Associations of perchlorate, nitrate, and thiocyanate exposure with arthritis and inflammation indicators in young and middle-aged adults, NHANES 2005-2016.

Background: Perchlorates, nitrates, and thiocyanates are prevalent environmental chemicals. Their potential association with arthritis remains unexplored. This study aimed to investigate the link between perchlorate, nitrate, and thiocyanate exposure and arthritis, as well as the potential role of inflammation in this context. Methods: Utilizing the National Health and Nutrition Examination Survey (NHANES) data spanning from 2005 to 2016, the study enrolled 6597 participants aged 20-59 (young and middle-aged), of which 1045 had arthritis. Employing multivariate logistic regression modeling, multiple linear regression models, restricted cubic spline analysis, Bayesian kernel machine regression (BKMR) modeling, and mediation analysis, we assessed these relationships. Results: There was a significant positive association between elevated urinary thiocyanate levels and arthritis risk [1.19 (1.11, 1.28)]. This association held true across subgroups of osteoarthritis (OA) [1.24 (1.10, 1.40)] and rheumatoid arthritis (RA) [1.33 (1.15, 1.55)]. Thiocyanate levels displayed a dose-dependent relationship with arthritis risk, showing a linear trend (nonlinear P > 0.05). Conversely, perchlorate and nitrate did not exhibit associations with arthritis risk. BKMR outcomes highlighted a positive correlation between a mixture of perchlorate, nitrate, and thiocyanate and arthritis risk, with thiocyanate being the predominant predictors. Moreover, BKMR and generalized linear model analyses unveiled no significant synergistic effect of urinary perchlorate, nitrate, and thiocyanate on arthritis risk. Furthermore, thiocyanate exposure has been linked to elevated levels of inflammatory indicators (white blood cell, neutrophils, lymphocytes, and systemic immune-inflammatory index (SII)). Conclusion: Heightened thiocyanate exposure may be linked to elevated arthritis risk, either single or in combined effects. Additionally, thiocyanate exposure is associated with heightened inflammation levels.

Environmental exposure to perchlorate, nitrate, and thiocyanate in relation to chronic kidney disease in the general US population, NHANES 2005-2016.

BACKGROUND: Few studies have explored the impact of perchlorate, nitrate, and thiocyanate (PNT) on kidney function. This study aimed to evaluate the association of urinary levels of PNT with renal function as well as the prevalence of chronic kidney disease (CKD) among the general population in the United States. METHODS: This analysis included data from 13,373 adults (≥20 years) from the National Health and Nutrition Examination Survey 2005 to 2016. We used multivariable linear and logistic regression, to explore the associations of urinary PNT with kidney function. Restricted cubic splines were used to assess the potentially non-linear relationships between PNT exposure and outcomes. RESULTS: After traditional creatinine adjustment, perchlorate (P-traditional) was positively associated with estimated glomerular filtration rate (eGFR) (adjusted ß: 2.75; 95% confidence interval [CI]: 2.25 to 3.26; P  < 0.001), and negatively associated with urinary albumin-to-creatinine ratio (ACR) (adjusted ß: -0.05; 95% CI: -0.07 to -0.02; P  = 0.001) in adjusted models. After both traditional and covariate-adjusted creatinine adjustment, urinary nitrate and thiocyanate were positively associated with eGFR (all P values <0.05), and negatively associated with ACR (all P values <0.05); higher nitrate or thiocyanate was associated with a lower risk of CKD (all P values <0.001). Moreover, there were L-shaped non-linear associations between nitrate, thiocyanate, and outcomes. In the adjusted models, for quartiles of PNT, statistically significant dose-response associations were observed in most relationships. Most results were consistent in the stratified and sensitivity analyses. CONCLUSIONS: Exposures to PNT might be associated with kidney function, indicating a potential beneficial effect of environmental PNT exposure (especially nitrate and thiocyanate) on the human kidney.

Environmental exposure to perchlorate, nitrate and thiocyanate, and thyroid function in Chinese adults: A community-based cross-sectional study.

