Human Metabolism of Bis(2-ethylhexyl)phthalate

Abstract

To study the human metabolism of bis (2-ethylhexyl)-phthalate (DEHP) urine samples were analyzed from non-uremic psoriatic patients, uremic patients undergoing hemodialysis treatments and patients undergoing cardiac bypass surgery using High Performance Liquid Chromatography (HPLC). The urine of dialyzed non-uremic patients contained phthalic acid, mono (2-ethylhexyl) phthalate and bis (2-ethylhexyl) phthalate. Other compounds identified were p-hydroxy benzoic acid, m-hydroxy benzoic acid, o-hydroxy hippuric acid, o-hydroxy benzoic acid and benzoic acid, which may be either diet dependent normal urinary constituents or metabolites of bis (2-ethylhexyl) phthalate. The levels of phthalic acid and bis (2-ethylhexyl) phthalate found in the urine of patients who were on total body oxygenators containing a membrane during cardiac bypass surgery were comparable to levels obtained from non-uremic psoriatic patients. Significant levels of phthalic acid were detected in the urine of the uremic patients studied while mono (2-ethylhexyl) phthalate and bis (2-ethylhexyl)-phthalate were present only in small amounts or were completely absent. In general, the urinary phthalate content of uremic patients increased with urinary volume.     

Validation and application of an HPLC method for determination of di (2-ethylhexyl) phthalate and mono (2-ethylhexyl) phthalate in liver samples

A reversed-phase gradient elution, UV detection method is developed for the simultaneous determination of mono (2-ethylhexyl) phthalate [MEHP] and di (2-ethylhexyl) phthalate [DEHP] in tissue samples. The method is validated with respect to extraction recovery, inter and intra-day precision, linearity of response, detect ability, and specificity. The validated method has been successfully applied to the study of DEHP and MEHP in liver, kidney, testis, brain, and plasma samples from rat.     

HPLC with diode-array detection for the simultaneous determination of di(2-ethylhexyl)phthalate and mono(2-ethylhexyl)phthalate in seminal plasma

A high-performance liquid chromatographic method for the simultaneous determination of di(2-ethylhexyl)phthalate (DEHP) and its major metabolite mono(2-ethylhexyl)phthalate (MEHP) in seminal plasma was developed and validated. The method involves liquid-liquid extraction followed by isocratic reversed-phase chromatography with diode-array detection. The recovery, selectivity, linearity, precision and accuracy of the method were evaluated from the analysis of spiked seminal plasma samples. The effect of mobile-phase composition and pH on the retention of the target analytes was investigated. The limits of detection were 0.010 and 0.015 microg/mL, for DEHP and MEHP, respectively. This method was used to analyze real samples in support of clinical studies on these potential endocrine disruptors.     

Rapid determination of urinary di(2-ethylhexyl) phthalate metabolites based on liquid chromatography/tandem mass spectrometry as a marker for blood transfusion in sports drug testing

Methods of blood doping such as autologous and homologous blood transfusion are one of the main challenging doping practices in competitive sport. Whereas homologous blood transfusion is detectable via minor blood antigens, the detection of autologous blood transfusion is still not feasible. A promising approach to indicate homologous or autologous blood transfusion is the quantification of increased urinary levels of di(2-ethylhexyl) phthalate (DEHP) metabolites found after blood transfusion. The commonly used plasticizer for flexible PVC products, such as blood bags, is DEHP which is known to diffuse into the stored blood. Therefore, a straight forward, rapid and reliable assay is presented for the quantification of the main metabolites mono(2-ethyl-5-oxohexyl) phthalate, mono(2-ethyl-5-hydroxyhexyl) phthalate and mono(2-ethylhexyl) phthalate that can easily be implemented into existing multi-target methods used for sports drug testing. Quantification of the DEHP metabolites was accomplished after enzymatic hydrolysis of urinary glucuronide conjugates and direct injection using isotope-dilution liquid chromatography/tandem mass spectrometry. The method was fully validated for quantitative purposes considering the parameters specificity, linearity (1-250 ng/mL), inter- (2.4%-4.3%) and intra-day precision (0.7%-6.1%), accuracy (85%-105%), limit of detection (0.2-0.3 ng/mL), limit of quantification (1 ng/mL), stability and ion suppression effects. Urinary DEHP metabolites were measured in a control group without special exposure to DEHP (n?=?100), in hospitalized patients receiving blood transfusion (n?=?10), and in athletes (n?=?468) being subject of routine doping controls. The investigation demonstrates that significantly increased levels of secondary DEHP metabolites were found in urine samples of transfused patients, strongly indicating blood transfusion.     

