Search Results (45)

Background: Humans are consistently and increasingly exposed to phthalate products, but the effect of the combined exposure to phthalates on myocardial injury remains largely unexplored. The present study aimed to explore the effect of the combined exposure to phthalates on myocardial injury. Methods: A total of 1237 male adults (aged ≥20) without coronary artery disease (CAD) from the National Health and Nutrition Examination Survey (NHANES) in 1999–2004 were included in the current study. Multiple linear regression, Bayesian kernel machine regression (BKMR), and a weighted quantile sum (WQS) model were employed to examine the associations of urinary phthalate metabolites with two cardiac injury biomarkers, including troponin T (TNT) and troponin I, using four highly sensitive assays (Abbott, Chicago, IL, USA; Siemens, Erlangen, Germany; and Ortho, Raritan, NJ, USA) (TNIA, TNIS, TNIO). Results: According to the linear regression analysis, mono-(3-carboxypropyl) phthalate (MCPP, a metabolite of di-n-octyl phthalate) was found to be positively associated with serum TNT; a positive association was found between mono-isobutyl phthalate (MiBP, a metabolite of di-isobutyl phthalate) and TNIA, as well as MiBP and TNIS. Mono-benzyl phthalate (MBzP, a metabolite of butyl benzyl phthalate) and MCPP were positively associated with serum TNIO. The BKMR analyses showed a positive overall relationship of serum TNT, TNIA, TNIS, and TNIO with increased concentrations of phthalate metabolites. The WQS model showed MCPP and MBzP were the top two contributors to being an increased risk for elevated TNT levels. MCPP and mono-ethyl phthalate (MEP, a metabolite of diethyl phthalate) were identified as the leading contributors to increased TNIA and TNIS. MCPP and MBzP were the dominant contributors to elevated TNIO. Conclusions: As a combined mixture, phthalate metabolites were positively associated with serum TNT and TNI among adults without CAD, indicating the potential toxic effect of phthalate exposure on cardiac injury. Full article

Endocrine-disrupting chemicals (EDCs), including phthalates, have been implicated in the development of non-alcoholic fatty liver disease (NAFLD) and hepatic fibrosis. This study investigates the age-dependent effects of butyl benzyl phthalate (BBP) exposure on lipid metabolism in the livers of young and aged mice. Young (2-month-old) and aged (20-month-old) male C57BL/6 mice were exposed to BBP through drinking water at a dose of 169 μg/kg/day for 6 and 4 months, respectively. Young mice exposed to BBP showed fatty liver, with downregulation of key fatty acid oxidation genes (CPT1A, CPT1B, CPT2, and Acox1) and elevated pro-inflammatory cytokines (TNF-α and IL-6). In contrast, aged mice exhibited hepatic fibrosis, with increased collagen deposition and upregulation of genes related to fibrosis (Acta2, MMP2, TGF-ß1, and Col1a2), cirrhosis (CXCR4, SOX9, DCN, and MFAP4), and cancer (Bcl2, CDKN2a, c-Myc, and Fn1). Overall, these findings emphasize the importance of age when evaluating the risks of EDC exposure, such as BBP. Future research should focus on understanding the molecular mechanisms behind these age-related differences and explore Grem1 and SOCS3 as potential therapeutic targets for treating EDC-induced and age-related liver diseases. Full article

Development is a continuous process, but few studies have assessed the simultaneous impact of prenatal and postnatal phthalate exposure on children’s behavioral and emotional development. A total of 491 mother–child pairs from the general population in southern Taiwan were studied from 2021 to 2022. Urinary concentrations of bisphenol A (BPA) and phthalate metabolites—mono-ethyl phthalate (MEP), mono-n-butyl phthalate (MnBP), mono-benzyl phthalate (MBzP), and mono-2-ethylhexyl phthalate (MEHP)—were measured in pregnant mothers during the second trimester and in their corresponding children aged 1.5 to 3 years. Behavioral symptoms in children were evaluated using the Child Behavior Checklist (CBCL). Odds ratios (ORs) represent a 1-unit increase in log10-transformed creatinine-corrected maternal urine concentrations. Prenatal maternal urinary MnBP levels were associated with total problems (OR = 19.32, 95% CI: 1.80–43.13, p = 0.04), anxiety (OR = 33.58, 95% CI: 2.16–521.18, p = 0.01), and sleep problems (OR = 41.34, 95% CI: 1.04–1632.84, p = 0.04) in children. Additionally, urinary MnBP levels in children correlated with total problems (OR = 7.06, 95% CI: 1.01–49.05, p = 0.04) and internalizing problems (OR = 11.04, 95% CI: 1.27–95.72, p = 0.01). These findings suggest that prenatal and postnatal exposure to dibutyl phthalate (DBP), metabolized as MnBP, distinctly affects children’s behavioral development. Full article

