Comparing the effects and potencies of perchlorate and nitrate on amphibian metamorphosis using a modified amphibian metamorphosis assay (AMA).

A modified amphibian metamorphosis assay was performed in which Nieuwkoop and Faber (NF) stage 47 Xenopus laevis larvae were exposed to different concentrations of either perchlorate (ClO4 -) or nitrate (NO3 -) for 32 days. Larvae were exposed to 0.0 (control), 5, 25, 125, 625, and 3125 µg/L ClO4 -, or 0 (control), 23, 71, 217, 660, and 2000 mg/L NO3 -. The primary endpoints were survival, hind limb length (HLL), forelimb emergence and development, developmental stage (including time to NF stage 62 [MT62]), thyroid histopathology, wet weight, and snout-vent length (SVL). Developmental delay as evidenced by altered stage distribution and increased MT62, a higher degree of thyroid follicular cell hypertrophy, and an increase in the prevalence of follicular cell hyperplasia was observed at concentrations ≥125 µg/L ClO4 -. The no observed effect concentration (NOEC) for developmental endpoints was 25.0 µg/L ClO4 - and the NOEC for growth endpoints was 3125 µg/L ClO4 -. Exposure to nitrate did not adversely affect MT62, but a decreasing trend in stage distribution and median developmental stage at ≥217 mg/L NO3 - was observed. No histopathologic effects associated with nitrate exposure were observed. An increasing trend in SVL-normalized HLL was observed at 2000 mg/L NO3 -. Nitrate did not alter larval growth. The NOEC for developmental endpoints was 71 mg/L NO3 -, and 2000 mg/L NO3 - for growth endpoints. The present study provided additional evidence that the effects and potency of nitrate and perchlorate on metamorphosis and growth in X. laevis are considerably different.

Topical Application of Perchlorate: A Toxicity Study in Rats.

PURPOSE: To investigate the ocular safety profile of topical perchlorate as a potential preventive treatment for nasolacrimal obstruction associated with excessive use of radioactive iodine therapy. METHODS: Nine Wistar male rats (18 eyes) were randomly assigned to receive an ocular application (topical eye drop on the OD, 3 times a day for 5 days) consisting of either: 1) sterile saline solution, 2) 30 mg/ml NaClO4 or 3) 30 mg/ml KClO4. The rat eyes were examined daily for corneal cloudiness/clarity, discharge, mucous secretions, conjunctival injection, eyelid erythema, and/or changes in behavior. Seven days after the first dose, the rats were euthanized and OU were harvested, fixed, embedded in paraffin, and stained with H&E and Masson's trichrome using standard techniques. RESULTS: The data collected over the 7 days revealed no behavior changes or ocular complications in any of the 3 study groups. Pathologic analysis of the corneas revealed normal findings on all groups without signs of inflammation, fibrosis, or any other abnormality, and no difference between the treated and control eyes. CONCLUSIONS: The findings of this study suggest that the use of topical perchlorate is safe to use on eyes in high concentrations. The efficacy of this compound in minimizing fibrosis of the nasolacrimal sac and duct warrants further study.

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.

Aggregating exposures and toxicity equivalence approach into an integrated probabilistic dietary risk assessment for perchlorate, nitrate, and thiocyanate: Results from the National food monitoring study and National Food Consumption Database.

Perchlorate, nitrate, and thiocyanate, namely thyroid disrupting chemicals (TDCs), are found ubiquitously in the environment, leading to broad human exposure and primary uptake through the food web and drinking water. TDCs are all competitive inhibitors of thyroid iodide uptake activity, but limited studies have assessed the cumulative risk of dietary exposure to multiple TDCs. Thus, in this study, we analyzed the individual exposure risk from 310 food samples in 11 categories, and also assessed the cumulative health risks from TDCs for the Taiwanese population using a perchlorate equivalent concentration (PEC) approach. Consequently, this study not only demonstrated the non-carcinogenic health risks from individual exposure but also highlighted that the cumulative exposure to these TDCs may adversely affect human thyroid functioning. Vegetables, livestock, fruits, and dairy products are the most susceptible to PEC exposure. We highlighted nitrate as the main contributor to PEC exposure. Finally, controlling the overall TDC concentrations from vegetables, livestock, fruits, and dairy products is emphasized in this study. This is the first study to conduct a cumulative risk assessment of dietary exposure to TDCs using the PEC approach for the Taiwanese population through probabilistic and sensitivity analyses.

