Perchlorate Exposure Research Articles

Thyroid hormones and thyroid disease in relation to perchlorate dose and residence near a superfund site

Perchlorate is a widely occurring contaminant, which can competitively inhibit iodide uptake and thus thyroid hormone production. The health effects of chronic low dose perchlorate exposure are largely unknown. In a community-based study, we compared thyroid function and disease in women with differing likelihoods of prior and current perchlorate exposure. Residential blocks were randomly selected from areas: (1) with potential perchlorate exposure via drinking water; (2) with potential exposure to environmental contaminants; and (3) neighboring but without such exposures. Eligibility included having lived in the area for ≥6 months and aged 20-50 years during 1988-1996 (during documented drinking water well contamination). We interviewed 814 women and collected blood samples (assayed for thyroid stimulating hormone and free thyroxine) from 431 interviewed women. Daily urine samples were assayed for perchlorate and iodide for 178 premenopausal women with blood samples. We performed multivariable regression analyses comparing thyroid function and disease by residential area and by urinary perchlorate dose adjusted for urinary iodide levels. Residential location and current perchlorate dose were not associated with thyroid function or disease. No persistent effect of perchlorate on thyroid function or disease was found several years after contaminated wells were capped.

Perchlorate and thiocyanate exposure and thyroid function in first‐trimester pregnant women from Greece

Thyroid hormone, requiring adequate maternal iodine intake, is critical for neurodevelopment in utero. Perchlorate and, less so, thiocyanate decrease uptake of iodine into the thyroid gland by competitively inhibiting the sodium/iodide symporter (NIS). It remains unclear whether environmental perchlorate exposure adversely affects thyroid function in first-trimester pregnant women. Cross-sectional. 134 pregnant women from Athens, Greece, at mean±SD 10·9±2·3weeks' gestation. Urinary iodide, perchlorate, and thiocyanate and thyroid function tests were measured. The median urinary iodide was 120μg/l. Urinary perchlorate levels were detectable in all women: median (range) 4·1 (0·2-118·5)μg/l. Serum thyroperoxidase antibodies (TPO Ab) were detectable in 16% of women. Using Spearman's rank correlation analyses, there was no correlation between urinary perchlorate concentrations and serum TSH, although inverse correlations were seen between urine perchlorate and free T3 and free T4 values. In univariate analyses, urine thiocyanate was positively correlated with serum TSH, but was not associated with serum free T3 or free T4. Urine perchlorate was positively correlated with gestational age. In multivariate analyses adjusting for urinary iodide concentrations, urine thiocyanate, gestational age, maternal age and TPO Ab titres, urine perchlorate was not a significant predictor of thyroid function. Low-level perchlorate and thiocyanate exposure is ubiquitous, but, in adjusted analyses, is not associated with alterations in thyroid function tests among mildly iodine-deficient Greek women in the first trimester of pregnancy.

Comparative effects of in ovo exposure to sodium perchlorate on development, growth, metabolism, and thyroid function in the common snapping turtle (Chelydra serpentina) and red-eared slider (Trachemys scripta elegans)

Perchlorate is a surface and groundwater contaminant found in areas associated with munitions and rocket manufacturing and use. It is a thyroid-inhibiting compound, preventing uptake of iodide by the thyroid gland, ultimately reducing thyroid hormone production. As thyroid hormones influence metabolism, growth, and development, perchlorate exposure during the embryonic period may impact embryonic traits that ultimately influence hatchling performance. We topically exposed eggs of red-eared sliders (Trachemys scripta) and snapping turtles (Chelydra serpentina) to 200 and 177μg/g of perchlorate (as NaClO4), respectively, to determine impacts on glandular thyroxine concentrations, embryonic growth and development, and metabolic rates of hatchlings for a period of 2months post-hatching. In red-eared sliders, in ovo perchlorate exposure delayed hatching, increased external yolk size at hatching, increased hatchling mortality, and reduced total glandular thyroxine concentrations in hatchlings. In snapping turtles, hatching success and standard metabolic rates were reduced, liver and thyroid sizes were increased, and total glandular thyroxine concentrations in hatchlings were reduced after exposure to perchlorate. While both species were negatively affected by exposure, impacts on red-eared sliders were most severe, suggesting that the slider may be a more sensitive sentinel species for studying effects of perchlorate exposure to turtles.

