Plasticizer Diethylhexyl Phthalate Research Articles

Tissue-specific accumulation of DEHP and involvement of endogenous arachidonic acid in DEHP-induced spleen information and injury

The plasticizer Diethylhexyl phthalate (DEHP), one of the most common contaminants, is widely detected in environmental and biological samples. However, the accumulation of DEHP in tissue and the molecular mechanisms underlying its physiological damage in the spleen of aquatic organisms have not yet been reported. In this study, gas chromatography–mass spectrometry (GC–MS), histology and multi-omics analysis were used to investigate DEHP exposure-induced alterations in transcriptomic profiles and metabolic network of zebrafish model. After exposure to DEHP, higher concentrations of DEHP were found in the intestine, liver and spleen. Anatomical and histological analyses showed that the zebrafish spleen index was significantly increased and inflammatory damage was observed. Increased splenic neutrophil counts indicate inflammation and tissue damage. Transcriptomic filtering showed that 3579 genes were significantly altered. Metabolomic analysis detected 543 differential metabolites. Multi-omics annotation results indicated that arachidonic acid and 12-Hydroperoxyicosatetraenoic acid (HPETE) are involved in the key inflammatory pathway “Inflammatory mediator regulation of TRP channels”. This study demonstrated the accumulation characteristics of DEHP in aquatic zebrafish and the mechanisms of inflammation and tissue damage in the spleen which involve endogenous arachidonic acid. This will provide theoretical basis and data support for health risk assessments and tissue damage of DEHP.

Evodiamine alleviates DEHP-induced hepatocyte pyroptosis, necroptosis and immunosuppression in grass carp through ROS-regulated TLR4 / MyD88 / NF-κB pathway.

Di (2-ethylhexyl) phthalate (DEHP) is a neuroendocrine disruptor that can cause multi-tissue organ damage by inducing oxidative stress. Evodiamine (EVO) is an indole alkaloid with anti-inflammatory, antitumor, and antioxidant pharmacological activity. In this manuscript, the effects of DEHP and EVO on the pyroptosis, necroptosis and immunology of grass carp hepatocytes (L8824) were investigated using DCFH-DA staining, PI staining, IF staining, AO/EB staining, LDH kit, qRT-PCR and protein Western blot. The results showed that DEHP exposure upregulated reactive oxygen species (ROS) levels, promoted the expression of TLR4/MyD88/NF-κB pathway, increased the expression of genes involved in cell pyroptosis pathway (LDH, NLRP3, ASC, caspase1, IL-1β, IL-18 and GSDMD) and necroptosis-related genes (RIPK1, RIPK3 and MLKL). The expression of DEHP can also affect immune function, which can be demonstrated by variationsin the activation of antimicrobial peptides (LEAP2, HEPC, and β-defensin) and inflammatory cytokines (TNF-α, IL-2, IL-6 and IL-10). EVO regulates cellular antioxidant capacity by inhibiting ROS burst, reduces DEHP-induced cell pyroptosis and necroptosis to some extent, and restores cellular immune function, after co-exposure with EVO. The TLR4 pathway was inhibited by the co-treatment of TLR4 inhibitor TLR-IN-C34 and DEHP, which attenuated the expression of cell pyroptosis, necroptosis, and immunosuppression. Thus, DEHP induced pyroptosis, necroptosis and abnormal immune function in L8824cells by activating TLR4/MyD88/NF-κB pathway. In addition, EVO has a therapeutic effect on DEHP-induced toxic injury. This study further provides a theoretical basis for the risk assessment of plasticizer DEHP on aquatic organisms.

Prenatal DEHP exposure predicts neurological disorders via transgenerational epigenetics

Recent experimental and observational research has suggested that childhood allergic asthma and other conditions may be the result of prenatal exposure to environmental contaminants, such as di-(2-ethylhexyl) phthalate (DEHP). In a previous epidemiological study, we found that ancestral exposure (F0 generation) to endocrine disruptors or the common plasticizer DEHP promoted allergic airway inflammation via transgenerational transmission in mice from generation F1 to F4. In the current study, we employed a MethylationEPIC Beadchip microarray to examine global DNA methylation in the human placenta as a function of maternal exposure to DEHP during pregnancy. Interestingly, global DNA hypomethylation was observed in placental DNA following exposure to DEHP at high concentrations. Bioinformatic analysis confirmed that DNA methylation affected genes related to neurological disorders, such as autism and dementia. These results suggest that maternal exposure to DEHP may predispose offspring to neurological diseases. Given the small sample size in this study, the potential role of DNA methylation as a biomarker to assess the risk of these diseases deserves further investigation.

