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 ... -  《-》

Associations between organophosphate esters and sex hormones among 6-19-year old children and adolescents in NHANES 2013-2014.

Organophosphate esters (OPEs) are a class of alternative replacements for polybrominated diphenyl ethers. In vitro and in vivo studies suggested that OPEs may disrupt the homeostasis of sex steroid hormones. However, human evidence in children and adolescents is limited. We conducted a cross-sectional analysis of the associations between OPE biomarkers and sex steroid hormones among children (6-11 years) and adolescents (12-19 years) in the U.S. National Health and Nutrition Examination Survey, 2013-2014. Participants aged 6-19 years who had available data on urinary OPE metabolites, serum sex hormones [total testosterone (TT), estradiol (E2)] and sex hormone binding globulin (SHBG) were included (n = 544). Free androgen index (FAI) calculated as TT divided by SHBG and a ratio of TT to E2 (TT/E2) were generated. Five urinary OPE metabolites were examined. A constructed puberty status was defined as either high steroid hormone levels (TT ≥ 50 ng/dL in males and E2 ≥ 20 pg/ml in females) or onset of menarche. Multiple linear regression and weighted quantile sum (WQS) regression analyses stratified by sex-age and sex-puberty-status groups were conducted to examine the associations of OPE metabolites and its mixture with sex hormone levels. After adjusting for covariates, dibutyl phosphate (DBUP) and dibutyl phosphate (DPHP) were significantly inversely associated with TT (or FAI) and E2; DBUP was negatively associated with SHBG; and DPHP was positively associated with SHBG and TT/E2 in female adolescents. In male adolescents, we observed monotonic negative associations of bis(1,3-dichloro-2-propyl) phosphate (BDCPP), DBUP or DPHP with TT (or FAI) and E2, and positive associations of BDCPP and DPHP with SHBG. Among adolescents, the OPEs index was negatively associated with TT [WQS beta = -0.29 (95% confidence interval: -0.51, -0.07) in males and -0.15 (-0.28, -0.01) in females ], FAI [-0.46 (-0.71, -0.2) in males and -0.23 (-0.41, -0.05) in females] and E2 [-0.25 (-0.41, -0.1) in males and -0.33 (-0.59, -0.08) in females], with stronger associations with TT and FAI in males and a slightly stronger association with E2 in females. In addition, the OPEs index presented a comparable positive association with SHBG in both sexes of adolescents. In contrast, significant associations of individual OPE metabolites or OPEs index with sex hormones were sparse in children. Results by sex-puberty status in single pollutant and WQS regression analyses presented a similar pattern, where most of the significant associations were limited to the pubertal individuals. Of note, stronger inverse associations of the OPEs index with TT and FAI remained in pubertal boys. But the association between the OPEs index and E2 was non-significant in pubertal girls, and only in pubertal boys did the OPEs index show a significant and stronger inverse association with E2. Exposure to OPEs, either individually or as a mixture, was associated with decreased levels of certain sex steroid hormones (TT, FAI, and E2) and increased levels of SHBG in adolescents or pubertal individuals, with the associations presenting somewhat sex-dependent pattern. However, there is little evidence of the significant associations in children or prepubescent ones. Given the cross-sectional nature of the analysis, our findings need further confirmation.

Luo K ，Liu J ，Wang Y ，Aimuzi R ，Luo F ，Ao J ，Zhang J ... -  《-》

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》

Associations between urinary organophosphate ester metabolites and measures of adiposity among U.S. children and adults: NHANES 2013-2014.

