Association between exposure to a mixture of metals, parabens, and phthalates and fractional exhaled nitric oxide: A population-based study in US adults.

The effects of environmental endocrine-disrupting chemicals (EDCs) (e.g., phthalates) on fractional exhaled nitric oxide (FeNO) in children have received much attention. However, few studies evaluated this relationship in adults, and the previous studies have considered only a unitary exposure or a set of similar exposures instead of mixed exposures, which contain complicated interactions. We aimed to evaluate simultaneously the relationship between three types of EDCs (six phthalate metabolites and two parabens in urine, two heavy metals in blood) and FeNO (as a continuous variable) in adults. Data of adults aged ≥20 years from the National Health and Nutrition Examination Survey (NHANES, 2007-2012) were collected and analyzed. The generalized linear (GLM) regression model was used to explore the association of chemicals with FeNO. The combined effect of 10 chemicals on the overall association with FeNO was evaluated by the weighted quantile sum regression (WQS) model. In addition, The Bayesian kernel machine regression (BKMR) model was explored to investigate the interaction and joint effects of multiple chemicals with FeNO. Of the 3296 study participants ultimately included, among the GLMs, we found that mercury (Hg) (β = 0.84, 95%CI:0.32-1.36, FDR = 0.01) and methyl paraben (MPB) (β = 0.47, 95%CI:0.16-0.78, FDR = 0.015) were positively correlated with FeNO. In the WQS model, the combined effect of chemicals almost had a significantly positive association with FeNO and the top three contributors to the WQS index were Hg (40.2%), MECPP (22.1%), and MPB (19.3%). BKMR analysis showed that there may be interactions between MPB and Hg, Mono (carboxyoctyl) phthalate (MCOP) and Hg and the overall effect of the mixture showed a positive correlation with FeNO. In conclusion, our study strengthens the credibility of the view that EDCs can affect respiratory health. In the future, we should be particularly careful with products containing Hg, MECPP, MPB, and MEHP for the prevention of respiratory diseases.

Wu Y ，Song J ，Li Y ，Jin X ，Liang Y ，Qin W ，Yi W ，Pan R ，Yan S ，Sun X ，Mei L ，Song S ，Cheng J ，Su H ... -  《-》

Associations between exposure to a mixture of phenols, parabens, and phthalates and sex steroid hormones in children 6-19 years from NHANES, 2013-2016.

Humans are typically exposed to mixtures of environmental endocrine-disrupting chemicals simultaneously, but most studies have considered only a single chemical or a class of similar chemicals. We examined the association of exposure to mixtures of 7 chemicals, including 2 phenols [bisphenol A (BPA) and bisphenol S (BPS)], 2 parabens [methylparaben (MeP) and propyl paraben (PrP)], and 3 phthalate metabolites [Mono-benzyl phthalate (MBzP), mono-isobutyl phthalate (MiBP), mono (carboxyoctyl) phthalate (MCOP)] with sex steroid hormones. A total of 1179 children aged 6-19 years who had complete data on both 7 chemicals and sex steroid hormones of estradiol (E2), total testosterone (TT), and sex hormone-binding globulin (SHBG) were analyzed from the U.S. National Health and Nutrition Examination Survey 2013-2016. Free androgen index (FAI) calculated by TT/SHBG, and the ratio of TT to E2 (TT/E2) were also estimated. Puberty was defined if TT ≥ 50 ng/dL in boys, E2 ≥ 20 pg/mL in girls; otherwise prepuberty was defined. Linear regression, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) were performed to estimate the associations of individual chemical or chemical mixtures with sex hormones. The linear regression showed that 2 phenols, 2 parabens, and 3 phthalate metabolites were generally negatively associated with E2, TT, FAI, and TT/E2, while positively with SHBG. Moreover, these associations were more pronounced among pubertal than prepubertal children. The aforementioned associations were confirmed when further applying WQS and BKMR, and the 3 phthalates metabolites were identified to be the most heavily weighing chemicals. Exposure to phenols, parabens, and phthalates, either individuals or as a mixture, was negatively associated with E2, TT, FAI and TT/E2, while positively with SHBG. Those associations were stronger among pubertal children.

Hu P ，Pan C ，Su W ，Vinturache A ，Hu Y ，Dong X ，Ding G ... -  《-》

Association between exposure to a mixture of phenols, pesticides, and phthalates and obesity: Comparison of three statistical models.