Perchlorate Contamination: Sources, Effects, and Technologies for Remediation.

Perchlorate is a persistent pollutant, generated via natural and anthropogenic processes, that possesses a high potential for endocrine disruption in humans and biota. It inhibits iodine fixation, a major reason for eliminating this pollutant from ecosystems. Remediation of perchlorate can be achieved with various physicochemical treatments, especially at low concentrations. However, microbiological approaches using microorganisms, such as those from the genera Dechloromonas, Serratia, Propionivibrio, Wolinella, and Azospirillum, are promising when perchlorate pollution is extensive. Perchlorate-reducing bacteria, isolated from harsh environments, for example saline soils, mine sediments, thermal waters, wastewater treatment plants, underground gas storage facilities, and remote areas, including the Antarctica, can provide removal yields from 20 to 100%. Perchlorate reduction, carried out by a series of enzymes, such as perchlorate reductase and superoxide chlorite, depends on pH, temperature, salt concentration, metabolic inhibitors, nutritional conditions, time of contact, and cellular concentration. Microbial degradation is cost-effective, simple to implement, and environmentally friendly, rendering it a viable method for alleviating perchlorate pollution in the environment.

A comparison of thyroidal protection by iodine and perchlorate against radioiodine exposure in Caucasians and Japanese.

Radioactive iodine released in nuclear accidents may accumulate in the thyroid and by irradiation enhances the risk of cancer. Radioiodine uptake into the gland can be inhibited by large doses of stable iodine or perchlorate. Nutritional iodine daily intake may impact thyroid physiology, so that radiological doses absorbed by the thyroid as well as thyroid blocking efficacy may differ in Japanese with a very rich iodine diet compared to Caucasians. Based on established biokinetic-dosimetric models for the thyroid, we derived the parameters for Caucasians and Japanese to quantitatively compare the effects of radioiodine exposure and the protective efficacy of thyroid blocking by stable iodine at the officially recommended dosages (100 mg in Germany, 76 mg in Japan) or perchlorate. The maximum transport capacity for iodine uptake into the thyroid is lower in Japanese compared to Caucasians. For the same radioiodine exposure pattern, the radiological equivalent thyroid dose is substantially lower in Japanese in the absence of thyroid blocking treatments. In the case of acute radioiodine exposure, stable iodine is less potent in Japanese (ED50 = 41.6 mg) than in Caucasians (ED50 = 2.7 mg) and confers less thyroid protection at the recommended dosages because of a delayed responsiveness to iodine saturation of the gland (Wolff-Chaikoff effect). Perchlorate (ED50 = 10 mg in Caucasians) at a dose of 1000 mg has roughly the same thyroid blocking effect as 100 mg iodine in Caucasians, whereas it confers a much better protection than 76 mg iodine in Japanese. For prolonged exposures, a single dose of iodine offer substantially lower protection than after acute radioiodine exposure in both groups. Repetitive daily iodine administrations improve efficacy without reaching levels after acute radioiodine exposure and achieve only slightly better protection in Japanese than in Caucasians. However, in the case of continuous radioiodine exposure, daily doses of 1000 mg perchlorate achieve a high protective efficacy in Caucasians as well as Japanese (> 0.98). In Caucasians, iodine (100 mg) and perchlorate (1000 mg) at the recommended dosages seem alternatives in case of acute radioiodine exposure, whereas perchlorate has a higher protective efficacy in the case of longer lasting radioiodine exposures. In Japanese, considering protective efficacy, preference should be given to perchlorate in acute as well as prolonged radioiodine exposure scenarios.

Impact of Simulated Martian Conditions on (Facultatively) Anaerobic Bacterial Strains from Different Mars Analogue Sites.