Combined negative effects of microplastics and plasticizer DEHP: The increased release of Nets delays wound healing in mice

Environmental harmful pollutants microplastics (MPs) and di (2-ethyl) hexyl phthalate (DEHP) are widely residual in the environment, which may cause lesion to multiple apparatus by inducing oxidative stress, threatening the health of human and animals. Neutrophil extracellular traps (Nets) are involved in skin wound healing. Most studies focused on the individual effects of different poisons on animals and ecosystems, but there are few studies on the accumulation and interaction of multiple poisons. The purpose of this study is to explore the effect of DEHP and MPs co-exposure on skin wound healing and the formation of Nets. For this purpose, we detected this hypothesis by replicating the DEHP and MPs-exposed skin wound model in mice, as well as the co-culture system of neutrophil and fibroblast. The results displayed that MPs and DEHP exposure delayed skin healing, which was more pronounced in the combined exposure group. In vitro and in vivo experiments confirmed that compared with the DEHP or MPs group, the DEHP+MPs group had more significant oxidative stress, increased Nets release and inflammatory factors, and inhibited the Wnt/β-catenin pathway and fibrosis-related factors. N-acetylcysteine (NAC) attenuated these phenomena. Through the co-culture system, we confirmed that the overproduction of Nets induced fibroblasts to exacerbate inflammatory responses and inhibit Wnt pathway and fibrosis. Overall, DEHP and MPs can produce synergistic toxic injury in mice skin wounds, and the excessive activation of ROS/Nets can aggravate inflammatory and inhibit fibrosis, resulting in delayed wound healing.

Multi-omics reveals the mechanisms of DEHP driven pulmonary toxicity in ovalbumin-sensitized mice

The plasticizer di- (2-ethylhexyl) phthalate (DEHP) is considered a risk factor for allergic diseases and has attracted public attention for its adverse effects on health. However, respiratory adverse effects after DEHP exposure in food allergies have rarely been reported. MiRNAs are considered to be key regulators in the complex interrelationships between the host and microbiome and may be a potential factor involved in DEHP-induced pulmonary toxicity. To investigate the adverse effects of DEHP on the lung during sensitization, we established an ovalbumin (OVA)-sensitized mouse model exposed to DEHP and performed 16S rDNA gene sequencing, miRNA sequencing, and correlation analysis. Our results showed that DEHP aggravated the immune disorder in OVA-sensitized mice, which was mainly characterized by an increase in the proportion of Th2 lymphocytes, and further enhanced OVA-induced airway inflammation without promoting pulmonary fibrosis. Compared with the OVA group, DEHP interfered with the lung microbial community, making Proteobacteria the dominant phylum, while Bacteroidetes were significantly reduced. Differentially expressed miRNAs were enriched in the PI3K/AKT pathway, which was closely related to immune function and airway inflammation. The expression of miR-146b-5p was elevated in the DEHP group, which was positively correlated with the proportion of Th2 cells and significantly negatively correlated with the abundance of Bacteroidetes. The results indicate that DEHP may interfere with the expression of miR-146b-5p, affect the composition of the lung microbiota, induce an imbalance in T cells, and lead to immune disorders and airway inflammation. The current study uses multi-omics to reveal the potential link between the plasticizer DEHP and allergic diseases and provides new insights into the ecotoxicology of environmental exposures to DEHP.