Biomarkers of perchlorate exposure are correlated with circulating thyroid hormone levels in the 2007–2008 NHANES

Previous epidemiological studies provide conflicting evidence as to whether environmental perchlorate exposure can affect levels of circulating thyroid hormones in the general population. We investigated the statistical relationships between biomarkers of perchlorate exposure and serum thyroid hormone levels in 2007–2008 National Health and Nutrition Evaluation Survey (NHANES) subjects. Generalized additive mixed models (GAMMs) were developed to estimate the relationships between T3 and T4 levels and creatinine-adjusted urinary perchlorate excretion. The models included covariates related to gender, age, ethnicity, income, smoking status, prescription medications, and biomarkers of exposures to other goitrogenic ions and phthalate ester metabolites. Where necessary, relationships between hormone levels and covariates were represented as nonlinear smoothed terms. The effect of the hypothalamic–pituitary–thyroid (HPT) axis on serum hormone levels was taken into account by including a term for thyroid stimulating hormone (TSH) in the models. Regression coefficients for perchlorate were significant and negative in GAMMs predicting total T4 and free T3 levels in males, females, and for the entire cohort when phthalate ester biomarkers and other covariates were included. Coefficients for perchlorate were also significant and negative in regressions predicting free T4 levels in males and in the entire study population. The consistency of these results suggests that HPT axis controls do not completely compensate for small changes in thyroid hormone levels associated with perchlorate and phthalate ester exposures.

Environmental Perchlorate and Thiocyanate Exposures and Infant Serum Thyroid Function

Breastfed infants rely on maternal iodine for thyroid hormone production required for neurodevelopment. Dietary iodine among women of childbearing age in the United States may be insufficient. Perchlorate (competitive inhibitor of the sodium/iodide symporter [NIS]) exposure is ubiquitous. Thiocyanate, from cigarettes and diet, is a weaker NIS inhibitor. Environmental perchlorate and thiocyanate exposures could decrease breast milk iodine by competitively inhibiting NIS in lactating breasts (thus impairing infants' iodine availability), and/or infants' thyroidal NIS to directly decrease infant thyroid function. The current study assessed the relationships between environmental perchlorate and thiocyanate exposures and infant serum thyroid function. Iodine, perchlorate, and thiocyanate in breast milk, maternal and infant urine, and infant serum thyroid function tests were cross-sectionally measured in Boston-area women and their 1-3 month-old breastfed infants. Univariate and multivariable analyses assessed relationships between iodine, perchlorate, thiocyanate, thyroid-stimulating hormone (TSH), and free thyroxine (FT4) levels. In 64 mothers and infants, median (range) iodine levels were 45.6 μg/L (4.3-1080) in breast milk, 101.9 μg/L (27-570) in maternal urine, and 197.5 μg/L (40-785) in infant urine. Median perchlorate concentrations were 4.4 μg/L (0.5-29.5) in breast milk, 3.1 μg/L (0.2-22.4) in maternal urine, and 4.7 μg/L (0.3-25.3) in infant urine. There were no correlations between infant TSH or FT4 and iodine, perchlorate, and thiocyanate levels in breast milk, maternal urine, and infant urine. In multivariable analyses, perchlorate and thiocyanate levels in breast milk, maternal urine, and infant urine were not significant predictors of infant TSH or FT4. Boston-area mothers and their breastfed infants are generally iodine sufficient. Although environmental perchlorate and thiocyanate are ubiquitous, these results do not support the concern that maternal and infant environmental perchlorate and thiocyanate exposures affect infant thyroid function.

Using a physiologically based pharmacokinetic model to link urinary biomarker concentrations to dietary exposure of perchlorate

Exposure to perchlorate is widespread in the United States and many studies have attempted to character the perchlorate exposure by estimating the average daily intakes of perchlorate. These approaches provided population-based estimates, but did not provide individual-level exposure estimates. Until recently, exposure activity database such as CSFII, TDS and NHANES become available and provide opportunities to evaluate the individual-level exposure to chemical using exposure surveillance dataset. In this study, we use perchlorate as an example to investigate the usefulness of urinary biomarker data for predicting exposures at the individual level. Specifically, two analyses were conducted: (1) using data from a controlled human study to examine the ability of a physiologically based pharmacokinetic (PBPK) model to predict perchlorate concentrations in single-spot and cumulative urine samples; and (2) using biomarker data from a population-based study and a PBPK model to demonstrate the challenges in linking urinary biomarker concentrations to intake doses for individuals. Results showed that the modeling approach was able to characterize the distribution of biomarker concentrations at the population level, but predicting the exposure–biomarker relationship for individuals was much more difficult. The type of information needed to reduce the uncertainty in estimating intake doses, for individuals, based on biomarker measurements is discussed.

