Diethylhexyl Phthalate Research Articles

Protective effect of N-acetylcysteine (NAC) against Di-ethylhexyl phthalate (DEHP) induced pulmonary toxicity in male albino rats (histological and immunohistochemical study)

Di-ethylhexyl phthalate (DEHP) is a global environmental pollutant. Human exposure to DEHP occurs through environmental sources. Community exposure (food, air, water) as well as medical settings’ exposure impose crucial effects on the human health. DEHP had been reported to have cytotoxic, immunotoxic, genotoxic, and reproductive toxic properties. This work aims to assess the possible toxic effects of DEHP on adult albino rats' lungs and to evaluate the possible protective effects of N-acetylcysteine (NAC) using body weight and relative lung weight parameters. Assessment of DHEP toxicity is measured by biochemical, histopathological and immunohistochemical methods. Fifty male adult albino rats were divided into five equal groups as follows: Group Ι (Negative control group), Group ΙΙ (Positive control group), Group IΙΙ (NAC-treated group): was given NAC orally (200 mg/kg/day), Group IV (DEHP-treated group): was given DEHP orally (3gm/kg once daily for 4 weeks) and Group V: (DEHP + NAC-treated group): was treated with DEHP concomitantly with NAC at the same previous doses. The results of the present study revealed that DEHP has significantly increased the lipid peroxidation level and significantly reduced glutathione content (GSH), superoxide dismutase (SOD) activity and catalase activity. The histological results of group IV showed inflammatory cellular infiltration of the lungs associated with interstitial edema, hemorrhage and inter-alveolar septal thickening that were markedly reduced in group V. Also, group V, showed a significant decrease in the collagen fibers accumulation and in caspase-3 expression as compared to group IV. Conclusion: treatment with NAC can protect against DEHP induced pulmonary toxicity in rats by decreasing oxidative stress, inflammation and apoptosis.

New Analytical Method for Determination of Phthalates in Wastewater by on Line LC-GC-MS Using the TOTAD Interface and Fraction Collector

There is an increasing demand for automatic, reliable and sensitive analytical methods for determining trace levels of phthalic acid esters (PAEs) in environmental samples. While on line coupled liquid chromatography-gas chromatography (LC-GC) has been proof to be a powerful tool for trace-level analyses in complex matrices, the present work presents a new totally automated on line LC-GC method, using the Through Oven Transfer Adsorption Desorption (TOTAD) interface, for the analysis of four of the main phthalates, dibuthyl phthalate (DBP), diethyl phthalate (DEP), dimethyl phthalate (DMP) and diethylhexyl phthalate (DEHP), in a matrix as complex as leachate. The sample is directly injected into the LC injector valve with no sample pretreatment other than simple filtration. The LC step separates the target analytes from matrix interference. Two different LC fractions are collected in a purposely designed fraction collector and then transferred to the TOTAD interface, which concentrates the analytes, totally eliminates the solvent and transfers the analytes to the GC-MS system, where the analysis is carried out. The LOD of the method varied from 0.1 µg/L (DEHP) to 1.4 µg/L (DMP), RSD for retention time below 0.14% and for absolute peak areas below 12% and linearity from 1 µg/L to 1000 µg/L (R2 > 0.99), except in the case of DEHP (linearity from 1 to 250 µg/L, R2 = 0.94). The method was applied to the analysis of the target analytes in samples collected from a municipal solid waste (MSW) landfill in Rosario (Argentina).

Seasonal distribution and ecological risk of phthalate esters in surface water and marine organisms of the Bohai Sea

The spatiotemporal variability and ecological risks related to 16 phthalate esters (PAEs) were investigated in surface water and marine organisms of the Bohai Sea. The average PAE concentrations in the surface water were 8.02, 4.53, and 3.16 μg L−1 in spring, summer, and winter, respectively. Additionally, suspended particle matter was positive related to PAE content in seawater in spring and winter. The predominant PAEs in both water and biota were dimethyl phthalate (DMP), di-butyl phthalate (DBP), di-isobutyl phthalate (DIBP), and diethylhexyl-phthalate (DEHP). Because they do not exhibit long-distance migratory behavior, Chaeturichthys hexanema, Cynoglossus lighti, and Loligo japonica were good candidate indicator organisms for PAE pollution in Bohai Sea. The risk quotient method revealed that DIBP, DBP, and DEHP posed relatively greater risks to the aquatic system. This research establishes baseline data from which future management strategies to control PAEs in the Bohai Sea can be developed.