Application of on-line solid-phase extraction-gas chromatography-mass spectrometry to the determination of endocrine disruptors in water samples

We have applied a method based on solid-phase extraction (SPE), on-line coupled to gas chromatography-mass spectrometry through an on-column interface, to determine a group of endocrine-disrupting compounds in water samples. We have optimised the parameters affecting the SPE process and transfer step and used the method to analyse river, coastal and tap waters. In the full-scan acquisition mode, all the compounds were determined by preconcentrating only 15 ml of water sample. Di-n-butyl phthalate, benzylbutyl phthalate, bis(2-ethylhexyl) phthalate and bis(2-ethylhexyl) adipate at concentrations between 0.02 and 0.5 microg l(-1) were determined in some real samples.     

以固体光气为原料合成氯代甲酸(2-乙基)己酯

氯代甲酸(2-乙基)己酯是一种化工中间体,主要用来制备过氧化二碳酸二(2-乙基)己酯(简称EHP),EHP是一种高活性聚合引发剂。由固体光气和2-乙基己醇为原料合成氯代甲酸(2-乙基)己酯的研究未见报道。本文以固体光气和2-乙基己醇为原料合成了氯代甲酸(2-乙基)己酯,研究了反应物加入顺序、反应时间、反应温度、催化剂种类及用量对氯代甲酸(2-乙基)己酯收率和纯度的影响,得到了优化的合成工艺,对产物结构进行了分析,进一步用其合成了常用的高活性聚合引发剂过氧化二碳酸二(2-乙基)己酯(EHP)。     

One-step in-syringe dispersive liquid–liquid microextraction and GC-FID determination of trace amounts of di(2-ethylhexyl) phthalate and its metabolite in human urine samples

Di(2-ethylhexyl) phthalate (DEHP) is used as plasticizer in polyvinylchloride (PVC) plastics. Its metabolites and the parent phthalates are considered toxic. As the DEHP plasticizers are not chemically bound to PVC, they can migrate, evaporate or be leached into indoor air and atmosphere, foodstuff, and other materials. We have reported a novel, easy and available analytical method for the determination of DEHP and its metabolite, mono(2-ethylhexyl) phthalate (MEHP) in human urine samples by the in-syringe dispersive liquid–liquid microextraction method coupled with gas chromatography with flame ionization detector. The limits of detection and precision (RSD) were 2.5 μg/L and 1.4% for DEHP and 1.1 μg/L and 3.0% for MEHP, respectively. This method could be utilized for routine monitoring of the trace DEHP and MEHP in urine of human exposure to plasticizers.     

