Association between urinary organophosphate ester metabolite exposure and thyroid disease risk among US adults: National Health and Nutrition Examination Survey 2011-2014.

Organophosphate esters (OPEs) may interfere with thyroid function, but the relationship between OPEs and thyroid disease remains unclear. This study aims to elucidate the relationship between OPEs exposure and thyroid disease risk in the general population in the United States. Data were obtained from the 2011-2014 National Health and Nutrition Examination Survey cycle. All participants were tested for seven OPE metabolites in their urine and answered questions about whether they had thyroid disease through questionnaires. Logistic regression was employed to analyze the association between exposure to individual OPE metabolites and thyroid disease. Weighted Quantile Sum (WQS) regression modeling was utilized to assess exposure to mixed OPE metabolites and risk of thyroid disease. Bayesian kernel machine regression(BKMR) models to analyze the overall mixed effect of OPE metabolites. A total of 2,449 participants were included in the study, 228 of whom had a history of thyroid disease. Bis(1,3-dichloro-2-propyl) phos (BDCPP), Diphenyl phosphate (DPHP) and Bis(2-chloroethyl) phosphate (BCEP) were the top three metabolites with the highest detection rates of 91.75%, 90.77% and 86.57%, respectively. In multivariate logistic regression models, after adjustment for confounding variables, individuals with the highest tertile level of BCEP were significantly and positively associated with increased risk of thyroid disease (OR=1.57, 95% CI=1.04-2.36), using the lowest tertile level as reference. In the positive WQS regression model, after correcting for confounding variables, mixed exposure to OPE metabolites was significantly positively associated with increased risk of thyroid disease (OR=1.03, 95% CI=1.01-1.06), with BCEP and DPHP having high weights. In the BKMR model, the overall effect of mixed exposure to OPE metabolites was not statistically significant, but univariate exposure response trends showed that the risk of thyroid disease decreased and then increased as BCEP exposure levels increased. The study revealed a significant association between exposure to OPE metabolites and an increased risk of thyroid disease, with BCEP emerging as the primary contributor. The risk of thyroid disease exhibits a J-shaped pattern, whereby the risk initially decreases and subsequently increases with rising levels of BCEP exposure. Additional studies are required to validate the association between OPEs and thyroid diseases.

Lin Y ，Lin R ，Wang W ，Xie M ，Li Y ，Zhang Q ... -  《Frontiers in Endocrinology》

Association of organophosphate ester exposure with cardiovascular disease among US adults: Cross-sectional findings from the 2011-2018 National Health and Nutrition Examination Survey.

Organophosphate esters (OPEs) are widely used as flame retardants and plasticizers worldwide. Therefore, the potentially deleterious effect of OPE on human beings deserves extensive attention. The primary objective of this present study was to untangle the relationship between OPE exposure and cardiovascular disease (CVD) among general population. Detailed information about participants' baseline characteristics, involving socioeconomic data, demographic data and key covariates was obtained from National Health and Nutrition Examination Survey (NHANES) 2011-2018. Multivariate logistic regression models with adjustment for prior-determined covariates were utilized to examine the relationship between various OPEs and CVD among US adults and calculate odd ratios (ORs) and corresponding confidence intervals (CIs). Two multi-pollutant statistical strategies (weighted quantile sum regression and Bayesian kernel machine regression) were employed to investigate the joint effect of OPE mixture on CVD. A total of 5067 participants were included in this study. In completely-adjusted logistic model, the highest tertiles of OPE metabolites were positively associated with CVD risk, while the relationships did not reach statistical significance. The weighted quantile sum (WQS) index was significantly correlated with increased prevalence of CVD (adjusted OR: 1.25; CI: 1.02, 1.53, p value = 0.032) and Diphenyl phosphate (DPHP) was the greatest contributor (31.38%). The BKMR also indicated that mixed OPE exposure associated with an increased risk of CVD. Taken together, the present study demonstrated that there were possible links between OPE exposures and increased risk of CVD, while the relationships did not reach statistical significance. Our study provided the suggestive evidence that cumulative effect of OPE mixtures on CVD. DPHP may be a major driver of this positive association. Given the limitation of cross-sectional design and relatively limited kinds of OPE metabolites, further studies are warranted to longitudinally evaluate the potential effect of a wider range of OPEs on CVD or cardiac metabolism.

Guo X ，Wu B ，Xia W ，Gao J ，Xie P ，Feng L ，Sun C ，Liang M ，Ding X ，Zhao D ，Ma S ，Liu H ，Lowe S ，Bentley R ，Huang C ，Qu G ，Sun Y ... -  《-》

Exposure to Organophosphate esters and metabolic syndrome in adults.