Measurement of phthalate acid esters in non-alcoholic malt beverages by MSPE-GC/MS method in Tehran city: chemometrics.

Phthalic acid esters (PAEs) are compounds that are used in the bottle as the main plasticizers. Therefore, the possibility of releasing phthalate esters into beverages is very high and there is a concern to consumer health and monitoring organizations. The aim of this research was to assess the phthalic acid esters (di-n-octyl phthalate (DNOP), butyl benzyl phthalate (BBP), dimethyl phthalate (DMP), diethyl phthalate (DEP) and dibutyl phthalate (DBP), bis(di-ethylhexyl) phthalate (DEHP), and total PAEs) in bottled non-alcoholic malt beverages (n = 120) by multi-walled carbon nanotubes were magnetized with iron (MWCNT-Fe3O4) using gaschromatography/mass spectrometry (GC-MS). The results showed that the highest and the lowest levels of total phthalate esters in samples were 9483.93 and 2412.50 ng/L, respectively. The mean of DEHP which has also been found to be carcinogenic in all samples was lower than 5944.73 ng/L. The highest concentration of DEHP in four samples was upper than 8957.87 ng/L. Perceived limit of detection (LOD) ranged from 13 to 30 ng/L and the limit of quantification (LOQ) ranged from 39 to 90 ng/L. Multivariate techniques and heat map visualization were used to assess the correlation among the type and levels of PAEs with the brand, color, product date, pH, sugar, volume, and gas pressure. Therefore, based on heat map and principal component analysis (PCA) results, the DEHP and total PAEs were the closest accessions, indicating that these variables had similar trends. Based on the results, it can be stated that due to the low average of total phthalate esters in non-alcoholic malt beverages, there is no serious health hazard of these compounds for humans.

Preparation of MgCl2-Supported Ziegler-Natta Catalysts via New Surfactants Emulsion for Propylene Polymerization

This article describes a MgCl2-supported Ziegler-Natta catalyst for propylene polymerization prepared via an in situ emulsion technique with new surfactants. The effect of preparation conditions such as the TiCl4/toluene molar ratio, TiCl4-contacting temperature, amount of phthaloyl dichloride, stirring rate, mixing time of TiCl4/toluene with the Mg complex, and the n-butyl chloride loading was investigated in detail. Scanning electron microscopy and laser particle size analyzer measurements showed that the catalyst particles exhibit a perfectly spherical shape, narrow particle size distribution, and low fine powder content. Energy-dispersive X-ray spectrometry indicated that the Ti, Mg, and Cl elements were evenly distributed throughout the particles. Powder X-ray diffraction measurements indicated the presence of δ-MgCl2 in the catalyst, and FTIR and GC-MS studies confirmed the presence of in situ formed di(ethylhexyl)phthalate (DEHP). Bulk polymerization of propylene using the catalyst was studied, and it was found that the catalyst displayed high activity, high bulk density with high stereospecificity, and excellent hydrogen sensitivity. The polymer produced by the catalyst has a narrow particle size distribution with a low fine powder content.

Maternal exposure to a mixture of Bisphenol A and Diethyl Hexyl Phthalate predisposes female offspring to growth retardation and metabolic dysfunction in adulthood

