SEARCH · Search PubMed
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
A method is presented for the determination of di (2-ethylhexyl) phthalate, mono (2-ethylhexyl) phthalate and phthalic acid in anticoagulant solutions using reverse phase high pressure liquid chromatography.
The formation of mono(ethylhexyl)phthalate (MEHP) from di(ethylhexyl)phthalate in human plasma stored in bags of polyvinylchloride has been studied. Substantial amounts were formed and in ten bags from 4 to 56microgram/ml were found. After 2 weeks at room temperature the concentration of MEHP had increased to values between 27 and 79 microgram/ml. However, MEHP was also disappearing as shown in a recovery experiment. Of the fractionated proteins albumin contained MEHP in amounts from less than 3 to 290 microgram/g.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Plasma DEHP concentrations were measured weekly in whole blood and red cell concentrates (RCC) during 21 days of storage in standard CPD within PL-130 blood bags. In addition, DEHP and MEHP accumulation patterns were investigated in blood stored for 42 days in modified CPD with adenine within PL-146 and BB-69 storage containers. Total per-unit plasma DEHP of RCC units was 49 to 71 per cent of the total in plasma of whole blood units (PL-130). From 28 to 42 days, mean DEHP levels were 12 to 19 per cent higher in whole blood stored in PL-146 than in BB-69. Although MEHP was not found in any blood bag plastic, MEHP accumulated in plasma during whole blood storage. MEHP concentrations were 2.8 to 3.8 times higher in plasma stored in BB-69 than in PL-146. It is postulated that MEHP arises from hydrolysis of DEHP by plasma lipase, even in frozen plasma sample, and that the rate of this reaction is influenced by blood bag plastic surface characteristics.
Explore the source record for details and available documents.
BACKGROUND: The menopausal transition involves significant sex hormone changes. Environmental chemicals, such as urinary phthalate metabolites, are associated with sex hormone levels in cross-sectional studies. Few studies have assessed longitudinal associations between urinary phthalate metabolite concentrations and sex hormone levels during menopausal transition. METHODS: Pre- and perimenopausal women from the Midlife Women's Health Study (MWHS) (n = 751) contributed data at up to 4 annual study visits. We quantified 9 individual urinary phthalate metabolites and 5 summary measures (e.g., phthalates in plastics (∑Plastic)), using pooled annual urine samples. We measured serum estradiol, testosterone, and progesterone collected at each study visit, unrelated to menstrual cycling. Linear mixed-effects models and hierarchical Bayesian kernel machine regression analyses evaluated adjusted associations between individual and phthalate mixtures with sex steroid hormones longitudinally. RESULTS: We observed associations between increased concentrations of certain phthalate metabolites and lower testosterone and higher sub-ovulatory progesterone levels, e.g., doubling of monoethyl phthalate (MEP), monobenzyl phthalate (MBzP), di-2-ethylhexyl phthalate (∑DEHP) metabolites, ∑Plastic, and ∑Phthalates concentrations were associated with lower testosterone (e.g., for ∑DEHP: -4.51%; 95% CI: -6.72%, -2.26%). For each doubling of MEP, certain DEHP metabolites, and summary measures, we observed higher mean sub-ovulatory progesterone (e.g., ∑AA (metabolites with anti-androgenic activity): 6.88%; 95% CI: 1.94%, 12.1%). Higher levels of the overall time-varying phthalate mixture were associated with lower estradiol and higher progesterone levels, especially for 2nd year exposures. CONCLUSIONS: Phthalates were longitudinally associated with sex hormone levels during the menopausal transition. Future research should assess such associations and potential health impacts during this understudied period.
The amount of a phthalate plasticizer on the surface of a sheet of polyvinyl chloride used in the fabrication of blood storage bags was quantified using attenuated total reflectance spectroscopy, water contact angle measurement, and weight loss due to methanol extraction. Water wettability increased as the amount of surface phthalate extracted by methanol increased, which indicates that the accumulation of phthalate on the surface increases hydrophobicity. The extraction of phthalate by methanol consists of two steps: (a) methanol first dissolves surface phthalate, and (b) phthalate in the bulk then diffuses through the surface. The adsorption of plasma proteins was investigated to determine the initial events as blood contacts the surface. The composition of adsorbed proteins on the methanol-cleansed surface differs from that on the uncleansed polyvinyl chloride surface. Albumin adsorption onto phthalate-contaminated surfaces is less than on cleansed surfaces while adsorption of gamma-globulin and fibrinogen is greater on phthalate-contaminated surfaces. Protein adsorption can be related to surface thrombus formation. Increases in platelet numbers appeared on phthalate-contaminated surfaces as compared with methanol-treated surfaces. A phthalate may enhance platelet adhesion and aggregation when it exists on a polymer surface.