BACKGROUND: Evidence on environmental exposure to perchlorate, nitrate, and thiocyanate, three thyroidal sodium iodine symporter (NIS) inhibitors, and thyroid function in the Chinese population remains limited. OBJECTIVE: To investigate the associations of environmental exposure to perchlorate, nitrate, and thiocyanate with markers of thyroid function in Chinese adults. METHODS: A total of 2441 non-pregnant adults (mean age 50.4 years and 39.1% male) with a median urinary iodine of 180.1 µg/L from four communities in Shenzhen were included in this cross-sectional study. Urinary perchlorate, nitrate, thiocyanate, and thyroid profiles, including serum free thyroxine (FT4), total thyroxine (TT4), free triiodothyronine (FT3), total triiodothyronine (TT3), and thyroid stimulating hormone (TSH), were measured. Generalized linear model was applied to investigate the single-analyte associations. Weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) models were used to examine the association between the co-occurrence of three anions and thyroid profile. RESULTS: The median levels of urinary perchlorate, nitrate, and thiocyanate were 5.8 µg/g, 76.4 mg/g, and 274.1 µg/g, respectively. After adjusting for confounders, higher urinary perchlorate was associated with lower serum FT4, TT4, and TT3, and higher serum FT3 and TSH (all P < 0.05). Comparing extreme tertiles, subjects in the highest nitrate tertile had marginally elevated TT3 (ß: 0.02, 95% CI: 0.00-0.04). Each 1-unit increase in log-transformed urinary thiocyanate was associated with a 0.04 (95% CI: 0.02-0.06) pmol/L decrease in serum FT3. The WQS indices were inversely associated with serum FT4, TT4, and FT3 (all P < 0.05). In the BKMR model, the mixture of three anions was inversely associated with serum FT4, TT4, and FT3. CONCLUSIONS: Our study provides evidence that individual and combined environmental exposure to perchlorate, nitrate, and thiocyanate are associated with significant changes in thyroid function markers in the Chinese population with adequate iodine intake.

High pressures increase α-chymotrypsin enzyme activity under perchlorate stress.

Deep subsurface environments can harbour high concentrations of dissolved ions, yet we know little about how this shapes the conditions for life. We know even less about how the combined effects of high pressure influence the way in which ions constrain the possibilities for life. One such ion is perchlorate, which is found in extreme environments on Earth and pervasively on Mars. We investigated the interactions of high pressure and high perchlorate concentrations on enzymatic activity. We demonstrate that high pressures increase α-chymotrypsin enzyme activity even in the presence of high perchlorate concentrations. Perchlorate salts were shown to shift the folded α-chymotrypsin phase space to lower temperatures and pressures. The results presented here may suggest that high pressures increase the habitability of environments under perchlorate stress. Therefore, deep subsurface environments that combine these stressors, potentially including the subsurface of Mars, may be more habitable than previously thought.

Perfluorooctane sulfonic acid, a persistent organic pollutant, inhibits iodide accumulation by thyroid follicular cells in vitro.

Poly- and perfluoroalkyl substances (PFAS) are a class of endocrine disrupting chemicals (EDCs) reported to alter thyroid function. Iodide uptake by thyroid follicular cells, an early step in the synthesis of thyroid hormones, is a potential target for thyroid disruption by EDCs. The aim of the present study was to evaluate the acute effects of perfluorooctane sulfonic acid (PFOS) and perfluorooctane carboxylic acid (PFOA), two of the most abundant PFAS in the environment, on iodide transport by thyroid follicular cells in vitro. Dynamic changes in intracellular iodide concentration were monitored by live cell imaging using YFP-H148Q/I152, a genetically encoded fluorescent iodide biosensor. PFOS, but not PFOA, acutely and reversibly inhibited iodide accumulation by FRTL-5 thyrocytes, as well as by HEK-293 cells transiently expressing the Sodium Iodide Symporter (NIS). PFOS prevented NIS-mediated iodide uptake and reduced intracellular iodide concentration in iodide-containing cells, mimicking the effect of the NIS inhibitor perchlorate. PFOS did not affect iodide efflux from thyroid cells. The results of this study suggest that disruption of iodide homeostasis in thyroid cells may be a potential mechanism for anti-thyroid health effects of PFOS. The study also confirms the utility of the YFP-H148Q/I152 cell-based assay to screen environmental PFAS, and other EDCs, for anti-thyroid activity.