Organophosphate esters (OPEs) are synthetic chemicals found in many consumer products, including furniture, electronics, processed foods, and building materials. Emerging in vitro and in vivo studies suggest that OPEs are metabolism disrupting compounds; however, epidemiologic studies investigating their associations with adiposity markers are sparse. We examined cross-sectional associations between OPE biomarkers and adiposity measures among U.S. children and adults participating in the National Health and Nutrition Examination Survey (NHANES: 2013-2014). Concentrations of five OPE metabolites were quantified in urine: diphenyl phosphate (DPHP), bis(1,3-dichloro-2-propyl) phosphate (BDCPP), bis(2-chloroethyl) phosphate (BCEP), dibutyl phosphate (DBUP), and bis(1-chloro-2-propyl) phosphate (BCPP). We conducted covariate-adjusted logistic and linear regressions to examine associations between log2-transformed and dichotomized OPE metabolite concentrations and obesity, body mass index (BMI), and waist circumference (WC), separately among 784 children (6-19 years) and 1672 adults (≥20 years). We also assessed heterogeneity of associations by sex. DBUP concentrations were inversely associated with the prevalence odds of being obese vs. normal weight in children (adjusted Prevalence Odds Ratio, aPOR: 0.82, 95% Confidence Interval, 95% CI: 0.70, 0.95) and adults (aPOR: 0.83, 95% CI: 0.72, 0.96). DBUP was also significantly associated with lower BMI z-scores (β:-0.08, 95% CI:-0.17, 0.01) and WC (β:-0.71, 95% CI: -1.49, 0.07) in children. BCEP concentrations were associated with increased prevalence odds of being overweight vs. normal weight (aPOR: 1.15, 95% CI: 1.01, 1.32) among children; similar, albeit not statistically significant, relationships were observed with other child adiposity outcomes. Among adults, detectable BCPP concentrations were associated with increased prevalence odds of being obese vs. normal weight (aPOR: 1.70, 95% CI: 1.21, 2.38) and having a high vs. normal WC (aPOR: 1.51, 95% CI: 1.11, 2.07) as well as higher BMI (β: 1.31, 95% CI: 0.30, 2.33). Other OPE metabolites were not consistently associated with adiposity measures among adults. Although associations of BCPP exposure with adiposity outcomes were generally inverse among boys, but not girls, we did not observe consistent evidence of sexually-dimorphic associations for other OPE metabolites. Exposure to select OPEs may be differentially associated with body size among children and adults. Given the cross-sectional design of the present study, future prospective studies are needed to confirm these findings.

Boyle M ，Buckley JP ，Quirós-Alcalá L 《-》

Environmental exposure to organophosphate esters and suspected non-alcoholic fatty liver disease among US adults: A mixture analysis.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. We evaluated NAFLD using the US FLI to determine whether there is an association between urinary organophosphorus (OPE) levels and the "prevalence" of NAFLD in US individuals. The current study included 1,102 people aged 20 years and older with information from the 2011-2014 U.S. National Health and Nutrition Examination Survey. NAFLD was assessed using the U.S. FLI. Individual OPE metabolites and OPE combinations were linked to NAFLD using logistic regression and weighted quantile sum (WQS) regression. All analyzes were carried out separately on males and females. The possible impacts of age, serum total testosterone (TT), and menopausal state, as well as the importance of the interaction term with exposure, were investigated using stratified analysis. Bis (2-chloroethyl) phosphate and bis (1,3-dichloro-2-propyl) phosphate were associated with NAFLD in all males after adjusting for covariates (P < 0.05). A combination of OPEs (OPE index) was positively linked with NAFLD in the WQS analysis of all males (odds ratio for OPE index: 1.52; 95% CI: 1.06, 2.19). Stratified analyzes for males revealed that considerable connections were largely confined to individuals over 60 years old or with low total testosterone. In women, the connection was limited and inconsistent, except for the OPE index, which was positively linked with NAFLD in post-menopausal women. In this study, environmental exposure to OPE was linked to an elevated risk of NAFLD in males, particularly those over 60 years old or with low TT levels. Aside from the continuous positive connection of a combination of OPEs with NAFLD risk in post-menopausal women, these correlations were weaker in women. However, these findings should be taken with caution and verified in future investigations by collecting numerous urine samples in advance to strengthen OPE exposure estimates.

Chai H ，Hu W ，Dai Y ，Zhu X ，Qian P ，Zhu J ... -  《Frontiers in Public Health》