Trendsetting Ideas of the Children's Hospital "Kinderklinik Glanzing" Since 1915

Die Kinderklinik Glanzing hatte seit ihrer Gründung 1915 viele innovative Vorstände, deren Lebenslauf und Aktivitäten hier chronologisch dargestellt werden. Leopold Moll setzte mit Kriegspatenschaften und Erholungsurlauben für bedürftige Kinder sowie Mutterberatungsstellen wesentliche sozialpädiatrische Aspekte. August Reuss gründete Säuglingsstationen und Kinderabteilungen. Er etablierte eine eigene Ausbildung für Kinderärzte. Alfred Rosenkranz gründete 1974 die erste neonatologische Intensivstation in Österreich. Im Jahr 1992 führte Andreas Lischka Qualitätmanagement (QM) an der Kinderklinik Glanzing als eines der ersten Krankenhäuser in Europa erfolgreich ein. Als zweites europäisches Zentrum nahm die Kinderklinik Glanzing am Vermont Oxford Neonatal Network (VONN) zur Qualitätssicherung der Versorgung Frühgeborener teil. Die erste Babyklappe für eine anonyme straffreie Abgabe eines Neugeborenen wurde 2000 im Wilhelminenspital gegründet, um (zusätzlich zur Möglichkeit einer anonymen Geburt) ungewollten Babys eine Chance zum Überleben zu geben. Seit 1999 wurde in Zusammenarbeit mit der Musikuniversität an der neonatologischen Intensivstation Musiktherapie im Rahmen eines wissenschaftlichen Projekts angeboten.Publikationen über die Toxizität des Weichmachers Diethylhexylphthalat (DEHP) in Polyvinylchlorid-haltigen Medikalprodukten waren Anlass, eine PVC-freie Intensivstation zu etablieren.Stillförderung insbesondere bei Frühgeborenen war schon immer ein besonderes Anliegen der Kinderklinik Glanzing. Den Umweltbelastungen durch polychlorierte Biphenyle (PCBs), Dioxine oder Furane in der Muttermilch kann niemand ausweichen, nur ein gesetzliches Verbot führte zum Rückgang dieser Schadstoffe.Zum Angstabbau der Kinder vor dem Spital etablierte die Kinderklinik Glanzing seit 1994 ein jährliches Kinderfest vor Schulschluss, 2007 mit mehr als 2500 Eltern und Kindern. Großen Stellenwert hatte die umfassende Ausbildung angehender Kinderärztinnen und Kinderärzte in allen Bereichen unseres Fachs, die durch Rotation an der eigenen Abteilung mit vielen Schwerpunkten vermittelt werden konnte.Gerade die derzeitige Situation der Covid-19-Pandemie zeigt, wie wichtig nicht nur Intensivbetten, sondern auch die Ausbildung von ausreichendem Pflege- und medizinischem Personal ist.

Designing anti-migration furan-based plasticizers and their plasticization properties in poly (vinyl chloride) blends

The use of bio-based plasticizers with low toxicity and good compatibility with polyvinyl chloride (PVC) has attracted more attention in the recent years. With bio-based 2, 5-furandicarboxylic acid (FDCA) and butyl oligo-glycol ethers as raw materials, three liquid furan-based plasticizers of di(butyl glycol) furan-2,5-dicarboxylate, di(butyldiglycol) furan-2,5-dicarboxylate and di(butyltriglycol) furan-2,5-dicarboxylate were synthesized by direct esterification. The chemical structure of three plasticizers was characterized with FTIR, 1H NMR and 13C NMR. From DMA measurement, the glass transition temperature (Tg) of the plasticized PVC was decreased gradually when furan-based plasticizers were added to PVC formulation from 30 up to 50 phr. Due to lots of ether bonds in furan-based plasticizers, they expressed over two-fold lower migration in organic solvent compared with the traditional plasticizer diethylhexyl phthalate (DEHP). Through the characterization of elongation at break, hardness and thermal stability, furan-based plasticizers presented the same plasticization properties as DEHP, and had potential industrial application prospects.

Plasticizer exposure of infants during cardiac surgery

In the present study we investigated the internal exposure situation of infant patients to the plasticizers TEHTM (tri-2-ethylhexyl trimellitate) and DEHP (di-2-ethylhexyl phthalate). The study collective included 21 infant patients aged 2–22 months that had to undergo cardiac surgery using cardio pulmonary bypass (CPB). Each patient, but one, received blood products during surgery. A special feature was that the used CPB tubings were exclusively plasticized with the alternative plasticizer TEHTM and were free of the standard plasticizer DEHP, that raises increasing toxicological concern. The blood products were stored in DEHP plasticized blood bags. Blood and urine samples of each infant patient were analysed before and after the surgery for the levels of the plasticizers DEHP and TEHTM and their metabolites. In general, the plasticizers were detected in the post-surgery blood samples only, with TEHTM in low levels (median 18.4 μg/L) and DEHP in rather elevated levels (median 1046 μg/L). With respect to the urine samples, TEHTM metabolites were not detected in any of the samples. DEHP metabolites were found in all urine samples, however, in significantly increased median levels in the post-surgery urine samples of the infants (increase factor 5–26). Thus, the present study clearly demonstrates the strong contribution of standard medical procedures to the internal plasticizer burden of patients. Particularly with regard to the suspected endocrine disrupting activities of the phthalate plasticizer DEHP, the elevated internal levels of this plasticizer and its metabolites in infants following cardiac surgery are alarming.