Five bacterial (facultatively) anaerobic strains, namely Buttiauxella sp. MASE-IM-9, Clostridium sp. MASE-IM-4, Halanaerobium sp. MASE-BB-1, Trichococcus sp. MASE-IM-5, and Yersinia intermedia MASE-LG-1 isolated from different extreme natural environments were subjected to Mars relevant environmental stress factors in the laboratory under controlled conditions. These stress factors encompassed low water activity, oxidizing compounds, and ionizing radiation. Stress tests were performed under permanently anoxic conditions. The survival rate after addition of sodium perchlorate (Na-perchlorate) was found to be species-specific. The inter-comparison of the five microorganisms revealed that Clostridium sp. MASE-IM-4 was the most sensitive strain (D10-value (15 min, NaClO4) = 0.6 M). The most tolerant microorganism was Trichococcus sp. MASE-IM-5 with a calculated D10-value (15 min, NaClO4) of 1.9 M. Cultivation in the presence of Na-perchlorate in Martian relevant concentrations up to 1 wt% led to the observation of chains of cells in all strains. Exposure to Na-perchlorate led to a lowering of the survival rate after desiccation. Consecutive exposure to desiccating conditions and ionizing radiation led to additive effects. Moreover, in a desiccated state, an enhanced radiation tolerance could be observed for the strains Clostridium sp. MASE-IM-4 and Trichococcus sp. MASE-IM-5. These data show that anaerobic microorganisms from Mars analogue environments can resist a variety of Martian-simulated stresses either individually or in combination. However, responses were species-specific and some Mars-simulated extremes killed certain organisms. Thus, although Martian stresses would be expected to act differentially on microorganisms, none of the expected extremes tested here and found on Mars prevent the growth of anaerobic microorganisms.

We are what we eat: Regulatory gaps in the United States that put our health at risk.

The American diet has changed dramatically since 1958, when Congress gave the United States Food and Drug Administration (FDA) the authority to ensure the safety of chemicals in food. Since then, thousands of chemicals have entered the food system. Yet their long-term, chronic effects have been woefully understudied, their health risks inadequately assessed. The FDA has been sluggish in considering scientific knowledge about the impact of exposures-particularly at low levels and during susceptible developmental stages. The agency's failure to adequately account for the risks of perchlorate-a well-characterized endocrine-disrupting chemical-to vulnerable populations is representative of systemic problems plaguing the regulation of chemicals in food. Today, we are faced with a regulatory system that, weakened by decades of limited resources, has fallen short of fully enforcing its mandates. The FDA's inability to effectively manage the safety of hundreds of chemicals is putting our children's health at risk.

Effects of sodium perchlorate and exogenous L-thyroxine on growth, development and leptin signaling pathway of Bufo gargarizans tadpoles during metamorphosis.

Sodium perchlorate (NaClO4) and exogenous L-thyroxine (T4), two kinds of endocrine-disrupting chemicals (EDCs), mainly affect the circulating thyroid hormones, which regulate the initiation and rate of metamorphosis in amphibian. The aim of this study is to evaluate the potential role of EDCs in regulating the development of tadpoles and leptin signaling pathway of liver during the metamorphosis of Bufo gargarizans. There was completely opposite result of average development stage of tadpoles and morphological parameters between the NaClO4 and T4 exposure groups. Histological analysis revealed that NaClO4 and T4 exposure both caused liver injury, such as the decreased size of hepatocytes, atrophy of nucleus, increased melanomacrophage centres and disappearance of hepatocyte membranes. In addition, the results of RT-qPCR revealed that NaClO4 treatment significantly inhibited the transcript levels of genes related to thyroid hormone (D2, TRα and TRß) and leptin signaling pathway (LepR, JAK1, JAK2, and TYK2), while there was an increase of mRNA expression of these genes in the liver of tadpoles administrated with T4 compared with control. This work lays an important foundation for assessing the risk of EDCs in relation to amphibian development during metamorphosis.

Environmental exposure to perchlorate: A review of toxicology and human health.

