Associations of Trimester-Specific Exposure to Perchlorate, Thiocyanate, and Nitrate with Childhood Neurodevelopment: A Birth Cohort Study in China.

Studies about the impacts of maternal exposure to perchlorate, thiocyanate, and nitrate on offspring neurodevelopment are scarce. Based on a birth cohort in China, 1,028 mothers provided urine samples at three trimesters for determination of the three target analytes, and their offspring neurodevelopment was evaluated at 2 years old. Associations of maternal exposure to the three chemicals with offspring neurodevelopment were estimated using three statistical methods. Trimester-specific analyses using generalized estimating equation models showed that double increment of thiocyanate and nitrate during the first trimester was associated with 1.56 (95% CI: -2.82, -0.30) and 1.22 (-2.40, -0.03) point decreases in the offspring mental development index (MDI), respectively. Weighted quantile sum (WQS) regression analyses showed that the mixture exposure at the first and second trimesters was negatively associated with the offspring MDI (ß = -2.39, 95% CI: -3.85, -0.93; ß = -1.75, 95% CI: -3.04, -0.47, respectively) and thiocyanate contributed the most to the association (65.0 and 91.6%, respectively). Bayesian kernel machine regression analyses suggested an inverted U-shape relationship of maternal urinary thiocyanate with the offspring MDI. These findings suggested that prenatal exposure to the three chemicals (at current levels), especially thiocyanate and nitrate, may impair neurodevelopment. Early pregnancy seems to be the sensitive window.

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.

Assessment of Iodine Nutritional Status of School-Age Children in Kolkata District of West Bengal State in Post-Iodation Scenario.

To evaluate the state of iodine nutrition in post-iodation scenario, 3500 children were examined clinically for endemic goitre. Iodine and thiocyanate were measured in 240 urine samples; iodine content in 210 salt samples was measured. Total goitre prevalence was 6.1%. Median urinary iodine level was 21.80 µg/dl, and mean (±SD) urinary thiocyanate was 0.89 ± 0.49 mg/dl. Iodine content of only 11.9% salt samples was below recommended level of 15 ppm, 25.2% was between 15 and 30 ppm and 62.9% was >30 ppm. Iodine deficiency disorders are thus clinically mild public health problem of the studied population; however, they have no biochemical iodine deficiency. Studied population found exposed to thiocyanate load that might be the possible cause for persistence of endemic goitre. People of Kolkata should be advised to eat commonly consumed goitrogenic foods after boiling and decanting the water. Periodical monitoring and evaluation of iodine status should be mandatory.

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.

[Determination of thiocyanate within human urine by ion chromatography method].

Objective: To establish ion chromatography method to determine thiocyanate within urine of workers who were exposed to cyanide. Methods: After the workers work, used 50 ml centrifuge tube to collect the urine of workers about 20 ml.The urine were tested by centrifugation, dilution and filtration by C(18) column, thiocyanate was separated by AS(16) and mobile phase elution by KOH, detected by electrical circuitryconductivity detector, quantitative by the standard curve method. Results: The linear correlation coefficient of thiocyanate within the range of 0.1-5.0 µg/ml was more than 0.999. The method detection limit was 0.11µg/ml (in 1ml urine) , the method quantitative limit was 0.35 µg/ml. The method recoveries were 95.1%-99.7%. The within-day precision range was 0.54%-2.05%, The between-run precision range was 2.06%-5.09%. Sample stability test showed that thiocyanate samples could be stored for 5 days at room temperature and 7 days at 4 ℃, could be stored for 14 days at-20 ℃. Conclusion: The technical indicator of method compliance with rule of Guide for establishing occupation health standards-Part 5: determination methods of chemicals in biological materials (GBZ/T 210.5-2008) , the method applies to workers who were exposed to cyanide.

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).

Characterization of a Mouse Model of Oral Potassium Cyanide Intoxication.