Synthesis of Bio-Plasticizer from Soybean Oil and Its Application in Poly(Vinyl Chloride) Films

Herein, epoxidized soybean oil methyl ester (ESOM) plasticizer was synthesized for the preparation of plasticized poly(vinyl chloride) (PVC) films by the alcoholysis and epoxidation. The chemical structure of ESOM was investigated by infrared spectrum and 1H nuclear magnetic resonance. The effect of content of ESOM and petroleum based plasticizer di-2-ethylhexyl phthalate (DEHP) on the performance of plasticized PVC films was studied. The result showed that substituting DEHP with ESOM can improve the thermal stability of plasticized PVC films. When the weight ratio of ESOM and PVC is fixed at 1:2, plasticized PVC film presents higher elongation at break (350.8% vs. 345.1%) and lower tensile strength (14.21 MPa vs. 15.8 MPa) compared with PVC plasticized with DEHP. ESOM showed less weight loss than DEHP in all solvents. The excellent migration resistance of ESOM is helpful to improve stability of plasticized PVC films. In all, the obtained bio-based plasticizer will be potential to replace petroleum based plasticizer DEHP in flexible PVC materials.

Probing the molecular toxic mechanism of di-(2-ethylhexyl) phthalate with glutathione transferase Phi8 from Arabidopsis thaliana

As the most widely used plasticizer, di-(2-ethylhexyl) phthalate (DEHP) has been extensively applied to agriculture. However, its excessive accumulation may cause the active oxygen damage in plants and further lead to the destruction of antioxidant enzymes. As a core component of the glutathione antioxidant enzyme system, glutathione S-transferases (GSTs) have been reported as biomarkers for assessing oxidative damage induced by environmental pollutants, but the underlying toxic molecular mechanism has rarely been exploited. In this article, the interaction mechanism of Arabidopsis thaliana glutathione S-transferase AtGSTF8 and plasticizer DEHP was investigated at the molecular level by multispectral methods. The enzyme activity changes of AtGSTF8 upon binding with DEHP were also evaluated. A single binding site of AtGSTF8 towards DEHP was predicted and the binding force was presumed mainly by Van der Waals' force and hydrogen bonding based on static quenching mechanism. Besides, the deconstructions of the protein skeleton were also deduced based on the multispectral results and the hazardous effects of DEHP on plants growth were further demonstrated. This work will help to clarify the functional mechanism between the plasticizer DEHP and the antioxidant enzyme AtGSTF8 at the molecular level, and providing useful information for further study of the toxic effects of DEHP on plant antioxidant systems.

Endoplasmic reticulum stress, a novel significant mechanism responsible for DEHP-induced increased distance between seminiferous tubule of mouse testis.

Di(2-ethylhexyl) phthalate (DEHP), a widely existed endocrine disruptor, has been concerned for many years owing to its toxicity in male reproductive development. In this study, we investigated the reproductive effects and the mechanism of mouse testis after in uterus exposure to the plasticizer DEHP. We found that the UPR signaling pathway could be fully activated after DEHP treatment. In uterus DEHP exposure significantly increased abnormal morphology seminiferous tubules, expanded the distance between the tubules as well as caused abnormal endoplasmic reticulum (ER) ultrastructure, which could be reversed by 4-phenylbutyrate (4-PBA), an ER stress inhibitor. In addition, DEHP-induced ER stress pathway promoted a decline in protein expression, including cadherin protein N-cadherin in testis, which could also be reversed by 4-PBA. Taken together, our results provide compelling evidence that the ER stress would be a novel significant mechanism responsible for DEHP-induced the increased the distance between seminiferous tubule by reducing the N-cadherin expression.

