International audience | Endocrine disrupting compounds (EDCs) have been found in surface waters worldwide. They are known for exerting adverse effects on animals of many species, including humans. EDCs comprise compounds of anthropogenic origin. They can enter waterways via either discharges from wastewater treatment plant (WWTPs), combined sewer overflows (CSO) or atmospheric deposition. In this work, the fate and removal of four phthalates and two alkylphenols: Diethyl phthalate (DEP), Di-n-Butyl phthalate (DnBP), Butyl Benzyl phthalate (BBP), Di-(2-ethylhexyl) phthalate (DEHP), nonylphenol (NP) and octylphenol (OP) were investigated within a wastewater treatment plant (WWTP) using lamellar clarification and biofiltration. This plant receives about 240,000 m 3 d -1 of wastewater. The whole treatment process comprises: screening, grit removal, primary sedimentation using coagulant and flocculant, followed by biofiltration units. Phthalates and alkylphenols were monitored at three locations, including raw sewage, before primary treatment, decanted effluents, before biological treatment, and final effluents, just before discharge to receiving waters. Nine campaigns were performed in 2011 during different seasons. In raw wastewater, DEHP was the major compound (32.42 to 71.88, median 42.95 μg.l -1), followed by DEP (7.00 to 36.03, median 21.00 μg.l -1) and NP (4.08 to 10.63, median 5.95 μg.l -1). Other compounds averaged few μg.l -1. During the WWTP treatment, DEP becomes major contaminant (0.46 to 6.77, median 2.95 μg.l -1), followed by DEHP (0.95 to 6.43, median 2.30 μg.l -1) and NP (0.31 to 1.36, median 0.63 μg.l -1). Contaminant removal depends on the physicochemical characteristics of the compounds. For example, for lamellar clarification, removal efficiency was found to be strongly dependent to log Kow and, hence, to be highly correlated with their sorption coefficient (Kd). As a consequence, compounds with high log Kow (>3) were removed to a significant extent. DEHP was highly removed by lamellar clarification (68.8%), followed by BBP (61.5%) and NP (51.0%). Besides, DEP (log Kow < 3) was slightly removed (13.8%). During biofiltration, both hydrophilic and hydrophobic compounds were equally eliminated. Therefore, DEP (87.3%), OP (88.0%) and DEHP (81.9%) were mostly removed during biological treatment. © 201 WIT Press.

International audience | The gut microbiota is a collection of symbiotic microorganisms in the gastrointestinal tract. Its sensitivity to chemicals with widespread exposure, such as phthalates, is little known. We aimed to investigate the impact of perinatal exposure to phthalates on the infant gut microbiota at 12 months of age. Within SEPAGES cohort (Suivi de l'Exposition à la Pollution Atmosphérique durant la Grossesse et Effet sur la Santé), we assessed 13 phthalate metabolites and 2 di(isononyl) cyclohexane-1,2-dicarboxylate (DINCH) metabolites in repeated urine samples collected in pregnant women and their offspring. We obtained stool samples from 356 children at 12 months of age and sequenced the V3-V4 region of the 16S rRNA gene, allowing gut bacterial profiling. We used single-chemical (linear regressions) and mixture (BKMR, Bayesian Kernel Machine Regression) models to examine associations of phthalates and DINCH metabolites, with gut microbiota indices of α-diversity (specific richness and Shannon diversity) and the relative abundances of the most abundant microbiota phyla and genera. After correction for multiple testing, di(2-ethylhexyl) phthalate (ΣDEHP), diethyl phthalate (DEP) and bis(2-propylheptyl) phthalate (DPHP) metabolites 12-month urinary concentrations were associated with higher Shannon α-diversity of the child gut microbiota in single-chemical models. The multiple-chemical model (BKMR) suggested higher α-diversity with exposure to the phthalate mixture at 12 months, driven by the same phthalates. There were no associations between phthalate and DINCH exposure biomarkers at other time points and α-diversity after correction for multiple testing. ΣDEHP metabolites concentration at 12 months was associated with higher Coprococcus genus. Finally, ΣDEHP exposure at 12 months tended to be associated with higher phylum Firmicutes, an association not maintained after correction for multiple testing. Infancy exposure to phthalate might disrupt children's gut microbiota. The observed associations were cross-sectional, so that reverse causality cannot be excluded.