The evaluation of the chemical impact on human health is usually constrained to the analysis of the health effects of exposure to a single chemical or a group of similar chemicals at one time. The effects of chemical mixtures are seldom analyzed. In this study, we applied three statistical models to assess the association between the exposure to a mixture of seven xenobiotics (three phthalate metabolites, two phenols, and two pesticides) and obesity. Urinary levels of environmental phenols, pesticides, and phthalate metabolites were measured in adults who participated in the U.S.-based National Health and Nutrition Examination Survey (NHANES) from 2013 to 2014. Body examination was conducted to determine obesity. We fitted multivariable models, using generalized linear (here both logistic and linear) regression, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) models to estimate the association between chemical exposures and obesity. Of 1269 individuals included in our final analysis, 38.5% had general obesity and 58.0% had abdominal obesity. In the logistic regression model established for each single chemical, bisphenol S (BPS), mono (carboxyoctyl) phthalate (MCOP), and mono (2-ethyl-5-carboxypentyl) phthalate (MECPP) were associated with both general and abdominal obesity (fourth vs. first quartile). In linear regression, MCOP was associated with BMI and waist circumference. In WQS regression analysis, the WQS index was significantly associated with both general obesity (OR = 1.63, 95% CI: 1.21-2.20) and abdominal obesity (OR = 1.66, 95% CI: 1.18-2.34). MCOP, bisphenol A (BPA), bisphenol S (BPS), and mono ethyl phthalate (MEP) were the most heavily weighing chemicals. In BKMR analysis, the overall effect of mixture was significantly associated with general obesity when all the chemicals were at their 60th percentile or above it, compared to all of them at their 50th percentile. MCOP, BPA, and BPS showed positive trends. By contrast, MECPP showed a flat and modest inverse trend. When comparing results from these three models, MCOP, BPA, and BPS were identified as the most important factors associated with obesity. We recommend estimating the joint effects of chemical mixtures by applying diverse statistical methods and interpreting their results together, considering their advantages and disadvantages.

Zhang Y ，Dong T ，Hu W ，Wang X ，Xu B ，Lin Z ，Hofer T ，Stefanoff P ，Chen Y ，Wang X ，Xia Y ... -  《-》

Combined Exposure to Multiple Endocrine Disruptors and Uterine Leiomyomata and Endometriosis in US Women.

Uterine leiomyomata (UL) and endometriosis (EM) are common gynecological diseases damaging the reproductive health of fertile women. Among all the potential factors, environmental endocrine-disrupting chemicals are insufficiently addressed considering the multiple pollutants and mixture exposure. Women aged 20 to 54 years old in the National Health and Nutrition Examination Survey (NHANES) 2001-2006, having a complete measurement of ten commonly exposed endocrine-disrupting chemicals (including urinary phthalate metabolites, equol, and whole blood heavy metals) and answered questions about UL and EM were included (N=1204). Multivariable logistic regression model, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) models were implemented to analyze the combined effect of chemicals on the overall association with UL and EM. In single chemical analysis, equol (OR: 1.90, 95% CI: 1.11, 3.27) and mercury (Hg) (OR: 1.91, 95% CI: 1.14, 3.25) were found positively associated with UL in tertile 3 vs. tertile 1. In WQS regression and BKMR models, the significant positive association between WQS index and UL (OR: 2.54, 95% CI: 1.52, 4.29) was identified and the positive relationship between equol and Hg exposure and UL were further verified. Besides, the mixture evaluation models (WQS and BKMR) also found MEHP negatively associated with UL. Although none of the single chemicals in tertile 3 were significantly associated with EM, the WQS index had a marginally positive association with EM (OR: 2.01, 95% CI: 0.98, 4.15), and a significant positive association was identified in subanalysis with participants restricted to premenopausal women (OR: 2.18, 95% CI: 1.03, 4.70). MIBP and MBzP weighted high in model of EM and MEHP weighted the lowest. Comparing results from these three statistical models, the associations between equol, Hg, and MEHP exposure with UL as well as the associations of MIBP, MBzP, and MEHP exposure with EM warrant further research.

Zhang Y ，Lu Y ，Ma H ，Xu Q ，Wu X ... -  《Frontiers in Endocrinology》

Association between trimester-specific exposure to thirteen endocrine disrupting chemicals and preterm birth: Comparison of three statistical models.

Growing evidence indicated that maternal exposure to some endocrine disrupting chemicals (EDCs) may increase the risk of preterm birth (PTB). However, few studies have evaluated the joint effect of EDCs on PTB. This study aimed to evaluate the associations of maternal EDCs mixture in the 1st, 2nd, and 3rd trimesters during pregnancy with PTB, and identify the vital components that mainly contribute to PTB. This study included 847 pregnant women that provided urine samples for all three trimesters. Urinary concentrations of thirteen EDC metabolites (four phthalates, two parabens, three phenols, and four benzotriazoles and benzothiazoles) were examined. Logistic regression model, quantile g-computation and Bayesian kernel machine regression (BKMR) models were applied to study the association. Logistic regression model suggested that only bisphenol A (BPA) in the 1st trimester significantly increased the OR of PTB after adjusting for BPA exposure in the 2nd and 3rd trimesters. Quantile g-computation model identified that urinary EDCs mixture in the 1st trimester were positively associated with PTB [OR (95 % CI): 1.98 (1.10, 3.58)], and the most heavily weighted component for PTB was BPA (26 %), followed by mono-2ethylhexyl phthalate (MEHP) (22 %). BKMR model determined a significant association between EDCs mixture in the 1st trimester and PTB when all EDC concentrations were at or above their 55th percentile compared with the median. The BKMR model found that BPA and MEHP were associated with an increase in the estimated probability of PTB, when the other EDCs were held to their 50th and 75th percentiles, respectively, in the 1st trimester. The results of mixture analysis models indicated that exposure to higher EDCs mixture in the 1st trimester may increase the risk of PTB. BPA was considered as the most contributing factor for PTB among the detected EDCs.

Chen Y ，Xiao H ，Namat A ，Liu J ，Ruan F ，Xu S ，Li R ，Xia W ... -  《-》