Interference on Iodine Uptake and Human Thyroid Function by Perchlorate-Contaminated Water and Food.

BACKGROUND: Perchlorate-induced natrium-iodide symporter (NIS) interference is a well-recognized thyroid disrupting mechanism. It is unclear, however, whether a chronic low-dose exposure to perchlorate delivered by food and drinks may cause thyroid dysfunction in the long term. Thus, the aim of this review was to overview and summarize literature results in order to clarify this issue. METHODS: Authors searched PubMed/MEDLINE, Scopus, Web of Science, institutional websites and Google until April 2020 for relevant information about the fundamental mechanism of the thyroid NIS interference induced by orally consumed perchlorate compounds and its clinical consequences. RESULTS: Food and drinking water should be considered relevant sources of perchlorate. Despite some controversies, cross-sectional studies demonstrated that perchlorate exposure affects thyroid hormone synthesis in infants, adolescents and adults, particularly in the case of underlying thyroid diseases and iodine insufficiency. An exaggerated exposure to perchlorate during pregnancy leads to a worse neurocognitive and behavioral development outcome in infants, regardless of maternal thyroid hormone levels. DISCUSSION AND CONCLUSION: The effects of a chronic low-dose perchlorate exposure on thyroid homeostasis remain still unclear, leading to concerns especially for highly sensitive patients. Specific studies are needed to clarify this issue, aiming to better define strategies of detection and prevention.

Perspectives from the Society for Pediatric Research: contaminants of water and children's health: Can we do better?

Children are uniquely susceptible to the health consequences of water contamination. In this review, we summarize the existing, robust literature supporting the importance of examining specific water contaminants (i.e., lead, pesticides, nitrates, arsenic, perchlorate) and the routes of contamination in the United States and globally. We also discuss the health effects of exposure to contaminated water and significant disparities related to access to clean water. Lastly, we offer strategies for prevention and intervention-including those focused on the individual patient level-and review the current US policy framework pertaining to regulation of these toxicants. IMPACT: A key message in this article is that exposure to water contaminants have serious and long-lasting consequences on children's health. This review summarizes current existing literature and adds policy recommendations supporting clean water for children. Information from this review has two potential impacts: Guide health professionals in screening and/or treating children's health problems resulting from water contaminant exposure. Guide policy makers in using evidence-based approaches to improve water quality and clean water access.

Bacterial Growth in Chloride and Perchlorate Brines: Halotolerances and Salt Stress Responses of Planococcus halocryophilus.

Extraterrestrial environments encompass physicochemical conditions and habitats that are unknown on Earth, such as perchlorate-rich brines that can be at least temporarily stable on the martian surface. To better understand the potential for life in these cold briny environments, we determined the maximum salt concentrations suitable for growth (MSCg) of six different chloride and perchlorate salts at 25°C and 4°C for the extremotolerant cold- and salt-adapted bacterial strain Planococcus halocryophilus. Growth was measured through colony-forming unit (CFU) counts, while cellular and colonial phenotypic stress responses were observed through visible light, fluorescence, and scanning electron microscopy. Our data show the following: (1) The tolerance to high salt concentrations can be increased through a stepwise inoculation toward higher concentrations. (2) Ion-specific factors are more relevant for the growth limitation of P. halocryophilus in saline solutions than single physicochemical parameters like ionic strength or water activity. (3) P. halocryophilus shows the highest microbial sodium perchlorate tolerance described so far. However, (4) MSCg values are higher for all chlorides compared to perchlorates. (5) The MSCg for calcium chloride was increased by lowering the temperature from 25°C to 4°C, while sodium- and magnesium-containing salts can be tolerated at 25°C to higher concentrations than at 4°C. (6) Depending on salt type and concentration, P. halocryophilus cells show distinct phenotypic stress responses such as novel types of colony morphology on agar plates and biofilm-like cell clustering, encrustation, and development of intercellular nanofilaments. This study, taken in context with previous work on the survival of extremophiles in Mars-like environments, suggests that high-concentrated perchlorate brines on Mars might not be habitable to any present organism on Earth, but extremophilic microorganisms might be able to evolve thriving in such environments.

Endocrine Disruption Alters Developmental Energy Allocation and Performance in Rana temporaria.

