Objective To examine associations of urinary phthalate levels with blood pressure (BP) and serum triglyceride and lipoprotein levels in children. Study design We performed a cross-sectional analysis ...of a subsample of US children aged 6-19 years who participated in the National Health and Nutrition Examination Survey between 2003 and 2008. We quantified exposure to 3 families of phthalates—low molecular weight, high molecular weight and di-2-ethylhexylphthalate (DEHP)—based on molar concentration of urinary metabolites. We assessed descriptive, bivariate, and multivariate associations with BP and lipid levels. Results Controlling for an array of sociodemographic and behavioral factors, as well as diet and body mass index, levels of metabolites of DEHP, a phthalate commonly found in processed foods, were associated with higher age-, sex-, and height-standardized BP. For each log unit (roughly 3-fold) increase in DEHP metabolites, a 0.041 SD unit increase in systolic BP z -score was identified ( P = .047). Metabolites of low molecular weight phthalates commonly found in cosmetics and personal care products were not associated with BP. Phthalate metabolites were not associated with triglyceride levels, high-density lipoprotein level, or prehypertension. Conclusions Dietary phthalate exposure is associated with higher systolic BP in children and adolescents. Further work is needed to confirm these associations, as well as to evaluate opportunities for intervention.
Phthalates (diesters of phthalic acid) are widely used as plasticizers and additives in many consumer products. Laboratory animal studies have reported the endocrine-disrupting and reproductive ...effects of phthalates, and human exposure to this class of chemicals is a concern. Several phthalates have been recognized as substances of high concern. Human exposure to phthalates occurs mainly via dietary sources, dermal absorption, and air inhalation. Phthalates are excreted as conjugated monoesters in urine, and some phthalates, such as di-2-ethylhexyl phthalate (DEHP), undergo secondary metabolism, including oxidative transformation, prior to urinary excretion. The occurrence of phthalates and their metabolites in urine, serum, breast milk, and semen has been widely reported. Urine has been the preferred matrix in human biomonitoring studies, and concentrations on the order of several tens to hundreds of nanograms per milliliter have been reported for several phthalate metabolites. Metabolites of diethyl phthalate (DEP), dibutyl- (DBP) and diisobutyl- (DiBP) phthalates, and DEHP were the most abundant compounds measured in urine. Temporal trends in phthalate exposures varied among countries. In the United States (US), DEHP exposure has declined since 2005, whereas DiNP exposure has increased. In China, DEHP exposure has increased since 2000. For many phthalates, exposures in children are higher than those in adults. Human epidemiological studies have shown a significant association between phthalate exposures and adverse reproductive outcomes in women and men, type II diabetes and insulin resistance, overweight/obesity, allergy, and asthma. This review compiles biomonitoring studies of phthalates and exposure doses to assess health risks from phthalate exposures in populations across the globe.
Hazardous chemicals in building and construction plastics can lead to health risks due to indoor exposure and may contaminate recycled materials. We systematically sampled new polyvinyl chloride ...floorings on the Swiss market (n = 151). We performed elemental analysis by X-ray fluorescence, targeted and suspect gas chromatography–mass spectrometry analysis of ortho‑phthalates and alternative plasticizers, and bioassay tests for cytotoxicity and oxidative stress, and endocrine, mutagenic, and genotoxic activities (for selected samples). Surprisingly, 16% of the samples contained regulated chemicals above 0.1 wt %, mainly lead and bis(2-ethylhexyl) phthalate (DEHP). Their presence is likely related to the use of recycled PVC in new flooring, highlighting that uncontrolled recycling can delay the phase-out of hazardous chemicals. Besides DEHP, 29% of the samples contained other ortho-phthalates (mainly diisononyl and diisodecyl phthalates, DiNP and DiDP) above 0.1 wt %, and 17% of the samples indicated a potential to cause biological effects. Considering some overlap between these groups, they together make up an additional 35% of the samples of potential concern. Moreover, both suspect screening and bioassay results indicate the presence of additional potentially hazardous substances. Overall, our study highlights the urgent need to accelerate the phase-out of hazardous substances, increase the transparency of chemical compositions in plastics to protect human and ecosystem health, and enable the transition to a safe and sustainable circular economy.
