Association between environmental exposure to perchlorate, nitrate, and thiocyanate and serum α-Klotho levels among adults from the National Health and nutrition examination survey (2007-2014).

BACKGROUND & AIMS: Aging is a pathophysiological process driven by a diverse set of complex biological processes, and environmental pollution plays an important role in this process. This study aimed to explore the association between serum α-Klotho levels and urinary perchlorate, nitrate, and thiocyanate levels. METHODS: This secondary dataset analysis included 4875 participants (mean age, 57.69 year; male, 49.58%; non-Hispanic White, 47.67%) from the US National Health and Nutrition Examination Survey (2007-2014). Enzyme-linked immunosorbent assay was used to quantify α-Klotho levels, and ion chromatography coupled with electrospray tandem mass spectrometry was used to quantify thiocyanate, nitrate, and perchlorate levels. Multivariate linear regression models were applied to estimate the association between perchlorate, nitrate, and thiocyanate levels and serum α-Klotho levels. RESULTS: Urinary thiocyanate levels were negatively associated with α-Klotho levels (ß = - 0.006; 95% confidence interval, - 0.010 to - 0.003; P = 0.0004) after adjusting for age, sex, body mass index, race, alcohol consumption, estimated glomerular filtration rate, underlying disease, physical activity, smoking status, usual energy intake, and urinary creatinine and serum cotinine levels and mutual adjustment of urinary perchlorate, urinary nitrate, and urinary thiocyanate levels. The α-Klotho level in participants in the highest quartile was higher by 50.567 ng/mL (ß = 50.567; 95% confidence interval, 14.407 to 86.726; P = 0.009) than that in participants in the lowest quartile of urinary perchlorate. A linear relationship was observed between urinary thiocyanate and α-Klotho levels. CONCLUSIONS: Urinary thiocyanate levels were negatively associated with serum α-Klotho levels. Urinary thiocyanate should be further investigated as a potential mediator of aging and age-related diseases.

Thiocyanate in excess develops goiter followed by auto immune thyroid diseases even after effective salt iodization in a rural community of north east India.

PURPOSE: Salt iodization in Manipur of north-east India failed to prevent endemic goiter, therefore an in depth study carried out to evaluate thyroid functions of goitrous subjects in a randomly selected region. METHODS: Goiter survey conducted in children and women of reproductive ages by palpation followed by measurement of urinary iodine, thiocyanate and house-hold salt iodine to evaluate iodine nutritional status and consumption pattern of bamboo-shoots (BS). In all grade-2 goitrous subjects, free thyroxine, triiodothyronine, TSH, TPO and Tg antibodies, thyroid volume and echogenecity by ultrasonography and cytomorphology of thyroid by FNAC studied. RESULTS: Study population was 2486 children and 1506 women, goiter prevalence was 12.59% and 16.27% respectively; median urinary iodine and mean thiocyanate were 166 µg/l and 0.729 ± 0.408 mg/dl while salt iodine was ≥30 ppm. Serum thyroid hormones and TSH profiles of all grade-2 goitrous subjects showed 16.21% were subclinically hypothyroid, 2.16% overt hypothyroid, 4.86% subclinically hyperthyroid and 6.48% overt hyperthyroid, serum TPO- and Tg-antibodies found positive in 41.62%. Ultrasonographic results showed 24% had enlarged thyroid and 86.4% hypoechoic. Cytomorphological studies showed prevalence of colloid goiter (41.08%), lymphocytic thyroiditis (37.83%), Hashimoto's thyroiditis (8.10%), autoimmune thyroiditis (4.32%), sub-acute thyroiditis (2.16%) and 1.62% each papillary, medullary carcinoma, simple diffused hyperplasia and adenomoid nodular goiter. CONCLUSIONS: Grade-2 goitrous individuals in this mild goiter endemic region were affected by hypo- and hyperthyroidism with hypoechoic thyroid and thyroiditis. Thiocyanate that originates from BS even in presence of adequate iodine developed goiter and led goitrous population towards such diseases.

Absorption and metabolism of isothiocyanates formed from broccoli glucosinolates: effects of BMI and daily consumption in a randomised clinical trial.

