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 《-》

Urinary organophosphate ester concentrations in relation to ultra-processed food consumption in the general US population.

Ultra-processed foods are highly processed foods which are manufactured with industrial substances to increase convenience and palatability. Some organophosphate esters (OPEs) are used as flame retardants and plasticizers and have been detected in food samples, particularly processed foods. However, little is known about dietary sources of OPEs or whether higher consumption of ultra-processed foods increases exposures. We evaluated whether higher consumption of ultra-processed food is associated with urinary OPE metabolite concentrations in a nationally representative sample of US children and adults. Among 2242 participants (≥6 years) in the National Health and Nutrition Examination Survey (NHANES) 2013-2014, we used the NOVA classification system to calculate percent of total energy from ultra-processed food using a 24 h dietary recall. Concentrations of 7 OPE metabolites, including diphenyl phosphate (DPHP), bis(1,3-dichloro-2-propyl) phosphate (BDCPP), bis(2-chloroethyl) phosphate (BCEP), dibutyl phosphate (DBUP), di-p-cresyl phosphate (DPCP), 2,3,4,5-tetrabromobenzoic acid (TBBA), and bis(1-chloro-2-propyl) phosphate (BCPP) were measured in urine. We used multivariable linear or logistic regressions to examine associations per 10% higher total energy from ultra-processed foods with percent changes or prevalence of detectable levels of creatinine-standardized OPEs. In a model adjusting for only urinary creatinine, each 10% higher total energy from ultra-processed food was associated with 3.5% (95% CI: 0.7%, 6.3%) higher DPHP and 8.2% (95% CI: 4.6, 11.9%) higher BDCPP concentrations. However, none of the OPE metabolites was associated with ultra-processed food consumption in models adjusted for sociodemographic characteristics, health behaviors, and BMI (all p-values >0.05). Ultra-processed breads and tortillas; sauces, dressing, and gravies; and milk-based drinks were associated with higher concentrations of BDCPP while frozen and shelf-stable plate meals were associated with lower concentrations. Reconstituted meat or fish products and ultra-processed milk-based desserts were associated with greater odds of detectable levels of BCPP. While some food groups were associated with urinary OPE metabolite concentrations, ultra-processed foods do not appear to be a major source of current OPE exposure in the US.

Kim H ，Rebholz CM ，Wong E ，Buckley JP ... -  《-》

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 ... -  《-》

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 ... -  《-》

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 ... -  《-》