Background: School-aged children living near plastics–producing factories may have higher risk of exposure to phthalates released during the manufacturing processes. Objectives: We aimed to investigate the urinary concentrations of phthalate metabolites in school-aged children living near a petrochemical complex and estimate the cumulative risk of phthalate exposure. Methods: We used a well-established cohort (Taiwan Petrochemical Complex Cohort for Children, TPE3C) of school-aged children (6–13 years old) living near polyvinyl chloride (PVC) and vinyl chloride monomer (VCM) factories in central Taiwan from October 2013 to September 2014. A total of 257 children were included from five elementary schools: Syu-Cuo Branch (n = 58, school A, ~0.9 km), Feng-An (n = 40, school B, ~2.7 km), Ciao-Tou (n = 58, school C, ~5.5 km), Mai-Liao (n = 37, school D, ~6.9 km), and Lung-Feng (n = 57, school E, ~8.6 km). We analyzed 11 metabolites of seven phthalates (including di-2-ethylhexyl phthalate (DEHP) and di-n-butyl phthalate (DnBP)) in urine. Daily intakes (DIs) were compared with acceptable intake levels to calculate the hazard quotient (HQ) for individual phthalates, and the cumulative risk for each child was assessed using a hazard index (HI), which was the sum of the the individual HQs. Results: The geometric mean and proportion of participants with HIs exceeding one for hepatic (HI_hep) and reproductive (HI_rep) effects were 0.33 (13.2%) and 0.24 (7.8%), respectively. The major contributors to phthalate exposure risk were DEHP, di-iso-butyl phthalate (DiBP) and DnBP in all children. Moreover, we observed a U shaped distribution of DEHP exposure by school distance from the PVC and VCM factories (school A: 7.48 μg/kg/day and school E: 80.44 μg/kg/day). This may be due to emissions (closest) and and being located downwind of PVC scrap incineration (farthest). Conclusions: Our findings suggest that children living near a petrochemical complex were at a greater risk of phthalate exposure than normal school-aged children and that phthalate exposure was mainly attributed to DEHP, DiBP and DnBP. In addition, inhalation may have been a risk factor for people living near to PVC and VCM factories. Full article

Bisphenol A (BPA) is an endocrine-disrupting chemical that affects lipid metabolism and contributes to non-alcoholic fatty liver disease (NAFLD). The mechanism of BPA exposure in hepatic lipid accumulation and its potential effect on NAFLD remain unclear. This study investigated the effect of BPA-exposure-induced hepatic lipid deposition on the pathology of NAFLD and its underlying mechanism in vitro and in vivo. BPA increased intracellular reactive oxygen species (ROS) levels, and promoted fatty acid uptake through upregulation of a free fatty acid uptake transporter, cluster of differentiation 36 (CD36), in HUH-7 cells. Additionally, C57BL/6 mice administered a high-fat/high-cholesterol/high-cholic acid diet (HFCCD) and BPA (50 mg/kg body weight) for 8 weeks developed a steatohepatitis-like phenotype, characterized by alpha-smooth muscle actin (α-SMA, an indicator of hepatic fibrosis) and cleaved caspase 3 (an indicator of apoptosis) in hepatic tissue; moreover, they had a higher oxidative stress index of 8-hydroxydeoxyguanosine (8-OHdG) in liver tissue compared to the control group. Treatment with ROS scavenger n-acetylcysteine (NAC) ameliorated BPA-mediated HFCCD-induced lipid accumulation and steatohepatitis in the livers of treated mice. Our study indicates that BPA acts synergistically to increase hepatic lipid uptake and promote NAFLD development by stimulating ROS-induced CD36 overexpression. Full article

Bisphenol A (BPA), which is contained in numerous plastic products, is known to act as an endocrine-disruptive, toxic, and carcinogenic chemical. This experimental series sought to determine the influence of BPA exposure on the femoral bone architecture and biomechanical properties of male and female Wistar rats. BPA was applied subcutaneously by using osmotic pumps. After 12 weeks, the bones were analyzed by micro-computed tomography (micro-CT) and a three-point bending test. Comparing the female low- and high-dose groups, a significantly greater marrow area (p = 0.047) was identified in the group exposed to a higher BPA concentration. In addition, the trabecular number tended to be higher in the female high-dose group when compared to the low-dose group (p > 0.05). The area moment of inertia also tended to be higher in the male high-dose group when compared to the male low-dose group (p > 0.05). Considering our results, BPA-related effects on the bone morphology in female Wistar rats are osteoanabolic after high-dose exposure, while, in male rats, a tendency toward negative effects on the bone morphology in terms of a reduced cross-sectional cortical area and total area could be demonstrated. Full article