THE EFFECTS OF HIGH IODINE INTAKE ON PERCHLORATE-RELATED DECREASES IN THYROID HORMONE, NHANES 2001-2

Background: Perchlorate is an oxidizing agent used to manufacture rocket fuel, munitions, and other products, and exposure in the U.S. is ubiquitous. Perchlorate inhibits iodide uptake into the thyroid and can decrease thyroid hormone production. Thyroid hormone is critical for proper neurodevelopment, and even small decreases in thyroid hormone during pregnancy have been linked with significant developmental effects in children. Recent evidence suggests that common environmental perchlorate exposures could decrease thyroid hormones in people with low iodine intake. This has led to the suggestion that all pregnant women should receive iodine supplementation. However, some data suggest that high iodine intake might also cause thyroid suppression. Methods: Data from the 2001-2 National Health and Nutrition Examination Survey on serum thyroid hormones and urine perchlorate and iodine, and linear regression analyses,were used to assess whether previously observed perchlorate-related decreases in thyroid hormone might be greater in people with high iodine intakes. Results: In women with urinary iodine <100 μg/L, a 10-fold increase in urinary perchlorate (about the 10th to the 90th percentile) was associated with an 11.4% decrease in serum thyroid hormone levels (p<0.01; n=383). In women with high urinary iodine (>95th percentile of 600 μg/L)the effect was 3-times greater. That is, a 10-fold increase in urinary perchlorate was associated with a 34.7% decrease in serum thyroid hormone levels (p=0.02; n=53). No clear effect was seen in women with moderate urinary iodine levels (100-600 μg/L). Conclusions: These data provide some indication that high iodine intake might worsen the thyroid effects of perchlorate. Although the sample size was small, the finding in the high iodine group is consistent with other studies in high iodine populations. These findings highlight the need to consider further research on the potential adverse effects of high iodine before new widespread iodine supplementation programs are begun.

Analysis and Exposure Assessment of Perchlorate in Korean Dairy Products with LC-MS/MS

ObjectivesPerchlorate is an emerging contaminant that is found everywhere, including various foods. Perchlorate is known to disturb the production of thyroid hormones and leads to mental disorders in fetuses and infants, as well as metabolic problems in adults. In this study, we attempted to establish an LC-MS/MS method for measuring perchlorate in dairy products and used this developed method to investigate perchlorate levels in Korean milk and yogurt samples.MethodsThe developed method of perchlorate analysis requires a shaker and 1% acetic acid/acetonitrile as the extracting solvent. Briefly, the samples were extracted and then centrifuged (4000 rpm, 1hour), and the supernatant was then passed through a Envi™ Carb SPE cartridge that had been prewashed sequentially with 6 mL of acetonitrile and 6 mL of 1% acetic acid in water. The final volume of the sample extract was adjusted to 40 mL with reagent water and the final sample was filtered through a 0.20-µm pore size PTFE (Polytetrafluoroethylene) syringe filter prior to LC-MS/MS.ResultsThe average levels of perchlorate in milk and yogurt samples were 5.63 ± 3.49 µg/L and 3.65 ± 2.42 µg/L, respectively. The perchlorate levels observed in milk samples in this study were similar to those reported from China, Japan, and the United States.ConclusionsThe exposure of Koreans to perchlorate through the consumption of dairy products was calculated based on the results of this study. For all age groups, the calculated exposure to perchlorate was below the reference of dose (0.7 µg/kg-day) proposed by the National Academy of Science, USA, but the perchlorate exposure of children was higher than that of adults. Therefore, further investigation of perchlorate in other food samples is needed to enable a more exact assessment of exposure of children to perchlorate.