Mono-2-ethylhexyl phthalate induces the expression of genes involved in fatty acid synthesis in HepG2 cells

Mono-2-ethylhexyl phthalate (MEHP) is a major bioactive metabolite in the widely used industrial plasticizer diethylhexyl phthalate (DEHP) that has been found to be toxic to the liver. The aim of this study is to determine whether MEHP exposure can change the expression of fatty acid metabolism-related genes in HepG2 cells, which might be related to non-alcoholic fatty liver disease (NAFLD). The results revealed that exposure to MEHP promoted lipid accumulation in HepG2 cells. The levels of intracellular triglycerides in the hepatocytes increased after exposure to 0.8–100 μM MEHP for 24 h and 48 h. The genetic expressions of SREBP-1c, ChREBP, ACC1, FASN, and SCD significantly increased at 6 h after exposure to MEHP. At 24 h, the expression of the SREBP-1c and ChREBP genes remained increased, while the expression of the FASN and SCD genes decreased. At 48 h, the expression of SREBP-1c, ChREBP, ACC1, FASN, and SCD decreased. Furthermore, the levels of proteins including ACC1, FASN, SCD, and ChREBP (except SREBP-1c) increased at 24 h. These findings suggest that MEHP exposure can promote fatty acid synthesis in hepatocytes by regulating the expression of relevant genes and proteins, contributing to NAFLD.

Effect of the Plasticizer DEHP in Blood Collection Bags on Human Plasma Fraction Unbound Determination for Alpha-1-Acid Glycoprotein (AAG) Binding Drugs.

Fraction unbound (fu) is a critical drug distribution parameter commonly utilized for modeling efficacious dosage and safety margin predictions. An over-estimation of fu for 13 chemically diverse small molecule drugs primarily bound to alpha-1-acid glycoprotein (AAG) in human plasma was discovered when in vitro results from our screening lab were compared to literature values. Di-(2-ethylhexyl) phthalate (DEHP), a plasticizer known to be used in the manufacture of blood collection bags, was extracted from plasma obtained through three common techniques that allowed contact with DEHP, and drug fu values in plasma from each collection method were estimated using the HTDialysis protein binding methodology. Additionally, fu of test compounds in plasma spiked with varying concentrations of DEHP (0-800μM) was determined, and DEHP extractions were performed from plasma stored in Terumo bags over 7days. Blood stored in Terumo bags, blood collected in Terumo bags, but immediately transferred to conical vials, and vacutainer-collected blood yielded DEHP concentrations of 300-1000μM, 1-10μM, and 0.1-2μM, respectively. This finding corresponded with the fu of tested drugs in DEHP-spiked plasma increasing between 2- and 5-fold. Additionally, DEHP was discovered to leach from the Terumo bag, with concentrations increasing 10-fold over a 7-day test period. In summary, the presence of DEHP in commercially available blood collection bags confounds in vitro fu estimation for drugs that bind primarily to AAG. It is recommended that vacutainer-collected human plasma, which contains negligible DEHP, be used for the most accurate estimation of fu in human plasma.

Migration of stabilizers and plasticizer from recycled polyvinylchloride

The migration of lead, cadmium, and zinc stabilizers from recycled unplasticized and plasticized polyvinylchloride (PVC) into deionized water (DW), saliva (SAS), and sweat (SWS) simulants was investigated. With the results obtained with DW diffusion coefficients in the plastics and partition coefficients at the plastic‐water interface for these additives were determined. The results indicate that organic stabilizers diffuse faster than inorganic ones in the matrix of the PVC. This fact is confirmed also by the low diffusion coefficients found for antimony oxide used as flame retardant in plasticized PVC. The migration rates of the metal (and especially lead) containing stabilizers from unplasticized PVC in DW are very low due to their low diffusion coefficients in the polymer and low solubilities in water. These migration rates are, as expected, higher from plasticized PVC, mainly because of the higher diffusion coefficients in the polymer. The migration levels of lead stabilizers from PVC into SAS are comparable with those into DW. However, for SWS considerably higher lead migration levels were found, probably due to the ability of the lactic acid and/or ammonium hydroxide components of SWS to coordinate the Pb ions resulting in an increase of the solubility of the lead containing stabilizers in this liquid. Migration of the plasticizer diethylhexyl phthalate (DEHP) from plasticized PVC samples into the same liquids was also investigated. The results obtained indicate that these migration processes are mainly controlled and limited by the low solubility of DEHP in these liquids. No enhanced DEHP migration into SWS was observed. J. VINYL ADDIT. TECHNOL., 24:E112–E124, 2018. © 2017 Society of Plastics Engineers