Sulphoraphane originates from glucoraphanin in broccoli and is associated with anti-cancer effects. A preclinical study suggested that daily consumption of broccoli may increase the production of sulphoraphane and sulphoraphane metabolites available for absorption. The objective of this study was to determine whether daily broccoli consumption alters the absorption and metabolism of isothiocyanates derived from broccoli glucosinolates. We conducted a randomised cross-over human study (n 18) balanced for BMI and glutathione S-transferase µ 1 (GSTM1) genotype in which subjects consumed a control diet with no broccoli (NB) for 16 d or the same diet with 200 g of cooked broccoli and 20 g of raw daikon radish daily for 15 d (daily broccoli, DB) and 100 g of broccoli and 10 g of daikon radish on day 16. On day 17, all subjects consumed a meal of 200 g of broccoli and 20 g of daikon radish. Plasma and urine were collected for 24 h and analysed for sulphoraphane and metabolites of sulphoraphane and erucin by triple quadrupole tandem MS. For subjects with BMI >26 kg/m2 (median), plasma AUC and urinary excretion rates of total metabolites were higher on the NB diet than on the DB diet, whereas for subjects with BMI <26 kg/m2, plasma AUC and urinary excretion rates were higher on the DB diet than on the NB diet. Daily consumption of broccoli interacted with BMI but not GSTM1 genotype to affect plasma concentrations and urinary excretion of glucosinolate-derived compounds believed to confer protection against cancer. This trial was registered as NCT02346812.

Diverse Excretion Pathways of Benzyl Glucosinolate in Humans after Consumption of Nasturtium (Tropaeolum majus L.)-A Pilot Study.

SCOPE: Different metabolic and excretion pathways of the benzyl glucosinolate breakdown products benzyl isothiocyanate and benzyl cyanide are investigated to obtain information about their multiple fate after ingestion. Detailed focus is on the so far underestimated transformation/excretion pathways-protein conjugation and exhalation. METHODS AND RESULTS: Metabolites, protein conjugates, and non-conjugated isothiocyanates are determined in plasma, urine, and breath of seven volunteers after consuming freeze-dried nasturtium or bread enriched with nasturtium. Samples are collected up to 48 h at selected time points. The metabolites of the mercapturic acid pathway are detectable in plasma up to 24 h after consumption. Additionally, mercapturic acid is the main metabolite in urine, but non-conjugated benzyl isothiocyanate is detectable as well. Protein conjugates show high amounts in plasma even 48 h after consumption. In breath, benzyl isothiocyanate and benzyl cyanide are detectable up to 48 h after consumption. CONCLUSION: Isothiocyanates are not only metabolized via the mercapturic acid pathway, but also form protein conjugates in blood and are exhaled. To balance intake and excretion, it is necessary to investigate all potential metabolites and excretion routes. This has important implications for the understanding of physiological and pharmacological effects of isothiocyanate-containing products.

A case-control study of urinary levels of iodine, perchlorate and thiocyanate and risk of papillary thyroid cancer.

BACKGROUND: The incidence of thyroid cancer has recently increased worldwide. With the exception of radiation exposure, the effects of potential risk factors on thyroid cancer incidence remain controversial. OBJECTIVES: The association between exposure to iodine, perchlorate, and thiocyanate and papillary thyroid cancer (PTC) incidence was evaluated and risk factors were predicted. METHODS: A pair-matching case-control study was performed including 116 age- and sex-matched PTC cases and 116 non-PTC controls. Iodine, perchlorate, and thiocyanate concentrations in urine specimens were determined by inductively coupled plasma mass spectrometry and ultra-performance liquid chromatography-tandem mass spectrometry. The association between iodine, perchlorate, and thiocyanate urinary concentrations and PTC was evaluated using univariable conditional regression logistic analysis followed by multivariable conditional logistic regression analyses with backward stepwise selection to predict risk factors for PTC. RESULTS: After adjusting for confounders and creatinine standardization, urinary concentrations of iodine [odds ratio (OR) = 11.01, 95% confidence interval (CI): 1.97-30.52] and perchlorate (OR = 2.27, 95% CI: 1.03-5.03) were associated with the risk of PTC, whereas urinary thiocyanate concentration showed a negative association (OR = 0.24, 95% CI: 0.09-0.65). CONCLUSIONS: Increased exposure to iodine and perchlorate may affect PTC development, whereas high thiocyanate exposure may have a beneficial effect.

Urinary Iodine, Perchlorate, and Thiocyanate Concentrations in U.S. Lactating Women.

