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.

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.

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.

To investigate tissue distribution, spatial difference, temperature variation, and potential health risks of PAEs in vegetables, celery was used as a model plant. Celery samples were collected from open fields and greenhouses from two provinces in China over four seasons. Celery tissues were analyzed for 16 PAE compounds by gas chromatography–tandem mass spectrometry. The total content of PAEs was 89.0–1130.3 μg kg⁻¹ dry weight (dw) in stems and 155.0–2730.8 μg kg⁻¹ dw in leaves. Concentrations of PAEs in celeries showed notable spatial differences (P < 0.05), and the levels in samples from open fields were lower than those in samples from plastic greenhouses. In celeries from greenhouses, higher PAE concentrations were observed for plants grown at high temperatures than in plants grown at low temperatures. Discrepancies in tissue distribution indicated different uptake pathways of PAE contaminants. Risk assessments to humans found that both carcinogenic risks and non-carcinogenic risks of PAEs via celery consumption were at an acceptable level. Further research should consider other exposure pathways of PAEs and pay special attention to reducing PAE contents in vegetables.

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.

Urban stormwater is an important pathway for transporting anthropogenic pollutants to water bodies. Phthalate esters (PAEs) are endocrine disruptors owing to their estrogenic activity and potential carcinogenicity and their ubiquitous presence has garnered global interest. However, their transportation by urban stormwater has been largely overlooked. This study, for the first time, investigated 15 PAEs in stormwater from six major stormwater drains in the highly urbanized Hong Kong, a major metropolitan city in China. The results showed that PAEs were ubiquitous in the stormwater of Hong Kong, with total concentrations (∑₁₅PAEs) spanning from 195 to 80,500 ng/L. Bis(2-n-butoxyethyl) phthalate (DBEP), diisopentyl phthalate (DiPP), dicyclohexyl phthalate (DCHP) and di-n-pentyl phthalate (DnPP) were detected in stormwater for the first time. Spatial variations in PAEs were observed among different stormwater drains, possibly due to the different land use patterns and intensities of human activities in their respective catchments. The highest and lowest levels of ∑₁₅PAEs were found in Kwai Chung (3860 ± 1960 ng/L) and the Ng Tung River (672 ± 557 ng/L), respectively. Additionally, significantly higher concentrations of ∑₁₅PAEs in stormwater were found in the wet season (2520 ± 2050 ng/L) than in the dry season (947 ± 904 ng/L). Principal component analysis classified domestic and industrial origins as two important sources of PAEs in the stormwater of Hong Kong. Stormwater played a crucial role in transporting PAEs, with an estimated annual flux of 0.705–29.4 kg. Thus, possible stormwater management measures were proposed to protect the receiving environment and local ecosystems from stormwater.

DEHP is commonly found in the environment, biota, food, and humans, raising significant health concerns. Whether developmental stage and exposure duration modify the obesogenic effects of DEHP is unclear, especially the underlying mechanisms by which chronic exposure to DEHP as well as its metabolites remain largely unknown. This study investigated the obesogenic effects of chronic DEHP exposure, with levels below environmentally-relevant amounts and provide the mechanism in Caenorhabditis elegans. We show that early-life DEHP exposure resulted in an increased lipid and triglyceride (TG) accumulation mainly attributed to DEHP itself, not its metabolite mono-2-ethylhexyl phthalate (MEHP). In addition, developmental stage and exposure timing influence DEHP-induced TG accumulation and chronic DEHP exposure resulted in the most significant effect. Analysis of fatty acid composition shows that chronic DEHP exposure altered fatty acid composition and TG, resulting in an increased ω-6/ω-3 ratio. The increased TG content by chronic DEHP exposure required lipogenic genes fat-6, fat-7, pod-2, fasn-1, and sbp-1. Moreover, chronic DEHP exposure induced XBP-1-mediated endoplasmic reticulum (ER) stress which might lead to up-regulation of sbp-1. This study suggests the possible involvement of ER stress and SBP-1/SREBP-mediated lipogenesis in chronic DEHP-induced obesogenic effects. Results from this study implies that chronic exposure to DEHP disrupts lipid metabolism, which is likely conserved across species due to evolutionary conservation of molecular mechanisms, raising concerns in ecological and human health.