Environmental change exposes wildlife to a wide array of environmental stressors that arise from both anthropogenic and natural sources. Many environmental stressors with the ability to alter endocrine function are known as endocrine disruptors, which may impair the hypothalamus-pituitary-thyroid axis resulting in physiological consequences to wildlife. In this study, we investigated how the alteration of thyroid hormone (TH) levels due to exposure to the environmentally relevant endocrine disruptor sodium perchlorate (SP; inhibitory) and exogenous L-thyroxin (T4; stimulatory) affects metabolic costs and energy allocation during and after metamorphosis in a common amphibian (Rana temporaria). We further tested for possible carry-over effects of endocrine disruption during larval stage on juvenile performance. Energy allocated to development was negatively related to metabolic rate and thus, tadpoles exposed to T4 could allocate 24% less energy to development during metamorphic climax than control animals. Therefore, the energy available for metamorphosis was reduced in tadpoles with increased TH level by exposure to T4. We suggest that differences in metabolic rate caused by altered TH levels during metamorphic climax and energy allocation to maintenance costs might have contributed to a reduced energetic efficiency in tadpoles with high TH levels. Differences in size and energetics persisted beyond the metamorphic boundary and impacted on juvenile performance. Performance differences are mainly related to strong size-effects, as altered TH levels by exposure to T4 and SP significantly affected growth and developmental rate. Nevertheless, we assume that juvenile performance is influenced by a size-independent effect of achieved TH. Energetic efficiency varied between treatments due to differences in size allocation of internal macronutrient stores. Altered TH levels as caused by several environmental stressors lead to persisting effects on metamorphic traits and energetics and, thus, caused carry-over effects on performance of froglets. We demonstrate the mechanisms through which alterations in abiotic and biotic environmental factors can alter phenotypes at metamorphosis and reduce lifetime fitness in these and likely other amphibians.

Risk assessment of dietary exposure to perchlorate for the Austrian population.

Perchlorate is frequently found as contaminant in a variety of food. Based on analytical data of perchlorate occurrence in food products from the Austrian market, this study calculated dietary perchlorate exposure of the Austrian population for the three age classes of adults, children and infants. Furthermore, a detailed risk assessment was conducted based on the tolerable daily intake (TDI) of 0.3 µg/kg body weight/day, established by the European Food Safety Authority in 2014. Calculations of a scenario of average food consumption did not indicate elevated health risks by dietary perchlorate uptake. Exposure estimates reached only 12%, 26% and 24% of the TDI for adults, children and infants, respectively. However, in a scenario of high consumption, the TDI was exceeded by all age classes with 132%, 161% and 156%. The major cause for this exceedance is the comparatively high perchlorate contamination of spinach, but also other leaf vegetables, legumes and pineapples, leading to elevated exposure of high consumers. Our calculations reveal that the current provisional intra-Union trade reference level for perchlorate in spinach of 0.2 mg/kg, advocated by the European Commission, is not sufficient to protect high consumers against possible health risks. In order to reduce health risks to a tolerable level for all consumers, lowering of the regulatory maximum perchlorate concentrations is indicated. Moreover, a generally diversified diet can also counteract excessive exposure to perchlorate as well as to other harmful food contaminants.

Identifying Subpopulations Vulnerable to the Thyroid-Blocking Effects of Perchlorate and Thiocyanate.

Context: Common environmental contaminants can disrupt normal thyroid function, which plays essential but varying roles at different ages. Objective: To evaluate the relationship of perchlorate, thiocyanate, and nitrate, three sodium-iodide symporter (NIS) inhibitors, and thyroid function in different age-sex-stratified populations. Design, Setting, Participants, and Intervention: This was a cross-sectional analysis of data from the 2009 to 2012 National Health and Nutrition Examination Survey evaluating the exposure to perchlorate, thiocyanate, and nitrate in 3151 participants aged 12 to 80. Main Outcome Measure: Blood serum free thyroxine (FT4) as both a continuous and categorical variable. We also assessed blood serum thyroid stimulating hormone. Results: Controlling for serum cotinine, body mass index, total daily energy consumption, race/ethnicity, and poverty-to-income ratio, for each log unit increase in perchlorate, FT4 decreased by 0.03 ng/dL in both the general population (P = 0.004) and in all women (P = 0.005), and by 0.06 ng/dL in adolescent girls (P = 0.029), corresponding to 4% and 8% decreases relative to median FT4, respectively. For each log unit increase thiocyanate, FT4 decreased by 0.07 ng/dL in adolescent boys (P = 0.003), corresponding to a 9% decrease relative to median FT4, respectively. Conclusions: Our results indicate that adolescent boys and girls represent vulnerable subpopulations to the thyroid-blocking effects of NIS symporter inhibitors. These results suggest a valuable screening and intervention opportunity.