BACKGROUND: Phthalates are environmental endocrine-disrupting chemicals widely used in plastics, cosmetics, food packaging, and personal care products. Women may experience frequent exposure through everyday consumer and household products. Improving phthalate-related health literacy may support informed exposure-reduction decisions; however, conventional health education provides limited opportunities for repeated, interactive, and individually tailored learning. OBJECTIVE: This randomized controlled trial evaluated the effectiveness of an eHealth educational intervention (Phthalates Free) in improving women's overall and domain-specific phthalate-related health literacy and examined the association between platform engagement and health literacy outcomes. METHODS: A double-blind randomized controlled trial was conducted in the outpatient department of a regional teaching hospital in Taipei, Taiwan. A total of 114 women were randomly assigned to an intervention group (n=58) receiving a 6-month eHealth platform-based education program and a control group (n=56) receiving conventional paper-based education. Assessments were conducted at baseline (T0), 3 months (T1), and 6 months (T2). The Phthalate Health Literacy Scale (10 items; α=.90, content validity index=0.93) measured overall and domain-specific literacy (health care, disease prevention, and health promotion). Longitudinal outcomes were analyzed using generalized estimating equations based on all available observations according to participants' original randomized assignments, with adjustment for waist circumference and pregnancy history. Analysis of covariance (ANCOVA) was used to compare 6-month outcomes after adjustment for baseline scores. Platform engagement and perceived usability were assessed using back-end analytics and the System Usability Scale (SUS). RESULTS: At 6 months, the intervention group showed a significantly greater increase in total health literacy than the control group (+9.93 points, Wald χ²1=17.74; P<.001). Domain analyses revealed significant improvements in health care (+1.52; P=.001), disease prevention (+1.32; P=.001), and health promotion (+1.12; P=.001) domains. ANCOVA confirmed the between-group difference at T2 after adjusting for baseline scores (F1,109=11.43; P=.001; adjusted mean difference=7.15, 95% CI 2.96-11.34). Engagement analysis showed that high-engagement users (n=10) scored significantly higher in overall health literacy (t55=-3.00; P=.004) and all domains than general users. The SUS results (mean 84.7, SD 5.2; n=46, 79.3%) indicated high perceived usability. CONCLUSIONS: The Phthalates Free eHealth educational intervention significantly improved women's overall and domain-specific health literacy over 6 months. Higher platform engagement was associated with better health literacy outcomes. The intervention may serve as a practical adjunct to nurse-led education in outpatient and community settings by providing accessible, continuous, and evidence-based guidance on reducing phthalate exposure.
INTRODUCTION: Phthalates, or dieters of phthalic acid, are a ubiquitous type of plasticizer used in a variety of common consumer and industrial products. They act as endocrine disruptors and are associated with increased risk for several diseases. Once in the body, phthalates are metabolized through partially known mechanisms, involving phase I and phase II enzymes. OBJECTIVE: In this study we aimed to identify common single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) associated with the metabolism of phthalate compounds in children through genome-wide association studies (GWAS). METHODS: The study used data from 1,044 children with European ancestry from the Human Early Life Exposome (HELIX) cohort. Ten phthalate metabolites were assessed in a two-void pooled urine collected at the mean age of 8 years. Six ratios between secondary and primary phthalate metabolites were calculated. Genome-wide genotyping was done with the Infinium Global Screening Array (GSA) and imputation with the Haplotype Reference Consortium (HRC) panel. PennCNV was used to estimate copy number variants (CNVs) and CNVRanger to identify consensus regions. GWAS of SNPs and CNVs were conducted using PLINK and SNPassoc, respectively. Subsequently, functional annotation of suggestive SNPs (p-value < 1E-05) was done with the FUMA web-tool. RESULTS: We identified four genome-wide significant (p-value < 5E-08) loci at chromosome (chr) 3 (FECHP1 for oxo-MiNP_oh-MiNP ratio), chr6 (SLC17A1 for MECPP_MEHHP ratio), chr9 (RAPGEF1 for MBzP), and chr10 (CYP2C9 for MECPP_MEHHP ratio). Moreover, 115 additional loci were found at suggestive significance (p-value < 1E-05). Two CNVs located at chr11 (MRGPRX1 for oh-MiNP and SLC35F2 for MEP) were also identified. Functional annotation pointed to genes involved in phase I and phase II detoxification, molecular transfer across membranes, and renal excretion. CONCLUSION: Through genome-wide screenings we identified known and novel loci implicated in phthalate metabolism in children. Genes annotated to these loci participate in detoxification, transmembrane transfer, and renal excretion.