Objective: Bisphenol A and phthalate are known endocrine disruptors and capable of inducing epigenetic changes in the human population. However, their impact on the placenta is less well studied. Our objective was to measure the effect of exposure to bisphenol A and benzyl butyl phthalate in first-trimester HTR8-SVneo and third-trimester 3A-sub E trophoblast cells by profiling the DNA methylation pattern of the imprinting control region of the IGF2 (insulin-like growth factor) and H19 genes. Methods: Human placental HTR8-SVneo and 3A-sub E cell lines were treated with two sub-lethal concentrations of bisphenol A and benzyl butyl phthalate. Demethylating agent, 5-azacytidine, was used as a positive control. Cells were harvested on post-treatment days 1 and 4. The methylation profile of six CpG dinucleotide sites, part of the CTCF 6 binding site of the IGF2/H19 imprinting control region, was determined by pyrosequencing. Results: In the first-trimester HTR8-SVneo cell line, we observed a significant increased methylation of the CpG sites 3, 4 when treated with a high concentration of bisphenol A or benzyl butyl phthalate while increased methylation at site 6 for both high and low dose treatment on day 4. Demethylation of the CpG sites 1, 4, and 6 was observed when treated with 5-azacytidine on day 4. In the third-trimester 3A-sub E cell line, no significant changes in the methylation profile were observed under any treatment conditions. Conclusions: The results of this study demonstrate the capability of epigenetic changes in human placenta cells induced by bisphenol A and benzyl butyl phthalate. The observed methylation changes only in the first-trimester HTR8-SVneo cells phthalate may reflect a window of epigenetic susceptibility related to these environmental toxicants. Full article

Plastic bottles have gained widespread popularity due to their durability, affordability, and recyclable nature. Phthalic acid esters (PAEs) are used as plasticizers in PET bottle production, which has raised concerns regarding their presence in the environment and potential adverse effects on health, including carcinogenic and endocrine-disrupting properties. PAEs can migrate from PET bottles into the contents, especially when exposed to high temperatures. This study is the first study in Qatar to determine the leaching of DBP, BBP, and DEHP in local PET drinking water bottles under different stressful thermal conditions. GC–MS is a susceptible instrument, and it is an ideal technique to detect and quantify PAEs in collected local plastic water bottles under different storage temperatures, namely at room temperature, 24 °C; 50 °C; and cyclic temperatures of 70 °C. The limits of detection for DBP, BBP, and DEHP were 0.09, 0.33, and 0.93 µg/L, respectively. Five local brands of PET bottles in Qatar were collected and stored under thermal conditions (24, 50, and 70 °C cyclic). Three kinds of leached PAEs, including dibutyl phthalate (DBP), Benzyl butyl phthalate (BBP), and Bis(2-ethylhexyl) phthalate (DEHP), were detected by GC–MS , ranging from 2.84 to 17.32, 1.16 to 21.35, and 0.01 to 19.59 ng/L, respectively. Significant differences were observed between room temperature 24 °C, 50 °C, and cyclic temperature for concentrations of DBP, BBP, and DEHP. Full article

Phthalates are chemical compounds, mainly used as additives in plastics, which are known to induce harmful impacts to the environment and human health due to their ability to act as hormone-mimics. Few studies have been reported on the relationship between human exposure to phthalates and the level of circulating microRNAs (miRs), especially those miRs encapsulated in extracellular vesicles/exosomes or exosome-like vesicles (ELVs). We examined the relationship of ELV-miR expression patterns and urine of adult men with five phthalate metabolites (i.e., mono isobutyl phthalate, mono-n-butyl phthalate, mono benzyl phthalate, mono-(2-ethyl-5-oxohexyl) phthalate, mono-(2-ethylhexyl) phthalate) to identify potential biomarkers and relevant pathways. We found significant positive associations which were further confirmed by multivariable analysis. Overall, our analyses showed that the Σ phthalate metabolite concentration was associated with a significant increase in the expression level of two miRs found in ELV: miR-202 and miR-543. Different pathways including cancer and immune-related responses were predicted to be involved in this relationship. Analyzing the specific downstream target genes of miR-202 and miR-543, we identified the phosphatase and tensin homolog (PTEN) as the key gene in several converging pathways. In summary, the obtained results demonstrate that exposure to environmental phthalates could be related to altered expression profiles of specific ELV-miRs in adult men, thereby demonstrating the potential of miRs carried by exosomes to act as early effect biomarkers. Full article