Pathological Study of Acute Oral Toxicity Induced by Plasticizer Di (2- ethyl hexyl) Phthalate in Japanese Common Quails Coturnix coturnix japanies

The current study aimed to identified the pathological changes of oral toxicity induced by Di (2-ethyl hexyl) phthalate (DEHP) in Japanese common quail. To a chief this aim a pilot study conducted to determine the median lethal dose (LD50) of DEHP. Forty male quails one day old were divided randomly into two equal groups, the first group was orally administrated by 10% of LD50 of DEHP daily for fourteen days, while second group was considered as control group and left without treatment all over the experimental time. The result of pilot study showed that the LD50 of DEHP in quails is 5574,1 mg/kg of body weight and the dose used in experiment to induced the acute oral toxicity was 557.4 mg/kg of quail's body weight. The result of gross pathological appearance of euthanized quails at fourteen days of experiment revealed presence of sever congestion in kidney lobules as well as congestion of liver with hemorrhagic ecchymotic patches while at other case the liver appear pale in color. The histopathology of kidney revealed presence of degenerative changes represented by cloudy swelling of the cell lining renal tubules lead to narrowing the lumen of affected tubules as well as interstitial edema with coagulative necrosis associated by infiltration of inflammatory cells as well as interstitial hemorrhage. The liver sections revealed presence of fatty change in hepatocytes in which the liver cell contained vacuoles of different size and shape also hepatocytes suffered from coagulative necrosis with infiltration of mononuclear inflammatory cells as macrophages with presence of hemorrhage. We conducted from current study that the oral administration of plasticizer DEHP in fourteen days at dose of 557.4 mg/kg of quail body weight induced degenerative and coagulative necrosis in both kidney and liver tissue in Japanese common quail.

Fetal Exposure to Low Levels of the Plasticizer DEHP Predisposes the Adult Male Adrenal Gland to Endocrine Disruption.

In utero exposure to endocrine disrupting chemicals (EDCs) may affect adult health. Di-(2-ethylhexyl) phthalate (DEHP) is an EDC widely used in the production of polyvinyl chloride products and an ubiquitous environmental contaminant. We used a rat model system to show that fetal exposure to DEHP decreased levels of major steroid hormones in adulthood and that environmentally-relevant levels of DEHP affected both gene expression and epigenomic loci that were affected by exposure to high levels. In the adrenal gland, we reported that the peroxisome proliferator-activated receptor (PPAR) and cholesterol biosynthesis pathways were sensitive targets of DEHP. We hypothesized that low levels of DEHP exposure insult the endocrine system (a "first hit") and increase its susceptibility to later exposure ("second hit") and subsequent disease. Here, we demonstrate that a second hit in the adult offspring exposed in utero to low levels of DEHP affected serum aldosterone levels. To unveil the first hit influence of early DEHP exposure, we treated in utero DEHP-exposed adult offspring with stressors that targeted the PPAR or cholesterol biosynthesis pathways. Treatment with the PPAR-gamma antagonist T0070907 reduced serum aldosterone compared to animals not exposed to DEHP in utero. Analysis of gene expression in animals that were subjected to both early and late exposure revealed deregulation of genes for the potassium channel Kcnk5 and the retinoid-X receptors (RXR) Rxra and Rxrb, indicating that these entities are linked to endocrine disruption. We propose that early exposure to environmental doses of DEHP predisposes the animal for disease later in life.

Simultaneous determination of polyvinylchloride plasticizers di(2-ethylhexyl) phthalate and tri(2-ethylhexyl) trimellitate and its degradation products in blood by liquid chromatography-tandem mass spectrometry

