Research & Studies

Research & Studies

Learn more about the science of perchlorate via:

• Scientific Reviews
• Perchlorate Reference Dose Findings
• Studies on the effects of perchlorate on:
  • Humans
  • Infants, Pregnant Women and Fetuses
  • Rats
  • Other

Scientific Reviews

• Epidemiology of Environmental Perchlorate Exposure and Thyroid Function: A Comprehensive Review (Tarone, et al, June 2010)
  This review examined all studies investigating possible adverse effects of perchlorate exposure in adults, pregnant women and newborns and concluded that there is no credible or consistent evidence that environmental exposure to perchlorate has any adverse effect on thyroid function.
• 2011 Perchlorate, the Safe Drinking Water Act and Public Health
  A comprehensive analysis of where U.S. EPA's science is either incomplete or out of date in its determination to set a regulatory standard for perchlorate.
• 2011 State of the Perchlorate Science
  This review, prepared by Intertox at the request of the Perchlorate Study Group, examines all the studies on perchlorate since the 2005 NAS report and finds that none of the foundational science on perchlorate has changed: low levels do not pose a public health concern.
• 2010 U.S. Environmental Protection Agency (EPA) Report, "Scientific Analysis of Perchlorate"
  The U.S. EPA's Office of the Inspector General concluded that  EPA’s perchlorate reference dose (RfD) is conservative and protective of human health, and further reducing the perchlorate exposure below the RfD does not effectively lower risk.
• 2005 NAS Report "Health Implications of perchlorate Ingestion"
  This report concluded, among other findings, that levels of perchlorate below the equivalent of 245 parts per billion in water do not have a measureable effect on human health.

Human Studies
Data from human studies shows that exposure to low levels of perchlorate (below 250 ppb) has no adverse effects on adults, children or newborns.

• Steinmaus et. al (2010)
  The Steinmaus study uses data collected within thin the first 24 hours of birth in an attempt to show that in some cases of perchlorate exposure some infants had greater odds of increased levels of Thyroid Stimulating hormone or TSH. While this in itself is actually harmless, it is also a well documented scientific fact that the first 24 hours after birth is a period of natural “TSH surge.” This makes the Steinmaus conclusions highly suspect. See Tarone et. al 2010 and the American Academy of Pediatrics (2006).
• Tarone et. al (2010)
  In their review, Tarone et al. (2010) state:“…analyses of TSH in the first day after birth, even if tightly controlled statistically for hours since birth, would be of questionable validity for making inferences about adverse effects of perchlorate or any other potential goitrogen on thyroid function. Results of analyses of TSH values during the first 24 hours after birth cannot be interpreted as evidence of thyroid disease, and thus there is no biologic rationale or scientific justification for evaluating these very early TSH measurements in studies of potential harm from perchlorate exposure.” These conclusions cast further doubt on the conclusions of Steinmaus et al 2010.
• Blount et al. (2006)
  Based on NHANES 2001-2002 data, Blount et al. reported that in women (but not men) with spot urinary iodine measures less than 100 ?g/l, perchlorate exposure was a negative predictor of total T4 and a positive predictor of serum TSH. However, exposures to perchlorate were not associated with serum total T4 or serum TSH levels outside of normal ranges. The mean urine concentration of perchlorate was 2.84 ppb and the range was 2.54-3.18 ppb.
• Steinmaus et al. (2007)
  Based on the same data set as Blount et al., NHANES 2001-2002, and the same results were reported. This manuscript also evaluated the influence of thiocyanate (an iodide inhibitor, obtained from cigarette smoking in this case) which strengthened the predictive power reported in Blount et al. (2006). The mean urine concentration of perchlorate was 2.52 ± 0.55 ppb for current smokers and 3.15 ± .88 ppb for nonsmokers.
• Braverman, et al. (2006)
  This group studied the effects of prolonged exposure - six months - to perchlorate at different levels (250 ppb and 1500 ppb) on 13 healthy volunteers. The study found that even at the highest dose, perchlorate had no effect on thyroid function, again supporting the NAS conclusions.
• Kelsh et al. study
  This study evaluated whether newborns had higher rates of primary congenital hypothyroidism (PCH) or elevated concentrations of thyroid-stimulating hormone 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.
• Lamm and Doemland study
  The actual number of cases of congenital hypothyroidism was compared to the expected number in seven counties in Nevada and California where perchlorate is present in water at levels of 4-16 ppb. The study determined that perchlorate in drinking water at these low levels has no measurable effect on thyroid development of newborns.
• Li et al. (2000b)
  This study, similar to the one above, examined the thyroid function of more than 540 newborns in Las Vegas and Reno. Scientists looked for changes in thyroid stimulating hormone (TSH) as evidence that the Las Vegas newborns were compensating for decreased levels of thyroid hormones. There was no difference in TSH levels in newborns in the two cities.
• Li et al. (2001)
  The study compared the prevalence of thyroid disease in Medicaid-eligible residents of Clark County, Nevada, which has perchlorate in drinking water up to 24 ppb, to Medicaid-eligible residents in other Nevada counties where perchlorate is not present in drinking water. It found no evidence of a higher rate of any thyroid disease in Clark County.
• Greer study
  Healthy adult volunteers, including both men and women, consumed perchlorate in drinking water at various dose levels for 14 days. At the low dose, equivalent to 180-220 ppb, there was no detectable inhibition of iodide uptake by the thyroid. (The thyroid uses iodine to produce hormones essential to growth and metabolism.) There was no adverse change in thyroid hormone levels associated with any dose level.
• Braverman study
  Healthy male volunteers consumed perchlorate equivalent to either 1,500 or 5,000 ppb in drinking water for 14 days. There was approximately 10% and 38% inhibition of iodide uptake at the lower and upper levels, respectively. No adverse changes in thyroid hormone levels were observed at either level.
• Gibbs et al.
  These studies examined employees who worked with perchlorate and were exposed to it in the air for several years. Breathing perchlorate is the same as drinking perchlorate in terms of its health effects. Workers in the highest exposure category absorbed doses of perchlorate equal to drinking two liters of water per day containing an average of 17,000 ppb of perchlorate. No differences in blood chemistry or thyroid hormones were found in the workers, nor was evidence of thyroid abnormalities observed in any group. The Lamm data showed that the lowest dose of perchlorate that could possibly cause an adverse effect to thyroid hormone levels, if ingested regularly for years, was 20,000 ppb.