Background A newly recognized primary cause of the obesity epidemic is the developmental programming effects of plastic-derived environmental contaminants, Bisphenol A (BPA) and Diethyl-Hexyl-Phthalate (DEHP), which are known to be endocrine disrupting chemicals (EDCs). Research addressing the effects of a mixture of these EDCs is limited. Objective To assess the metabolic consequences of developmental exposure to individual as well as mixtures of BPA and DEHP in female Sprague-Dawley rats. Methods From gestational days 6-21, pregnant Sprague Dawley dams were orally administered either saline (control), BPA (5mg/Kg BW/day), DEHP (7.5 mg/Kg BW/day), or a combination of BPA and DEHP (B+D). Postnatal growth trajectory and intakes were monitored weekly from postnatal weeks 3-12 and daily from weeks 14-16. Female offspring were allowed to reach 14 weeks of age and were then challenged with either a high fat diet (HFD) or normal rat chow for 2 weeks. Body composition and glucose intolerance were measured before the HFD challenge, and after 1 and 2 weeks of HFD treatment. Offspring were sacrificed at week 16, and organs were dissected and weighed. Serum was assayed for insulin and corticosterone levels. Liver cholesterol levels were measured. Results No major changes were seen in female offspring prenatally exposed to BPA or DEHP alone. However, exposure to a combination of B+D induced a postnatal growth retardation that is significant from postnatal week 6 onwards (p=0.014) and a decrease in cumulative food intake (p=0.032) from weeks 3-12 when compared to controls. B+D female offspring had decreased fat (p=0.05), fluid (p=0.0009), and lean (p=0.002) mass at week 14 compared to control groups, impaired fasting glucose tolerance at week 14, significantly higher % gain in fluid (p=0.0008), lean (0.0043), and body weight (p=0.044) from weeks 14-16, and an increase in liver cholesterol levels (p=0.047). These changes were apparent in chow fed, but not HFD-fed animals. No changes were seen in insulin and corticosterone levels between the groups. Conclusion The results indicate that prenatal exposure to B+D altered the postnatal growth trajectory and metabolic profile in female offspring. This suggests a great need to reconsider the possible additive effects of exposure to EDC mixtures during pregnancy.

Compound specific isotope analysis (CSIA) of phthalates and non-targeted isotope analysis (NTIA) of SPE-extractable organic carbon in dilute aquatic environments

Isotope ratio analysis of total organic carbon (TOC) is well-established for the study of rivers, lakes, and oceans. Similarly, these aquatic systems are routinely surveyed to quantify natural and anthropogenic organic compounds and pollutants, including such things as pharmaceuticals, illicit drugs, and phthalates. We merged these two approaches to demonstrate compound specific isotope analysis (CSIA) on four phthalate esters and non-targeted isotope analysis (NTIA) on a gas chromatography isotope ratio mass spectrometry (GC-IRMS) platform. Water from the Rivers Foss and Trent and a waste-water treatment plant (WWTP) effluent was sampled, followed by solid phase extraction (SPE) and GC-IRMS. Di–ethyl hexyl phthalate (DEHP) concentration in the effluent was 0.20 µg/L while it was 0.22 µg/L and 0.14 µg/L in the Trent and Foss Rivers, respectively. CSIA δ 13C values for selected phthalates measured in river and effluent samples ranged from −24.3‰ to −28.8‰. NTIA returned over 100 compounds which in aggregate aligned well with published values for isotope analysis of TOC. NTIA demonstrated that the volatile SPE-extractable fraction of TOC has high heterogeneity with δ 13C from −26.8‰ to −44.3‰ for matched compounds in both rivers. GC-IRMS can be applied to dilute environmental systems using both compound specific and non-targeted strategies.

Association between Urinary Metabolites and the Exposure of Intensive Care Newborns to Plasticizers of Medical Devices Used for Their Care Management.

Care management of newborns in the neonatal intensive care unit (NICU) requires numerous PVC (PolyVinyl Chloride) medical devices (MD) containing plasticizers that can migrate and contaminate the patient. We measured the magnitude of neonates’ exposure to plasticizers (di-ethylhexylphthalate (DEHP) and alternatives) in relation to urinary concentrations of their metabolites. Plasticizers’ exposure was evaluated (1) by calculating the amounts of plasticizers prone to be released from each MD used for care management, and (2) by measuring the patients’ urinary levels of each plasticizers’ metabolites. 104 neonates were enrolled. They were exposed to di-isononylphthalate (DINP), especially via transfusion and infusion MD, and to DEHP via ECMO (Extra Corporeal Membrane Oxygenation) and respiratory assistance MD. Mean exposure doses exceeded the derived no-effect level of DINP and DEHP by a 10-fold and a 1000-fold factor. No PVC MD were plasticized with di-isononylcyclohexane-1,2-dicarboxylate (DINCH). High urinary concentrations of DEHP metabolites were directly correlated with DEHP exposure through ECMO MD. Urinary concentrations of DINP metabolites in transfused patients were also high. DINCH metabolites were found in urine, suggesting another route of exposure. Neonates in NICU are considerably exposed to plasticizers, with magnitudes varying with the type of MD used. The high exposure to DEHP and DINP leads to a risk of their metabolites’ toxicity.