Modulation of Thyroid Hormone Concentrations in Serum of Rats Coadministered with Perchlorate and Iodide-Deficient Diet

Perchlorate can perturb thyroid hormone (TH) homeostasis by competitive inhibition of iodide uptake by the thyroid gland. Until recently, the effects of perchlorate on TH homeostasis were examined by measuring serum concentrations of THs by immunoassay (IA) methods. IA methods are sensitive, but for TH analysis they are compromised by lack of adequate specificity. In this study, we determined the concentrations of six THs: L-thyroxine (T₄), 3,3',5-triiodo-L-thyronine (T₃), 3,3',5'-triiodo-L-thyronine (rT₃), 3,5-diiodo-L-thyronine, 3,3'-diiodo-L-thyronine, and 3-iodo-L-thyronine in the serum of rats administered perchlorate by isotope (¹³C₆-T₄)-dilution liquid chromatography-tandem mass spectrometry. The method recoveries for THs spiked into a serum matrix were between 97.0% and 115%, with a coefficient of variation of 2.1% to 9.4%. Rats were placed on an iodide-deficient or iodide-sufficient diet for 2.5 months, and for the last 2 weeks of that period they were provided drinking water either without or with perchlorate (10 mg/kg body weight/day). No significant differences in serum concentrations of T₃ and T₄ were observed between rats given iodide-deficient and iodide-sufficient diets for 2 or 2.5 months. After 24 h of perchlorate exposure, significantly lower concentrations of T₃ and T₄ were found in the serum of rats administered the iodide-deficient diet but not in rats administered the iodide-sufficient diet. However, after 2 weeks of perchlorate exposure, TH levels in rats fed the iodide-sufficient diet were also significantly lower than those in control rats. Our results suggest that perchlorate affects TH homeostasis and that such effects are more pronounced under iodide-deficient nutrition.

Effect of Environmental Perchlorate on Thyroid Function in Pregnant Women from Córdoba, Argentina, and Los Angeles, California

To determine whether environmental perchlorate exposure adversely affects thyroid function in women in the first trimester of pregnancy. First-trimester pregnant women were recruited from prenatal clinics in the Los Angeles County Hospital, Los Angeles, California, and in the Hospital Universitario de Maternidad dependent Universidad Nacional de Córdoba, Córdoba, Argentina, between 2004 and 2007. Spot urine and blood specimens were obtained during the clinic visit. Urinary perchlorate, iodine, and creatinine were measured, and thyroid function tests were performed. The study included 134 pregnant women from Los Angeles, California (mean gestational age ± SD = 9.1 ± 2.2 weeks), and 107 pregnant women from Córdoba, Argentina (mean gestational age = 10.0 ± 2.0 weeks). Median urinary iodine values were 144 μg/L in California and 130 μg/L in Argentina. Urinary perchlorate levels were detectable in all women (California: median, 7.8 μg/L [range, 0.4-284 μg/L] and Argentina: median, 13.5 μg/L [range, 1.1-676 μg/L]). Serum thyroperoxidase antibodies were detectable in 21 women from California (16%) and in 17 women from Argentina (16%). Using Spearman rank correlation analyses, there was no association between urinary perchlorate concentrations and serum thyrotropin, free thyroxine index, or total triiodothyronine values, including within the subset of women with urinary iodine values less than 100 μg/L. In multivariate analyses using the combined Argentina and California data sets and adjusting for urinary iodine concentrations, urinary creatinine, gestational age, and thyroperoxidase antibody status, urinary perchlorate was not a significant predictor of thyroid function. Low-level perchlorate exposure is ubiquitous, but is not associated with altered thyroid function among women in the first trimester of pregnancy.

Chronic perchlorate exposure causes morphological abnormalities in developing stickleback.

Few studies have examined the effects of chronic perchlorate exposure during growth and development, and fewer still have analyzed the effects of perchlorate over multiple generations. We describe morphological and developmental characteristics for threespine stickleback (Gasterosteus aculeatus) that were spawned and raised to sexual maturity in perchlorate-treated water (G(1,2003)) and for their offspring (G(2,2004)) that were not directly treated with perchlorate. The G(1,2003) displayed a variety of abnormalities, including impaired formation of calcified traits, slower growth rates, aberrant sexual development, poor survivorship, and reduced pigmentation that allowed internal organs to be visible. Yet these conditions were absent when the offspring of contaminated fish (G(2,2004)) were raised in untreated water, suggesting a lack of transgenerational effects and that surviving populations may be able to recover following remediation of perchlorate-contaminated sites.

