Low Di-(2-ethylhexyl) Phthalate Research Articles

Reduced ovarian cholesterol and steroid biosynthesis along with increased inflammation are associated with high DEHP metabolite levels in human ovarian follicular fluids

The plasticizer di(2-ethylhexyl) phthalate (DEHP) is known to have endocrine-disrupting properties mediated by its many metabolites that form upon exposure in biological systems. In a previous study, we reported an inverse association between DEHP metabolites in the human ovarian follicular fluid (FF) and the responsiveness of the follicles to controlled ovarian stimulation during in vitro fertilization (IVF) treatments. Here, we explored this association further through molecular analysis of the ovarian FF samples.Ninety-six IVF patients from Swedish (N = 48) and Estonian (N = 48) infertility clinics were selected from the previous cohort (N = 333) based on the molar sum of DEHP metabolites in their FF samples to arrive at “high” (mean 7.7 ± SD 2.3 nM, N = 48) and “low” (0.8 ± 0.4 nM, N = 48) exposure groups. Extracellular miRNA levels and concentrations of 15 steroid hormones were measured across FF samples. In addition, FF somatic cells, available for the Estonian patients, were used for RNA sequencing.Differential expression (DE) and interactions between miRNA and mRNA networks revealed that the expression levels of genes in the cholesterol biosynthesis and steroidogenesis pathways were significantly decreased in the high compared to the low DEHP group. In addition, the DE miRNAs were predicted to target key enzymes within these pathways (FDR < 0.05). A decreased 17-OH-progesterone to progesterone ratio was observed in the FF of the high DEHP group (p < 0.05). Additionally, the expression levels of genes associated with inflammatory processes were elevated in the FF somatic cells, and a computational cell-type deconvolution analysis suggested an increased immune cell infiltration into the high DEHP follicles (p < 0.05).In conclusion, elevated DEHP levels in FF were associated with a significantly altered follicular milieu within human ovaries, involving a pro-inflammatory environment and reduced cholesterol metabolism, including steroid synthesis. These results contribute to our understanding of the molecular mechanisms of female reprotoxic effects of DEHP.

Prenatal exposure to phthalates and emotional/behavioral development in young children

IntroductionEndocrine disrupting chemicals (EDCs) such as phthalates, found in our daily environment, are nowadays suggested to be associated with adverse outcomes. Prenatal exposure was found associated with neurodevelopmental complications such as behavioral difficulties in school age children. AimTo explore the association between intrauterine exposure to phthalates and emotional/behavioral development of 24 months old toddlers. MethodsWomen were recruited at 11–18 weeks of gestation and provided spot urine samples, analyzed for phthalate metabolites (DEHP, DiNP, MBzBP). Offspring were examined at 24 months of age, using standard maternal report, regarding developmental and behavioral problems (CBCL, ASQ-3, HOME questionnaires) (N = 158). To explore the associations between metabolite levels and developmental outcomes, multivariate GLM analysis (General Linear Model) was used according to tertiles and developmental scores on each developmental outcome. ResultsAssociations of Di-(2-ethylhexyl) phthalate (DEHP) maternal exposure with behavioral-developmental outcomes were found only in boys. Compared with boys with lower DEHP maternal exposure, boys with high DEHP maternal exposure had lower developmental score in personal social abilities in the ASQ-3 questionnaire (50.68 + 8.06 and 44.14 + 11.02, high and low DEHP, respectively, p = 0.03), and more internalizing problems (for example, emotionally reactive score in high and low DEHP: 53.77 + 7.41 and 50.50 + 1.19, respectively, p = 0.029; anxious or depressed score: 53.38 + 5.01 and 50.75 + 1.34, respectively, p = 0.009; and somatic complaints scores 64.03 + 10.1 and 55.84 + 7.84, respectively, p = 0.003), and externalizing problems (49.28 + 8.59 and 43.33 + 9.11, respectively, p = 0.039). No differences were found in the development and behavior problems between high and low DEHP maternal exposure level in girls. ConclusionMaternal DEHP metabolite concentrations measured in first trimester urine was associated with children’s emotional/behavioral developmental problems in 24-months old boys, supporting accumulating evidence of DEHP as a potentially harming chemical and call for environmental attention.