BACKGROUND: Iodine is an essential micronutrient for thyroid hormone production. Adequate iodine intake and normal thyroid function are important during early development, and breastfed infants rely on maternal iodine excreted in breast milk for their iodine nutrition. The proportion of women in the United States of childbearing age with urinary iodine concentration (UIC) <50 µg/L has been increasing, and a subset of lactating women may have inadequate iodine intake. UIC may also be influenced by environmental exposure to perchlorate and thiocyanate, competitive inhibitors of iodine transport into thyroid, and lactating mammary glands. Data regarding UIC in U.S. lactating women are limited. To adequately assess the iodine sufficiency of lactating women and potential associations with environmental perchlorate and thiocyanate exposure, we conducted a multicenter, cross-sectional study of urinary iodine, perchlorate, and thiocyanate concentrations in healthy U.S. lactating women. METHODS: Lactating women ≥18 years of age were recruited from three U.S. geographic regions: California, Massachusetts, and Ohio/Illinois from November 2008 to June 2016. Demographic information and multivitamin supplements use were obtained. Iodine, perchlorate, and thiocyanate levels were measured from spot urine samples. Correlations between urinary iodine, perchlorate, and thiocyanate levels were determined using Spearman's rank correlation. Multivariable regression models were used to assess predictors of urinary iodine, perchlorate, and thiocyanate levels, and UIC <100 µg/L. RESULTS: A total of 376 subjects (≥125 from each geographic region) were included in the final analyses [mean (SD) age 31.1 (5.6) years, 37% white, 31% black, and 11% Hispanic]. Seventy-seven percent used multivitamin supplements, 5% reported active cigarette smoking, and 45% were exclusively breastfeeding. Median urinary iodine, perchlorate, and thiocyanate concentrations were 143 µg/L, 3.1 µg/L, and 514 µg/L, respectively. One-third of women had UIC <100 µg/L. Spot urinary iodine, perchlorate, and thiocyanate levels all significantly positively correlated to each other. No significant predictors of UIC, UIC <100 µg/L, or urinary perchlorate levels were identified. Smoking, race/ethnicity, and marital status were significant predictors of urinary thiocyanate levels. CONCLUSION: Lactating women in three U.S. geographic regions are iodine sufficient with an overall median UIC of 143 µg/L. Given ubiquitous exposure to perchlorate and thiocyanate, adequate iodine nutrition should be emphasized, along with consideration to decrease these exposures in lactating women to protect developing infants.

Exposure to perchlorate, nitrate and thiocyanate, and prevalence of diabetes mellitus.

Background: It is known that perchlorate, nitrate and thiocyanate have the property of inhibiting sodium iodide symporter. Animal studies have suggested that these compounds, especially perchlorate, might also interfere with insulin secretion. However, the association between their exposure and diabetes risk is largely unknown in humans. Methods: Among 11 443 participants (mean age 42.3 years) from the National Health and Nutritional Examination Survey 2001-14, urinary perchlorate, nitrate and thiocyanate were measured by using ion chromatography coupled with electrospray tandem mass spectrometry. Diabetes was defined as self-reported doctor diagnosis, use of oral hypoglycaemic medication or insulin, fasting plasma glucose ≥ 126 mg/dl or glycated haemoglobin A1c (HbA1c) ≥ 6.5%. Results: The median (interquartile range) levels of urinary perchlorate, nitrate and thiocyanate were 3.32 (1.84, 5.70) µg/l, 46.4 (27.9, 72.0) mg/l and 1.23 (0.59, 2.78) mg/l, respectively. Higher levels of urinary perchlorate were associated with elevated levels of fasting glucose, HbA1c, insulin and homeostatic model assessment of insulin resistance (all Ptrend < 0.001). After multivariate adjustment including urinary creatinine, smoking status and body mass index (BMI), higher urinary perchlorate, but not nitrate or thiocyanate, was associated with an increased prevalence of diabetes mellitus. Comparing extreme quintiles, the odds ratio (95% confidence interval) of diabetes was 1.53 (1.21, 1.93; Ptrend < 0.001) for perchlorate, 1.01 (0.77, 1.32; Ptrend = 0.44) for nitrate and 0.98 (0.73, 1.31; Ptrend = 0.64) for thiocyanate. When urinary perchlorate, nitrate and thiocyanate were further mutually adjusted, the results did not materially change. Similar results were observed when analyses were stratified by smoking status, as well as by age, gender, kidney function and BMI. Conclusions: Higher urinary perchlorate levels are associated with an increased prevalence of diabetes mellitus, independent of traditional risk factors. Future prospective studies are needed to confirm these findings.