We aimed to investigate the associations between chemical mixtures and the risk of nonalcoholic fatty liver disease (NAFLD) in this study. A total of 127 exposure analytes within 13 chemical mixture groups were included in the current analysis. Associations between chemical mixture exposure and prevalence of NAFLD were examined using weighted quantile sum (WQS) regressions. NAFLD was diagnosed by hepatic steatosis index (HSI) and US fatty liver index (USFLI). In USFLI-NAFLD cohort, chemical mixtures positively associated with NAFLD development included urinary metals (OR: 1.10, 95% CI: 1.04–1.16), urinary perchlorate, nitrate and thiocyanate (OR: 1.06, 95% CI: 1.02–1.11), urinary pesticides (OR: 1.24, 95% CI: 1.09–1.40), urinary phthalates (OR: 1.18, 95% CI: 1.09–1.28), urinary polyaromatic hydrocarbons (PAHs) (OR: 1.08, 95% CI: 1.03–1.14), and urinary pyrethroids, herbicides, and organophosphate pesticides metabolites (OR: 1.32, 95% CI: 1.15–1.51). All of the above mixtures were also statistically significant in WQS regressions in the HSI-NAFLD cohort. Besides, some chemical mixtures were only significant in HSI-NAFLD cohort including urinary arsenics (OR: 1.07, 95% CI: 1.02–1.12), urinary phenols (OR: 1.10, 95% CI: 1.02–1.19) and blood polychlorinated dibenzo-p-dioxins (OR: 1.10, 95% CI: 1.03–1.17). Three types of chemical mixtures only showed significant associations in the healthy lifestyle score (HLS) of 3–4 subgroup, including urinary perchlorate, nitrate and thiocyanate, urinary PAHs and blood polychlorinated dibenzo-p-dioxins. In conclusion, the exposure of specific types of chemical mixtures were associated with elevated NAFLD risk, and the effects of some chemical mixtures on NAFLD development exhibited differences in participants with different lifestyles.

Rising evidence of both experimental and epidemiological studies suggests that phthalate exposure may contribute to increased risks of metabolic disorders. But there is limited research on the childhood dyslipidemia. Our cohort study was conducted in Xiamen city, Fujian Province, China. A total of 829 children (mean age 8.5 years) were included with collection of urine, blood samples and demographic data in May 2018 and followed up once a year from 2018 to 2020. We performed adjusted log-binomial regressions to examine associations between sex-specific tertiles of seven phthalate metabolites and dyslipidemia in visit 1, as well as persistent dyslipidemia and occasional dyslipidemia. We also used generalized estimating equation models (GEE) to explore the relationships between log-transformed phthalate metabolites and lipid profiles. In adjusted models, the prevalence and RRs of dyslipidemia increased with tertile group of mono-n-butyl phthalate (MnBP), mono-2-ethyl-5-oxohexyl phthalate (MEOHP), mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP), and summed di-(2-ethylhexyl) phthalate (∑DEHP) metabolites with a dose-response relationship in visit 1, as well as persistent dyslipidemia. Higher MnBP, ∑LMWP, MEHHP, MEOHP, and ∑DEHP concentrations were also associated with higher levels of log-transformed triglycerides (TG). Boys were more vulnerable to phthalates exposure than girls. In conclusion, children in China were widely exposed to phthalates, and phthalates exposure during childhood might significantly increase the risk of dyslipidemia and a higher level of lipid profiles, particularly in boys.

Although an association between urinary phthalate (PAE) metabolites and respiratory symptoms and diseases has been reported, knowledge regarding its effect on pulmonary function is limited, especially in adolescents. Using cross-sectional data from 1389 adolescents (aged 10–19 years) in the 2007–2012 National Health and Nutrition Examination Survey, the association of mixed urinary PAE metabolites with pulmonary function was evaluated using the weighted quantile sum. Moreover, multivariate linear regression was performed to investigate associations between each urinary PAE metabolite and pulmonary function indicators and to estimate the interaction effects between urinary PAE metabolites and demographic characteristics. We found that mixed urinary PAE metabolites were negatively associated with forced expiratory volume at the 1 s (FEV1, p < 0.001) and forced vital capacity (FVC, p = 0.008) levels. In individual PAE metabolite analyses, mono (carboxynonyl) pthalate (MCNP), mono-n-butyl pthalate (MnBP), mono-isobutyl pthalate (MiBP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) and mono-benzyl phthalate (MBzP) correlated negatively with both FVC and FEV1 values (Holm-Bonferroni corrected p < 0.05). Mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) was negatively associated with the FVC value. Significant interactions between sex and urinary MnBP or MBzP levels for the risk of FEV1 decrease in girls were found (p = 0.005), as was a significant interaction between sex and urinary MBzP level for the risk of FVC decline. Our findings suggest that higher PAE exposure is associated with respiratory dysfunction; the association is more pronounced among girls.

