Associations of perchlorate, nitrate, and thiocyanate with metabolic syndrome and its components among US adults: A cross-sectional study from NHANES.

Perchlorate, nitrate and thiocyanate are common endocrine disruptors. Herein, this study was undertaken to evaluate the associations between perchlorate, nitrate, and thiocyanate exposures (alone or in combination) and risk of metabolic syndrome (MetS) among adults, which has not been explored so far. Analytical data were extracted from different datasets in the National Health and Nutrition Examination Survey (NHANES) database. Multivariate logistic regression models were constructed to investigate the associations between perchlorate, nitrate, and thiocyanate exposures, and the prevalence of MetS. Subsequently, odds ratios (OR) and their corresponding 95 % confidence intervals (CIs) were adopted to represent the magnitude of the effect size. We performed a series of subgroup analyses and sensitivity analyses as well. Moreover, three commonly used mixture modeling strategies [Weighted quantile sum (WQS) regression, quantile-based g-computation (Qgcomp), and Bayesian kernel machine regression (BKMR)] were utilized to evaluate the joint mixture effect on MetS. This study included 12,007 participants in the subsequent analyses. After adjustment for confounding factors, higher levels of perchlorate, and thiocyanate concentrations were significantly associated with the risk of MetS (OR = 1.15, 95%CI:1.00, 1.32; OR = 1.21, 95%CI:1.04, 1.41, respectively). Analyses of WQS and Qgcomp showed that a quartile increase in chemical mixture was correlated with the occurrence of MetS with ORs of 1.07 (95%CI: 0.99, 1.16) and 1.07 (95%CI: 1.00, 1.14), respectively. This positive association was mainly driven by perchlorate and thiocyanate. Analysis of BKMR revealed that perchlorate, nitrate, and thiocyanate mixture was positively associated with the risk of MetS while perchlorate, and thiocyanate were major predictors in the mixture. In summary, our study reveals positive relationships between perchlorate, thiocyanate and MetS. Co-exposure to perchlorate, nitrate and thiocyanate is positively associated with the risk of MetS, with perchlorate and thiocyanate contributing the most to the overall mixture effect.

Guo X ，Wu B ，Hu W ，Wang X ，Su W ，Meng J ，Lowe S ，Zhao D ，Huang C ，Liang M ，Qu G ，Zhou X ，Sun Y ... -  《-》

Associations of urinary perchlorate, nitrate and thiocyanate with central sensitivity to thyroid hormones: A US population-based cross-sectional study.

Perchlorate, nitrate, and thiocyanate are three well-known sodium iodine symporter inhibitors, however, associations of their individual and concurrent exposure with central thyroid hormones sensitivity remain unclear. To investigate the associations of urinary perchlorate, nitrate, thiocyanate, and their co-occurrence with central thyroid hormones sensitivity among US general adults. A total of 7598 non-pregnant adults (weighted mean age 45.9 years and 52.9% men) from National Health and Nutritional Examination Survey 2007-2012 were included in this cross-sectional study. Central sensitivity to thyroid hormones was estimated with the Parametric Thyroid Feedback Quantile-based Index (PTFQI). Ordinary least-squares regression, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) models were performed to examine the associations of three anions and their co-occurrence with PTFQI. The weighted mean values of urinary perchlorate, nitrate, thiocyanate, and perchlorate equivalent concentration (PEC) were 5.48 μg/L, 57.59 mg/L, 2.65 mg/L, and 539.8 μg/L, respectively. Compared with the lowest quartile, the least-square means difference (LSMD) of PTFQI was -0.0516 (LSMD ± SE: -0.0516 ± 0.0185, P < 0.01) in the highest perchlorate quartile. On average, PTFQI decreased by 0.0793 (LSMD ± SE: -0.0793 ± 0.0205, P < 0.001) between the highest and lowest thiocyanate quartile. Compared with those in the lowest quartile, participants in the highest PEC quartile had significantly decreased PTFQI levels (LSMD ± SE: -0.0862 ± 0.0188, P < 0.001). The WQS of three goitrogens, was inversely associated with PTFQI (β: -0.051, 95% CI: -0.068, -0.034). In BKMR model, PTFQI significantly decreased when the levels of three anions were at or above their 60th percentiles compared to the median values. Higher levels of urinary perchlorate, thiocyanate, and co-occurrence of three goitrogens were associated with increased central thyroid hormones sensitivity among US general adults. Further studies are warranted to replicate our results and elucidate the underlying causative mechanistic links.

King L ，Huang Y ，Li T ，Wang Q ，Li W ，Shan Z ，Yin J ，Chen L ，Wang P ，Dun C ，Zhuang L ，Peng X ，Liu L ... -  《-》

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

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. To investigate the associations of environmental exposure to perchlorate, nitrate, and thiocyanate with markers of thyroid function in Chinese adults. 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. 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 (β: 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. 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.

King L ，Wang Q ，Xia L ，Wang P ，Jiang G ，Li W ，Huang Y ，Liang X ，Peng X ，Li Y ，Chen L ，Liu L ... -  《-》

Concurrent dietary intake to nitrate, thiocyanate, and perchlorate is negatively associated with hypertension in adults in the USA.

We aimed to comprehensively evaluate the association of urinary nitrate, thiocyanate, and perchlorate metabolites with hypertension among a nationally representative sample of the US adult population. This cross-sectional study investigated data from 15,717 adults aged more than 20 years obtained from the National Health and Nutritional Examination Survey (NHANES) for the years 2005-2016. In the survey, urinary levels of nitrate, thiocyanate, and perchlorate were measured using ion chromatography combined with electrospray tandem mass spectrometry. Blood pressure was calculated as the mean of three measurements. Hypertension was defined as (a) systolic BP ≥130 and/or diastolic BP ≥80 mmHg and/or (b) self-report. Multivariate logistic regression and weighted quantile sum (WQS) regression models were applied to estimate the association between exposure to multiple inorganic anions and hypertension. Restricted cubic spline (RCS) regressions were fitted to discern the potential relationship between the anion exposure and hypertension. These innovation methods used to support our results. Overall, 7533 (49.95%) people with and 7638 (50.35%) without hypertension were included in this study. In the multivariable-adjusted logistic regression models, urinary nitrate (P < 0.001) and perchlorate (P < 0.001) were independently negatively associated with increased occurrence of hypertension, while urinary thiocyanate was insignificantly associated with hypertension (P = 0.664). The WQS regression index showed that, in combination, the three inorganic anions mixture were negatively correlated with hypertension (adjusted OR 0.89; 95% CI 0.83-0.95, P < 0.001). Urinary nitrate was the most heavily weighted component in the hypertension model (weight = 0.784). RCS regression demonstrated that nitrate (nonlinearity P = 0.205) and perchlorate (nonlinearity P = 0.701) were linearly associated with decreased occurrence of hypertension. Concurrent exposure to nitrate, thiocyanate, and perchlorate is associated with a decreased risk of hypertension, with the greatest influence coming from nitrate probably; urinary specific thiocyanate alone had an insignificant association with hypertension.

Xu D ，Zhu X ，Xie X ，Huang C ，Fang X ，Yin T ... -  《-》

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

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. 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. 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)). 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.

Zhao H ，Chen X ，Ni J ，Fang L ，Chen Y ，Ma Y ，Cai G ，Pan F ... -  《Frontiers in Immunology》