Plasticizers are ubiquitous pollutants in the environment, whereas few efforts have been made to elucidate their emission sources in the atmosphere. In this research, the spatioseasonal variations ...and sources of particle-bound (PM
2.5
) phthalates (PAEs) and their substitutes (APs) at residential sites in seven districts and at four potential point-source sites across a megacity in South China were revealed. The total concentrations of PAEs ranging from 10.7 to 528 ng/m
3
were substantially higher than those of APs (1.45.58.5 ng/m
3
). Significant spatial variations in the concentrations of the pollutants were observed, which were generally higher at the sites with intensive industrial activities and the point-source sites. Most atmospheric plasticizer levels peaked in summer, probably due to the temperature-promoted volatilization. Seven sources of plasticizers were identified by the positive matrix factorization (PMF) model. The sources in less industrialized districts are mainly associated with domestic and commercial emissions and with industry in the industrialized districts. Specifically, plastics and personal care products together contributed 60% of the plasticizers in the atmosphere of this city, followed by solvents and polyester industry sources. The incremental lifetime cancer risk of inhalation exposure to bis(2-ethylhexyl) phthalate in the study city is below the acceptable level. Relatively higher risks were found for residents living around sites with intensive industrial activities and around wastewater treatment plant.
The prevalence of obesity and type 2 diabetes mellitus epidemics presents a great health problem worldwide. Beside the changes in diet and decreased physical activity, there is growing interest in ...endocrine disrupting chemicals that may have effects on these conditions. Among them, the role of certain phthalates and bisphenol A is confirmed. We have summarized the existing literature on this issue including cross-sectional, follow up epidemiological studies and in vivo and in vitro studies. Most data support the effects of bisphenol A and some phthalates, such as di-2-ethyl-hexyl phthalate, diethyl phthalate, dibuthyl phthalate, dimethyl phthalate, dibenzyl phthalate, diisononyl phthalate and others on the development obesity and type 2 diabetes mellitus. These endocrine disrupting chemicals interfere with different cell signaling pathways involved in weight and glucose homeostasis. Since the data are rather inconsistent, there is a need for new, well-designed prospective studies.
In recent years, phthalates and their metabolites have been associated with metabolic diseases such as diabetes mellitus. To investigate the effects of phthalate metabolites exposure on insulin ...production and release, 1.1B4 pancreatic beta cells were treated with different concentrations (0.001–1000 µM) of monoethylhexyl phthalate (MEHP) and monobutyl phthalate (MBP). For such purpose, the 1.1B4 cells were evaluated for their viability, apoptosis rate, lysosomal membrane permeabilization (LMP), mitochondrial membrane potential (ΔΨm), oxidative stress, ER stress status, in addition to their secretory functions. MEHP, not MBP, exhibited a notable reduction in metabolic viability, particularly at higher concentrations (500 and 1000 µM) following 24-hour exposure. Similarly, both MEHP and MBP induced decreased metabolic viability at high concentrations after 48- and 72-hour exposure. Notably, neither MEHP nor MBP demonstrated a significant impact on apoptosis rates after 24-hour exposure, and MBP induced mild necrosis at 1000 µM concentration. Cell proliferation rates, indicated by PCNA expression, decreased with 10 and 1000 µM MEHP and 0.1 and 10 µM MBP exposures. LMP analysis revealed an increase in 1000 µM MBP group. Exposure to 0.001 µM of both MEHP and MBP significantly reduced cellular glutathione (GSH) levels. No significant change in intracellular reactive oxygen species (ROS) levels and ΔΨm was observed, but MBP-exposed cells exhibited elevated levels of lipid peroxidation. Functional assessments of pancreatic beta cells unveiled reduced insulin secretion at low glucose concentrations following exposure to both MEHP and MBP, with concurrent alterations in the expression levels of key proteins associated with beta cell function, including GLUT1, GCK, PDX1, and MafA. Moreover, MEHP and MBP exposures were associated with alterations in ER stress-related pathways, including JNK, GADD153, and NF-κB expression, as well as PPARα and PPARγ levels. In conclusion, this study provides comprehensive insights into the diverse impacts of MEHP and MBP on 1.1B4 pancreatic beta cells, emphasizing their potential role in modulating cell survival, metabolic function, and stress response pathways.