Effect of Nitrates, Thiocyanates and Selenium on the Iron and Iodine Status of Postpartum Women.

AIM: To find correlations between high thiocyanate and nitrate levels and low selenium levels and the indicators of the iodine and iron status of postpartum women. MATERIALS AND METHODS: The study included 41 mothers aged 26.4±5.9 yrs from Asenovgrad and nearby villages. Urinary iodine was determined by the Sandell-Kolthoff reaction and thiocyanate - by the interaction of these ions with acidic solution of KMnO4; for serum nitrates we used the colorimetric method; serum selenium was assessed by electro-thermal atomic-absorption spectrophotometry; thyroxin (FT4), the thyroid stimulating hormone (TSH), serum ferritin (SF), and serum transferrin receptor (sTfR) were determined using ELISA; Hb levels were determined by hematology analyzer. RESULTS: Assessing the iodine status, we found a negative correlation between the levels of iodine and thiocyanates in urine (R=-0.717, р<0.0001), a positive correlation between nitrates and TSH (R=0.487, р=0.003) and a negative correlation between nitrates and FT4 (R=-0.312, р=0.06). For the iron status, we found a negative correlation between nitrates and SF (R=-0.429, р=0.009) and between nitrates and Hb (R=-0.383, р=0.021). The Mann-Whitney U-test showed that in women with nitrate levels higher than the mean value there was low FT4 level (р=0.06), high TSH level (р=0.013), low Hb concentration (р=0.061) and low SF concentration (р=0.005). The combined effects of environmental factors (elevated nitrate levels and low selenium level) on the iodine and iron status are manifested by low concentrations of FT4 (р=0.033), Hb (р=0.06) and SF (р=0.05) and high level of TSH (р=0.05). In conclusion, we found that environmental factors, especially when combined, have a negative impact on the iron and iodine status of females.

Development of a PBPK model of thiocyanate in rats with an extrapolation to humans: A computational study to quantify the mechanism of action of thiocyanate kinetics in thyroid.

Thyroid homeostasis can be disturbed due to thiocyanate exposure from the diet or tobacco smoke. Thiocyanate inhibits both thyroidal uptake of iodide, via the sodium-iodide symporter (NIS), and thyroid hormone (TH) synthesis in the thyroid, via thyroid peroxidase (TPO), but the mode of action of thiocyanate is poorly quantified in the literature. The characterization of the link between intra-thyroidal thiocyanate concentrations and dose of exposure is crucial for assessing the risk of thyroid perturbations due to thiocyanate exposure. We developed a PBPK model for thiocyanate that describes its kinetics in the whole-body up to daily doses of 0.15mmol/kg, with a mechanistic description of the thyroidal kinetics including NIS, passive diffusion, and TPO. The model was calibrated in a Bayesian framework using published studies in rats. Goodness-of-fit was satisfactory, especially for intra-thyroidal thiocyanate concentrations. Thiocyanate kinetic processes were quantified in vivo, including the metabolic clearance by TPO. The passive diffusion rate was found to be greater than NIS-mediated uptake rate. The model captured the dose-dependent kinetics of thiocyanate after acute and chronic exposures. Model behavior was evaluated using a Morris screening test. The distribution of thiocyanate into the thyroid was found to be determined primarily by the partition coefficient, followed by NIS and passive diffusion; the impact of the latter two mechanisms appears to increase at very low doses. Extrapolation to humans resulted in good predictions of thiocyanate kinetics during chronic exposure. The developed PBPK model can be used in risk assessment to quantify dose-response effects of thiocyanate on TH.

Thyroid antagonists and thyroid indicators in U.S. pregnant women in the Vanguard Study of the National Children's Study.

