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.

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.

Urinary perchlorate, thiocyanate, and nitrate and their associated risk factors among Chinese pregnant women.

Perchlorate, nitrate, and thiocyanate are well-known inhibitors of iodide uptake and thyroid-disrupting chemicals. Widespread human exposure to them has been identified, whereas studies on their internal exposure levels among Chinese pregnant women are scarce and factors associated with them are not well recognized. The objective of this study is to determine their levels and identify the associated factors among pregnant women (n = 1120), based on a prospective birth cohort in Wuhan, central China, using repeated urine samples of three trimesters. Urinary perchlorate, thiocyanate, and nitrate were 100% detected in the samples, and specific gravity-adjusted median concentrations of them in all the samples were 12.6 ng/mL, 367 ng/mL, and 63.7 µg/mL, respectively. Their concentrations were weakly-to-moderately correlated with each other, with Spearman correlation coefficients ranging from 0.27 to 0.54. Poor reproducibility were observed for the three analytes over the three trimesters, with intraclass correlation coefficient of 0.07, 0.19, 0.04 for perchlorate, thiocyanate, and nitrate, respectively. The women who were overweight or used tap water as drinking water had significantly higher perchlorate concentrations, while those with excessive gestational weight gain had significantly higher thiocyanate concentrations (p < 0.05). The women with a college degree or above had lower nitrate concentrations (p < 0.05). Meanwhile, the median concentration of perchlorate in urine samples collected in spring, thiocyanate in those collected in winter, and nitrate in those collected in autumn, was significantly higher compared to their median concentrations in the samples collected in other three seasons (p < 0.05), respectively. Urinary perchlorate and nitrate concentrations of pregnant women in this study were higher than the concentrations of pregnant women in other countries, while thiocyanate concentrations were lower than that of most other countries. This study suggested potential covariates for future epidemiological analyses.

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.

Effects of perchlorate, nitrate, and thiocyanate exposures on serum total testosterone in children and adolescents.

Perchlorate, nitrate, and thiocyanate are common thyroid disruptors in daily life and alter testosterone levels in animals. However, little is known about the effects of perchlorate, nitrate, and thiocyanate on serum total testosterone (TT) in the general population. The study was designed to assess the associations between urinary levels of perchlorate, nitrate, and thiocyanate and serum total testosterone (TT) in the general population. The present study utilized data from the 2011-2016 National Health and Nutritional Examination Survey (NHANES). A total of 6201 participants aged 6-79 with information on urinary perchlorate, nitrate, thiocyanate, and serum total testosterone were included. We conducted multiple linear regression models and Bayesian Kernel Machine Regression (BKMR) models to estimate the associations by sex-age groups. Children (ages 6-11) have higher levels of perchlorate and nitrate than the rest. After adjusting for covariates, urinary perchlorate was significantly negatively associated with serum TT in male adolescents (ß = -0.1, 95 % confidence interval: -0.2, -0.01) and female children [-0.13, (-0.21, -0.05)]. Urinary nitrate was significantly negatively associated with serum TT in female children, while urinary thiocyanate was significantly positively associated with serum TT in female adults aged 20 to 49 [0.05 (0.02, 0.08)]. BKMR analysis indicated that no other interactions were found between urinary perchlorate, nitrate, and thiocyanate. Our findings suggested that urinary perchlorate, nitrate, and thiocyanate levels may relate to serum total testosterone levels in specific sex-age groups. We identified male adolescents and female children as are most sensitive subgroups where testosterone is susceptible to interference.

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.

Environmental exposure to perchlorate, nitrate, and thiocyanate in relation to chronic kidney disease in the general US population, NHANES 2005-2016 / 中华医学杂志(英文版)

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 β: 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 β: -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.

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.

The Association Between Environmental Perchlorate, Nitrate, and Thiocyanate Exposure and Oral Pain in NHANES.

Aim: To examine the human exposure to perchlorate, nitrate, and thiocyanate, and their associations with oral pain (OP) in the general population from the U.S. Methods: A total of 13,554 participants were enrolled in the National Health and Nutrition Examination Survey. The urinary perchlorate, nitrate, and thiocyanate were measured using ion chromatography coupled with an electrospray tandem mass spectrometry. The multivariable linear and logistic regressions were performed to explore the associations of the urinary perchlorate, nitrate, and thiocyanate, with the prevalence of oral pain. Restricted cubic splines were used to explore the non-linearity. Results: There are 3,129 OP cases. There was a higher urinary level of perchlorate, nitrate, and thiocyanate in OP. We found that urinary thiocyanate was positively associated with OP (odds ratio [OR] = 1.06; [1, 1.13]; p = 0.049). Restricted cubic spines revealed that urinary thiocyanate was in a U-shape association with OP. Conclusions: Urinary thiocyanate was in a U-shape association with OP, suggesting that we should keep the exposure of thiocyanate under a reasonable range.