Perchlorate exposure and dose estimates in infants.

Perchlorate is a naturally occurring inorganic anion used as a component of solid rocket fuel, explosives, and pyrotechnics. Sufficiently high perchlorate intakes can modify thyroid function by competitively inhibiting iodide uptake in adults; however, little is known about perchlorate exposure and health effects in infants. Food intake models predict that infants have higher perchlorate exposure doses than adults. For this reason, we measured perchlorate and related anions (nitrate, thiocyanate, and iodide) in 206 urine samples from 92 infants ages 1-377 days and calculated perchlorate intake dose for this sample of infants. The median estimated exposure dose for this sample of infants was 0.160 μg/kg/day. Of the 205 individual dose estimates, 9% exceeded the reference dose of 0.7 μg/kg/day; 6% of infants providing multiple samples had multiple perchlorate dose estimates above the reference dose. Estimated exposure dose differed by feeding method: breast-fed infants had a higher perchlorate exposure dose (geometric mean 0.220 μg/kg/day) than infants consuming cow milk-based formula (geometric mean 0.103 μg/kg/day, p < 0.0001) or soy-based formula (geometric mean 0.027 μg/kg/day, p < 0.0001), consistent with dose estimates based on dietary intake data. The ability of perchlorate to block adequate iodide uptake by the thyroid may have been reduced by the iodine-sufficient status of the infants studied (median urinary iodide 125 μg/L). Further research is needed to see whether these perchlorate intake doses lead to any health effects.

Direct measurement of perchlorate exposure biomarkers in a highly exposed population: a pilot study.

Exposure to perchlorate is ubiquitous in the United States and has been found to be widespread in food and drinking water. People living in the lower Colorado River region may have perchlorate exposure because of perchlorate in ground water and locally-grown produce. Relatively high doses of perchlorate can inhibit iodine uptake and impair thyroid function, and thus could impair neurological development in utero. We examined human exposures to perchlorate in the Imperial Valley among individuals consuming locally grown produce and compared perchlorate exposure doses to state and federal reference doses. We collected 24-hour urine specimen from a convenience sample of 31 individuals and measured urinary excretion rates of perchlorate, thiocyanate, nitrate, and iodide. In addition, drinking water and local produce were also sampled for perchlorate. All but two of the water samples tested negative for perchlorate. Perchlorate levels in 79 produce samples ranged from non-detect to 1816 ppb. Estimated perchlorate doses ranged from 0.02 to 0.51 µg/kg of body weight/day. Perchlorate dose increased with the number of servings of dairy products consumed and with estimated perchlorate levels in produce consumed. The geometric mean perchlorate dose was 70% higher than for the NHANES reference population. Our sample of 31 Imperial Valley residents had higher perchlorate dose levels compared with national reference ranges. Although none of our exposure estimates exceeded the U. S. EPA reference dose, three participants exceeded the acceptable daily dose as defined by bench mark dose methods used by the California Office of Environmental Health Hazard Assessment.

Exposure Assessment of the Developing Fetus and Newborn Infants: Methods to Measure Perchlorate and Related Anions in Maternal and Fetal Matrices

S-30B9-3 Background/Aims: Perchlorate is a commonly occurring environmental toxicant that may impair iodide transport, and thus compromise development of the fetus and neonate. Therefore, we developed analytical methods for quantifying perchlorate and toxicologically related anions (iodide, nitrate, thiocyanate) in physiological fluids relevant to fetal and neonatal exposure. Methods: We used ion chromatography coupled with electrospray ionization tandem mass spectrometry to accurately and precisely quantify background levels of perchlorate and related anions in urine and serum from pregnant women; amniotic fluid from the fetus; and cord blood, dried blood spots, and diaper press urine from newborns. Additionally, we validated methods for quantifying perchlorate and related anions in breast milk and infant formula so that perchlorate intake could also be calculated. We found that sample collection materials (eg, diapers and blood spot paper) are potential sources of perchlorate contamination. Results: Perchlorate was commonly found in maternal, fetal, and newborn matrices. Maternal urinary perchlorate levels were positively correlated with perchlorate levels in amniotic fluid (r = 0.57). Maternal serum perchlorate was generally higher than cord serum perchlorate (median ratio 2.4:1 for paired samples); conversely, iodide levels were typically higher in fetal fluids compared to maternal fluids. Perchlorate exposure doses were subsequently estimated for 91 infants based on multiple urine samples collected over the first year of life. The median estimated exposure dose was 0.160 μg/kg/d, with 9% of the estimated doses exceeding the US EPA reference dose of 0.7 μg/kg/d, and breast-fed infants having greater perchlorate exposure than formula-fed infants. Conclusion: Maternal urine perchlorate is an effective surrogate measure of fetal perchlorate exposure. Perchlorate does not appear to disproportionately accumulate in the fetal compartment; however, infants likely have higher perchlorate exposure doses than adults (medians of 0.160 and 0.064 μg/kg/d, respectively).