The potential effect of gestational exposure to phthalates on the lung function levels during childhood is unclear. Therefore, we examined this association at different ages (from 4 to 11 years) and over the whole childhood. Specifically, we measured 9 phthalate metabolites (MEP, MiBP, MnBP, MCMHP, MBzP, MEHHP, MEOHP, MECPP, MEHP) in the urine of 641 gestating women from the INMA study (Spain) and the forced vital capacity (FVC), forced expiratory volume in 1 s (FEV₁) and FEV₁/FVC in their offspring at ages 4, 7, 9 and 11. We used linear regression and mixed linear regression with a random intercept for subject to assess the association between phthalates and lung function at each study visit and for the overall childhood, respectively. We also assessed the phthalate metabolites mixture effect on lung function using a Weighted Quantile Sum (WQS) regression. We observed that the phthalate metabolites gestational levels were consistently associated with lower FVC and FEV₁ at all ages, both when assessed individually and jointly as a mixture, although most associations were not statistically significant. Of note, a 10% increase in MiBP was related to lower FVC (−0.02 (−0.04, 0)) and FEV₁ z-scores (−0.02 (−0.04, −0.01) at age 4. Similar significant reductions in FVC were observed at ages 4 and 7 associated with an increase in MEP and MnBP, respectively, and for FEV₁ at age 4 associated with an increase in MBzP. WQS regression consistently identified MBzP as an important contributor to the phthalate mixture effect. We can conclude that the gestational exposure to phthalates was associated with children's lower FVC and FEV₁, especially in early childhood, and in a statistically significant manner for MEP, MiBP, MBzP and MnBP. Given the ubiquity of phthalate exposure and its established endocrine disrupting effects in children, our findings support current regulations that limit phthalate exposure.

The coexistence of di (2-ethylhexyl) phthalate (DEHP), Cd, and Zn poses a serious challenge to soil ecosystems. This study aimed to evaluate the phytoremediation potential of rice assisted with a plant growth promoting rhizobacteria (PGPR) consortium for the remediation of DEHP, Cd, and Zn co-contaminated soil. The consortium consisted of four bacterial strains, all of which exhibited Cd–Zn resistance and DEHP degradability. The results showed that the rice assisted by the bacterial consortium dissipated 86.1% DEHP while removing 76.0% Cd²⁺ and 92.2% Zn²⁺ from soil within 30 d. The presence of the PGPR consortium promoted plant growth and improved soil enzymatic activity, which may have helped enhance the removal of DEHP and heavy metals from the soil. Moreover, the application of the consortium modified the bacterial community and increased the relative abundance of bacteria related to DEHP degradation (Sphingomonas, Xanthobacteraceae), heavy metal immobilization (Massilia), and soil nutrient cycling (Nitrospira, Vicinamibacterales), which promoted plant growth and the removal of DEHP and heavy metals from soil. Notably, the DEHP and heavy metal contents in rice decreased substantially during the phytoremediation process. Therefore, the PGPR consortium could be beneficial for enhancing the removal of DEHP and heavy metals from the soil, without inducing the accumulation of these pollutants in rice. In general, this study confirmed that the combined use of rice and the PGPR consortium could remedy DEHP and heavy metal co-contaminated soil economically and ecologically without simultaneously posing risks for rice consumption.