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•MEHP and MBP at high concentrations affect the metabolic viability of 1.1B4 cells.•Exposure to high concentrations of MBP leads to an increase in LMP.•MBP, but not MEHP, induces lipid peroxidation in 1.1B4 cells.•Exposure to MEHP and MBP increases ER stress associated GADD153 and Nf-κB proteins.•Study doses encompass human-relevant and environmentally reported concentrations.
Phthalates are chemicals widely used in plastic-based consumer products, and human exposure is universal. They are classified as endocrine disruptors, and specific phthalate metabolites have been ...associated with an increased risk of cardiometabolic diseases. The aim of this study was to assess the association between phthalate exposure and the metabolic syndrome in the general population. A comprehensive literature search was performed in four databases (Web of Science, Medline, PubMed, and Scopus). We included all the observational studies that evaluate the association between phthalate metabolites and the metabolic syndrome available until January 31st, 2023. Pooled Odds Ratios (OR) and their 95% confidence intervals were calculated by using the inverse-variance weighted method. Nine cross-sectional studies and 25,365 participants aged from 12 to 80 were included. Comparing extreme categories of phthalate exposure, the pooled ORs for the metabolic syndrome were: 1.08 (95% CI, 1.02–1.16, I2 = 28%) for low molecular weight phthalates, and 1.11 (95% CI, 1.07–1.16, I2 = 7%) for high molecular weight phthalates. For individual phthalate metabolites, the pooled ORs that achieved statistical significance were: 1.13 (95% CI, 1.00–1.27, I2 = 24%) for MiBP; 1.89 (95% CI, 1.17–3.07, I2 = 15%) for MMP in men; 1.12 (95% CI, 1.00–1.25, I2 = 22%) for MCOP; 1.09 (95% CI, 0.99–1.20, I2 = 0%) for MCPP; 1.16 (95% CI, 1.05–1.28, I2 = 6%) for MBzP; and 1.16 (95% CI, 1.09–1.24, I2 = 14%) for DEHP (including ΣDEHP and its metabolites). In conclusion, both low molecular weight and high molecular weight phthalates were associated with an 8 and 11% higher prevalence of the MetS, respectively. The exposure to six specific phthalate metabolites was associated with a higher prevalence of the MetS.
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•Low Molecular Weight phthalates are associated with an 8% higher prevalence of MetS.•High Molecular Weight phthalates are associated with an 11% higher prevalence of MetS.•Six individual phthalate metabolites are statistically associated with the MetS.
Several phthalates, particularly diethyl phthalate (DEP) and di-n-butyl phthalate, can be used in personal care products (PCPs) to fix fragrance and hold color. We investigated associations between ...women's reported use of PCPs within the 24 h before urine collection and concentrations of several urinary phthalate metabolites. Between 2002 and 2005, 337 women provided spot urine samples and answered questions regarding their use of 13 PCPs at a follow-up visit 3-36 months after pregnancy. We examined associations between urinary concentrations of several phthalate metabolites and use of PCPs using linear regression. Use of individual PCPs ranged from 7% (nail polish) to 91% (deodorant). After adjusting for age, education, and urinary creatinine, women reporting use of perfume had 2.92 times higher (95% CI: 2.20-3.89) concentration of monoethyl phthalate (MEP; the primary metabolite of DEP) than other women. Other PCPs that were significantly associated with MEP concentrations included: hair spray, nail polish, and deodorant. MEP concentrations increased with the number of PCPs used. PCP use was widespread in this group of recently pregnant women. Women's use of PCPs, particularly of perfumes and fragranced products, was positively associated with urinary concentration of multiple phthalate metabolites.