Influence of Water Temperature on Perchlorate-induced Toxicity in Oryzias latipes

PP-29-086 Background/Aims: Thyroid hormones play an essential role in the metabolism, growth, and development in vertebrate. Some synthetic chemicals such as perchlorate have been reported to disrupt thyroid function. Perchlorate interferes with iodine uptake in the thyroid hormone synthesis process. Water temperature can induce stress hormone cortisol, which may influence thyroid function as well. However, the effect of water temperature on perchlorate-induced thyroid toxicity is not well understood. Methods: In this study, Oryzias latipes were exposed to sublethal concentration (100 mg/L) of sodium perchlorate at 3 different water temperature, that is, low (26°C), medium (29°C), and high temperature (33°C) for 7 days, and the effect of water temperature on perchlorate toxicity was observed. Results: Perchlorate exposure decreased transcription of both thyroid hormone receptor alpha and beta mRNAs. Perchlorate exposure at high water temperature induced upregulations of mRNA levels of both NaKATPase alpha and beta, presumably because of increased induction of stress hormone cortisol. Moreover, as water temperature increased, fecundity of fish, eg, number of eggs per pair was decreased. Conclusion: The results of our study suggested that the decrease of reproduction might be partly explained by disruption in thyroid function, which was resulted from inhibition of thyroid hormone synthesis by perchlorate exposure and interference of tissue response to thyroid hormone signal by high water temperature.

Regulation of iodothyronine deiodinases and sodium iodide symporter mRNA expression by perchlorate in larvae and adult Chinese rare minnow (Gobiocypris rarus)

Perchlorate is a widespread contaminant in the aquatic environment. In the present work, the expressions of deiodinase enzymes (d1, d2, and d3) and sodium iodide symporter (nis) genes were determined after larval and adult rare minnow (Gobiocypris rarus) exposed to 5 and 50μg/L perchlorate for 21days. The results showed that deflation of swim bladder development was observed in larvae at 50μg/L perchlorate treatment. An up-regulation of the d2 and nis mRNA levels were observed in the larve and in brain of adults. Meanwhile the expressions of d3 mRNA levels were significantly down-regulated in the liver. These results indicate the changes in d2, nis, and d3 mRNA expression brings about increased outer-ring deiodination, idodine uptake, and a further decrease of inner-ring deiodination, respectively reflecting auto-regulation of hypothalamic-pituitary-thyroid (HPT) axis in adult after perchlorate exposure. The larval fish development could be affected by perchlorate at environmentally relevant concentrations.

Perchlorate in Drinking Water During Pregnancy and Neonatal Thyroid Hormone Levels in California

To evaluate associations between maternal drinking water perchlorate exposure during pregnancy and newborn thyroid hormone levels. Elevation in thyroid stimulating hormone (TSH), which may reflect reduced thyroxin concentration, was assessed in 497,458 newborns in California in 1998. A total of 800 perchlorate water measurements were used to classify California communities as exposed (>5 μg/L) or unexposed. Results were stratified by age at TSH collection because of the normal postbirth TSH surge, and because water sources and perchlorate exposure can change soon after birth. In TSH samples collected within 24 hours of birth, the odds ratio for a TSH greater than 25 μU/mL in exposed communities was 1.53 (P < 0.0001). After 24 hours, the odds ratio for a TSH more than the 95th percentile was 1.27 (P < 0.0001). These findings suggest that perchlorate is associated with increased neonatal TSH levels.