Uptake and toxicity of di-(2-ethylhexyl) phthalate in Brassica chinensis L

This work focuses on the bioaccumulation and toxic effects of di-(2-ethylhexyl) phthalate (DEHP) in the leafy vegetable Shanghaiqing (SHQ) (Brassica chinensis L.). The accumulated DEHP amount in the edible part and roots of SHQ increased as the DEHP concentration in the soil increased. DEHP accumulation was higher in the roots than in the edible part of the plant. The root concentration factors and bioaccumulation factors for DEHP in SHQ were 0.13–2.49 and 0.03–2.00, respectively. The DEHP translocation factors were below 1.0, indicating that DEHP preferentially accumulated in plant roots. The DEHP risk index in the edible part of SHQ in relation to the human body and in terms of dietary exposure risk assessment was also below 1.0, indicating a low health risk. High DEHP concentrations caused 1) inhibition of SHQ growth, 2) an increase in SHQ chlorophyll and malondialdehyde contents and 3) a decrease in soluble sugar and vitamin contents. Low DEHP concentrations stimulated total superoxide dismutase, peroxidase and catalase activities, while high DEHP levels showed an inhibitory effect. DEHP presence in soil affected not only SHQ growth but also quality. Our results provide the data needed for the proper assessment of food safety and the ecological impact of DEHP contamination in agricultural soils.

Evaluation of the temperature and molecular weight dependent migration of di(2-ethylhexyl) phthalate from isotactic polypropylene composites

The development of a process for the bioremediation of di(2-ethylhexyl) phthalate (DEHP) blended in various polymers, with a low DEHP release rate, has become an essential mission in the packaging materials industry, especially for blood-component storage materials. Hence, polypropylene and DEHP composites were prepared to evaluate their DEHP release behavior at 90°C and 25°C. The physical and chemical properties of the composites were evaluated with various analytical tools. Polypropylene of three different molecular weights was used to compare the different DEHP releasing rates. The incorporation and migration of DEHP significantly followed the crystalline nature of the polymer matrix. The temperature-dependent migration behavior was evaluated by UV–Vis spectroscopy and LC/MS analyses. Among the three different molecular weight PP/DEHP composites, a significantly lower amount of DEHP was released from the higher molecular weight polymer composite due to its enriched crystalline nature. Moreover, the release behavior of DEHP was affected by the molecular weight and crystalline nature of PP, which can strongly hold the plasticizer, and therefore slow down its release. The high molecular weight iPP/DEHP composite may be suitable for blood-component backing materials because of its lower DEHP migration.

Degradation of di-2-ethylhexyl phthalate in aqueous solution by advanced oxidation process

Aims: This study was conducted to compare the effectiveness of conventional technologies, UV irradiation and ozonation process, and UV/O3 as advanced oxidation processes to remove phthalate from aqueous solutions. Materials and Methods: The initial concentration of di-2-ethylhexyl phthalate (DEHP) was 5 mg/L. The photolysis, ozonation, and UV/O3 processes were conducted separately at different contact times (5-30 min). Then, the DEHP residuals in the solutions were analyzed by gas chromatography mass spectrometry. The effect of ozone dosage was also evaluated in the range of 50-400 mg/h on DEHP degradation. Kinetic and the rate constants were determined. Results: The results indicated that using UV and ozonation alone, the maximum DEHP removal efficiency were 43% and 50%, respectively. The UV/O3 process considerably improved the degradation of DEHP up to 80%. The synergistic effect observed in the combined processes mainly due to the effects of UV in enhancing the ozone decomposition, led to higher degradation for 30 min treatment. A kinetic study showed the degradation in UV/O3 followed the first-order model. In addition, the maximum DEHP removal rate was 74% with 200 mg/h ozone dosage by ozonation alone process, but it was 93% at same condition by UV/O3 process. Conclusion: It could be found that the UV/O3 process is a method for DEHP degradation in aqueous solution and may be recommended as a supplement with other processes for treatment of solutions containing low DEHP concentrations.