Fate and removal of pentachlorophenol and diethylhexyl phthalate from textile industry wastewater by sequencing batch biofilm reactor: Effects of hydraulic and solid retention times

This study aimed to examine the effects of hydraulic retention time (HRT) and solid retention time (SRT) on the removal of diethylhexyl phthalate (DEHP) and pentachlorophenol (PCP) from real textile wastewater. Experiments were conducted daily and at different SRTs (10 d, 15 d, and 20 d) and HRTs (36 h, 48 h, and 60 h). The results showed that the optimal HRT and SRT for DEHP removal were 48 h and 20 d, respectively, and the removal efficiency reached 83.27%. Meanwhile, the highest removal efficiency was 75.5% for PCP at an HRT of 60 h and an SRT of 15 d. The addition of biocarriers to the reactor system was intended to facilitate microorganism growth and increase the average removal efficiencies of PCP and DEHP. Short HRTs and SRTs resulted in low micropollutant removal efficiencies. Based on the mass balance calculations, it was determined that biodegradation and sorption onto sludge were the main removal mechanisms for PCP and DEHP. The findings also revealed that using the optimal HRT and SRT is critical to achieve the highest growth of the bacteria responsible for the biodegradation of selected micropollutants. In the biocarrier amended system, biodegradation served and sorption onto sludge contributed to PCP removal. Conversely, the major removal mechanism for DEHP varied depending on the operating conditions. In particular, with increasing SRT, biodegradation became the dominant removal mechanism.

Environmental chemicals in dog testes reflect their geographical source and may be associated with altered pathology

In humans and dogs, a temporal decline in semen quality and increased incidence of testicular cancer is hypothesised to be associated with exposure to anthropogenic chemicals, particularly during fetal development. Human studies suggest that differential exposures to environmental chemicals may be associated with geographical differences in male reproductive health. Here we investigate testicular chemical profiles and pathologies in dogs residing in the UK [West Midlands (WM), East Midlands (EM), South East (SE)], Denmark (Copenhagen) and Finland (Vantaa). Testes, surplus from routine castrations, contained region specific differences in relative concentrations of diethylhexyl phthalate (DEHP), polybrominated diphenyl ethers (PBDE) and polychlorinated biphenyls (PCB). Relative to UK regions, testes from dogs living in Finland and Denmark had higher concentrations of PBDE and lower concentrations of DEHP and PCBs. Regional differences in the UK in PCB concentrations were also observed. Dog testes from Finland had fewer pathologies, reduced testicular area stained for Sertoli and germ cells and evidence of reduced cellular proliferation. Since the geographical differences in testis pathologies in dogs parallel reports of regional differences in human testicular cancer, we postulate that this may reflect chemical effects within the testis and that this may be related to environmental influences on male reproductive function.

AN ASSESSMENTOF PHTHALATES IN COSMETIC PRODUCTS BY DISPERSIVE LIQUID-LIQUID EXTRACTION METHOD USING HPLCAND LC-MS/MS

A Dispersive liquid-liquid microextraction (DLLME) based analytical method was developed and validated using HPLC-PDA and LC-MS/MS for quantitative determination of phthalates (Dimethyl phthalate (DMP), Diethyl phthalate (DEP), Benzyl Butyl Phthalate (BzBP), Dibutylphthalate(DBP), Diethylhexyl phthalate(DEHP), Di-n-octyl phthalate (DOP) in different cosmetic products (After Shave Lotion, Deodorants, Perfume and Liquid Body Lotion). The DLLME based developed and validated analytical method was found specific, sensitive, accurate and precise. The accuracy (% recovery) of the method at a spiking level of 0.1, 0.5 and 1.0 mg L-1 in the different cosmetic product was found in the range of 92-108. The interday and intraday precision (%RSD) of the method was found less than 15. Out of six analyzed phthalates, only four phthalates were detected in different cosmetic products. Dimethyl phthalate (DMP) and Di-n-octyl phthalate (DOP) were detected in aftershave lotion. Diethyl phthalate (DEP) was detected in deodorants. Dibutyl phthalate (DBP) and Diethyl phthalate (DEP) were detected in perfumes. None of the phthalates were detected in liquid body lotion.

Diethylhexyl phthalate (DEHP) regulates the proliferation and chemosensitivity of esophageal squamous cell carcinoma cells via regulation of PTEN.