Perchlorate exposure in lactating women in an urban community in New Jersey

Perchlorate is most widely known as a solid oxidant for missile and rocket propulsion systems although it is also present as a trace contaminant in some fertilizers. It has been detected in drinking water, fruits, and vegetables throughout New Jersey and most of the United States. At sufficiently high doses, perchlorate interferes with the uptake of iodine into the thyroid and may interfere with the development of the skeletal system and the central nervous system of infants. Therefore, it is important to quantify perchlorate in breast milk to understand potential perchlorate exposure in infants. In this study we measured perchlorate in breast milk, urine, and drinking water collected from 106 lactating mothers from Central New Jersey. Each subject was asked to provide three sets of samples over a 3-month period. The average ± SD perchlorate level in drinking water, breast milk, and urine was 0.168 ± 0.132 ng/mL (n = 253), 6.80 ± 8.76 ng/mL (n = 276), and 3.19 ± 3.64 ng/mL (3.51 ± 6.79 μg/g creatinine) (n = 273), respectively. Urinary perchlorate levels were lower than reference range values for women of reproductive age (5.16 ± 11.33 μg/g creatinine, p = 0.03), likely because of perchlorate secretion in breast milk. Drinking water perchlorate levels were ≤ 1.05 ng/mL and were not positively correlated with either breast milk or urine perchlorate levels. These findings together suggest that drinking water was not the most important perchlorate exposure source for these women. Creatinine-adjusted urine perchlorate levels were strongly correlated with breast milk perchlorate levels (r = 0.626, p = < 0.0005). Breast milk perchlorate levels in this study are consistent with widespread perchlorate exposure in lactating women and thus infants. This suggests that breast milk may be a source of exposure to perchlorate in infants.

Perchlorate, Nitrate, and Iodide Intake through Tap Water

Perchlorate is ubiquitous in the environment, leading to human exposure and potential impact on thyroid function. Nitrate can also competitively inhibit iodide uptake at the sodium-iodide symporter and thus reduce thyroid hormone production. This study investigates the intake of perchlorate, nitrate, and iodide attributable to direct and indirect tap water consumption. The National Health and Nutrition Examination Survey collected tap water samples and consumption data from 3262 U.S. residents during the years 2005-2006. The median perchlorate, nitrate, and iodide levels measured in tap water were 1.16, 758, and 4.55 μg/L, respectively. Measured perchlorate levels were below the United States Environmental Protection Agency (U.S. EPA) drinking water equivalent level for perchlorate (24.5 μg/L). Significant correlations were found between iodide and nitrate levels (r = 0.17, p < 0.0001) and perchlorate and nitrate levels (r = 0.25, p < 0.0001). On the basis of 24 h recall, 47% of the study participants reported drinking tap water; 89% reported either direct or indirect consumption of tap water. For the adult population (age ≥ 20 yrs) the median tap water consumption rate was 11.6 mL/kg-day. Using individual tap water consumption data and body weight, we estimated the median perchlorate, nitrate, and iodide dose attributable to tap water as 9.11, 11300, and 43.3 ng/kg-day, respectively, for U.S. adults. This perchlorate exposure dose from tap water is relatively small compared to the total perchlorate exposure dose previously characterized for the U.S. adults (median 64 ng/kg-day) and the U.S. EPA reference dose (700 ng/kg-day).

The Impact of Perchlorate Exposure in Early Pregnancy: Is It Safe to Drink the Water?

A large number of environmental agents have been identified that interfere with thyroid function, including those that target thyroid hormone production, metabolism, transport, and action (1,2). Perchlorate (ClO4−) is an inorganic anion that blocks iodine uptake into the thyroid and, at sufficiently high levels and duration of exposure, impairs thyroid hormone production (3). It has been used therapeutically in limited clinical situations, such as for hyperthyroidism associated with amiodarone (typical dose up to 1000 mg/d along with antithyroid drug for 40 d) (3,4). Perchlorate is water soluble and very stable and is found in municipal water supplies, in crops irrigated with perchlorate-containing water, and even in breast milk (3,4). It is used in manufacturing solid rocket fuel, matches, airbag inflation systems, and fireworks. There is also natural formation of perchlorate in the atmosphere that accumulates in groundwater and soil, and it has been detected around the world (3,4). The principal areas of concern over the health consequences of perchlorate exposure have been the effects in susceptible populations such as pregnant women and young children, the role of low iodine intake in increasing perchlorate toxicity, and the permissible levels of perchlorate in the water supply (2,3,4,5).