The distributions of di-(2-ethylexyl) phthalate and mono-(2-ethylhexyl) phthalate among the protein constituents of human plasma were studied by selective precipitation and chromatographic procedures. The distributions resulting from the leaching of phthalates from blood bags were simulated conveniently by allowing plasma to extract phthalates from coated Celite. More than 80 per cent of the diester was associated with lipoproteins, in the order: LDL greater than VLDL greater than HDL greater than chylomicrons. The remaining diester was apparently adsorbed weakly and nonspecifically to other proteins, including albumin. Mono-(2-ethylhexyl) phthalate was in equilibrium between free in solution and adsorbed to albumin; none was bound to lipoproteins. Extraction of phthalate from Celite into plasma should provide a convenient preparation for toxicity or pharmacokinetic studies.
The effects of phthalate esters on the oxidation of succinate, glutamate, beta-hydroxybutyrate and NADH by rat liver mitochondria were examined and it was found that di-n-butyl phthalate (DBP) strongly inhibited the succinate oxidation by intact and sonicated rat mitochondria, but did not inhibit the State 4 respiration with NAD-linked substrates such as glutamate and beta-hydroxybutyrate. However, oxygen uptake accelerated by the presence of ADP and substrate (State 3) was inhibited and the rate of oxygen uptake decreased to that without ADP (State 4). It was concluded that phthalate esters were electron and energy transport inhibitors but not uncouplers. Phthalate esters also inhibited NADH oxidation by sonicated mitochondria. The degree of inhibition depended on the carbon number of alkyl groups of phthalate esters, and DBP was the most potent inhibitor of respiration. The activity of purified beef liver glutamate dehydrogenase [EC 1.4.1.3] was slightly inhibited by phthalate esters.
The effect of various phthalate esters on the lecithin/cholesterol acyltransferase activity in man was studied in vitro. The enzymatic activity was strongly reduced with all phthalates except for the dimethyl phthalate. The inhibition rate depends on the phthalate concentration and also on the carbon number of the alkyl groups of phthalates.
BACKGROUND: Endocrine disrupting compounds (EDCs) such as phthalates and phenols can affect placental functioning and fetal health, potentially via epigenetic modifications. We investigated the associations between pregnancy exposure to synthetic phenols and phthalates estimated from repeated urine sampling and genome wide placental DNA methylation. METHODS: The study is based on 387 women with placental DNA methylation assessed with Infinium MethylationEPIC arrays and with 7 phenols, 13 phthalates, and two non-phthalate plasticizer metabolites measured in pools of urine samples collected twice during pregnancy. We conducted an exploratory analysis on individual CpGs (EWAS) and differentially methylated regions (DMRs) as well as a candidate analysis focusing on 20 previously identified CpGs. Sex-stratified analyses were also performed. RESULTS: In the exploratory analysis, when both sexes were studied together no association was observed in the EWAS. In the sex-stratified analysis, 114 individual CpGs (68 in males, 46 in females) were differentially methylated, encompassing 74 genes (36 for males and 38 for females). We additionally identified 28 DMRs in the entire cohort, 40 for females and 42 for males. Associations were mostly positive (for DMRs: 93% positive associations in the entire cohort, 60% in the sex-stratified analysis), with the exception of several associations for bisphenols and DINCH metabolites that were negative. Biomarkers associated with most DMRs were parabens, DEHP, and DiNP metabolite concentrations. Some DMRs encompassed imprinted genes including APC (associated with parabens and DiNP metabolites), GNAS (bisphenols), ZIM2;PEG3;MIMT1 (parabens, monoethyl phthalate), and SGCE;PEG10 (parabens, DINCH metabolites). Terms related to adiposity, lipid and glucose metabolism, and cardiovascular function were among the enriched phenotypes associated with differentially methylated CpGs. The candidate analysis identified one CpG mapping to imprinted LGALS8 gene, negatively associated with ethylparaben. CONCLUSIONS: By combining improved exposure assessment and extensive placental epigenome coverage, we identified several novel genes associated with the exposure, possibly in a sex-specific manner.