Perchlorate Reference Dose
Studies show that the perchlorate Reference Dose recommended by the National Academy of Sciences is conservative and health protective, and that exposure to perchlorate is unlikely to be above this level.

• Mendez et al. (2009)
  This is another PBPK model, but it uses data from a range of human and animal studies to set the model’s parameters. The modeling predicts that for women of reproductive age, the 95th percentile (meaning that most of the population will have lower exposures) of the population’s perchlorate dose from food and water is 0.15 ?g/kg-d which is 21% of the RfD set by EPA.
• Blount et al. (2007)
  Based on the NHANES 2001-2002 data set, Blount et al. estimate that the mean dose of perchlorate based on urinary output was 0.066 ?g/kg-d and the 95th percentile was0.234 ?g/kg-d. These values are 9% and 33%, respectively, below the RfD of 0.7 ?g /kg-d. This manuscript also reports that all samples analyzed for perchlorate detected low levels of perchlorate.
• Murray et al. (2008)
  Testing different types of food from around the US, this study reports the amount of iodine and perchlorate in these foods. This report lists the amounts of perchlorate and iodine in these foods. From this data, and estimating what might be consumed, the authors develop a model. The paper reports that the greatest dietary exposure (highest upper bound) to perchlorate was in children age 2 (0.39 ?g /kg-day). This dose was 56% of the U.S. EPA RfD of 0.7 ?g /kg-day.

Infants, Pregnant Women and Fetuses
Studies show no adverse effects to infants, pregnant women or fetuses.