Perchlorate pharmacology and toxicology studies date back at least 65 years in the peer-reviewed literature. Repeated studies in animals and humans have demonstrated perchlorate's mechanism of action, dose-response, and adverse effects over a range of doses. The first measurable effect of perchlorate is inhibition of iodine uptake to the thyroid gland. Adequate levels of thyroid hormones are critical for the development of the fetal nervous system. With sufficient dose and exposure duration, perchlorate can reduce thyroid hormones in the pregnant or non-pregnant woman via this mechanism. The developing fetus is the most sensitive life stage for chemical agents that affect iodide uptake to the thyroid. Perchlorate has a half-life of eight hours, is not metabolized, does not bioaccumulate, is not a mutagen or carcinogen, and is not reprotoxic or immunotoxic. More recently, epidemiological and biomonitoring studies have been published in the peer-reviewed literature characterizing the thyroidal effects of perchlorate and other goitrogens. While the results from most populations report no consistent association, a few studies report thyroidal effects at environmentally relevant levels of perchlorate. We reviewed the literature on health effects of perchlorate at environmental exposure levels, with a focus on exposures during pregnancy and neurodevelopmental effects. Based on the studies we reviewed, health effects are expected to only occur at doses substantially higher than environmental levels.

A cross sectional study of urinary phthalates, phenols and perchlorate on thyroid hormones in US adults using structural equation models (NHANES 2007-2008).

BACKGROUND: Biomonitoring data shows that people are exposed to phthalates, phenols and perchlorates. Many of these compounds are endocrine disrupting compounds that affect thyroid hormone levels. Yet the effect of these compounds on thyroid hormone levels are often evaluated individually rather than as a mixture. Our objective was to examine the association between 11 urinary endocrine disrupting compounds and thyroid hormones using structural equation models. METHODS: Using data from the National Health and Nutrition and Examination Survey 2007-2008, we fit a latent variable utilizing urinary measurements of 9 compounds in females (perchlorate, bisphenol A, benzophenone-3, mono-2ethyl5carboxypentyl phthalate, mono-n-butyl phthalate, mono-(3-carboxypropyl) phthalate, mono(2ethyl5hydroxyhexyl) phthalate, mono-benzyl phthalate, and mono-isobutyl phthalate) and 8 compounds in males (without benzophenone-3). The association of the latent variable with serum thyroid hormones (Total T3, Total T4, and Thyroid Stimulating Hormones) was assessed in females (N = 710) and males (N = 850) over the age of 12 controlling for age, race, and urinary creatinine. RESULTS: In males, urinary endocrine disrupting compound levels were negatively associated with thyroxine (ß: -0.19, 95% Confidence Interval (95% CI): -0.31, -0.05). In females, urinary endocrine disrupting compound levels were positively associated with triiodothyronine serum concentrations (ß: 0.09, 95% CI: -0.03, 0.21) however this association was not statistically significant. CONCLUSIONS: This cross-sectional analysis provides additional evidence that environmental exposure to phthalates and phenols is associated with endocrine-related processes. Furthermore, these results suggested sex-specific differences in exposure to endocrine disrupting mixtures, and the exposure-response between endocrine disrupting mixtures and thyroid hormone levels. Specifically, higher exposure to a mixture of endocrine disrupting compounds was associated with lower levels of total T4 in males but not in females. While a structural methodological framework was used to assess these complex relationships, the cross sectional nature of this analysis limits causal inference and further research is needed to determine the clinical significance of these findings.

Altered thyroid hormone levels affect body condition at metamorphosis in larvae of Xenopus laevis.

Chemical, physical and biological environmental stressors may affect the endocrine system, such as the thyroid hormone (TH) axis in larval amphibians with consequences for energy partitioning among development, growth and metabolism. We studied the effects of two TH level affecting compounds, exogenous l-thyroxine (T4 ) and sodium perchlorate (SP), on various measures of development and body condition in larvae of the African clawed frog (Xenopus laevis). We calculated the scaled mass index, hepatosomatic index and relative tail muscle mass as body condition indices to estimate fitness. Altered TH levels significantly altered the growth, development, survival and body condition in metamorphic larvae in different directions. While exogeno us T4 reduced growth and accelerated development, SP treatment increased growth but slowed down development. Altered TH levels improved body conditions in both treatments and particularly in larvae of the SP treatment but to the detriment of lower survival rates in both TH level altering treatments. The hepatosomatic index was negatively affected by exogenous T4 , but not by SP treatment indicating a lower lipid reserve in the liver in larvae of T4 treatment. These altered TH levels as caused by several environmental stressors may have an influence on individual fitness across life, as body condition at the onset of metamorphosis determines metamorphic and juvenile survival. Further research is needed to determine synergetic effects of environmental stressors on TH levels and its effects on physiological traits such as metabolic rate.