Widely used phthalates, especially di-(2-ethylhexyl) phthalate (DEHP), increase breast cancer risk in experimental animals and humans, but long-term follow-up evidence of its human breast carcinogenicity remains inconclusive. This nested case-control study included 119 invasive breast cancer cases and 245 matched controls from a longitudinal cohort of 11,923 women recruited in 1991-1992 and followed to 2010 in Taiwan. Urine samples at baseline and follow-up visit were tested for 11 metabolites of seven phthalates using LC-ESI-MS/MS. DEHP metabolism susceptibility was evaluated by the percentage of mono-2-ethylhexyl phthalate (MEHP%) in the sum of five DEHP metabolites (∑DEHP). Odds ratios (ORs) with 95% CI from conditional logistic regression were used to examine risk predictors. DEHP was the only phthalate significantly associated with breast cancer risk. Risk increased significantly with elevated urinary levels of ∑DEHP (> 0.381 μmol/g creatinine, OR = 1.71, 95% CI = 1.02 to 2.43), MEHP (> 0.022 μmol/g creatinine, OR = 1.87, 95% CI = 1.07 to 3.25), and MEHP% (> 6.7%, OR = 1.65, 95% CI = 0.96 to 2.82). Elevated ∑DEHP and MEHP% combined with early menarche (≤ 14 years) was associated with further increased risk (OR = 7.52, 95% CI = 2.68 to 21.05). The intraclass correlation coefficient between paired baseline and follow-up samples of 152 women was 0.06 for ∑DEHP and 0.31 for MEHP%. High DEHP exposure, high MEHP%, and early menarche were associated with increased breast cancer risk. MEHP% was a better biomarker for DEHP metabolism.
Phthalate ester plasticizers have been detected in the open-ocean environment. Samples consisting of water, sediment, air, and biota from the Gulf of Mexico and of water and air from the North Atlantic were analyzed and found to contain two phthalate esters, di-(2-ethylhexyl) phthalate (DEHP) and di-n-dibutyl phthalate (DBP): the concentrations of polychlorinated biphenyls (PCB's) and DDT's (p,p'-DDT and p,p'-DDE) were also determined. Like the ubiquitous PCB's and DDT's, the phthalate plasticizers were found in almost all samples analyzed; DEHP was present at higher concentrations than the PCB's or DDT's in water and sediment. The environmental impact of the concentrations found in these studies, coupled with the continued high production and wise use of these plasticizers, requires assessment.
1. The ability of a number of methylenedioxyphenyl compounds and paraoxon to inhibit the hydrolysis and oxidation of di-2-ethylhexyl phthalate by rainbow trout tissue preparations was examined. 2. In addition to paraoxon, only the methylenedioxyphenyl compounds with long side-chains (piperonyl butoxide and tropital) inhibited the hydrolysis of di-2-ethylhexyl phthalate by trout liver subcellular fractions and trout serum. 3. Paraoxon decreased the production of the major metabolite of di-2-ethylhexyl phthalate by trout liver microsomes (+ NADPH) suggesting that this metabolite arises via further metabolism of mono-2-ethylhexyl phthalate.
A method was investigated in which all of the phthalate esters in biological samples were determined as phthalic acid by gas-liquid chromatography. The method is based on the separation of phthalate esters from the sample with n-hexane, saponification of the esters with an alkaline ethanolic solution to give phthalic acid, purification of the acid by extraction with diethyl ether and column chromatography using silica gel, and conversion of the acid into bis(2,2,2-trifluoroethyl) phthalate with a 2,2,2-trifluoroethanol solution containing boron trifluoride. The derivative obtained is highly sensitive to an electron-capture detector, giving a sensitivity of 0.1 pg. Biological samples fortified with di(2-ethylhexyl) phthalate at levels of 5-100 ppb were analyzed, with recoveries of 70-100%.