The adverse effects of fine atmospheric particulate matter with aerodynamic diameters of ≤2.5 μm (PM₂.₅) are closely associated with particulate chemicals. In this study, PM₂.₅ samples were collected from highway and industry sites in Hangzhou, China, during the autumn and winter, and their cytotoxicity and pulmonary toxicity and endocrine-disrupting potential (EDP) were evaluated in vitro and in vivo; the particulate polycyclic aromatic hydrocarbons (PAHs), phthalate esters (PAEs), and heavy metals were then characterized. The toxicological results suggested that the PM₂.₅ from highway site induced higher cytotoxicity (cell viability inhibition, intracellular oxidative stress, and cell membrane injury) and pulmonary toxicity (inflammatory response (IR) and oxidative stress (OS)) than the samples from industry site, while the PM₂.₅ from industry site exhibited higher EDP (estrogenic and anti-androgenic activity). The cytotoxicity and pulmonary toxicity of PM₂.₅ in the winter were higher than those in the autumn, while no seasonal difference in the endocrine-disrupting potential was observed (p > 0.05). The Pearson correlation analysis between the biological effects and particulate chemicals revealed that the PM₂.₅-induced inflammatory response and oxidative stress were closely associated with the particulate PAHs and heavy metals (Pearson correlation coefficients: rIR, PAHₛ = 0.822–0.988, rIR, ₕₑₐᵥy ₘₑₜₐₗₛ = 0.895–0.971, rOS, PAHₛ = 0.843–0.986, and rOS, ₕₑₐᵥy ₘₑₜₐₗₛ = 0.887–0.933), while particulate di (2-ethylhexyl)phthalate (DEHP) substantially contributed to the EDP of PM₂.₅ (rEDP, DEHP = 0.981). This study indicated that the toxicity and EDP of PM₂.₅ could vary with the surrounding environment and season, which was closely associated with the variations of particulate chemicals. Further studies are needed to clarify the associations between the harmful effects of PM₂.₅ and other contributing factors.

Prior human studies have explored effects of phthalate exposures on thyroid function, but the underlying biological mechanisms remain poorly unclear. We aimed to explore the associations between phthalate exposures and thyroid function among a potentially susceptible population such as patients with thyroid nodules, and further to assess the mediating role of oxidative stress. We measured eight phthalate metabolites, three oxidative stress biomarkers [8-hydroxy-2-deoxyguanosine (8-OHdG), 8-iso-prostaglandin F₂α (8-isoPGF₂α) and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA)] in urine and three thyroid function biomarkers [thyroid-stimulating hormone (TSH), free triiodothyronine (FT3) and free thyroxine (FT4)] in serum among 214 patients with thyroid nodules. Multivariate regression models were applied to assess the associations among urinary phthalate metabolites, oxidative stress and thyroid function biomarkers. The potential mediating role of oxidative stress was explored by mediation analysis. We observed that multiple urinary phthalate metabolites were associated with altered FT4 and increased oxidative stress biomarkers (all FDR-adjusted P ≤ 0.05). Meanwhile, we found that 8-isoPGF₂α was negatively associated with FT3/FT4 among patients with benign thyroid nodules (FDR-adjusted P = 0.08). The mediation analysis indicated that 8-isoPGF₂α mediated the associations of urinary MEHHP and %MEHP with FT3/FT4, with 55.6% and 32.6% proportion of the mediating effects, respectively. Our data suggest that lipid peroxidation may be an intermediate mechanism involved in the effects of certain phthalate exposures on altered thyroid function among patients with benign thyroid nodules.