Phthalates (PAEs) are known environmental endocrine disruptors that have been widely detected in several environments, and many studies have reported the immunotoxic effects of these compounds. Here, we reviewed relevant published studies, summarized the occurrence and major metabolic pathways of six typical PAEs (DMP, DEP, DBP, BBP, DEHP, and DOP) in water, soil, and the atmosphere, degradation and metabolic pathways under aerobic and anaerobic conditions, and explored the molecular mechanisms of the toxic effects of eleven PAEs (DEHP, DPP, DPrP, DHP, DEP, DBP, MBP, MBzP, BBP, DiNP, and DMP) on the immune system of different organisms at the gene, protein, and cellular levels. A comprehensive understanding of the mechanisms by which PAEs affect immune system function through regulation of immune gene expression and enzymes, increased ROS, immune signaling pathways, specific and non-specific immunosuppression, and interference with the complement system. By summarizing the effects of these compounds on typical model organisms, this review provides insights into the mechanisms by which PAEs affect the immune system, thus supplementing human immune experiments. Finally, we discuss the future direction of PAEs immunotoxicity research, thus providing a framework for the analysis of other environmental pollutants, as well as a basis for PAEs management and safe use.

The association of co-exposure to polycyclic aromatic hydrocarbons (PAHs) and phthalates (PAEs) with blood cell-based inflammatory biomarkers is largely unknown. We conducted a panel study of 144 children aged 4–12 years, with up to 3 repeated visits across 3 seasons. For each visit, we collected the first-morning urine for 4 consecutive days and fasting blood on the day of physical examination. We developed a gas chromatography/tandem mass spectrometry method to detect the metabolites of 10 PAHs (OH-PAHs) and 10 PAEs (mPAEs) in urine samples. We employed linear mixed-effects models to evaluate the individual associations of each OH-PAH and mPAE with blood cell-based inflammatory biomarkers over different lag times. Bayesian kernel machine regression (BKMR) and quantile g-computation were used to evaluate the overall associations of OH-PAHs and mPAEs mixtures with blood cell-based inflammatory biomarkers. After multiple adjustments, we found positive associations of summed hydroxylphenanthrene (∑OHPHE), summed OH-PAHs, and mono-n-butyl phthalate with inflammatory biomarkers such as neutrophil count, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and the systemic immune-inflammation index (SII) at lag 0 (the day of physical examination). Each 1% increase in ∑OHPHE was related to a 0.18% (95% confidence interval: 0.10%, 0.25%) increase in SII, which was the strongest among the above associations. The results of BKMR and quantile g-computation suggested that co-exposure to PAHs and PAEs mixture was associated with an elevated white blood cell count, neutrophil count, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and SII, to which ∑OHPHE and 1-hydroxypyrene (1-OHPYR) might be the major contributors. In addition, gender and age modified the associations of ∑OHPHE and 1-OHPYR with inflammatory biomarkers, where girls and younger children were more susceptible. In conclusion, co-exposure to PAHs and PAEs was associated with elevated inflammation in children, in which ∑OHPHE and 1-OHPYR might play important roles.

Endocrine-disrupting chemicals (EDCs) are ubiquitous in daily life, but their harmful effects on the human body have not been fully explored. Recent studies have shown that EDCs exposure could lead to infertility, menstrual disorder and menopause, resulting in subsequent effects on female health. Therefore, it is of great significance to clarify and summarize the impacts of EDCs on ovarian aging for explaining the etiology of ovarian aging and maintaining female reproductive health. Here in this review, we focused on the impacts of ten typical environmental contaminants on the progression of ovarian aging during adult exposure, including epidemiological data in humans and experimental models in rodents, with their clinical phenotypes and underlying mechanisms. We found that both persistent (polychlorinated biphenyls, perfluoroalkyl and polyfluoroalkyl substances) and non-persistent (phthalates) EDCs exposure could increase an overall risk of ovarian aging, leading to the diminish of ovarian reserve, decline of fertility or fecundity, irregularity of the menstrual cycle and an earlier age at menopause, and/or premature ovarian insufficiency/failure in epidemiological studies. Among these, the loss of follicles can also be validated in experimental studies of some EDCs, such as BPA, phthalates, parabens and PCBs. The underlying mechanisms may involve the impaired ovarian follicular development by altering receptor-mediated pro-apoptotic pathways, inducing signal transduction and cell cycle arrest and epigenetic modification. However, there were inconsistent results in the impacts on fertility/fecundity, menstrual/estrous cycle and hormone changes response to different EDCs, and differences between human and animal studies. Our review summarizes the current state of knowledge on ovarian disrupters, highlights their risks to ovarian aging and identifies knowledge gaps in humans and animals. We therefore propose that females adopt healthy lifestyle changes to minimize their exposure to both persistent and non-persistent chemicals, that have the potential damage to their reproductive function.