Evaluation of hypothalamus-pituitary-thyroid axis function by chronic perchlorate exposure in male rats.

Perchlorate is a widespread endocrine disruptor that was previously correlated with increased serum TSH levels and decreased thyroid hormones production both in animals and humans. Even so, the regulation of gene/protein expression in the hypothalamus, pituitary and thyroid by chronic perchlorate exposure was not completely elucidated. Therefore, this study aimed to investigate the underlying mechanisms involved in the disruption of hypothalamus-pituitary-thyroid axis by chronic perchlorate exposure. Male Wistar rats were treated or not with NaClO4 in the drinking water (35 mg/Kg/day) for 60 days. Thereafter, hormone/cytokines serum levels were measured through multiplex assays; genes/proteins expression were investigated by qPCR/Western Blotting and thyroid morphology was evaluated through histological analysis. Serum TSH levels were increased and serum T4 /T3 levels were decreased in perchlorate-treated animals. This treatment also altered the thyrotropin-releasing hormone mRNA/protein content in the hypothalamus. Additionally, the expression of both subunits of TSH were increased in the pituitary of perchlorate-treated rats, which also presented significant alterations in the thyroid morphology/gene expression. Furthermore, perchlorate exposure reduced liver Dio1 mRNA expression and increased the content of pro-inflammatory cytokines in the thyroid and the serum. In conclusion, our study adds novel findings about the perchlorate-induced disruption of the hypothalamus-pituitary-thyroid axis gene/protein expression in male rats. The data presented herein also suggest that perchlorate induces thyroid and systemic inflammation through the increased production of cytokines. Taken together, our results suggest that perchlorate contamination should be monitored, especially in the individuals most susceptible to the deleterious effects of reduced levels of thyroid hormones.

Seasonal Variation and Exposure Risks of Perchlorate in Soil, Indoor Dust, and Outdoor Dust in China.

A total of 97 paired soil, outdoor dust, and indoor dust samples were collected in the national scale of China in summer, and the perchlorate levels were compared with those in soil and outdoor dust samples collected in winter in our previous study. The median perchlorate concentrations in the outdoor dust, indoor dust, and soil samples were 8.10, 11.4, and 0.05 mg/kg, respectively, which were significantly lower than those in the winter samples due to the natural factors and human activities. No significant differences in perchlorate concentrations were found between Northern and Southern China in the dust samples, whereas the difference was obtained in the soil samples. In the terms of possible source, the perchlorate levels in the outdoor dust exhibited strong correlation with SO42- (r2 = 0.458**) and NO3- (r2 = 0.389**), indicating part of perchlorate in outdoor environment was likely from atmospheric oxidative process in summer. The perchlorate, SO42-, and Cl- levels in the indoor dust were significantly related to those in the outdoor dust, suggesting that outdoor contaminants might be an important source for indoor environment. Furthermore, the human exposure to perchlorate was under relatively safe state in China except for special sites or periods with high perchlorate levels. Dust made an unexpected contribution of 41.3% to the total daily perchlorate intake for children, whereas 2.46% for adults in China based on biomonitoring, which deserves more attention.

Evaluation of the risk of perchlorate exposure in a population of late-gestation pregnant women in the United States: Application of probabilistic biologically-based dose response modeling.