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.

Konzo outbreak in the Western Province of Zambia.

OBJECTIVE: To identify the etiology of an outbreak of spastic paraparesis among women and children in the Western Province of Zambia suspected to be konzo. METHODS: We conducted an outbreak investigation of individuals from Mongu District, Western Province, Zambia, who previously developed lower extremity weakness. Cases were classified with the World Health Organization definition of konzo. Active case finding was conducted through door-to-door evaluation in affected villages and sensitization at local health clinics. Demographic, medical, and dietary history was used to identify common exposures in all cases. Urine and blood specimens were taken to evaluate for konzo and alternative etiologies. RESULTS: We identified 32 cases of konzo exclusively affecting children 6 to 14 years of age and predominantly females >14 years of age. Fourteen of 15 (93%) cases ≥15 years of age were female, 11 (73%) of whom were breastfeeding at the time of symptom onset. Cassava was the most commonly consumed food (median [range] 14 [4-21] times per week), while protein-rich foods were consumed <1 time per week for all cases. Of the 30 patients providing urine specimens, median thiocyanate level was 281 (interquartile range 149-522) µmol/L, and 73% of urine samples had thiocyanate levels >136 µmol/L, the 95th percentile of the US population in 2013 to 2014. CONCLUSION: This investigation revealed the first documented cases of konzo in Zambia, occurring in poor communities with diets high in cassava and low in protein, consistent with previous descriptions from neighboring countries.

Socioeconomic status of the population - a prime determinant in evaluating iodine nutritional status even in a post salt iodization scenario.

Background To compare the state of iodine nutrition among school age children (SAC) in high- (HSGs) and low-socioeconomic groups (LSGs) during a post iodation scenario in Kolkata. Methods Clinical examinations of the goiter, median urinary iodine (MUI), mean urinary thiocyanate (MUSCN) in SAC (6-12 years) from both sexes in the different socioeconomic groups were carried out and the iodine content of edible salt was measured. Results A total of 5315 SAC, of which 2875 SAC were from a HSG and another 2440 SAC from an LSG were clinically examined for goiter. In the HSGs the total goiter prevalence (TGP) was 3.2% and in the LSGs the TGP was 9.1% and the difference was statistically significant (p<0.001). The MUI of the HSGs was 242 µg/L as compared to 155 µg/L in the LSGs (p<0.001). MUSCN of the HSGs was 0.77±0.45 mg/dL while in the LSGs it was 0.94±0.44 mg/dL and the difference was statistically significant (p<0.01). In the HSGs 19.4% salt samples had 15-30 ppm iodine and 80.6% salt samples were above 30 ppm as compared to 26.3% salt samples which were below 15 ppm, 37.1% salt samples which were between 15 and 30 ppm and 36.6% salt samples which were above 30 ppm in the LSGs. Conclusions The population of the LSGs was clinically mildly iodine deficient having no biochemical iodine deficiency while in the HSGs it was more than the adequate requirement and the HSG children are possibly at risk of excess iodine induced thyroid diseases. Existing goiter prevalence in the LSGs was from their relatively high consumption of dietary goitrogens. Therefore, socioeconomic status plays a pivotal role in the management of iodine nutrition even in a post salt iodation scenario.

Ultrasensitive and recyclable superstructure of AuSiO2@Ag wire for surface-enhanced Raman scattering detection of thiocyanate in urine and human serum.

Thiocyanate level in the human system can serve as a biomarker to distinguish smokers from non-smokers. Thiocyanate is a potential goitrogen, thus an accurate determination may help to identify lactating mothers with high thiocyanate dosage, thereby preventing the transport of excess SCN- to infants. Surface-enhanced Raman spectroscopy has become a versatile and reliable technique to detect SCN- in different media. However, the conventional surface-enhanced Raman scattering (SERS) substrates used to detect SCN- are often discarded after use. The frequent disposal of such metal nanoparticles is detrimental to the environment and makes the SERS-based detection of SCN- uneconomical. In this study, we present fabrication of a new, ultrasensitive and recyclable SERS substrate, based on an AuSiO2@Ag wire (W) superstructure, to detect SCN- in different media. The hierarchical AuSiO2@AgW substrate was obtained by forming nano-sized patches of SiO2 on micron-sized AgW and anchoring 30 nm-sized gold nanoparticles on the patches with mercaptopropyltrimethoxysilane. This ultrasensitive substrate could detect SCN- at a low concentration of 0.001 µM in water, and 0.01 µM in urine and human serum. In addition, a facile procedure to regenerate and recycle the SCN- bound AuSiO2@AgW platform in different media has been demonstrated. The insight gained in the present study can serve as a promising and powerful method for fabrication of active and recyclable substrates for SERS-based detection of SCN-.