Phthalate esters (PAEs) are a group of chemicals used to improve the flexibility and durability of plastics. The chemical properties and the resistance to high temperatures promote their degradation and release into the environment. Food and beverages can be contaminated by PAEs through the migration from packaging material because they are not covalently bound to plastic and also via different kinds of environmental sources or during processing. For instance, alcoholic drinks in plastic containers are a particular risk, since the ethanol contained provides a good solubility for PAEs. According to its role as an endocrine disruptor compound and its adverse effects on the liver, kidney, and reproductive and respiratory systems, the International Agency on Research Cancer (IARC) classified di-(2-ethylhexyl) phthalate (DEHP) as a possible human carcinogen. For this reason, to control human exposure to PAEs, many countries prohibited their use in food as non-food substances. For example, in Europe, the Commission Regulation (EU) 2018/2005 restricts the use of DEHP, dibutyl phthalate (DBP), benzyl butyl phthalate (BBP), and diisobutyl phthalate (DiBP) to a concentration equal to or below 0.1 by weight in plasticizers in articles used by consumers or in indoor areas. There are reports from the US Food and Drug Administration (FDA) that some beverages (and food as well), particularly fruit juices, contain high levels of phthalates. In some cases, the deliberate adulteration of soft drinks with phthalate esters has been reported. This paper would like to show the difficulties of performing PAE analysis in beverage matrices, in particular alcoholic beverages, as well as the main solutions provided for quality control in the industrial branches. Full article

The aim and the novelty of the present review article was to provide the literature with a collective study focusing on the migration and safety issues in plastic food packaging materials that have been raised in recent years and proposing the use of safer and biodegradable ones. The conventional packaging materials used for the preservation of foods may exhibit many disadvantages that are related to the migration of micromolecular chemical substances incorporated in the packaging material net to the packaged food. There are many chemical substances in the matrix of plastic packaging materials and epoxy-resins that are used in food packaging materials, varnishes, and can coatings. Many migrants have high toxicity, such as acetaldehyde, antimony, antimony (III) oxide, 2,4-di-tert-butylphenol, tris (2,4-di-tert-butylphenol) phosphate, tris(2,4-di-tert-butylphenyl) phosphite, bisphenol A, and the plasticizers di(2-ethylhexyl) phthalate), di-n-butyl phthalate, benzyl-butylphthalate, di-isononylphthalate, and di-isododecylphthalate. It is therefore necessary to take a detailed look at the migrants in conventional packaging materials (plastics) used for foods, point out the migration of certain compounds into foods and the need to reconsider their use, and establish updated protocols for the safety of consumers and the industrial production of biodegradable packaging materials (films or coatings) based on natural sources. Full article

Phthalate use and the concentrations of their metabolites in humans vary by geographic region, race, ethnicity, sex, product use and other factors. Exposure during pregnancy may be associated with detrimental reproductive and developmental outcomes. No studies have evaluated the predictors of exposure to a wide range of phthalate metabolites in a large, diverse population. We examined the determinants of phthalate metabolites in a cohort of racially/ethnically diverse nulliparous pregnant women. We report on urinary metabolites of nine parent phthalates or replacement compounds—Butyl benzyl phthalate (BBzP), Diisobutyl phthalate (DiBP), Diethyl phthalate (DEP), Diisononyl phthalate (DiNP), D-n-octyl phthalate (DnOP), Di-2-ethylhexyl terephthalate (DEHTP), Di-n/i-butyl phthalate (DnBP), Di-isononyl phthalate (DiNP) and Di-(2-ethylhexyl) phthalate (DEHP) from urine collected up to three times from 953 women enrolled in the Nulliparous Mothers To Be Study. Phthalate metabolites were adjusted for specific gravity. Generalized estimating equations (GEEs) were used to identify the predictors of each metabolite. Overall predictors include age, race and ethnicity, education, BMI and clinical site of care. Women who were Non-Hispanic Black, Hispanic or Asian, obese or had lower levels of education had higher concentrations of selected metabolites. These findings indicate exposure patterns that require policies to reduce exposure in specific subgroups. Full article