Potassium cyanide (KCN) is an inhibitor of cytochrome C oxidase causing rapid death due to hypoxia. A well-characterized model of oral KCN intoxication is needed to test new therapeutics under the Food and Drug Administration Animal Rule. Clinical signs, plasma pH and lactate concentrations, biomarkers, histopathology, and cyanide and thiocyanate toxicokinetics were used to characterize the pathology of KCN intoxication in adult and juvenile mice. The acute oral LD50s were determined to be 11.8, 11.0, 10.9, and 9.9 mg/kg in water for adult male, adult female, juvenile male, and juvenile female mice, respectively. The time to death was rapid and dose dependent; juvenile mice had a shorter mean time to death. Juvenile mice displayed a more rapid onset and higher incidence of seizures. The time to observance of respiratory signs and prostration was rapid, but mice surviving beyond 2 hours generally recovered fully within 8 hours. At doses up to the LD50, there were no gross necropsy or microscopic findings clearly attributed to administration of KCN in juvenile or adult CD-1 mice from 24 hours to 28 days post-KCN challenge. Toxicokinetic analysis indicated rapid uptake, metabolism, and clearance of plasma cyanide. Potassium cyanide caused a rapid, dose-related decrease in blood pH and increase in serum lactate concentration. An increase in fatty acid-binding protein 3 was observed at 11.5 mg/kg KCN in adult but not in juvenile mice. These studies provide a characterization of KCN intoxication in adult and juvenile mice that can be used to screen or conduct preclinical efficacy studies of potential countermeasures.

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.

CO-occurring exposure to perchlorate, nitrate and thiocyanate alters thyroid function in healthy pregnant women.

BACKGROUND: Adequate maternal thyroid function during pregnancy is necessary for normal fetal brain development, making pregnancy a critical window of vulnerability to thyroid disrupting insults. Sodium/iodide symporter (NIS) inhibitors, namely perchlorate, nitrate, and thiocyanate, have been shown individually to competitively inhibit uptake of iodine by the thyroid. Several epidemiologic studies examined the association between these individual exposures and thyroid function. Few studies have examined the effect of this chemical mixture on thyroid function during pregnancy OBJECTIVES: We examined the cross sectional association between urinary perchlorate, thiocyanate and nitrate concentrations and thyroid function among healthy pregnant women living in New York City using weighted quantile sum (WQS) regression. METHODS: We measured thyroid stimulating hormone (TSH) and free thyroxine (FreeT4) in blood samples; perchlorate, thiocyanate, nitrate and iodide in urine samples collected from 284 pregnant women at 12 (±2.8) weeks gestation. We examined associations between urinary analyte concentrations and TSH or FreeT4 using linear regression or WQS adjusting for gestational age, urinary iodide and creatinine. RESULTS: Individual analyte concentrations in urine were significantly correlated (Spearman's r 0.4-0.5, p<0.001). Linear regression analyses did not suggest associations between individual concentrations and thyroid function. The WQS revealed a significant positive association between the weighted sum of urinary concentrations of the three analytes and increased TSH. Perchlorate had the largest weight in the index, indicating the largest contribution to the WQS. CONCLUSIONS: Co-exposure to perchlorate, nitrate and thiocyanate may alter maternal thyroid function, specifically TSH, during pregnancy.

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.

A study on exposure to cyanide among a community living near a gold mine in Malaysia.

Cyanidation in gold extraction has detrimental impacts on the ecosystem and the population in surrounding areas. The research described in this article aimed to assess the health effects of environmental exposure to cyanide in a community near a gold mining area in Malaysia. A total of 255 members of the exposed community and 117 members of the control community answered questionnaires on their exposure to a gold mine and health outcomes. Urine samples were collected for biomarker assessment (i.e., urinary thiocyanate). The authors found that the mean level of urinary thiocyanate was significantly higher among the exposed community (0.30 ± 0.26 mg/dL) than the control community (0.24 ± 0.23 mg/dL) (p = .0021). The exposed community had a significantly higher prevalence of headaches (prevalence odds ratio [pOR] = 2.6, p = .001), dizziness (pOR = 3.7, p < .001), skin irritation (pOR = 2.1, p = .040), and eye irritation (pOR = 5.1, p = .004). No association occurred between dietary exposure and urinary biomarkers. Smokers living near a gold mine had a higher urinary thiocyanate level (0.56 mg/dL) than smokers in the control community (0.49 mg/dL).

The effect of lipoic acid administration on the urinary excretion of thiocyanate in rats exposed to potassium cyanide.

The oxidation of cyanide (CN-) to a much less toxic thiocyanate (SCN-) is the main in vivo biochemical pathway for CN- detoxification. SCN- is excreted mainly in urine. This study was performed to investigate the effect of lipoic acid (LA) on the urinary excretion of thiocyanate (SCN-; rhodanate) in rats. Groups of the animals were treated intraperitoneally (i.p.) as follows: group 1: potassium cyanide (KCN) (1 mg/kg); group 2: KCN (1 mg/kg) + LA (100 mg/kg). Urine was collected for 24 h and the pooled samples were examined for SCN- levels. The obtained results indicated that the treatment of animals with potassium cyanide and LA in combination significantly increased the urinary excretion of SCN- in comparison with the respective values in the KCN-alone-treated group. It indicates that LA increased the rate of CN- detoxification in rats.

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.