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.

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.

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.

Dietary cyanogen exposure and early child neurodevelopment: An observational study from the Democratic Republic of Congo.

BACKGROUND: Dietary cyanogen exposure from ingesting bitter (toxic) cassava as a main source of food in sub-Saharan Africa is related to neurological impairments in sub-Saharan Africa. We explored possible association with early child neurodevelopmental outcomes. METHODS: We undertook a cross-sectional neurodevelopmental assessment of 12-48 month-old children using the Mullen Scale of Early Learning (MSEL) and the Gensini Gavito Scale (GGS). We used the Hopkins Symptoms Checklist-10 (HSCL-10) and Goldberg Depression Anxiety Scale (GDAS) to screen for symptoms of maternal depression-anxiety. We used the cyanogen content in household cassava flour and urinary thiocyanate (SCN) as biomarkers of dietary cyanogen exposure. We employed multivariable generalized linear models (GLM) with Gamma link function to determine predictors of early child neurodevelopmental outcomes. RESULTS: The mean (SD) and median (IQR) of cyanogen content of cassava household flour were above the WHO cut-off points of 10 ppm (52.18 [32·79]) and 50 (30-50) ppm, respectively. Mean (SD) urinary levels of thiocyanate and median (IQR) were respectively 817·81 (474·59) and 688 (344-1032) µmole/l in mothers, and 617·49 (449·48) and 688 (344-688) µmole/l in children reflecting individual high levels as well as a community-wide cyanogenic exposure. The concentration of cyanide in cassava flour was significantly associated with early child neurodevelopment, motor development and cognitive ability as indicated by univariable linear regression (p < 0.05). After adjusting for biological and socioeconomic predictors at multivariable analyses, fine motor proficiency and child neurodevelopment remained the main predictors associated with the concentration of cyanide in cassava flour: coefficients of -0·08 to -.15 (p < 0·01). We also found a significant association between child linear growth, early child neurodevelopment, cognitive ability and motor development at both univariable and multivariable linear regression analyses coefficients of 1.44 to 7.31 (p < 0·01). CONCLUSION: Dietary cyanogen exposure is associated with early child neurodevelopment, cognitive abilities and motor development, even in the absence of clinically evident paralysis. There is a need for community-wide interventions for better cassava processing practices for detoxification, improved nutrition, and neuro-rehabilitation, all of which are essential for optimal development in exposed children.

[Socioemotional disorders in children living in Konzo-affected areas, an epidemic paralytic disease associated with cyanide poisoning from food in sub-Saharan Africa]. / Troubles socio-émotionnels de l'enfant en milieu Konzo, un syndrome paralytique de nature épidémique associé à une intoxication cyanhydrique d'origine alimentaire en Afrique sub-saharienne.

INTRODUCTION: the aim of this study was to describe the socioemotional profile of children living in Konzo-affected areas, an epidemic toxico-nutritional palsy in sub-Saharan Africa. METHODS: we evaluated the socioemotional profile of 210 children, 123 with Konzo and 87 presumed to be healthy (4-17 years) based on a structured interview conducted with their parents during an epidemioclinic survey of Konzo in Congo-Kinshasa in 2011. Neurocognitive profile was identified by the KABC-II, the BOT-2 and the global neurological symptom index of Konzo. Associative tests were carried out by using chi-square test, logistic regression and, where applicable, generalized linear model, at the significance threshold of 0.05. RESULTS: in general, irritability, physical violence or inhibition with or without sadness were found in 46.0%, 30.2%, 18.7% of children respectively, with an increased risk of Konzo (OR = 2.6; CI95%: 1.4-4.8; p = 0.001). Socioemotional disorder was associated with underweight (OR: 0.49; CI95%: 0.31-0.78; p = 0.002) and with an elevated global neurological symptom index of Konzo (OR: 1.33; CI 95%: 1.1-1.63; p = 0.019); furthermore it exacerbated cognitive impairment in children with Konzo (interaction neurological status-socioemotional disorders D = 6.297; p = 0.013). High cognitive performances were observed in children without Konzo but with socioemotional disorders. The average concentration (standard deviation ± SD) of urinary thiocyanate was higher (554.8 ± 371.6 µmol/l) among children with Konzo associated with socioemotional disorders. CONCLUSION: children living in Konzo-affected areas have socioemotional disorders. Their psychopathological status and the effect of Konzo on cognition require in-depth studies.

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.