Organophosphate esters (OPEs) are increasingly used as flame retardants and plasticizers in various products. In vivo and in vitro studies suggest that OPEs can affect metabolic health but the human evidence is lacking. We analyzed data from the U.S. National Health and Nutrition Examination Survey, 2011-2014, to examine the associations between urinary OPE metabolites and metabolic syndrome (MetS) and its components in adults. We included a total of 1157 adults aged ≥20 years who had information on urinary OPE metabolites, components of MetS and essential covariates in the current analyses. MetS was composed of hyperglycemia, hypertension, hypertriglyceridemia, low high-density cholesterol, and central obesity. Binary logistic regression and weighted quantile sum (WQS) regression were used to assess the associations of individual OPE metabolites and OPEs mixture with MetS and its components. All analyses were conducted in men and women separately. Potential effect modification by age, serum total testosterone (TT) level and menopause status were also examined via stratified analyses as well as by testing the significance of the interaction term with exposure. After adjusting for confounders, bis(2-chloroethyl) phosphate (BCEP) and bis(1,3-dichloro-2-propyl) phosphate (BDCPP) were positively associated with MetS in a dose-dependent manner (P-trend = 0.02 and 0.02 for BCEP and BDCPP, respectively) in all men. Meanwhile, increasing quartiles of DPHP was positively associated with hyperglycemia (P-trend = 0.03), but DBUP was inversely associated with central obesity (P-trend = 0.02). WQS analyses in all men found that OPEs mixture (OPEs index) was positively associated with MetS [odds ratio (OR) for OPEs index: 1.65; 95%CI :1.21, 2.24], hyperglycemia (OR:1.47; 95%CI:1.09,2.00), and central obesity (OR:1.36; 95%CI:1.01,1.83). Although there was no significant interaction between exposure and effect modifiers, stratified analyses in men suggested that significant associations were mainly limited to those aged < 60 years or those with TT < 437 ng/dL (the median level in men). By contrast, the associations with MetS and its components were sparse and inconsistent in women except for the positive association between OPEs index and central obesity. In this cross-sectional study, exposure to OPEs was positively associated with elevated odds of MetS and individual components in men, especially among those aged <60 years or those with relatively low TT level. But the associations were less apparent in women except for the consistent positive association of OPEs mixture with central obesity. Nevertheless, these results need to be interpreted with caution and should be confirmed in future studies, ideally with multiple urine samples collected prospectively to improve the exposure measurement of OPEs.

Luo K ，Zhang R ，Aimuzi R ，Wang Y ，Nian M ，Zhang J ... -  《-》

Exploratory analysis of the association between organophosphate ester mixtures with high blood pressure of children and adolescents aged 8-17 years: cross-sectional findings from the National Health and Nutrition Examination Survey.

Epidemiological studies on the effect of organophosphate esters (OPEs) on high blood pressure (BP) among children and adolescents are scant. Therefore, the main objective of the present study was to explore the effect of exposure to OPEs on high BP among children and adolescents. A total of 1340 participants were included in the current analyses. Multivariable logistic regression models were implemented to calculate odds ratios (ORs) and corresponding 95% confidence intervals (CIs) to examine the association between OPE metabolites and high BP. We also assessed the modified effect of sex, age, and overweight/obesity on this association. Furthermore, quantile g-computation (Qgcomp) and Bayesian kernel machine regression (BKMR) were exhibited to analyze the association between multiple OPE metabolite mixtures and high BP. After adjusting for covariates, the highest (vs. lowest) tertiles of bis (1-choloro-2-propyl) phosphate (BCPP), bis-2-chloroethyl phosphate (BCEP), and di-n-butyl phosphate (DBUP) were associated with 1.23 (95% CI: 0.83, 1.83), 1.27 (95% CI: 0.85, 1.92), and 1.01 (95% CI: 0.67, 1.53) odds ratios for high BP, respectively. In the Qgcomp, a quartile increase in OPE metabolite mixtures was weakly associated with an elevated risk of high BP (adjusted OR: 1.06, 95CI%: 0.81, 1.37). The results from BKMR showed a positive trend of association between OPE metabolite mixture on the risk of high BP. In conclusion, our study demonstrated that higher levels of BCPP, BCEP, and DBUP were weakly associated with high BP among US children and adolescents. Moderate evidence suggested OPE metabolite mixtures had positive joint effects on high BP. Consequently, longitudinal studies with repeated measurements are warranted to examine the relationships between multiple OPE metabolites and high blood pressure among children and adolescents.

Guo X ，Ke Y ，Wu B ，Song Q ，Sun C ，Li Y ，Wang H ，Su W ，Liang Q ，Lowe S ，Bentley R ，Song EJ ，King B ，Zhou Q ，Xie R ，Deng F ... -  《-》

Associations between organophosphate esters and bone mineral density in adults in the United States: 2011-2018 NHANES.

Organophosphate esters (OPEs) are used extensively as flame retardants and plasticizers. Laboratory studies have shown that OPEs exhibit osteotoxicity by inhibiting osteoblast differentiation; however, little is known about how OPEs exposure is associated with bone health in humans. We conducted a cross-sectional study to investigate the association between OPEs exposure and bone mineral density (BMD) in adults in the United States using data from the 2011-2018 National Health and Nutrition Examination Survey (NHANES). Multivariate linear regression models were used to assess the association between concentrations of individual OPE metabolites and BMDs. We also used the Bayesian kernel machine regression (BKMR) and quantile g-computation (qgcomp) models to estimate joint associations between OPE mixture exposure and BMDs. All the analyses were stratified according to gender. A total of 3546 participants (median age, 40 years [IQR, 30-50 years]; 50.11% male) were included in this study. Five urinary OPE metabolites with a detection rate of > 50% were analyzed. After adjusting for the potential confounders, OPE metabolite concentrations were associated with decreased total-body BMD and lumbar spine BMD in males, although some associations only reached significance for bis(1-chloro-2-propyl) phosphate (BCPP), dibutyl phosphate (DBUP), and bis(2-chloroethyl) phosphate (BCEP) (β = -0.013, 95% CI: -0.026, -0.001 for BCPP and total-body BMD; β = -0.022, 95% CI: -0.043, -0.0001 for DBUP and lumbar spine BMD; β=-0.018, 95% CI: -0.034, -0.002 for BCEP and lumbar spine BMD). OPE mixture exposure was also inversely associated with BMD in males, as demonstrated in the BMKR and qgcomp models. This study provides preliminary evidence that urinary OPE metabolite concentrations are inversely associated with BMD. The results also suggested that males were more vulnerable than females. However, further studies are required to confirm these findings.

Guo JY ，Wang SN ，Zhang ZL ，Luan M ... -  《-》