The sodium iodide-symporter (NIS) mediates uptake of iodide into thyroid follicular cells. This key step in thyroid hormone synthesis is inhibited by perchlorate, thiocyanate (SCN) and nitrate (NO3) anions. When these exposures occur during pregnancy the resulting decreases in thyroid hormones may adversely affect neurodevelopment of the human fetus. Our objectives were to describe and examine the relationship of these anions to the serum thyroid indicators, thyroid stimulating hormone (TSH) and free thyroxine (FT4), in third trimester women from the initial Vanguard Study of the National Children's Study (NCS); and to compare urine perchlorate results with those in pregnant women from the National Health and Nutritional Examination Survey (NHANES). Urinary perchlorate, SCN, NO3, and iodine, serum TSH, FT4, and cotinine were measured and a food frequency questionnaire (FFQ) was administered to pregnant women enrolled in the initial Vanguard Study. We used multiple regression models of FT4 and TSH that included perchlorate equivalent concentration (PEC, which estimates combined inhibitory effects of the anions perchlorate, SCN, and NO3 on the NIS). We used multiple regression to model predictors of each urinary anion, using FFQ results, drinking water source, season of year, smoking status, and demographic characteristics. Descriptive statistics were calculated for pregnant women in NHANES 2001-2012. The geometric mean (GM) for urinary perchlorate was 4.04µg/L, for TSH 1.46mIU/L, and the arithmetic mean for FT4 1.11ng/dL in 359 NCS women. In 330 women with completed FFQs, consumption of leafy greens, winter season, and Hispanic ethnicity were significant predictors of higher urinary perchlorate, which differed significantly by study site and primary drinking water source, and bottled water was associated with higher urinary perchlorate compared to filtered tap water. Leafy greens consumption was associated with higher urinary NO3 and higher urinary SCN. There was no association between urinary perchlorate or PEC and TSH or FT4, even for women with urinary iodine <100µg/L. GM urinary perchlorate concentrations in the full sample (n=494) of third trimester NCS women (4.03µg/L) were similar to pregnant women in NHANES (3.58µg/L).

Trends and variability in the levels of urinary thiocyanate, perchlorate, and nitrate by age, gender, race/ethnicity, smoking status, and exposure to environmental tobacco smoke over 2005-2012.

Data from National Health and Nutrition Examination Survey for 2005-2012 were used to study the trends and variability in the levels of urinary thiocyanate (u-SCN), perchlorate (u-P8), and nitrate (u-NO3) by gender, race/ethnicity, active smoking, and exposure to environmental tobacco smoke (ETS) at home for those aged 12-19 and ≥20years old. For those aged ≥20years, adjusted levels of u-SCN, u-P8, and u-NO3 (i) were lower for males than females (p<0.01), and (ii) were higher for non-Hispanic white (NHW) than non-Hispanic black (NHB) (p<0.01). Also, for those aged ≥20years NHB had higher adjusted levels than Mexican American (MA) for u-SCN (p<0.01) but NHB had lower adjusted levels than MA for u-P8 (p<0.01) and u-NO3 (p<0.01). For those aged 12-19years, adjusted levels of u-SCN, u-P8, and u-NO3 did not vary by gender (p>0.05), and adjusted levels of u-P8 and u-NO3 for NHB were lower than for NHW (p<0.01) as well as higher for NHB than MA for u-SCN (p<0.01) and lower for NHB than MA (p<0.01) for u-P8 and u-NO3. Among those aged ≥20years, active smoking was associated with higher adjusted levels of u-SCN (p<0.01) in a dose-response manner and active smoking was associated with lower adjusted levels of u-P8 (p<0.01) in a dose-response manner. Exposure to ETS was associated with higher adjusted levels of u-SCN (p=0.02) and lower adjusted levels of u-P8 (p<0.01) among ≥20years old. Adjusted levels of u-P8 decreased over 2005-2012 among both 12-19 (p<0.01) and ≥20years old (p=0.04). There was borderline increase in the adjusted levels of u-NO3 for those aged ≥20years (p=0.05) over 2005-2012.

Synthesis and characterization of bis nitrato[4-hydroxyacetophenonesemicarbazone) nickel(II) complex as ionophore for thiocyanate-selective electrode.

The PVC based-ion selective electrode viz., bis nitrato[4-hydroxyacetophenone semicarbazone] nickel(II) as an ionophore was prepared for the determination of thiocyanate ion. The ionophore was characterized by FT-IR, UV-vis, XRD, magnetic moment and elemental analysis (CHN). On the basis of spectral studies an octahedral geometry has been assigned. The best performance was obtained with a membrane composition of 31% PVC, 63% 2-nitrophenyl octylether, 4.0% ionophore and 2.0% trioctylmethyl ammonium chloride. The electrode exhibited an excellent Nernstian response to SCN(-) ion ranging from 1.0 × 10(-7) to 1.0 × 10(-1)M with a detection limit of 8.6 × 10(-8)M and a slope of -59.4 ± 0.2 mV/decade over a wide pH range (1.8-10.7) with a fast response time (6s) at 25 °C. The proposed electrode showed high selectivity for thiocyanate ion over a number of common inorganic and organic anions. It was successfully applied to direct determination of thiocyanate in biological (urine and saliva) samples in order to distinguish between smokers and non-smokers, environmental samples and as an indicator electrode for titration of thiocyanate ions with AgNO3 solution.