Di(2-ethylhexyl) phthalate (DEHP) and tri(2-ethylhexyl) trimellitate (TEHTM or TOTM) are common plasticizers that are also largely used for PVC medical devices, e.g. bags and tubing for blood transfusions and infusions. The leachability of medical devices is a well-known situation of increasing toxicological concern. To assess the migration of plasticizers from PVC medical devices into human blood we developed and validated an analytical method for the determination of DEHP and TOTM in combination with the determination of their primary degradation products mono(2-ethylhexyl) phthalate (MEHP), 1,2-di(2-ethylhexyl) trimellitate (1,2-DEHTM) and 2-mono(2-ethylhexyl) trimellitate (2-MEHTM). The presented method involves liquid–liquid extraction of the analytes from the blood followed by the subsequent analytical separation and detection using LC–MS/MS analysis. The validation of the procedure showed a good precision in the range of 1.8 to 5.3%. Mean accuracy ranged from 86% for 1,2-DEHTM to 109% for MEHP. LOQ was found to be 2 to 5μg/L for each of the analytes. Additionally, the method is characterised by its wide linear range up to 2mg/L each for the degradation products of TOTM to 100mg/L for the parent plasticizer DEHP. The presented method promises to be of major advantage for further studies as it allows for the first time the simultaneous determination of DEHP and TOTM in human blood in combination with the analysis of their degradation products that render possible to investigate the leachability of a broad range of PVC medical devices in human blood using only one analytical method.

Neural and Behavioral Developmental Toxicity of the Plasticizer DEHP

Di-(2-ethylhexyl) phthalate (DEHP) is an environmental endocrine disruptor that possesses weak estrogenic and anti-androgenic activity. Humans and wildlife exposed to DEHP lifetime through different channels. Maternal DEHP can be transferred either to the fetus across the placenta during pregnancy, or to the nursing infant through breast milk during lactation. Perinatal DEHP exposure can interfere with the effect of estrogen on brain development through sex-specifically changing the activities of aromatase enzyme and estrogen receptor in hypothalamic preoptic area of rat offspring. DEHP and its metabolites affect the proliferation and differentiation of neurons, synapse formation, and the regulatory effects of amino acid neurotransmitters system on gonadotropin releasing hormone (GnRH) neurons which are modulated by sexual hormones. DEHP affects the development of dopamine neurotransmitter system of the midbrain and induces motor hyperactivity. These effects of DEHP ultimately lead to abnormal development of behaviors such as early behavior, learning and memory, and emotional behavior of animal.

Determination and pharmacokinetics of di-(2-ethylhexyl) phthalate in rats by ultra performance liquid chromatography with tandem mass spectrometry.

Di-(2-ethylhexyl) phthalate (DEHP) is used to increase the flexibility of plastics for industrial products. However, the illegal use of the plasticizer DEHP in food and drinks has been reported in Taiwan in 2011. In order to assess the exact extent of the absorption of DEHP via the oral route, the aim of this study is to develop a reliable and validated ultra performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS) method to evaluate the oral bioavailability of DEHP in rats. The optimal chromatographic separation of DEHP and butyl benzyl phthalate (BBP; used as internal standard) were achieved on a C18 column. The mobile phase was consisted of 5 mM ammonium acetate-methanol (11:89, v/v) with a flow rate of 0.25 mL/min. The monitoring ion transitions were m/z 391.4 → 149.0 for DEHP and m/z 313.3 → 149.0 for BBP. The mean matrix effects of DEHP at low, medium and high concentrations were 94.5 ± 5.7% and 100.1 ± 2.3% in plasma and feces homogenate samples, respectively. In conclusion, the validated UPLC-MS/MS method is suitable for analyzing the rat plasma sample of DEHP and the oral bioavailability of DEHP was about 7% in rats.

Rapid and sensitive determination of plasticizer diethylhexyl phthalate in drink by diffuse reflectance UV spectroscopy coupled with membrane filtration

A rapid, sensitive and selective method for the determination of illegal additive diethylhexyl phthalate (DEHP) in drink was proposed. The method was based on membrane filtration-enrichment and diffuse reflectance UV (DRUV) spectroscopy. The DEHP solution was passed through the membrane, and then quantified directly on the membrane surface by using an integrating sphere accessory of the UV spectrophotometer. Effects of pH value, sample volume and vacuum degree were investigated in order to optimize the sensitivity. The absorbance of the UV spectra was linearly related to the concentration of DEHP in the ranges of 0.03–0.7 mg/L and 1–5 mg/L, with the squared correlation coefficients (R2) being 0.9911 and 0.9928, respectively. Under the chosen optimal conditions, the limit of detection (LOD) was 0.0079 mg/L. The recoveries were between 99% and 105% when the real drinks were analyzed, and the relative standard deviation (RSD) ranged from 1.0% to 5.0%.