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 ... -  《-》

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 ... -  《-》

Using three statistical methods to analyze the association between exposure to 9 compounds and obesity in children and adolescents: NHANES 2005-2010.

Wu B ，Jiang Y ，Jin X ，He L ... -  《Environmental Health》

Bisphenol A and phthalates in utero and in childhood: association with child BMI z-score and adiposity.

To assess the relationship between in utero and concurrent child urinary exposures to bisphenol A (BPA) and phthalates with BMI z-score, waist circumference, and sum of triceps and subscapular skinfold thickness in Mexican children. Among participants (N=249) from the Early Life Exposure in Mexico to ENvironmental Toxicants study, we evaluated associations between maternal third trimester and concurrent urinary BPA and individual and summed phthalates metabolites (∑Di(2-ethylhexyl phthalate), ∑high molecular weight, ∑low molecular weight) with measures of weight status and adiposity in children aged 8-14 years. Linear regressions with specific-gravity corrected and natural log-transformed urinary concentrations were estimated, adjusting for covariates. Effect modification by sex was explored. Prenatal urinary exposure to monobenzyl phthalate (MBzP) was inversely associated with child's BMI z-score (β=-0.21, 95%CI: -0.41, -0.02) and child urinary exposure to mono(2-ethylhexyl)phthalate (MEHP) was inversely associated with waist circumference (β=-1.85, 95%CI: -3.36, -0.35) and sum of skinfold thicknesses (β=-2.08, 95%CI: -3.80, -0.37) after adjusting for confounders. In the childhood exposure period, sex modified the relationships with BPA, MEHP, MBzP, monoethyl phthalate (MEP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono(2-ethyl-5-carboxypentyl) phthalate (MECPP). In girls, increased BPA exposure was positively associated with sum of skinfold thickness (β=3.47, 95%CI: 0.05, 6.40) while increased MEHP was inversely associated with sum of skinfold thicknesses in boys (β=-2.95, 95%CI: -5.08, -0.82); these results remained in sensitivity analyses after excluding children who had initiated pubertal development (Tanner stage >1 for pubic hair). We did not observe relationships between summed phthalates metabolites at any exposure period with outcome measures. Our results identified associations between urinary BPA and phthalates metabolites with measures of weight status and adiposity that differed by timing of exposure, sex, and pubertal status. Additional studies are needed to explore how associations may differ between those who are pre- and post-pubertal.

Yang TC ，Peterson KE ，Meeker JD ，Sánchez BN ，Zhang Z ，Cantoral A ，Solano M ，Tellez-Rojo MM ... -  《-》

Association between co-exposure to phenols and phthalates mixture and infertility risk in women.

Exposure to phenols and phthalates has been separately linked to increased risks of infertility in women of reproductive age. However, the combined effect of phenols and phthalates exposure on infertility has not been explored. Data from the National Health and Nutrition Examination Surveys (NHANES) were used. A total of 857 women of reproductive age (18-45 years) with available information on urinary phenol and phthalate metabolites, reproductive questionnaires, and covariates were included in the present study. The definition of infertility was based on self-reports. Multivariable logistic regression, principal component analysis (PCA), and Bayesian kernel machine regression (BKMR) with stratified variable selection were applied to determine what associations were found between combined exposure to these mixtures and risk of infertility among women of reproductive age. After adjusting for potential confounders, bisphenol A (BPA), mono(3-carboxypropyl) phthalate (MCPP) and four di(2-ethylhexyl) phthalate (DEHP) metabolites [mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) and mono(2-ethyl-5-carboxypentyl) phthalate (MECPP)] were positively associated with infertility. PCA revealed that the DEHP-BPA factor's PC score was significantly positively related to the likelihood of infertility [adjusted odds ratio (aOR) = 1.45; 1.08, 1.82]. The DEHP-BPA component consistently had the highest group posterior inclusion probability (PIP) in BKMR models. The BKMR model also found that MEOHP, MEHHP, and BPA were positively associated with infertility risk when the remaining combination concentrations were held at their median values. In addition, we observed that the probability of infertility increased dramatically as the quantiles of total mixture concentration increased. Our findings indicate that a combination of phenol and phthalate metabolites is linked to infertility among reproductive-age women. BPA and DEHP, in particular, are significantly related to the risk of infertility.

Zhan W ，Yang H ，Zhang J ，Chen Q ... -  《-》