Effect of Thiocyanate on Iodine Status of Pregnant Women.

The aim of this study was to assess the thyroid status of pregnant women on the basis of biochemical indicators and to evaluate the potential risk of developing iodine deficiency as a result of tobacco smoke exposure by assessing the association between urinary thiocyanate levels and the manifestation of iodine deficiency. The study included 219 pregnant women from the town of Plovdiv and Plovdiv District in Southern Bulgaria. The levels of urinary iodine, thyroid-stimulating hormone (TSH), free thyroxine (FT4), and urinary thiocyanate as indicators of tobacco smoke exposure were measured. Most of the pregnant women (60.1 %) were found to have iodine deficiency, 10.6 % of them had TSH values greater than 4 mIU/L, and 16.4 % had FT4 below 9 pmol/L. There were negative correlations between urinary iodine levels and thiocyanate/creatinine ratio (R = -0.148, р = 0.034) and between thiocyanate/creatinine ratio and FT4 (R = -0.379, p < 0.0001); thiocyanate/creatinine ratio and serum TSH were positively correlated (R = 0.169, p = 0.019). Logistic regression analysis showed that pregnant women in whom the thiocyanate/creatinine ratio was greater than the median value of 3.57 mg/g had a 3.882-fold higher risk of developing iodine deficiency (urinary iodine <150 µg/L) than the pregnant women with lower thiocyanate levels (OR = 3.882, 95 % CI 1.402-10.751, p = 0.009). Higher levels of urinary thiocyanate were found in women exposed to tobacco smoke, and quantification of these ions in urine provided a fast non-invasive method to monitor thiocyanate load. Due to the competitive inhibition of iodine intake by thiocyanates, their levels should be carefully monitored, especially in cases of severe iodine deficiency.

Thyroid Antagonists (Perchlorate, Thiocyanate, and Nitrate) and Childhood Growth in a Longitudinal Study of U.S. Girls.

BACKGROUND: Perchlorate, thiocyanate, and nitrate are sodium/iodide symporter (NIS) inhibitors that block iodide uptake into the thyroid, thus affecting thyroid function. Thyroid dysfunction can adversely affect somatic growth and development in children. To our knowledge, no studies have examined effects of NIS inhibitors on body size measures. OBJECTIVE: We investigated associations between NIS inhibitors and childhood growth in 940 girls from the Puberty Study of the Breast Cancer and Environment Research Program. METHODS: Urine samples collected from girls 6-8 years of age at enrollment (2004-2007) from New York City, greater Cincinnati, Ohio, and the Bay Area in California were analyzed for NIS inhibitors and creatinine (C). The longitudinal association between NIS inhibitors and anthropometric measures [height, waist circumference, and body mass index (BMI)] during at least three visits was examined using mixed effects linear models, adjusted for race and site. RESULTS: Compared with girls in the low-exposure group (3.6, 626, and 500 mg/gC, median perchlorate, thiocyanate, and nitrate, respectively) girls with the highest NIS inhibitor exposure (9.6, 2,343, and 955 mg/gC, median perchlorate, thiocyanate, and nitrate, respectively) had slower growth in waist circumference and BMI but not height. Significant differences in the predicted mean waist circumference and BMI between the low- and high-exposure groups were observed beginning at 11 years of age. CONCLUSIONS: Higher NIS inhibitor exposure biomarkers were associated with reductions in waist circumference and BMI. These findings underscore the need to assess exposure to NIS inhibitors with respect to their influence on childhood growth. CITATION: Mervish NA, Pajak A, Teitelbaum SL, Pinney SM, Windham GC, Kushi LH, Biro FM, Valentin-Blasini L, Blount BC, Wolff MS, for the Breast Cancer and Environment Research Project (BCERP). 2016. Thyroid antagonists (perchlorate, thiocyanate, and nitrate) and childhood growth in a longitudinal study of U.S. girls. Environ Health Perspect 124:542-549; http://dx.doi.org/10.1289/ehp.1409309.

High-mobility group box 1 protein levels in serum of subjects after exposure to fire smoke--short communication.