The development of a rapid analytical approach for determining levels of antibacterial agents, plasticizers, and ultraviolet filters in biosamples is crucial for individual exposure assessment. We developed an analytical method to determine the levels of four parabens—bisphenols A (BPA) and its analogs, triclosan (TCS), triclocarban, and benzophenone-3 (BP-3)—in human urine. We further measured the levels of these chemicals in children and adolescents. We used a supported liquid extraction (SLE) technique coupled with an isotope-dilution ultraperformance liquid chromatography-tandem mass spectrometry (ID-UPLC-MS/MS) method to assess the detection performance for these chemicals. Forty-one urine samples from 13 children and 28 adolescents were assessed to demonstrate the capability and feasibility of our method. An acceptable recovery (75.6–102.4%) and matrix effect (precision < 14.2%) in the three-level spiked artificial urine samples were achieved, and good performance of the validated ID-UPLC-MS/MS method regarding linearity, limits of detection, and quantitation was achieved. The within-run and between-run accuracy and precision also demonstrated the sensitivity and stability of this analytical method, applied after SLE. We concluded that the ID-UPLC-MS/MS method with SLE pretreatment is a valuable analytical method for the investigation of urinary antibacterial agents, plasticizers, and ultraviolet filters in humans, useful for human biomonitoring. Full article

Phthalate exposure is associated with cardiovascular risk. Among the various phthalates, di-(2-ethylhexyl) phthalate (DEHP) is a deleterious plasticizer in our daily lives. This study investigated the association between DEHP exposure and the alteration of heart rate variability (HRV). During 2017–2019, we recruited 974 young adults to investigate the effects of living environments and dietary habits on cardiometabolic disorders in Taiwan. We quantitatively analyzed urinary metabolites of DHEP. A continuous electrocardiogram was recorded to obtain a 5-min ECG. Time-domain and frequency-domain HRV analyses were performed. Multiple linear regression showed that urinary oxidized DEHP metabolites MEHHP and MEOHP were associated with decreased HRV after controlling for associated cardiovascular risk factors. A higher MEHHP level was associated with a lower triangular interpolation of NN interval histogram (TINN), very low frequency (VLF), and low frequency/high frequency (LF/HF) ratio. A higher MEOHP level was associated with a decreased LF/HF ratio. In addition, trend analysis showed that higher MEHHP and MEOHP quantiles were significantly associated with a decreased LF/HF ratio. DEHP is a potentially harmful and invisible chemical. The urinary DEHP metabolites MEHHP and MEOHP are associated with decreased HRV, indicating an adverse effect on autonomic balance in young adults in Taiwan. Full article

This study investigates the disruptive activity of environmental toxicants on sex hormone receptors mediating type 2 diabetes mellitus (T2DM). Toxicokinetics, gene target prediction, molecular docking, molecular dynamics, and gene network analysis were applied in silico techniques. From the results, permethrin, perfluorooctanoic acid, dichlorodiphenyltrichloroethane, O-phenylphenol, bisphenol A, and diethylstilbestrol were the active toxic compounds that could modulate androgen (AR) and estrogen-α and –β receptors (ER) to induce T2DM. Early growth response 1 (EGR1), estrogen receptor 1 (ESR1), and tumour protein 63 (TP63) were the major transcription factors, while mitogen-activated protein kinases (MAPK) and cyclin-dependent kinases (CDK) were the major kinases upregulated by these toxicants via interactions with intermediary proteins such as PTEN, AKT1, NfKβ1, SMAD3 and others in the gene network analysis to mediate T2DM. These toxicants pose a major challenge to public health; hence, monitoring their manufacture, use, and disposal should be enforced. This would ensure reduced interaction between people and these toxic chemicals, thereby reducing the incidence and prevalence of T2DM. Full article

Due to the sparsity in knowledge, we investigated the presence of various estrogenic endocrine-disrupting chemicals (EEDCs), including phthalates (PAEs), bisphenol-A (BPA), and nonylphenol (NP), as well as microplastics (MPs) in samples of the most widely consumed fish collected from different estuaries in northern Taiwan. We then proceeded to determine the likely contribution that this exposure has on the potential for health impacts in humans following consumption of the fish. Six hundred fish caught from five river estuaries (producing 130 pooled samples) were analyzed to determine how different factors (such as the river, benthic, pelagic, and migratory species) influence EEDCs’ contamination and the possible impacts on human health following typical consumption patterns. The predominant EEDCs was diethyl phthalates (DEP), bis (2-ethylhexyl) phthalates (DEHP), and di-iso-nonylphthalate (DINP) in fish, present at 52.9 ± 77.3, 45.3 ± 79.8, and 42.5 ± 79.3 ng/g dry weight (d.w.), respectively. Residual levels of NP, BPA, and MPs in the fish were 17.4 ± 29.1 and 1.50 ± 2.20 ng/g d.w. and 0.185 ± 0.338 mg/g d.w., respectively. EEDCs and MPs levels varied widely among the five river estuaries sampled due, in part, to differences in habitat types and the associated diversity of fish species sampled. For DEP, the Lao-Jie River and pelagic environments produced the most severely contaminated fish species, respectively. DEP residues were also associated with the burden of MPs in the fish. Based on our analysis, we predict no substantial direct human health risk by EEDCs based on typical consumption rates of estuarine fish by the Taiwanese people. However, other sources of EEDC exposure cannot be ignored. Full article

