Perchlorate In Drinking Water Research Articles

Towards translating in vitro measures of thyroid hormone system disruption to in vivo responses in the pregnant rat via a biologically based dose response (BBDR) model

Despite the number of in vitro assays that have been recently developed to identify chemicals that interfere with the hypothalamic-pituitary-thyroid axis (HPT), the translation of those in vitro results into in vivo responses (in vitro to in vivo extrapolation, IVIVE) has received limited attention from the modeling community. To help advance this field a steady state biologically based dose response (BBDR) model for the HPT axis was constructed for the pregnant rat on gestation day (GD) 20. The BBDR HPT axis model predicts plasma levels of thyroid stimulating hormone (TSH) and the thyroid hormones, thyroxine (T4) and triiodothyronine (T3). Thyroid hormones are important for normal growth and development of the fetus. Perchlorate, a potent inhibitor of thyroidal uptake of iodide by the sodium iodide symporter (NIS) protein, was used as a case study for the BBDR HPT axis model. The inhibitory blocking of the NIS by perchlorate was associated with dose-dependent steady state decreases in thyroid hormone production in the thyroid gland. The BBDR HPT axis model predictions for TSH, T3, and T4 plasma concentrations in pregnant Sprague Dawley (SD) rats were within 2-fold of observations for drinking water perchlorate exposures ranging from 10 to 30,000 μg/kg/d. In Long Evans (LE) pregnant rats, for both control and perchlorate drinking water exposures, ranging from 85 to 82,000 μg/kg/d, plasma thyroid hormone and TSH concentrations were predicted within 2 to 3.4- fold of observations. This BBDR HPT axis model provides a successful IVIVE template for thyroid hormone disruption in pregnant rats.

Perchlorate contamination from the detonation of insensitive high-explosive rounds

The insensitive high-explosive PAX-21 was the first of its kind fielded in an artillery munition by the United States military. This formulation contains three main components: RDX, dinitroanisole, and ammonium perchlorate (AP). In March 2012, detonation tests were conducted on PAX-21 60mm mortar rounds to determine the energetic residues resulting from high-order and blow-in-place (BIP) detonations. Post-detonation residues were sampled and analyzed for the three main PAX-21 components. Concentrations of RDX and dinitroanisole in the samples were quite low, less than 0.1% of the munitions’ original organic explosive filler mass, indicating high order or near high order detonations. However, disproportionately high concentrations of AP occurred in all residues. The residues averaged 15% of the original AP following high-order detonations and 38% of the original AP mass following the BIP operations. There was no correlation between AP residues and the RDX and dinitroanisole. Perchlorate readily leached from the detonation residues, with over 99% contained in the aqueous portion of the samples. Use of these rounds will result in billions of liters of water contaminated above drinking water perchlorate limits. As a result of this research, PAX-21 mortar rounds are currently restricted from use on US training ranges.

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.

Evaluation of the U.S. EPA/OSWER Preliminary Remediation Goal for Perchlorate in Groundwater: Focus on Exposure to Nursing Infants

BackgroundPerchlorate is a common contaminant of drinking water and food. It competes with iodide for uptake into the thyroid, thus interfering with thyroid hormone production. The U.S. Environmental Protection Agency’s Office of Solid Waste and Emergency Response (OSWER) set a groundwater preliminary remediation goal (PRG) of 24.5 μg/L to prevent exposure of pregnant women that would affect the fetus. This does not account for the greater exposure that is possible in nursing infants or for the relative source contribution (RSC), a factor normally used to lower the PRG due to nonwater exposures.ObjectivesOur goal was to assess whether the OSWER PRG protects infants against exposures from breast-feeding, and to evaluate the perchlorate RSC.MethodsWe used Monte Carlo analysis to simulate nursing infant exposures associated with the OSWER PRG when combined with background perchlorate.ResultsThe PRG can lead to a 7-fold increase in breast milk concentration, causing 90% of nursing infants to exceed the reference dose (RfD) (average exceedance, 2.8-fold). Drinking-water perchlorate must be < 6.9 μg/L to keep the median, and < 1.3 μg/L to keep the 90th-percentile nursing infant exposure below the RfD. This is 3.6- to 19-fold below the PRG. Analysis of biomonitoring data suggests an RSC of 0.7 for pregnant women and of 0.2 for nursing infants. Recent data from the Centers for Disease Control and Prevention (CDC) suggest that the RfD itself needs to be reevaluated because of hormonal effects in the general population.ConclusionsThe OSWER PRG for perchlorate can be improved by considering infant exposures, by incorporating an RSC, and by being responsive to any changes in the RfD resulting from the new CDC data.