INTRODUCTION: Fire smoke inhalation a recognized etiologic factor of airway injuries. The objective of this study was evaluation of serum high-mobility group box 1 (HMGB1) protein concentration in subjects exposed to fire smoke (SEFS). MATERIAL AND METHODS: The study group consisted of 40 consecutive patients admitted to the Toxicology Unit, Lodz, Poland after exposure to fire smoke. Serum HMGB1 concentrations were measured upon admission to hospital and rechecked on the 2nd and on the day of discharge. Patients also underwent routine toxicological diagnostic procedures applied in case of those exposures, such as carboxyhaemoglobin (COHb) levels and urinary thiocyanate concentrations. The same diagnostic tests were performed in 10 healthy volunteers not exposed to smoke of the control group. RESULTS: The average serum SEFS concentration of HMGB1 protein was not significantly higher on admission in comparison with the respective values recorded on the 2nd day and on the day of discharge. The mean serum level of HMGB1 protein of exposed group was higher than that one in the control group, however the difference was not statistically significant. The highest concentration of HMGB1 protein was noted in serum of 28 subjects exposed to fire smoke reporting at least one symptom and the difference was statistically significant in a comparison with the control group. CONCLUSION: As indicated, an acute exposure to smoke may lead to transient increase of HMGB1 in serum in exposed subjects. Further studies are necessary in order to confirm the importance of this protein in pathogenesis of acute airway injury due to exposure to fire smoke.

Urinary heavy metals, phthalates, phenols, thiocyanate, parabens, pesticides, polyaromatic hydrocarbons but not arsenic or polyfluorinated compounds are associated with adult oral health: USA NHANES, 2011-2012.

Links between environmental chemicals and human health have emerged over the last few decades, but the effects on oral health have been less studied. Therefore, it was aimed to study the relationships of different sets of urinary chemical concentrations and adult oral health conditions in a national and population-based setting. Data was retrieved from the United States National Health and Nutrition Examination Surveys, 2011-2012 including demographics, self-reported oral health conditions and urinary environmental chemical concentrations (one third representative sample of the study population). Chi-square test, t test, and survey-weighted logistic and multi-nominal regression modeling were performed. Of 4566 American adults aged 30-80, 541 adults (11.9 %) reported poor teeth health while 1020 adults (22.4 %) reported fair teeth. Eight hundred fifty-five people (19.1 %) claimed to have gum disease, presented with higher levels of urinary cadmium, cobalt and polyaromatic hydrocarbons. Six hundred three adults (13.3 %) had bone loss around the mouth, presented with higher levels of cadmium, nitrate, thiocyanate, propyl paraben and polyaromatic hydrocarbons. Eight hundred forty-five adults (18.5 %) had tooth loose not due to injury, presented with higher level of cadmium, thiocyanate and polyaromatic hydrocarbons. Eight hundred forty-five adults (18.5 %) with higher levels of lead, uranium, polyaromatic hydrocarbons but lower level of triclosan noticed their teeth did not look right. Three hundred fifty-one adults (7.7 %) often had aching in the mouth and 650 (14.3 %) had it occasionally, presented with higher levels of phthalates, pesticides and polyaromatic hydrocarbons. Benzophenone-3 and triclosan elicited protective effects. Regulation of environmental chemicals in prevention of adult oral health might need to be considered in future health and environmental policies.

Synergic actions of polyphenols and cyanogens of peanut seed coat (Arachis hypogaea) on cytological, biochemical and functional changes in thyroid.

In animals, long-term feeding with peanut (Arachis hypogaea) seed coats causes hypertrophy and hyperplasia of the thyroid gland. However, to date there have been no detailed studies. Here, we explored the thyroidal effects of dietary peanut seed coats (PSC) in rats. The PSC has high levels of pro-goitrogenic substances including phenolic and other cyanogenic constituents. The PSC was mixed with a standard diet and fed to rats for 30 and 60 days, respectively. Animals fed with the PSC-supplemented diet showed a significant increase in urinary excretion of thiocyanate and iodine, thyroid enlargement, and hypertrophy and/or hyperplasia of thyroid follicles. In addition, there was inhibition of thyroid peroxidase (TPO) activity, 5'-deiodinase-I (DIO1) activity, and (Na+-K+)-ATPase activity in the experimental groups of rats as compared to controls. Furthermore, the PSC fed animals exhibited decreased serum circulating total T4 and T3 levels, severe in the group treated for longer duration. These data indicate that PSC could be a novel disruptor of thyroid function, due to synergistic actions of phenolic as well as cyanogenic constituents.