The phthalate and semi-volatile organic compounds (SVOCs) are modern chemical substances and extensively existing in the indoor environment. The European Commission stipulated the “European Unified Test Criteria”, since 2011, for the declared specifications of building products (CEN/TS 16516), based on the “lowest concentrations of interest (LCI)”, the index pollutants, test method, and emission standard of “phthalate” and “SVOC” were specified in detail. The purpose of this study is to use six common indoor floor construction products in Taiwan (regenerated pseudoplastic rubber flooring, healthy pseudoplastic imitation wood floor, regenerated pseudoplastic rubber flooring, PVC floor tile/floor, plastic click floor, composite floor covered with carpet) to detect the changes in the concentration of phthalate emitted to the air. The ISO 16000-25 Indoor air—Part 25: Determination of the emission of semi-volatile organic compounds by building products—micro-chamber method is used to build a DS-BMEMC (glass micro-chamber: volume 630 mL), the SVOC, including phthalate, is collected in two stages, in the stable conditions of temperature 25 °C, relative humidity 50% and air change rate 2 times/h, the Stage 1 emission detection experiment (24 h) is performed, and then the Stage 2 heating-up desorption emission detection experiment (40 min air sampling) is performed, the temperature rises to 200–220 °C, the phthalate and SVOC adsorbed on the glass micro-chamber is desorbed at a high temperature to catch the air substances, the air is caught by Tenax^®—TA and Florisil^® adsorption tube, and then the GC/MS and LC/MSMS analysis methods are used for qualitative and emission concentration analyses of SVOC of two-stage emission, respectively. The findings show that the floor construction materials emit nine phthalate SVOCs: DEHP, DINP, DNOP, DIDP, BBP, DBP, DIBP, DEP, and DMP, the two-stage emission concentrations are different, Stage 1 (normal temperature) emission concentration of six floor construction materials is 0.01–1.2% of Stage 2 (high temperature) emission concentration, meaning the phthalate SVOC of floor construction materials is unlikely to be volatilized or emitted at normal temperature. An interesting finding is that only S3 was detected DINP 72.6 (μg/m³) in stage 1. Others were detected DINP in stage 2. This might be because S3 has carpet on the surface. This implies that floor material with carpet may have an emission of DINP at normal temperature. The result of this study refers to the limited value evaluation of EU structural material standard emission TSVOC ≤ 0.1 ug/m³, the floor building material emissions are much higher than the evaluation criteria, increasing the health risk of users. The detection method and baseline can be used as the standard for controlling the emission of phthalate SVOC of Taiwan’s green building material labeling system in the future. Full article

Endothelial function is crucial in the pathogenesis of circulatory and cardiovascular toxicity; epidemiologic research investigating the association between phthalate exposure and endothelial dysfunction remains limited. We examined the associations between exposures to specific phthalates (di-2-ethylhexyl phthalate, DEHP; di-n-butyl phthalate, DnBP) and circulating endothelial and platelet microparticles (EMPs and PMPs) in adolescents and young adults. Of the 697 participants recruited, anthropometric measurements and health-related behaviors relevant to cardiovascular risks were collected and assessed. Urine and serum were collected and analyzed with liquid chromatography-tandem mass spectrometry (LC-MS/MS) and flow cytometry. Multiple linear regression indicated that increases in urinary concentrations of ΣDEHP and MnBP (mono-n-butyl phthalate), across quartiles, were positively associated with serum EMPs level (p for trend <0.001 and <0.001; β = 0.798 and 0.007; standard error = 0.189 and 0.001, respectively). Moreover, female and overweight subjects had higher MnBP, and males were more vulnerable to DnBP exposure compared to females. In conclusion, our results demonstrate a dose-response relationship between exposures to phthalates (ΣDEHP and MnBP) and microparticle formation (EMPs and PMPs) in adolescents and young adults. The findings indicate that exposures to phthalates of both low and high-molecular weight are positively associated with microparticle production, and might contribute to endothelial dysfunction; such damage might manifest in the form of atherosclerotic-related vascular diseases. Future in vivo and in vitro studies are warranted to elucidate whether a causal relationship exists between phthalate exposure and EMPs and PMPs. Full article

Exposure to bisphenols is related to negative effects on male reproduction. The bisphenols exposure is associated with several modes of action including negative impact on the blood–testis barrier (BTB) in testes or direct effect on spermatozoa. Bisphenols have been detected in human seminal plasma, but the possible mechanism of seminal transfer of bisphenols is not clear. Some authors consider the transfer through the blood–testis barrier to be crucial. Therefore, in this work, we compared normozoospermic men and men after vasectomy who have interrupted vas deferens and their ejaculate does not contain testicular products. We measured the concentration of bisphenol A (BPA), bisphenol S (BPS) and bisphenol F (BPF) in the urine and seminal plasma of these men using liquid chromatography tandem mass spectrometry (LC/MSMS). We found that the ratio of urinary and seminal plasma content of bisphenols did not differ in normozoospermic men or men after vasectomy. From the obtained data, it can be concluded that the pathways of transport of bisphenols into seminal plasma are not primarily through the testicular tissue, but this pathway is applied similarly to other routes of transmission by a corresponding ejaculate volume ratio. To a much greater extent than through testicular tissue, bisphenols enter the seminal plasma mainly as part of the secretions of the accessory glands. Full article