Long-Term Environmental Exposure to Perchlorate Through Drinking Water and Thyroid Function During Pregnancy and the Neonatal Period

We have conducted a longitudinal epidemiologic study among pregnant women from three cities in northern Chile: Taltal with 114 microg/L, Chañaral with 6 microg/L, and Antofagasta with 0.5 microg/L perchlorate in the public drinking water. We tested the hypothesis that long-term exposure to perchlorate at these levels may cause a situation analogous to iodine deficiency, thus causing increases in thyrotropin (TSH) and thyroglobulin (Tg) levels and decreased levels of free thyroxine (FT4), in either the mother during the early stages of gestation or the neonate at birth, or in the fetus cause growth retardation. We found no increases in Tg or TSH and no decreases in FT4 among either the women during early pregnancy (16.1 +/- 4.1 weeks), late pregnancy (32.4 +/- 3.0 weeks), or the neonates at birth related to perchlorate in drinking water. Neonatal birth weight, length, and head circumference were not different among the three cities and were consistent with current U.S. norms. Therefore, perchlorate in drinking water at 114 microg/L did not cause changes in neonatal thyroid function or fetal growth retardation. Median urinary iodine among the entire cohort was 269 microg/L, intermediate between that of pregnant women in the United States at National Health and Nutrition Examination Survey (NHANES) I and at NHANES III and consistent with current World Health Organization (WHO) recommendations. Median breast milk iodine was not decreased in the cities with detectable perchlorate. Analysis of maternal urinary perchlorate excretion indicates an additional dietary source of perchlorate.

An Evaluation of Neurobehavioral Tests Used to Assess the Neurodevelopmental Effects of Early Ammonium Perchlorate Exposure

Perchlorate is an anion known to interfere with normal production of thyroid hormones that are integrally involved in the development of the central nervous system and neurobehavioral capacities. Given the identification of drinking water contamination with perchlorate, there are efforts to investigate the effects of exposure in developing fetuses and children in order to guide the establishment of regulatory standards. Systematic neurobehavioral investigations in animal models have been completed to evaluate neurodevelopmental consequences of exposures at different concentrations in drinking water. However, these investigations have not directly addressed the public concern for increased incidences of childhood attention deficit disorders, autism, and lowered IQs of children in areas with known contamination. Although epidemio-logical data suggest there is not a relationship between drinking-water perchlorate exposure and these childhood disorders, it may be prudent to use animal models to systematically assess the potential for such problems. Given the behavioral complexity of these problems, an appro-priate evaluation will require the use of nontraditional neurobehavioral tests such as operant conditioning tasks of varying levels of complexity, and juvenile rat play. Such tests will provide a more direct evaluation of the potential for attention deficits, autism, and lowered IQ scores related to thyroid hormone disruption due to early perchlorate exposure.

Occurrence of perchlorate IN DRINKING WATER SOURCES

Perchlorate is of concern to drinking water suppliers because of its potential risk to human health, tendency to disperse rapidly in groundwater, and resistance to conventional water treatment processes. An occurrence survey was performed in 1997 and 1998 to assess the prevalence of perchlorate in surface and subsurface drinking water supplies of the American Water System. The survey examined 40 surface water sites in 11 states and 367 groundwater wells in 17 states. No perchlorate was detected in any of the surface waters. The presence of perchlorate was confirmed in nine (~2.5%) wells, all located in California or New Mexico. Positive perchlorate concentrations ranged from &lt; 4 to ~7 μg/L, well below the health advisory guideline value of 18 μg/L suggested by the California Department of Health Services. These results help confirm previous reports that perchlorate contamination is a localized problem affecting sites near military‐related facilities or other major sources of perchlorate.