Effectiveness of wetting method for control of konzo and reduction of cyanide poisoning by removal of cyanogens from cassava flour.

BACKGROUND: Konzo is an irreversible paralysis of the legs that occurs mainly among children and young women in remote villages in tropical Africa and is associated with a monotonous diet of bitter cassava. Konzo was discovered in 1938 by Dr. G. Trolli in the Democratic Republic of Congo (DRC). It also occurs in Mozambique, Tanzania, Cameroon, Central African Republic, and Angola. It was first controlled in Kay Kalenge village, DRC, in 2011 with the use of a wetting method to remove cyanogens from cassava flour. Fourteen months later, another visit was made to Kay Kalenge. OBJECTIVE: To determine whether Kay Kalenge women were still using the wetting method, whether there were new cases of konzo, and whether the wetting method had spread to other villages. METHODS: Meetings were held with chiefs, leaders, and heads of mothers' groups, women from 30 households were interviewed, and three nearby villages were visited. Total cyanide and thiocyanate were analyzed in cassava flour and urine samples, respectively. RESULTS: The women in Kay Kalenge village still used the wetting method. There were no new cases of konzo. The mean cyanide content of the flour samples was 9 ppm, and no child had a mean urinary thiocyanate content greater than 350 micromol/L. The use of the wetting method had spread naturally to three adjacent villages. CONCLUSIONS: The wetting method has been readily accepted by rural women as a simple and useful method to control konzo by removing cyanide from cassava flour, and its use has spread to nearby villages. The wetting method should be promoted by health authorities to control konzo and reduce cyanide poisoning from high-cyanide cassava flour.

Environmental perchlorate, thiocyanate, and nitrate exposures and bone mineral density: a national cross-sectional study in the US adults.

Associations of perchlorate, thiocyanate, and nitrate exposures with bone mineral density (BMD) in adults have not previously been studied. This study aimed to estimate the associations of individual and concurrent exposure of the three chemicals with adult BMD. Based on National Health and Nutrition Examination Survey (NHANES, 2011-2018), 1618 non-pregnant adults (age ≥ 20 years and 47.0% female) were included in this study. Survey-weighted linear regression models were used to estimate individual urinary perchlorate, thiocyanate, and nitrate concentrations with lumbar spine BMD and total BMD in adults. Then, weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) models were conducted to evaluate associations of co-occurrence of the three chemicals with adult BMD. In all participants, nitrate exposure was inversely associated with lumbar spine BMD (ß = - 0.054, 95%CI: - 0.097, - 0.010). In stratification analyses, significant inverse associations were observed in female and participants older than 40 years old. In WQS regressions, significant negative associations of the weighted sum of the three chemicals with total and lumbar spine BMD (ß = - 0.014, 95%CI: - 0.021, - 0.007; ß = - 0.011, 95%CI: - 0.019, - 0.004, respectively) were found, and the dominant contributor was nitrate. In the BKMR models, non-linear dose-response associations of nitrate exposure with lumbar spine and total BMD were observed. These findings suggested that environmental perchlorate, thiocyanate, and nitrate exposure may reduce adult BMD and nitrate is the main contributor.

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.

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.

Organ-specific exposure and response to sulforaphane, a key chemopreventive ingredient in broccoli: implications for cancer prevention.

Naturally occurring sulforaphane (SF) has been extensively studied for cancer prevention. However, little is known as to which organs may be most affected by this agent, which impedes its further development. In the present study, SF was administered to rats orally either in a single dose or once daily for 7 d. Tissue distribution of SF was measured by a HPLC-based method. Glutathione S-transferase (GST) and NAD(P)H:quinone oxidoreductase 1 (NQO1), two well-known cytoprotective phase 2 enzymes, were measured using biochemical assays to assess tissue response to SF. SF was delivered to different organs in vastly different concentrations. Tissue uptake of SF was the greatest in the stomach, declining rapidly in the descending gastro-intestinal tract. SF was rapidly eliminated through urinary excretion, and urinary concentrations of SF equivalents were 2-4 orders of magnitude higher than those of plasma. Indeed, tissue uptake level of SF in the bladder was second only to that in the stomach. Tissue levels of SF in the colon, prostate and several other organs were very low, compared to those in the bladder and stomach. Moreover, induction levels of GST and NQO1 varied by 3- to 6-fold among the organs of SF-treated rats, though not strictly correlated with tissue exposure to SF. Thus, there is profound organ specificity in tissue exposure and response to dietary SF, suggesting that the potential chemopreventive benefit of dietary SF may differ significantly among organs. These findings may provide a basis for prioritising organs for further chemopreventive study of SF.