analysis, leather tanning, fabric dyeing, and electroplating. In addition, small amounts of perchlorate can form naturally in the atmosphere (Dasgupta et al., 2006) and accumulate in nitrate-rich mineral deposits mined for use in fertilizers (Urbansky, 2002).

Perchlorate was added to the EPA's Contaminant Candidate List (CCL) for drinking water in 1998 following discoveries of its presence in drinking water supplies throughout the southwestern United States (U.S.EPA, 1998). Perchlorate has been characterized as a mobile and persistent ground and surface water contaminant. Drinking water, milk, and certain plants with high water content (e.g., lettuce) can be the main sources of intake for humans (FDA, 2007). Perchlorate is excreted unchanged from the human body with an estimated elimination half-life of about 7.5 hours and has a small estimated volume of distribution (Crump and Gibbs, 2005).

Animal and human studies have shown that perchlorate can inhibit thyroid hormone production (NAS, 2005). Large doses of perchlorate have been used as a medicine to treat hyperthyroidism and to diagnose disorders related to thyroid or iodine metabolism. Inhibition of iodine uptake by competition for the sodium/iodide symporter in the thyroid can be estimated in humans by measuring radioiodine uptake inhibition (RUI). Short term human studies of the effect of perchlorate on RUI have been used for risk estimation (Greer et al., 2002; Lawrence et al. 2001, 2002; NAS, 2005; U.S.EPA, 2005). In these small short-term experimental studies on males and studies of male perchlorate workers with doses or estimated exposures thousands-fold higher than known environmental exposures, up to 68% RUI has been demonstrated, but without effects on serum levels of thyroid stimulating hormone or thyroxine (Braverman et al., 2005; Greer et al., 2002). However, in a representative sample of U.S. women with urinary levels of iodine less than 100 micrograms per day, urinary perchlorate at environmental exposure levels were inversely associated with thyroxine levels and positively associated with levels of thyroid stimulating hormone (Blount et al., 2006; Steinmaus et al., 2007).

During gestation and infancy, it is known that maternal and congenital hypothyroidism adversely effects neurological development and decreases learning capability. In the U.S., congenital hypothyroidism is a condition for which nearly all newborn blood is screened. Ecologic studies from screening programs with elevated perchlorate in the regional drinking water have indicated no increased prevalence of abnormal neonatal screening tests for this disorder in these regions (Kelsh et al., 2003; Lamm and Doemland, 1999; Li et al., 2000). Also, altered thyroid function was not found in Chilean pregnant women or their newborns with mean urinary perchlorate levels about 40-fold higher than average U.S. levels, although iodine intake was higher than U.S. levels and sufficient in most participants (Tellez et al, 2005). Many factors may be important in consideration of perchlorate action on the thyroid: dose; dietary iodine intake; gender; age; menopausal status; chronicity of exposure; and the presence of other substances known to affect thyroid function (e.g., nitrate, thiocyanate, medications).

Though it produces follicular cell thyroid tumors in animal studies at goitrogenic doses, perchlorate is negative in most genotoxic assays (U.S.EPA, 2005), suggesting its tumorgenic effect is a result of a chronic increase in thyroid stimulating hormone indirectly resulting from iodine uptake inhibition. Follicular cell thyroid tumors would be unlikely to occur without overt perturbation of thyroid homeostasis. Additional information about exposure and health effects is available from the U.S.EPA at https://www.epa.gov/safewater/ccl/perchlorate/perchlorate.html and from ATSDR at https://www.atsdr.cdc.gov/toxprofiles/index.asp.

Biomonitoring Information

Urinary perchlorate levels reflect recent exposure. Blount et al. (2007) analyzed a subsample of NHANES 2001-2002 which demonstrated detectable perchlorate in all urinary samples and showed slightly higher levels in children as compared to adults. When these NHANES 2001-2002 urinary levels of perchlorate are used to calculate daily oral intakes for the U.S. population, most of the population is considered to be below the U.S. EPA reference dose (Blount et al., 2007). The levels in NHANES 2003-2004, 2005-2006, and 2007-2008 show a similar pattern to NHANES 2001-2002 (CDC, 2012). Compared to a previous study of pregnant women in three Chilean communities with varying perchlorate levels in the drinking water, the women in the community with the highest drinking water levels had mean urinary perchlorate levels about 40 times greater than the geometric mean for participants aged 20 years and older in NHANES 2001-2010 (Tellez et al., 2005). Also, the 95th percentile of the participants aged 20 years and older in NHANES 2001-2010 have urinary perchlorate levels that are several thousand times less than urinary levels measured during occupational exposure of perchlorate workers (Braverman et al., 2005; CDC, 2012).