Phthalic acid esters (PAEs), which are widespread environmental contaminants, can be efficiently biodegraded, mediated by enzymes such as hydrolases. Despite great advances in the characterization of PAE hydrolases, which are the most important enzymes in the process of PAE degradation, their molecular catalytic mechanism has rarely been systematically investigated. Acinetobacter sp. LUNF3, which was isolated from contaminated soil in this study, demonstrated excellent PAE degradation at 30 °C and pH 5.0–11.0. After sequencing and annotating the complete genome, the gene dphAN1, encoding a novel putative PAE hydrolase, was identified with the conserved motifs catalytic triad (Ser²⁰¹-Asp²⁹⁵-His³²⁵) and oxyanion hole (H¹²⁷GGG¹³⁰). DphAN1 can hydrolyze DEP (diethyl phthalate), DBP (dibutyl phthalate) and BBP (benzyl butyl phthalate). The high activity of DphAN1 was observed under a wide range of temperature (10–40 °C) and pH (6.0–9.0). Moreover, the metal ions (Fe²⁺, Mn²⁺, Cr²⁺ and Fe³⁺) and surfactant TritonX-100 significantly activated DphAN1, indicating a high adaptability and tolerance of DphAN1 to these chemicals. Molecular docking revealed the catalytic triad, oxyanion hole and other residues involved in binding DBP. The mutation of these residues reduced the activity of DphAN1, confirming their interaction with DBP. These results shed light on the catalytic mechanism of DphAN1 and may contribute to protein structural modification to improve catalytic efficiency in environment remediation. Full article

Many studies indicated that phthalates, a common plasticizer, lurk silently in water bodies and can potentially harm living organisms. Therefore, removing phthalates from water sources prior to consumption is crucial. This study aims to evaluate the performance of several commercial nanofiltrations (NF) (i.e., NF3 and Duracid) and reverse osmosis (RO) membranes (i.e., SW30XLE and BW30) in removing phthalates from simulated solutions and further correlate the intrinsic properties of membranes (e.g., surface chemistry, morphology, and hydrophilicity) with the phthalates removal. Two types of phthalates, i.e., dibutyl phthalate (DBP) and butyl benzyl phthalate (BBP), were used in this work, and the effects of pH (ranging from 3 to 10) on the membrane performance were studied. The experimental findings showed that the NF3 membrane could yield the best DBP (92.5–98.8%) and BBP rejection (88.7–91.7%) regardless of pH, and these excellent results are in good agreement with the surface properties of the membrane, i.e., low water contact angle (hydrophilicity) and appropriate pore size. Moreover, the NF3 membrane with a lower polyamide cross-linking degree also exhibited significantly higher water flux compared to the RO membranes. Further investigation indicated that the surface of the NF3 membrane was severely covered by foulants after 4-h filtration of DBP solution compared to the BBP solution. This could be attributed to the high concentration of DBP presented in the feed solution owing to its high-water solubility (13 ppm) compared to BBP (2.69 ppm). Further research is still needed to study the effect of other compounds (e.g., dissolved ions and organic/inorganic matters that might be present in water) on the performance of membranes in removing phthalates. Full article

Six phthalates: dimethyl phthalate (DMP), diethyl phthalate (DEP), di(n-butyl) phthalate (DnBP), butyl benzyl phthalate (BBzP), di(2-ethylhexyl) phthalate (DEHP), and di(n-octyl) phthalate (DOP) in settled dust on different indoor surfaces were measured in 30 university dormitories. A Monte Carlo simulation was used to estimate college students’ exposure via inhalation, non-dietary ingestion, and dermal absorption based on measured concentrations. The detection frequencies for targeted phthalates were more than 80% except for DEP (roughly 70%). DEHP was the most prevalent compound in the dust samples, followed by DnBP, DOP, and BBzP. Statistical analysis suggested that phthalate levels were higher in bedside dust than that collected from table surfaces, indicating a nonuniform distribution of dust-phase phthalates in the sleep environment. The simulation showed that the median DMP daily intake was 0.81 μg/kg/day, which was the greatest of the targeted phthalates. For the total exposures to all phthalates, the mean contribution of exposures during the daytime and sleeping time was 54% and 46%, respectively. Full article