Plasticizers,antioxidants, and other contaminants found in air delivered by PVC tubing used in respiratory therapy

Of the many compounds that leach from respiratory therapy tubing into air passing through it, we selected five compounds to analyze. The five compounds are known to be potentially carcinogenic, toxic or known to induce estrogenic activity. Parts-per-million and parts-per-billion concentrations of these species were found in the air passing through the tubing: the plasticizers di-(2-ethylhexyl) phthalate (DEHP) and di-ethyl phthalate (DEP), the antioxidants butylated hydroxy toluene (BHT) and p-nonylphenol (p-NP), and the contaminant (from commercial preparation of DEHP) 2-ethylhexanol (2-EH). These levels are high enough to cause some concern about exposure for patients who use oxygen on a long-term basis, those sensitive or allergic to these species, or those with asthma. A method was developed for analysis of solid tubing samples, showing great variability in concentrations of small, volatile molecules from sample to sample. A method was also developed for pre-concentration of small molecules onto Tenax adsorbants from air passing through the tubing. Both solid samples and adsorbant loaded with analyte were analyzed by direct dynamic thermal desorption gas chromatography mass spectrometry (GCMS). This study does not imply that adverse reactions by patients to chemical compounds leaching from respiratory medical tubing will occur but that further investigation is warranted.     

Determination of Phthalates in Milk by Ultrasound-Assisted Dispersive Liquid–Liquid Microextraction and Gas Chromatography–Mass Spectrometry

Ultrasound-assisted dispersive liquid–liquid microextraction was coupled with gas chromatography—mass spectrometry for the determination of phthalate esters in milk. Dimethyl phthalate, diethyl phthalate, dibutyl phthalate, benzyl butyl phthalate, bis(2-ethylhexyl) phthalate, and dioctyl phthalate were analyzed in five brands of pasteurized Turkish milk. The efficiencies of the extraction procedure for the analytes were between 66 and 100%. The linear dynamic ranges of the calibration curves were from 0.025 to 1.000 µg/mL with correlation coefficients exceeding 0.99. The precision of the method is acceptable with relative standard deviation values below 5%. Dibutyl phthalate and bis(2-ethylhexyl) phthalate were commonly observed in milk.     

室温离子液体催化巯基乙酸异辛酯的合成

巯基乙酸异辛酯是一种广泛应用于精细化工、树脂和塑料制造的中间体,尤其在聚氯乙烯无毒制品中有着重要用途[1],其合成方法的改进也成为研究的主要课题之一。巯基乙酸异辛酯的合成通常采用硫酸催化法[2],由于浓硫酸污染环境、腐蚀设备,特别是近年来环保法规对环境和安全性不断提高的要求,用固体酸(分子筛、离子交换树脂、固体超强酸)等取代H2SO4、HF、A lC l3等强腐蚀性酸作为催化剂的催化工艺获得明显进展[3],但这些催化剂也有自身的缺点[4]。室温离子液体是近年来受到极大关注的一类新材料,它为人们探索环境友好的催化体系和溶剂提供了…     

Method for determination of plasticizers in industrial emissions

Summary A simple method has been developed for the determination of dibutyl phthalate, di-(2-ethylhexyl) phthalate, diisodecyl phthalate, and di(2-ethylhexyl) adipate in industrial emissions. A cartridge packed with a modified silica gel is used as adsorbent and adsorbed compounds are eluted and analyzed by HPLC in normal and reversed phase system.Presented at the 2nd Conference on Solid Phase Extraction, Bratislava, Soovakian Republic, November 16–18, 1992.     

Synthesis of a New Benzoate Plasticizer for Polyvinyl Chloride Based on a 2-Ethylhexanol By-Product

Russian Journal of Applied Chemistry - When 2-ethylhexyl alcohol is produced by the propylene oxo synthesis, 2-ethylhexanol distillation residue (EDR), a large-tonnage by-product, is formed....     