Perchlorate Exposure Reduces Primordial Germ Cell Number in Female Threespine Stickleback.

Perchlorate is a common aquatic contaminant that has long been known to affect thyroid function in vertebrates, including humans. More recently perchlorate has been shown to affect primordial sexual differentiation in the aquatic model fishes zebrafish and threespine stickleback, but the mechanism has been unclear. Stickleback exposed to perchlorate from fertilization have increased androgen levels in the embryo and disrupted reproductive morphologies as adults, suggesting that perchlorate could disrupt the earliest stages of primordial sexual differentiation when primordial germ cells (PGCs) begin to form the gonad. Female stickleback have three to four times the number of PGCs as males during the first weeks of development. We hypothesized that perchlorate exposure affects primordial sexual differentiation by reducing the number of germ cells in the gonad during an important window of stickleback sex determination at 14-18 days post fertilization (dpf). We tested this hypothesis by quantifying the number of PGCs at 16 dpf in control and 100 mg/L perchlorate-treated male and female stickleback. Perchlorate exposure from the time of fertilization resulted in significantly reduced PGC number only in genotypic females, suggesting that the masculinizing effects of perchlorate observed in adult stickleback may result from early changes to the number of PGCs at a time critical for sex determination. To our knowledge, this is the first evidence of a connection between an endocrine disruptor and reduction in PGC number prior to the first meiosis during sex determination. These findings suggest that a mode of action of perchlorate on adult reproductive phenotypes in vertebrates, including humans, such as altered fecundity and sex reversal or intersex gonads, may stem from early changes to germ cell development.

Derivation of the critical effect size/benchmark response for the dose-response analysis of the uptake of radioactive iodine in the human thyroid.

Potential adverse effects of chemical substances on thyroid function are usually examined by measuring serum levels of thyroid-related hormones. Instead, recent risk assessments for thyroid-active chemicals have focussed on iodine uptake inhibition, an upstream event that by itself is not necessarily adverse. Establishing the extent of uptake inhibition that can be considered de minimis, the chosen benchmark response (BMR), is therefore critical. The BMR values selected by two international advisory bodies were 5% and 50%, a difference that had correspondingly large impacts on the estimated risks and health-based guidance values that were established. Potential treatment-related inhibition of thyroidal iodine uptake is usually determined by comparing thyroidal uptake of radioactive iodine (RAIU) during treatment with a single pre-treatment RAIU value. In the present study it is demonstrated that the physiological intra-individual variation in iodine uptake is much larger than 5%. Consequently, in-treatment RAIU values, expressed as a percentage of the pre-treatment value, have an inherent variation, that needs to be considered when conducting dose-response analyses. Based on statistical and biological considerations, a BMR of 20% is proposed for benchmark dose analysis of human thyroidal iodine uptake data, to take the inherent variation in relative RAIU data into account. Implications for the tolerated daily intakes for perchlorate and chlorate, recently established by the European Food Safety Authority (EFSA), are discussed.

[Should we fear the perchlorate ion in the environment?]. / Faut-il craindre les ions perchlorate dans l'environnement ?

Perchlorate ions (ClO4(-)) are present in groundwater and are then present in distribution networks of drinking water destined for human consumption. The perchlorate ion comes mainly from ammonium salt manufactured for industrial activities or from arms of the First World War. Perchlorate ion is a competitive inhibitor of the sodium-iodide symporter and inhibits the synthesis of thyroid hormones. Values of toxicity have been published by the French agency ANSES and are used by authorities to limit the consumption of drinking water of some distribution networks by children and pregnant women especially in Nord-Pas-de-Calais and Picardie. Epidemiological data in other countries show no or little clinical effect in areas with similar contamination; it is therefore a precautionary principle. An effective substitution with iodine would limit the effects of the iodine deficiency itself but also would counteract the potential effects of an excess of perchlorate ions and also of other symporter inhibitors (thiocyanate, nitrate). Further studies are nevertheless needed to determine possible extra-thyroid effects of perchlorate ions.