Phthalate esters (PEs) are esters that are used as plasticizers and are widely known for their contamination and toxicological effects on various environmental matrices. The present study is designed to observe the co-occurrence of phthalate esters and their ecotoxicological and human health risk assessments on Harike wetland, Ramsar, a site recognized globally, is the largest freshwater wetland in Northern India. During the winter, summer, and monsoon seasons, samples of the water and sediments were collected. These samples were then analyzed for ubiquitously detected seven PEs as per the literature survey using ultra-high performance liquid chromatography. According to the results, the total PEs content in the water sample ranged from 31.5 to 95.6 mg/L, whereas in the sediments it ranged from 35.1 to 345.2 mg/100 g dw. Prominent levels of PEs in water and sediments from the Harike wetland were discovered when compared to studies from different parts of the world. Based on drinking water consumption there is a potentially high risk of PEs especially benzyl butyl phthalate and dibutyl phthalate. Further, as per the US Environmental Protection Agency, chronic values of PEs levels in water and sediments are expected to possess a threat to sensitive organisms present in freshwater ecosystems. As far, as this is a detailed study that described the levels and ecotoxicological risks of PEs and is an important reference for the protection of aquatic organisms in the Harike wetland. Full article

Phthalates are mainly used as plasticizers and are associated inter alia with adverse effects on reproductive functions. While more and more national programs in Europe have started monitoring internal exposure to phthalates and its substitute 1,2-Cyclohexanedicarboxylic acid (DINCH), the comparability of results from such existing human biomonitoring (HBM) studies across Europe is challenging. They differ widely in time periods, study samples, degree of geographical coverage, design, analytical methodology, biomarker selection, and analytical quality assurance level. The HBM4EU initiative has gathered existing HBM data of 29 studies from participating countries, covering all European regions and Israel. The data were prepared and aggregated by a harmonized procedure with the aim to describe—as comparably as possible—the EU-wide general population’s internal exposure to phthalates from the years 2005 to 2019. Most data were available from Northern (up to 6 studies and up to 13 time points), Western (11; 19), and Eastern Europe (9; 12), e.g., allowing for the investigation of time patterns. While the bandwidth of exposure was generally similar, we still observed regional differences for Butyl benzyl phthalate (BBzP), Di(2-ethylhexyl) phthalate (DEHP), Di-isononyl phthalate (DiNP), and Di-isobutyl phthalate (DiBP) with pronounced decreases over time in Northern and Western Europe, and to a lesser degree in Eastern Europe. Differences between age groups were visible for Di-n-butyl phthalate (DnBP), where children (3 to 5-year olds and 6 to 11-year olds) had lower urinary concentrations than adolescents (12 to 19-year-olds), who in turn had lower urinary concentrations than adults (20 to 39-year-olds). This study is a step towards making internal exposures to phthalates comparable across countries, although standardized data were not available, targeting European data sets harmonized with respect to data formatting and calculation of aggregated data (such as developed within HBM4EU), and highlights further suggestions for improved harmonization in future studies. Full article

Phthalates can be found in personal care products as solvents and plasticizers in various polymers, especially PVC, wall coverings, certain paints, vinyl floor coverings, electronic devices, medical devices, food packages, toys, cables and other products. Humans are ingesting food products that contain phthalates, or they have dermal contact with phthalate-containing material, such as clothes, PVC gloves, personal care products or house dust. In this study, samples of dust from several houses in Kozani city, Greece, were collected and analyzed for phthalate concentration, and the potential association with building characteristics was examined utilizing detailed checklists. Samples were taken from the vacuum cleaner of the houses and extracted with ethyl acetate, and then analyzed with GC-MS in the SIM mode. The levels of phthalate ranged from 10.57 to 221.19 μg/g for Di-iso-butyl phthalate (DiBP), 4.03 to 264.91 μg/g for Di-n-butyl phthalate (DBP), 0.72 to 20.22 μg/g for benzyl-butyl phthalate (BBP) and 62.73 to 1233.54 μg/g for Di- (2-ethylhexyl) phthalate (DEHP), with detection limits of 4.5, 3.3, 11.6 and 13.1 ng/g, respectively. Using the Kruskal–Wallis statistical test, several associations were found between the measured phthalate and occupant activities (duration of ventilation and location of temporary garbage storage) and building characteristics (plastic or synthetic materials inside the houses). Full article