New contributions to the field of bead-injection spectroscopy—flow-injection analysis: determination of cobalt

A novel method based on column-switching high-performance liquid chromatography-electrospray mass spectrometry (LC-MS) coupled with an on-line extraction column containing conjugated avidin has been developed for direct injection analysis of di(2-ethylhexyl) phthalate (DEHP) and its metabolite, mono(2-ethylhexyl) phthalate (MEHP), in blood samples. The sample preparation for on-line extraction involved the mixing of blood samples with internal standards, DEHP-d(4) and MEHP-d(4), in LC glass vials. A linear response was found for column-switching LC-MS when tests were conducted within the validated range of 25 to 1000 ng mL(-1) for DEHP and 5 to 1000 ng mL(-1) for MEHP, with correlation coefficients (r) greater than 0.999. In addition, the recoveries of DEHP and MEHP from human plasma were calculated by using this method with on-line extraction, yielding recoveries of up to 91.2% (RSD<5%). We measured the background levels of DEHP and MEHP in six human plasma samples from healthy volunteers and three fetal bovine serum samples for cell-line culture. DEHP and MEHP were not detected in all human plasma samples (N.D. is <25 ng mL(-1) for DEHP, and N.D. is <5.0 ng mL(-1) for MEHP). In contrast, high DEHP contamination of commercially available fetal bovine serum samples was found by this method.     

Studies on the thermal decomposition of phthalate esters: IX. Thermal decomposition of bis(2-ethylhexyl) phthalate

A flow apparatus equipped with a spray nozzle was developed for investigating the thermal decomposition of esters with high boiling points and viscosities. The thermal decomposition of bis(2-ethylhexyl) phthalate (BEHP), which is a typical plasticizer for poly(vinyl chloride) with a high boiling point and viscosity, was carried out by the use of the flow apparatus. The thermal decomposition products were analysed by gas chromatography and the kinetic parameters were calculated. The kinetic parameter of bis(2-ethylhexyl) phthalate was k_BEHP (s^?1)=4.59·10¹¹ exp(?40600/RT). From a comparison with the values for phthalic esters, it is proposed that a cis-elimination reaction takes place with a two-step mechanism in which the rate-determining step is α-carbon cleavage.     

Heat capacities of some phthalate esters

Isobaric heat capacities C _p in the liquid phase of dimethyl phthalate, diethyl phthalate, dibutyl phthalate, bis(2-ethylhexyl) phthalate, and benzyl butyl phthalate were measured by commercial SETARAM heat conduction calorimeters. Results obtained cover the following temperature range: dimethyl phthalate 283 to 323 K, diethyl phthalate 306 to 370 K, dibutyl phthalate 313 to 447 K, bis(2-ethylhexyl) phthalate from 313 to 462 K, benzyl butyl phthalate from 313 to 383 K. The heat capacity data obtained in this work were merged with available experimental data from literature, critically assessed and sets of recommended data were developed by correlating selected data as a function of temperature. This revised version was published online in August 2006 with corrections to the Cover Date.     

Chiral ethylhexyl substituents for optically active aggregates of pi-conjugated polymers

We report an efficient synthesis of chiral (2S)-ethylhexanol for functionalizing and solubilizing conjugated polymers. The alpha-substituted chiral ethylhexyl side chains were obtained through a powerful and flexible asymmetric synthesis using pseudoephedrine as a chiral auxiliary. The dependence of the properties of conjugated polymers on molecular structure is investigated by circular dichroism, fluorescence, and absorption spectroscopy on two new chiral conjugated polymers, poly(3,3-bis((S)-2-ethylhexyl)-3,4-dihydro-2H-thieno[3,4-b][1,4]dioxepine) (PProDOT((2S)-ethylhexyl)(2)) and poly(3,3-bis((S)-2-methylbutyl)-3,4-dihydro-2H-thieno[3,4-b][1,4]dioxepine) (PProDOT((2S)-methylbutyl)(2)). The properties of PProDOT((2S)-ethylhexyl)(2)) differ significantly from those of its methylbutyl analog as investigated by chiral aggregation providing insight into the role of interchain interactions in these subsecond switching electrochromic polymers.     