Effect of Cone-Beam Computed Tomography Field of View and Acquisition Frame on the Detection of Chemically Simulated Peri-Implant Bone Loss In Vitro.

BACKGROUND: The aim of this study is to determine the influence of field of view (FOV) and number of acquisition projection images (frames) on the detection of chemically simulated peri-implant defects by cone-beam computed tomography (CBCT) using an in vitro bovine rib bone model. METHODS: Eighty implants were placed in bovine ribs in which small and large bone defects were created using 70% perchloric acid. CBCT images were acquired at three acquisition protocols: protocol 1 (FOV 4 × 4 cm, 0.08-mm voxel size, 1,009 frames [high fidelity]; protocol 2 (same as protocol 1 except 512 frames [standard]); and protocol 3 (FOV 14 × 5 cm, 0.25-mm voxel size; high fidelity). Two oral and maxillofacial radiologists (OMRs) and two oral and maxillofacial surgeons (OMSs) rated the presence or absence of bone defects on a five-point scale. κ and area under the curve (AUC) were calculated and compared using analysis of variance with post hoc Tukey test at P ≤ 0.05. RESULTS: Intra- and interobserver agreement for OMRs ranged from moderate to good and from slight to moderate for OMSs. For the detection of small lesions, protocol 1 (AUC 0.813 ± 0.045) provided higher detection rates than protocol 2 (AUC 0.703 ± 0.02) and protocol 3 (AUC 0.773 ± 0.55) [F(2,9) = 1.6377]. For larger defects, the trends were similar, with protocol 1 (AUC 0.852 ± 0.108) providing higher detection rates than protocol 2 (AUC 0.730 ± 0.045) and protocol 3 (AUC 0.783 ± 0.058) [F(2,9) = 1.9576]. CONCLUSION: Within the limits of this study, optimal detection of chemically simulated pericircumferential implant crestal bone defects is achieved at the least radiation detriment using the smallest FOV, the highest number of acquisition frames, and the smallest voxel.

A new method for generating distributions of biomonitoring equivalents to support exposure assessment and prioritization.

Biomonitoring data are now available for hundreds of chemicals through state and national health surveys. Exposure guidance values also exist for many of these chemicals. Several methods are frequently used to evaluate biomarker data with respect to a guidance value. The "biomonitoring equivalent" (BE) approach estimates a single biomarker concentration (called the BE) that corresponds to a guidance value (e.g., Maximum Contaminant Level, Reference Dose, etc.), which can then be compared with measured biomarker data. The resulting "hazard quotient" estimates (HQ=biomarker concentration/BE) can then be used to prioritize chemicals for follow-up examinations. This approach is used exclusively for population-level assessments, and works best when the central tendency of measurement data is considered. Complementary approaches are therefore needed for assessing individual biomarker levels, particularly those that fall within the upper percentiles of measurement distributions. In this case study, probabilistic models were first used to generate distributions of BEs for perchlorate based on the point-of-departure (POD) of 7µg/kg/day. These distributions reflect possible biomarker concentrations in a hypothetical population where all individuals are exposed at the POD. A statistical analysis was then performed to evaluate urinary perchlorate measurements from adults in the 2001 to 2002 National Health and Nutrition Examination Survey (NHANES). Each NHANES adult was assumed to have experienced repeated exposure at the POD, and their biomarker concentration was interpreted probabilistically with respect to a BE distribution. The HQ based on the geometric mean (GM) urinary perchlorate concentration was estimated to be much lower than unity (HQ≈0.07). This result suggests that the average NHANES adult was exposed to perchlorate at a level well below the POD. Regarding individuals, at least a 99.8% probability was calculated for all but two NHANES adults that a higher biomarker concentration would have been observed compared to what was actually measured if the daily dietary exposure had been at the POD. This is strong evidence that individual perchlorate exposures in the 2001-2002 NHANES adult population were likely well below the POD. This case study demonstrates that the "stochastic BE approach" provides useful quantitative metrics, in addition to HQ estimates, for comparison across chemicals. This methodology should be considered when evaluating biomarker measurements against exposure guidance values, and when examining chemicals that have been identified as needing follow-up investigation based on existing HQ estimates.