• Pearce et al (2010 - 2011)
  This study examined hundreds of pregnant women from Los Angeles, CA and Cordoba, Argentina and came to the same conclusion as Pearce (2010): 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.
• Pearce et al (2010)
  This study showed low level perchlorate exposure does not affect thyroid function in pregnant women based on an examination of thousands of women in Cardiff, Wales and Turin, Italy.
• Pearce et al. (2007)
  In a study of women in the northeast US, this paper reports that neither breast milk nor urinary perchlorate levels were statistically correlated to the amount of iodine in these fluids. Iodine is needed by the thyroid gland to make thyroid hormones. The median breast milk perchlorate concentration was 9.1 ppb and the range was 1.3-411 ppb.
• Dasgupta et al. 2008
  Using measures of perchlorate, thiocyanate, and iodine in breast milk and urine, the researchers estimated the doses of each to newborn breastfed infants using a mathematical calculation based on average infant body weights and intake levels (not actual values). The median breast milk perchlorate concentration was 7.3 ppb and the range was 0.01-48 ppb. The manuscript reports that 9 of the 13 infants in the study may have ingested perchlorate at greater than the RfD.
• Leung et al. (2008)
  In a study of women in the northeast US, no association was found between the amount of iodine, perchlorate, and cotinine (biomarker of tobacco smoke exposure) in colostrum (the first breast milk following birth) or urine. The median colostrum perchlorate concentration was 2.5 ppb and the range was <0.05-188.9 ppb.
• Schier et al. (2009)
  This study reports that perchlorate was detected in powdered infant formula (PIF). Iodine was also measured. They estimated mean and maximum doses from formula in 1 or 6 month old infants. They state “Infants consuming certain bovine milk-based PIFs with lactose may be at risk for exceeding the RfD…” but that “…clinical relevance of exceeding the perchlorate RfD in both an iodide-sufficient and iodide-deficient state are unclear.” The median bovine milk PIF perchlorate concentration was 1.37 ppb and the range was 0.68-5.05 ppb.
• Blount et al. (2009)
  In a study of newborn infants, there was no association between cord blood levels of perchlorate, nitrate, and thiocyanate and body weight, length, and head circumference. No doses were measured or estimated.
• Amitai et al. (2007)
  conducted in Israel - looked at the effect among newborns whose mothers lived in areas where perchlorate levels in drinking water were as low as 3 parts per billion (ppb) and as high as 340 parts per billion. The study found no differences in key hormone levels among any of the newborns, providing evidence that the NAS reference dose is conservative and health protective to the most sensitive individuals in the population.
• Tellez et al. (2005)
  This study 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-detect to 110 parts per billion (ppb), and daily intake of dietary iodide is equivalent with the U.S.
• Crump study
  This study of newborns and school-age children in three cities in northern Chile, where perchlorate occurs naturally in drinking water in varying concentrations up to 110 ppb, showed no adverse health effects even at the highest levels.
• Li et al. (2000a)
  This study, similar to the one above, examined the thyroid function of more than 540 newborns in Las Vegas and Reno. Scientists looked for changes in thyroid stimulating hormone (TSH) as evidence that the Las Vegas newborns were compensating for decreased levels of thyroid hormones. There was no difference in TSH levels in newborns in the two cities.
• Neonatal Thyroid Stimulating Hormone Level and Perchlorate in Drinking Water [link to document]
  The effect of perchlorate in drinking water on neonatal blood thyroid-stimulating hormone (thyrotopin; TSH0 levels was examined for Las Vegas and Reno, Nevada. This study of neonatal TSH levels in the first month of life found no effect from living in the areas with environmental perchlorate exposures of =15 µg/L (P= 0.97).

Rat Studies
Even in rats, which are much more sensitive than humans to perchlorate, it takes extremely high doses of perchlorate (above 14,000 ppb) – well beyond what would be found in nature or drinking water - to generate an adverse health effect.

• York et al. (2001)
  This study looked at whether perchlorate causes birth defects in rats. No adverse effects were found in either rat mothers or fetuses at doses of perchlorate equivalent to 1,050,000 ppb in water. The study confirms perchlorate is not a reproductive toxicant.
• Dasgupta et al.
  This study looked at how atmospheric processes can cause naturally occurring perchlorate.
• Dohán et al. (2007)
  This study uses Mardin-Darby canine kidney (MDCK) cells transfected with the human sodium iodide symporter, the “pump” the thyroid cell uses to uptake iodide into the cell to show that perchlorate is transported into the cell and does not simply block the uptake of iodide. As a follow up in rats, using high acute doses of sodium perchlorate (2 mg delivered directly into the abdomen followed by 245 ppb in drinking water vs. EPA RfD-equivalent water concentration of 24.5 ppb), perchlorate blocked iodide transport into the thyroid gland.
• McLanahan et al. (2009)
  This is another study that uses a model (PBPK) to predict possible effects from low doses of perchlorate. This model uses information from animal and human studies. At exposures of 10 mg/kg (350,000 ppb, based on a 70 kg adult drinking 2 L of water per day), their model failed to predict changes seen in rat exposure studies. They suggest that the inability of their model to predict in vivo response is due to an additional and unknown mechanism of action.

Other Studies

• American Academy of Pediatrics (2006)
  This report indicates that “…specimens collected in the first 24 to 48 hours of life may lead to false-positive TSH elevations…" As such, this information calls into question findings reported by Steinmaus et. al in December 2010.
• Lorber (2008)
  Lorber constructs a simple two compartment model (called a physiologically based pharmacokinetic model; PBPK) to predict perchlorate in blood and urine from exposure to perchlorate. Using the model, the paper estimates the doses of perchlorate needed to attain the urinary concentrations reported by NHANES 2001-2002 (see Blount et al., 2006) data at 0.064 ?g/kg-d.
• New GAO Report on Perchlorate Occurrence and Regulatory Actions Taken
  This report by the U.S. Government Accountability Office provides further evidence that perchlorate does not present a widespread public health concern requiring national regulation, and that where perchlorate may be of concern, steps have already been taken to ensure public health is protected.