Backgroundortho-phthalates and other plasticizers impart flexibility to plastics in food production, processing, and packaging; food consumption is a dominant plasticizer exposure pathway. Lower ...molecular weight ortho-phthalates are being replaced in plastic products due to toxicity concerns, but toxic hazards of and exposures to replacement ortho-phthalates and other plasticizers are poorly understood.ObjectiveWe measured 12 ortho-phthalates and 9 other plasticizers in conventional and organic U.S. food products to assess magnitude and profiles of contamination.MethodsWe measured plasticizers in 34 vegetable oils, 10 milks, 18 infant formulas, and 9 cheese powders from macaroni kits using gas chromatography coupled with mass spectrometry (GC-MS). We analyzed plastic packaging composition using FTIR spectroscopy.ResultsWe detected eight ortho-phthalates and three alternatives ((1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH), diethylhexyl terephthalate (DEHT), and diisobutyl adipate (DIBA). Diethylhexyl phthalate (DEHP) was measured in all 71 products. DEHT had the highest concentration of any plasticizer (>10,000 ng/g in three oils). Oils had the highest total plasticizer (median = 770 ng/g, max = 14,900 ng/g) and milk the lowest (median = 88 ng/g, max = 120 ng/g). Organic milk and refined oils had higher median plasticizer levels than conventional. Refined oils had significantly lower concentrations than unrefined oils. Maximum contributors for every category were non-ortho-phthalates: DEHT (powdered infant formula and oils) and DIBA (cheese powder, milk and liquid formula). Plasticizers were not detected in packaging except epoxidized soybean oil in liquid formula lids.Impact StatementHuman exposure to plasticizers is a significant public health concern. Nevertheless, sources of such exposures are poorly characterized. This study adds valuable information for estimating legacy and alternative plasticizer exposures from foods. The method developed for measuring DINCH, DINP and DIDP broadens the range of plasticizers other researchers may analyze in future work. The profiles of plasticizer contamination varied depending on the food type. We also document that food processing may be a source of plasticizer contamination in foods.
Phthalates (PAEs) are of wide concern because they are commonly used in various plastic products as plasticizers, and can found their way into the environment. However, their interaction with the ...environment and their toxicity in aquatic animals is still a matter of intense debate. In this review on PAEs in aquatic environments (lakes, rivers and seas), it is found that there is a large variety and abundance of PAEs in developing countries, and the total concentration of PAEs even exceeds 200 μg / L. The interaction between metabolic processes involved in the toxicity induced by various PAEs is summarized for the first time in the article. Exposure of PAEs can lead to activation of the detoxification system CYP450 and endocrine system receptors of aquatic animals, which in turn causes oxidative stress, metabolic disorders, endocrine disorders, and immunosuppression. Meanwhile, each system can activate / inhibit each other, causing genotoxicity and cell apoptosis, resulting in the growth and development of organisms being blocked. The mixed PAEs shows no cumulative toxicity changes to aquatic animals. For the combined pollution of other chemicals and PAEs, PAE can act as an agonist or antagonist, leading to combined toxicity in different directions. Phthalate monoesters (MPEs), the metabolites of PAEs, are also toxic to aquatic animals, however, the toxicity is weaker than the corresponding parent compounds. This review summarizes and analyzes the current ecotoxicological effects of PAEs on aquatic animals, and provides guidance for future research.
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•The extensive use of phthalates (PAEs) has resulted in exposure to aquatic environment.•The toxic pathway of PAEs to aquatic animals is integrated for the first time.•PAEs can act as agonists or antagonists in combined pollution.•Phthalate monoesters (MPEs) have lower toxicity to aquatic animals than PAEs.
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