Uptake of Di(2-ethylhexyl) Phthalate (DEHP) by the Plant Benincasa hispida and Its Use for Lowering DEHP Content of Intercropped Vegetables

Uptake of di(2-ethylhexyl) phthalate (DEHP) by the plant Benincasa hispida and its use for topical phytoremediation were investigated by cultivation of plants in DEHP-contaminated environments. The results showed that major plant organs of B. hispida , including leaves, stems, and fruits, readily absorbed DEHP from the air. The amount of DEHP that accumulated in leaves, stems, and fruits was mainly dependent upon exposure time, and most DEHP accumulated in their inner tissues. A single plant of B. hispida with a gourd was able to absorb more than 700 mg of DEHP when it was exposed to DEHP-contaminated air for 6 week. B. hispida reduced air DEHP concentration by 65-76% as the air DEHP concentration ranged from 2351 to 3955 μg/m³ (high DEHP level) and 85-92% as the air DEHP concentration ranged from 35.1 to 65.3 μg/m³ (low DEHP level) in greenhouse experiments. When intercropping of B. hispida and Brassica chinensis or Brassica campestris , B. hispida reduced more than 87% of DEHP accumulation in the latter, which indicates that B. hispida has excellent use potential for lowering the DEHP content of intercropped vegetables.

Gene expression profiling of DEHP-treated cardiomyocytes reveals potential causes of phthalate arrhythmogenicity

Background Di-(2-ethylhexyl)-phthalate (DEHP) is a widely used plasticizer that imparts flexibility to polyvinyl chloride. We have recently reported that clinically relevant concentrations of DEHP can affect electrical coupling between cardiac myocytes causing significant rhythm disturbances. The underlying causes for this effect are currently unknown. Objectives To use data on global mRNA expression as a tool to reveal possible pathways leading to arrhythmogenic effects of DEHP. Methods Rat neonatal cardiomyocytes were treated with 50 μg/mL DEHP for 72 h. Extracted RNA samples were hybridized onto Affymetrix Rat Gene 1.0 ST arrays. The mRNA expression of a subset of genes was validated by qRT-PCR. In a second set of experiments, cells were treated in a concentration dependent manner to identify genes affected by low DEHP concentrations. Results DEHP exposure is associated with global changes in mRNA expression, with differentially expressed genes overrepresented in 47 Gene Ontology categories. Modified expression was detected for genes associated with cell electrical activity, calcium handling, adhesion and microtubular transport. For a number of key proteins, including kinesin, TGFβ2, α-tubulin, and α1 & β1 integrins, changes in mRNA levels were confirmed on the level of the protein expression. A number of genes associated with cell adhesion and electrical activity were identified as early DEHP targets as they were affected by concentrations as low as 1 μg/mL. Conclusions Exposure of neonatal rat cardiomyocytes to clinically relevant DEHP concentrations leads to global changes in mRNA expression. These changes help to explain the arrhythmogenic effects of phthalates on these cells.

Platelet storage. Effects of leachable materials on morphology and function.

A polyolefin plastic (PL 732) bag formulated without liquid plasticizer allows storage of platelets for 5 and, now, up to 7 days. In order to assess the leaching of compounds from this new plastic, extracts of the supernatant from platelet concentrates stored in these bags were analyzed by high-performance liquid chromatography, mass spectrometry, and gas-liquid chromatography. A leachable material was detected and identified as di(2-ethylhexyl) phthalate (DEHP). During the sterilization process, migration of the DEHP occurs from the polyvinylchloride (PVC) bags into the PL 732 plastic bag. The level of DEHP was 12-fold less in the extracts of PC supernatant stored in the PL 732 bag than those in the polyvinyl chloride (PL 146) plastic bags which were used previously for platelet storage. Platelets stored in low DEHP concentrations in the PL 732 bags were composed of 10 to 35 percent of unclassifiable shapes. These shape changes were not observed in higher concentrations of plasticizer, although the morphology scores decreased during storage in PL 146 as well. This effect on morphology was not related directly to the dose of DEHP. When platelet membranes were isolated from platelets stored in the presence of radiolabeled DEHP, the amount of bound 14C-DEHP was found to be directly proportional to the concentration of DEHP in the plasma supernatant. However, while there was a linear relationship between the protein concentration in the membrane fraction and the amount of bound DEHP, no specific DEHP binding site could be identified by electrophoresis of the solubilized platelet membranes.