Finding a measurable amount of perchlorate in urine does not imply that the level of perchlorate causes an adverse health effect. Biomonitoring studies of urinary perchlorate provide physicians and public health officials with reference values so that they can determine whether or not people have been exposed to higher levels of perchlorate than levels found in the general population. Biomonitoring data can also help scientists plan and conduct research on exposure and health effects.

References

Blount BC, Pirkle JL, Osterloh JD, Valentin-Blasini L, Caldwell KL. Urinary perchlorate and thyroid hormone levels in adolescent and adult men and women living in the United States. Environ Health Perspect 2006;114(12):1865-71.

Blount BC, Valentin-Blasini L, Osterloh JD, Mauldin JP, Pirkle JL. Perchlorate Exposure of the US Population, 2001-2002. J Expo Sci Environ Epidemiol 2007;17(4):400-7.

Braverman LE, He X, Pino S, Cross M, Magnani B, Lamm SH, et al. The effect of perchlorate, thiocyanate, and nitrate on thyroid function in workers exposed to perchlorate long-term. J Clin Endocrinol Metab 2005;90(2):700-6.

Centers for Disease Control and Prevention (CDC). Fourth National Report on Human Exposure to Environmental Chemicals. Updated Tables. September 2012. [online] Available at URL: https://www.cdc.gov/exposurereport/. 12/28/12

Crump KS, Gibbs JP. Benchmark calculations for perchlorate from three human cohorts. Environ Health Perspect 2005;113(8):1001-8.

Dasgupta PK, Dyke JV, Kirk AB, Jackson WA. Perchlorate in the United States. Analysis of relative source contributions to the food chain. Environ Sci Technol 2006;40(21):6608-14.

Food and Drug Administration (FDA). CFSAN/Office of Plant & Dairy Foods. Preliminary Estimation of Perchlorate Dietary Exposure Based on FDA 2004/2005 Exploratory Data. May 2007. Available at URL: https://www.fda.gov/Food/FoodSafety/FoodContaminantsAdulteration/ChemicalContaminants/Perchlorate/ucm077653.htm. Page Last Updated: 06/18/2009. 1/10/13

Greer MA, Goodman G, Pleus RC, Greer SE. Health effects assessment for environmental perchlorate contamination: the dose response for inhibition of thyroidal radioiodine uptake in humans. Environ Health Perspect 2002;110(9):927-937. Erratum in: Environ Health Perspect 2005;113(11):A732.

Kelsh MA, Buffler PA, Daaboul JJ, Rutherford GW, Lau EC, Barnard JC, et al. Primary congenital hypothyroidism, newborn thyroid function, and environmental perchlorate exposure among residents of a Southern California community. J Occup Environ Med 2003;45(10):1116-1127. Erratum in: J Occup Environ Med 2004;46(5):509.

Lamm SH, Doemland M. Has perchlorate in drinking water increased the rate of congenital hypothyroidism? J Occup Environ Med 1999;41(5):409-11.

Lawrence J, Lamm S, Braverman LE. Low dose perchlorate (3 mg daily) and thyroid function. Thyroid 2001;11(3):295.

Lawrence JE, Lamm SH, Pino S, Richman K, Braverman LE. The effect of short-term low-dose perchlorate on various aspects of thyroid function. Thyroid 2000;10(8):659-63.

Li Z, Li FX, Byrd D, Deyhle GM, Sesser DE, Skeels MR, et al. Neonatal thyroxine level and perchlorate in drinking water. J Occup Environ Med 2000;42(2):200-5.

National Academy of Sciences (NAS). Health Implications of Perchlorate Ingestion. National Research Council of the National Academies. Washington (DC): National Academy Press; 2005. Available at URL: http://www.nap.edu/catalog.php?record_id=11202. 1/10/13

Steinmaus C, Miller MD, Howd R. Impact of smoking and thiocyanate on perchlorate and thyroid hormone associations in the 2001-2002 national health and nutrition examination survey. Environ Health Perspect 2007;115(9):1333-8.

Tellez RT, Chacon PM, Abarca CR, Blount BC, Landingham CB, Crump KS, et al. Long-term environmental exposure to perchlorate through drinking water and thyroid function during pregnancy and the neonatal period. Thyroid 2005;15(9):963-75.

U.S. Environmental Protection Agency (U.S. EPA). Perchlorate. Integrated Risk Information System (IRIS). Revised 2/18/05. Available from URL: https://cfpub.epa.gov/ncea/iris/index.cfm?fuseaction=iris.showQuickView&substance;_nmbr=1007.1/10/13

U.S. Environmental Protection Agency (U.S. EPA). Drinking Water Contaminant Candidate List. Doc. No. EPA/600/F-98/002 Washington (DC). 1988.

Urbansky TF. Perchlorate as an environmental contaminant. Environ Sci Pollut Res Int 2002;9(3):187-92.