Combined effects of perchlorate, thiocyanate, and iodine on thyroid function in the National Health and Nutrition Examination Survey 2007-08.

Perchlorate, thiocyanate, and low iodine intake can all decrease iodide intake into the thyroid gland. This can reduce thyroid hormone production since iodide is a key component of thyroid hormone. Previous research has suggested that each of these factors alone may decrease thyroid hormone levels, but effect sizes are small. We hypothesized that people who have all three factors at the same time have substantially lower thyroid hormone levels than people who do not, and the effect of this combined exposure is substantially larger than the effects seen in analyses focused on only one factor at a time. Using data from the 2007-2008 National Health and Nutrition Examination Survey, subjects were categorized into exposure groups based on their urinary perchlorate, iodine, and thiocyanate concentrations, and mean serum thyroxine concentrations were compared between groups. Subjects with high perchlorate (n=1939) had thyroxine concentrations that were 5.0% lower (mean difference=0.40 µg/dl, 95% confidence interval=0.14-0.65) than subjects with low perchlorate (n=2084). The individual effects of iodine and thiocyanate were even smaller. Subjects with high perchlorate, high thiocyanate, and low iodine combined (n=62) had thyroxine concentrations 12.9% lower (mean difference=1.07 µg/dl, 95% confidence interval=0.55-1.59) than subjects with low perchlorate, low thiocyanate, and adequate iodine (n=376). Potential confounders had little impact on results. Overall, these results suggest that concomitant exposure to perchlorate, thiocyanate, and low iodine markedly reduces thyroxine production. This highlights the potential importance of examining the combined effects of multiple agents when evaluating the toxicity of thyroid-disrupting agents.

[Health survey of plant workers for an occupational exposure to ammonium perchlorate].

OBJECTIVE: To understand the occupational hazards of ammonium perchlorate dust on operating workers and to provide the basis preventive measures for protecting the workers' health. METHODS: 36 workers exposed to ammonium perchlorate dust and 48 unexposed workers from one factory were selected as the exposure and control groups. Investigations on the general condition, sampling of dust in the workplaces and a special medical examination were conducted for two groups, including occupational history, clinical manifestations, blood routine test, hepatic and renal functions, indexes of thyroid hormone, spirometric test and chest X-ray. RESULTS: The total dust concentration of AP in the batch plant reached to 51.63 ± 43.27 mg/m(3), exceeding the U.S. Occupational Safety and Health Administration (OSHA) permission exposure limits. The systolic blood pressure in the exposure group was higher than that of the control group (146.14 ± 21.03 VS 134.67 ± 18.58), and the difference was statistically significant (P < 0.05). The detection rates of the cumulative total symptoms, short of breath and skin itch symptoms in the exposure group were significantly higher than those in the control group (86.11% VS 66.67%; 30.56% VS 12.50%) (P < 0.05), respectively. FT(3) level in the exposure group significantly lowered than the control group, and the difference was statistically significant (P < 0.01); The pulmonary function result showed that FEV1/FVC% in the exposure group was lower than that in the control group (106.50 ± 28.99 VS 111.70 ± 19.72), but the difference was not significant. X-ray examination revealed one case of pulmonary X-ray abnormalities in the exposure group, diagnosis of pneumoconiosis, and one case with about 1.0 × 1.0 small nodules detected on the left of lung door area in the control group. CONCLUSIONS: The systolic blood pressure of workers in the exposure group was significantly higher, which could not exclude related to the exposure to AP dust; The T(3) levels in the exposure workers were lower than those in the control group, which may due to AP exposure, suggesting that long-term chronic exposure to AP dust may affect thyroid function.

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.

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 177 µg/g of perchlorate (as NaClO(4)), respectively, to determine impacts on glandular thyroxine concentrations, embryonic growth and development, and metabolic rates of hatchlings for a period of 2 months 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.