食品包装材料中13种增塑剂的毛细管气相色谱法测定

建立了索氏提取、固相萃取净化浓缩、毛细管气相色谱法测定塑料食品包装材料中13种增塑剂的方法.优化了固相萃取淋洗剂、洗脱剂和洗脱剂体积等参数.样品经正己烷索氏提取后,用硅胶小柱净化浓缩.以正己烷-甲苯为淋洗剂,2 mL乙酸乙酯为洗脱剂.过滤后的洗脱液用气相色谱仪分析.结果显示,13种增塑剂在0.1～1000 mg/L范围...     

STUDIES ON METAL-CONTAINING POLYURETHANES BASED ON DIVALENT METAL SALTS OF MONO(HYDROXYETHOXYETHYL)PHTHALATE

By reacting phthalic anhydride with excess of diethylene glycol and metal acetate, the metal salts of mono(hydroxyethoxyethyl)phthalate were prepared (metal = Cu²⁺, Mn²⁺ and Zn²⁺). Polyurethanes containing metal ions in the main chain were synthesized by reacting hexamethylene diisocyanate (HMDI) or tolulylene 2,4-diisocyanate (TDI) with Cu²⁺, Mn²⁺ and Zn²⁺ salts of mono(hydroxyethoxyethyl)phthalate using di-n-butyltin dilaurate (DBTDL) as catalyst. The prepared monomers and polyurethanes were characterized by FT-IR, ¹H-NMR, ¹³C-NMR, UV spectra, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), elemental analysis, solubility and viscosity studies. The antibacterial activity of these polyurethanes have also been investigated using agar diffusion method.     

Synthesis of meso-tetraphenyl porphyrins via condensation of dipyrromethanes with N-tosyl imines

A new synthetic route for the synthesis of 5,10,15,20-tetraphenyl porphyrins has been developed based on the reaction of 5-substituted dipyrromethanes with N-tosyl imines in the presence of a metal triflate catalyst. meso-Substituted tetraphenyl porphyrins were synthesized in a two-step process. The first step of the method is the metal triflate-catalyzed condensation of 5-substituted dipyrromethanes with N-tosyl imines to form a porphyrinogen intermediate and the second step is the oxidation of the porphyrinogen to porphyrin. The method was applied to the synthesis of trans-A₂B₂-tetraarylporphyrins and the products were obtained with only a trace amount of one scrambling product. The synthesis of two important building blocks for porphyrin synthesis, mono and di-sulfonamide alkylated 5-substituted dipyrromethanes, was achieved by the addition of 5-substituted dipyrromethane to N-tosyl imine. The application of mono and di-sulfonamide alkylated 5-substituted dipyrromethanes in ‘2+2’ porphyrin formation reactions is presented.     

A rapid method for the quantification of urinary phthalate monoesters: A new strategy for the assessment of the exposure to phthalate ester by solid‐phase microextraction with gas chromatography and tandem mass spectrometry

In the following work, a new method for the analysis of the phthalate monoesters in human urine was reported. Phthalate monoesters are metabolites generated as a result of phthalate exposure. In compliance with the dictates of Green Analytical Chemistry, a rapid and simple protocol was developed and optimized for the quantification of phthalate monoesters (i.e., monoethyl phthalate, monoisobutyl phthalate, mono‐n‐butyl phthalate, mono‐(2‐ethylhexyl) phthalate, mono‐n‐octyl phthalate, monocyclohexyl phthalate, mono‐isononyl phthalate) in human urine, which entails preceding derivatization with methyl chloroformate combined with the use of commercial solid phase microextraction and the analysis by gas chromatography‐triple quadrupole mass spectrometry. The affinity of the derivatized analytes toward five commercial coatings was evaluated, and in terms of analyte extraction, the best results were reached with the use of the divinylbenzene/carboxen/polydimethylsiloxane fiber. The multivariate approach of experimental design was used to seek for the best working conditions of the derivatization reaction and the solid phase microextraction, thus obtaining the optimum response values. The proposed method was validated according to the guidelines issued by the Food and Drug Administration achieving satisfactory values in terms of linearity, sensitivity, matrix effect, intra‐ and inter‐day accuracy, and precision.