Monobenzyl Phthalate-[d4]

Background: 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. Objectives: 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. Methods: 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. Results: 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. Conclusions: 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.

Background: Breast cancer is the most common cancer and the second leading cause of cancer-related death amongst American women. Endocrine-disrupting chemicals (EDCs), especially bisphenol A (BPA) and phthalates, have adverse effects on human health. However, the association of BPA and phthalates with breast cancer remains conflicting. This study aims to investigate the association of BPA and phthalates with breast cancer. Methods: Correlative studies were identified by systematically searching three electronic databases, namely, PubMed, Web of Sciences, and Embase, up to November 2020. All data were analyzed using Stata 15.0. Results: A total of nine studies, consisting of 7820 breast cancer cases and controls, were included. The urinary phthalate metabolite mono-benzyl phthalate (MBzP) and mono-2-isobutyl phthalate (MiBP) were negatively associated with breast cancer (OR = 0.73, 95% CI: 0.60-0.90; OR = 0.75, 95% CI: 0.58-0.98, respectively). However, the overall ORs for BPA, mono-ethyl phthalate (MEP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-2-ethylhexyl phthalate (MEHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono-(3-carboxypropyl) phthalate (MCPP), and mono-butyl phthalate (MBP) were 0.85 (95% CI: 0.69-1.05), 0.96 (95% CI: 0.62-1.48), 1.12 (95% CI: 0.88-1.42), 1.13 (95% CI: 0.74-1.73), 1.01 (95% CI: 0.74-1.40), 0.74 (95% CI: 0.48-1.14), and 0.80 (95% CI: 0.55-1.15), respectively, suggesting no significant association. The sensitivity analysis indicated that the results were relatively stable. Conclusion: Phthalate metabolites MBzP and MiBP were passively associated with breast cancer, whereas no associations were found between BPA, MEP, MEHHP, MEHP, MEOHP, MCPP, and MBP and breast cancer. More high-quality case-control studies or persuasive cohort studies are urgently needed to draw the best conclusions.

Background: Growing evidence exists about the fetal and environmental origins of hypertension, but mainly limited to single-exposure studies. The exposome has been proposed as a more holistic approach by studying many exposures simultaneously. Objectives: This study aims to evaluate the association between a wide range of prenatal and postnatal exposures and blood pressure (BP) in children. Methods: Systolic and diastolic BP were measured among 1,277 children from the European HELIX (Human Early-Life Exposome) cohort aged 6 to 11 years. Prenatal (n = 89) and postnatal (n = 128) exposures include air pollution, built environment, meteorology, natural spaces, traffic, noise, chemicals, and lifestyles. Two methods adjusted for confounders were applied: an exposome-wide association study considering the exposures independently, and the deletion-substitution-addition algorithm considering all the exposures simultaneously. Results: Decreases in systolic BP were observed with facility density (β change for an interquartile-range increase in exposure: -1.7 mm Hg [95% confidence interval (CI): -2.5 to -0.8 mm Hg]), maternal concentrations of polychlorinated biphenyl 118 (-1.4 mm Hg [95% CI: -2.6 to -0.2 mm Hg]) and child concentrations of dichlorodiphenyldichloroethylene (DDE: -1.6 mm Hg [95% CI: -2.4 to -0.7 mm Hg]), hexachlorobenzene (-1.5 mm Hg [95% CI: -2.4 to -0.6 mm Hg]), and mono-benzyl phthalate (-0.7 mm Hg [95% CI: -1.3 to -0.1 mm Hg]), whereas increases in systolic BP were observed with outdoor temperature during pregnancy (1.6 mm Hg [95% CI: 0.2 to 2.9 mm Hg]), high fish intake during pregnancy (2.0 mm Hg [95% CI: 0.4 to 3.5 mm Hg]), maternal cotinine concentrations (1.2 mm Hg [95% CI: -0.3 to 2.8 mm Hg]), and child perfluorooctanoate concentrations (0.9 mm Hg [95% CI: 0.1 to 1.6 mm Hg]). Decreases in diastolic BP were observed with outdoor temperature at examination (-1.4 mm Hg [95% CI: -2.3 to -0.5 mm Hg]) and child DDE concentrations (-1.1 mm Hg [95% CI: -1.9 to -0.3 mm Hg]), whereas increases in diastolic BP were observed with maternal bisphenol-A concentrations (0.7 mm Hg [95% CI: 0.1 to 1.4 mm Hg]), high fish intake during pregnancy (1.2 mm Hg [95% CI: -0.2 to 2.7 mm Hg]), and child copper concentrations (0.9 mm Hg [95% CI: 0.3 to 1.6 mm Hg]). Conclusions: This study suggests that early-life exposure to several chemicals, as well as built environment and meteorological factors, may affect BP in children.