The risk of ubiquitous perchlorate exposure and the dose-response on thyroid hormone levels in pregnant women in the United States (U.S.) have yet to be characterized. In the current work, we integrated a previously developed perchlorate submodel into a recently developed population-based pregnancy model to predict reductions in maternal serum free thyroxine (fT4) levels for late-gestation pregnant women in the U.S. Our findings indicated no significant difference in geometric mean estimates of fT4 when perchlorate exposure from food only was compared to no perchlorate exposure. The reduction in maternal fT4 levels reached statistical significance when an added contribution from drinking water (i.e., 15µg/L, 20µg/L, or 24.5µg/L) was assumed in addition to the 90th percentile of food intake for pregnant women (0.198µg/kg/day). We determined that a daily intake of 0.45 to 0.50µg/kg/day of perchlorate was necessary to produce results that were significantly different than those obtained from no perchlorate exposure. Adjusting for this food intake dose, the relative source contribution of perchlorate from drinking water (or other non-dietary sources) was estimated to range from 0.25-0.3µg/kg/day. Assuming a drinking water intake rate of 0.033L/kg/day, the drinking water concentration allowance for perchlorate equates to 7.6-9.2µg/L. In summary, we have demonstrated the utility of a probabilistic biologically-based dose-response model for perchlorate risk assessment in a sensitive life-stage at a population level; however, there is a need for continued monitoring in regions of the U.S. where perchlorate exposure may be higher.

Ultrastructural Alterations in Thyrocytes of Zebrafish ( Danio rerio) after Exposure to Propylthiouracil and Perchlorate.

Histopathology is a widely used approach to evaluate effects of endocrine-active chemicals in the thyroid. However, effects at an ultrastructural level have hardly been examined in fish thyroids. In the present study, zebrafish was exposed to sublethal concentrations of propylthiouracil (PTU; 0-50 mg/L) and perchlorate (PER; 0-5,000 µg/L) for 5 weeks in a modified early life-stage test. None of the treatments caused significant mortality (no observed effect concentrations for survival ≥50 mg/L [PTU] and ≥5,000 µg/L [PER]). PTU induced dose-dependent alterations in the rough endoplasmic reticulum (rER) in all exposure groups, whereas only the 2 highest PER exposure groups (500 and 5,000 µg/L) resulted in alterations of the rER. Both substances caused an increase in the numbers of lysosomes and mitochondria, with mitochondria displaying distorted cristae. Increased mitochondrial diameters were only observed in the PTU treatment. PER-exposed samples displayed an increase in apical microvilli. The highest PTU concentration (50 mg/L) showed first signs of cellular degeneration. Ultrastructural changes in zebrafish thyrocytes thus appear specific for different chemicals, most likely depending on their specific modes of action. Additional knowledge of subcellular changes in thyrocytes can help to better understand and interpret existing histological data in the future.

Maternal perchlorate exposure in pregnancy and altered birth outcomes.

BACKGROUND: At high medicinal doses perchlorate is known to decrease the production of thyroid hormone, a critical factor for fetal development. In a large and uniquely exposed cohort of pregnant women, we recently identified associations between environmental perchlorate exposures and decreased maternal thyroid hormone during pregnancy. Here, we investigate whether perchlorate might be associated with birthweight or preterm birth in the offspring of these women. METHODS: Maternal urinary perchlorate, serum thyroid hormone concentrations, birthweight, gestational age, and urinary nitrate, thiocyanate, and iodide were collected in 1957 mother-infant pairs from San Diego County during 2000-2003, a period when the county's water supply was contaminated with perchlorate. Associations between perchlorate exposure and birth outcomes were examined using linear and logistic regression analyses adjusted for maternal age, weight, race/ethnicity, and other factors. RESULTS: Perchlorate was not associated with birth outcomes in the overall population. However, in analyses confined to male infants, log10 maternal perchlorate concentrations were associated with increasing birthweight (ß=143.1gm, p=0.01), especially among preterm births (ß=829.1g, p<0.001). Perchlorate was associated with male preterm births ≥2500g (odds ratio=3.03, 95% confidence interval=1.09-8.40, p-trend=0.03). Similar associations were not seen in females. CONCLUSIONS: This is the first study to identify associations between perchlorate and increasing birthweight. Further research is needed to explore the differences we identified related to infant sex, preterm birth, and other factors. Given that perchlorate exposure is ubiquitous, and that long-term impacts can follow altered birth outcomes, future research on perchlorate could have widespread public health importance.

Exogenous iodide ameliorates perchlorate-induced thyroid phenotypes in threespine stickleback.