Association between anaerobic components of the maximal accumulated oxygen deficit and 30-second Wingate test

The purpose of this study was to analyze the relationship between the anaerobic components of the maximal accumulated oxygen deficit (MAOD) and of the 30-second Wingate anaerobic test (30-WAnT). Nine male physical education students performed: a) a maximal incremental exercise test; b) a supramaximal constant workload test to determine the anaerobic components of the MAOD; and c) a 30-WAnT to measure the peak power (PP) and mean power (MP). The fast component of the excess post-exercise oxygen consumption and blood lactate accumulation were measured after the supramaximal constant workload test in order to determine the contributions made by alactic (ALMET) and lactic (LAMET) metabolism. Significant correlations were found between PP and ALMET (r=0.71; P=0.033) and between MP and LAMET (r=0.72; P=0.030). The study results suggested that the anaerobic components of the MAOD and of the 30-WAnT are similarly applicable in the assessment of ALMET and LAMET during high-intensity exercise.

Urinary thiocyanate concentrations are associated with adult cancer and lung problems: US NHANES, 2009-2012.

Links between environmental chemicals and human health have emerged but the effects from perchlorate, nitrate and thiocyanate were unclear. Therefore, it was aimed to study the relationships of urinary perchlorate, nitrate and thiocyanate concentrations and adult health conditions in a national and population-based study. Data was retrieved from US National Health and Nutrition Examination Surveys, 2009-2012, including demographics, blood pressure readings, self-reported health conditions and urinary perchlorate, nitrate and thiocyanate concentrations. Analyses included chi-square test, t test survey-weighted logistic regression models and population attributable risk estimation. There were no clear associations between urinary perchlorate concentrations and adult health conditions, although people with hearing loss and diabetes could be at the borderline risk. Urinary thiocyanate concentrations were significantly associated with emphysema (odds ratio (OR) 2.70 95% confidence intervals (CI) 1.91-3.82, P < 0.001), cancer (OR 1.21 95%CI 1.06-1.39, P = 0.008), chronic bronchitis (OR 1.23 95%CI 1.10-1.52, P = 0.003), wheezing (OR 1.24 95%CI 1.05-1.46, P = 0.011), coughing (OR 1.19 95%CI 1.03-1.37, P = 0.018) and sleep complaints (OR 1.14 95%CI 1.02-1.26, P = 0.019). The population attributable risks accounted for 3.3% (1.8-5.3%), 1.9% (0.6-3.5%), 1.2% (0.5-2.6%), 2.2% (0.5-4.1%), 1.8% (0.3-6.2%) and 1.3% (0.2-2.4%) for emphysema, cancer, chronic bronchitis, wheezing, coughing and sleep complaints, respectively. In addition, there was an inverse association observed between urinary nitrate level and heart failure. This is for the first time observing significant risk effects of urinary thiocyanate concentrations on adult cancer and lung problems, although the causality cannot be established. Elimination of such environmental chemical in humans should be included in future health policy and intervention programs.

A derivatization method for the simultaneous detection of glucosinolates and isothiocyanates in biological samples.

Various analytical methods have been established to quantify isothiocyanates (ITCs) that derive from glucosinolate hydrolysis. However, to date there is no valid method applicable to pharmacokinetic studies that detects both glucosinolates and ITCs. A specific derivatization procedure was developed for the determination of ITCs based on the formation of a stable N-(tert-butoxycarbonyl)-L-cysteine methyl ester derivative, which can be measured by high-performance liquid chromatography with ultraviolet detection after extraction with ethylacetate. The novel method, which is also applicable to the indirect determination of glucosinolates after their hydrolysis by myrosinase, was established for the simultaneous determination of glucoraphanin and sulforaphane. By derivatization, the sensitivity of ITC detection was increased 2.5-fold. Analytical recoveries from urine and plasma were greater than 75% and from feces were approximately 50%. The method showed intra- and interday variations of less than 11 and 13%, respectively. Applicability of the method was demonstrated in mice that received various doses of glucoraphanin or that were fed a glucoraphanin-rich diet. Besides glucoraphanin and sulforaphane, glucoerucin and erucin were detected in urine and feces of mice. The novel method provides an essential tool for the analysis of bioactive glucosinolates and their hydrolysis products and, thus, will contribute to the elucidation of their bioavailability.