Perchlorate is a ubiquitous environmental contaminant that has widespread endocrine disrupting effects in vertebrates, including threespine stickleback (Gasterosteus aculeatus). The target of perchlorate is thyroid tissue where it induces changes in the organization, activation, and morphology of thyroid follicles and surrounding tissues. To test the hypothesis that some phenotypes of perchlorate toxicity are not mediated by thyroid hormone, we chronically exposed stickleback beginning at fertilization to perchlorate (10, 30, 100ppm) or control water with and without supplementation of either iodide or thyroxine (T4). Stickleback were sampled across a one-year timespan to identify potential differences in responses to treatment combinations before and after sexual maturation. We found that most thyroid histomorphological phenotypes induced by perchlorate (follicle proliferation, reduced follicle area (adults only), colloid depletion, thyrocyte hypertrophy (subadults only)) were significantly ameliorated by exogenous iodide supplementation. In contrast, treatment with exogenous T4 did not correct any of the thyroid-specific histopathologies induced by perchlorate. Whole-body thyroid hormone concentrations were not significantly affected by perchlorate exposure; however, supplementation with iodide and T4 significantly increased T4 concentrations. This study also revealed an increased erythrocyte area in the thyroid region of perchlorate-exposed adults, while lipid droplet number increased in perchlorate-exposed subadults. Increased erythrocyte area was ameliorated by both iodide and T4, while neither supplement was able to correct lipid droplet number. Our finding on lipid droplets indicates that exposure to perchlorate in early development may have obesogenic effects.

Spatio-temporal distribution of perchlorate and its toxicity in Hydrilla verticillata.

The spatio-temporal distribution of perchlorate in water sources around an ammonium perchlorate production unit and its toxicity response on a dominant aquatic plant, Hydrilla verticillata are reported in this study. Samples (n=453) from ground water (open well) and surface water sources within 5km from the production unit over a period of 12 months (2014, June - 2015, May) were screened for ClO4-. During the period, ClO4-concentration in ground water samples close to the production unit increased to >40,000µg/L, and ClO4- was detected at 1740µg/L in well water 1.6km away from the production unit. A community pond in the area also showed an increase in ClO4- level up to 29,000µg/L. In all water sources, ClO4- level was maximum during the rainy season (July, monsoon). A natural degradation of ClO4- was not observed in the area as evident from its persistent level and spreading to more areas. H. verticillata, the dominant vegetation in the pond exhibited severe toxic response like massive decay and loss of photosynthetic pigments such as chlorophyll and carotene due to ClO4- exposure. The plant accumulated ClO4- up to 60±0.8mg/kg wet weight with a Bio-Concentration Factor 2.06±0.005. This is the first report on spatio-temporal distribution of ClO4- at higher levels in a natural environment and its toxicity response to plants under natural condition.

Toxicological effects of three types of silver nanoparticles and their salt precursors acting on human U-937 and HL-60 cells.

The growing popularity of nanomaterials requires a systematic study of their effects on the human body. Silver nanoparticles (AgNPs), due to their antiseptic properties, are used in almost every area of life. The purpose of the study was to examine whether the precursor used for the synthesis of nanoparticles affects their bio-influence and modifies their impact on cells of the human immune system. To compare the effects of precursor silver salts (AgNO3, CH3COOAg and AgClO4) and corresponding nanoparticles (TAN TAA and TAC) cytotoxicity study was conducted on two cell lines U-937 and HL-60. For both cell lines, silver salts are more toxic than the corresponding nanoparticles. Cell viability after treatment with the two forms of silver (salt/particle) is dependent on silver dose and degree of cells differentiation. Addition of the silver salt of doses greater than 5 mg/L results in decreased cell viability by over 60%, whereas nanoparticles' addition reduces cell viability on average by 30%. On the basis of the determined LD50 values it can be stated that for the tested cells the most toxic are AgClO4 and TAC. Production of nitric oxide, which is a mediator of inflammation, is the greatest after treatment of the cells by TAC. Different interactions of studied nanoparticles with albumin has been found and it was shown that addition of albumin to the cells treated by nanoparticles reduces their toxic effects. Obtained by us highly purified, mono-disperse AgNPs exhibit diverse effects relative to the biological systems, depending on the precursor salt used.