As one of the most prevalent and deadly cancers worldwide, esophageal squamous cell carcinoma (ESCC) can be directly exposed to endocrine-disrupting chemical (EDC). As a potential EDC, diethylhexyl phthalate (DEHP) can trigger the development of various cancers, while the potential effect of DEHP on the ESCC progression was not clear. Our present study revealed that DEHP can trigger the proliferation of ESCC cells and decrease the cisplatin (CDDP) and fluorouracil (5-FU) sensitivity. Mechanistical studies indicated that DEHP can decrease the transcription of PTEN, a well-characterized tumor suppressor, in ESCC cells. Over expression of PTEN can reverse DEHP-regulated ESCC cell proliferation and chemosensitivity. Further, DEHP can increase the expression of HES-1, which can bind with the promoter of PTEN to inhibit its transcription. Collectively, DEHP can increase proliferation while decrease chemosensitivity of ESCC cells via regulation of HES-1/PTEN axis. Further, daily expression of DEHP may be a potent risk factor for ESCC development.

Simple and rapid FTIR spectral data and chemometric analysis based method for evaluation of the quality of Indian Sandalwood oil

ABSTRACT The authentication of Indian Sandalwood oil and the detection of adulterants are issues of increasing importance in the sandalwood oil-based industries such as food, perfumery, cosmetics and aromatherapy industries. In this paper, Fourier-Transform Infrared (FT-IR) spectral data combined with Principal Component Analysis (PCA) and Partial Least Square Regression (PLSR) were used for the authentication of pure and adulterated sandalwood oil. The pure Indian sandalwood oil was extracted by three different methods (i.e. solvent extraction, hydro-distillation and steam distillation) and blended with various proportion of diethyl phthalate (DEP) and diethylhexyl phthalate (DEHP) separately. The pure and adulterated oil samples were evaluated using FTIR-ATR (attenuated total reflection) spectroscopic technique. The results lead to the conclusion that FT-IR spectroscopy with chemometric techniques could be successfully used as a simple, rapid and non-destructive method for the quality assessment of the high-valued Indian Sandalwood oil.

Phthalates leaching from plastic food and pharmaceutical contact materials by FTIR and GC-MS.

Phthalates are often used as plasticizers in the production of plastic food contact materials (FCMs) and pharmaceutical contact materials (PCMs), and having in mind that they are not bound to plastics, phthalates may easily leach from plastics under certain conditions. The aim of this research is determination of phthalates leaching potential from different plastic materials and quantitative determination of 5 phthalates (dimethyl phthalate (DMP), di-n-butyl phthalate (DnBP), benzyl butyl phthalate (BBP), diethyl hexyl phthalate (DEHP), and di-n-octyl phthalate (DOP)) in 44 different plastic articles of 7 different plastic polymers used as FCMs and PCMs by FTIR, GC-MS, and gravimetric methods. The FTIR technique is shown to be rapid method for determination of phthalate content in PVC articles. Comparing of FTIR method with GC-MS and gravimetric showed that separation and quantitative determination of each phthalate separately favor the GC-MS method, because FTIR method determines the total amount of phthalate content. However, the FTIR method is less expensive and demanding in terms of sample preparation, which is suited for use in pre-screening analysis. The results of GC-MS phthalates determination showed that PVC articles used as PCMs contain DEHP in significant amount, from 5.19 to 28.76% by weight and could be a potential risk to human health.

Association between Phthalate Exposure and Frailty among Community-Dwelling Older Adults: A Repeated Panel Data Study.

Only a few studies have examined the impacts of environmental exposure on frailty. This study investigated the association between phthalates and frailty among community-dwelling older adults. The Korean Elderly Environmental Panel II (KEEP II) study is a repeated panel data study of 800 community-dwelling older adults in South Korea. Frailty was measured with five items defined by Fried and colleagues. Environmental pollutants in the form of two types of metabolites for Di-ethylhexyl phthalate (DEHPs)—Mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and Mono (2-ethyl-5-oxohexyl) phthalate (MEOHP)—were obtained from urine specimens. Analyses were performed using repeated linear mixed models. The concentration levels of both MEOHP and MEHHP in urine were significantly higher in the pre-frail or frail group than its counterparts. While adjusting for covariates, MEOHP level was positively associated with the likelihood of being pre-frail or frail in both males and females; the concentration level of MEHHP also had a positive impact on the likelihood of being pre-frail or frail in females. The DEHP metabolite concentrations were significantly lower among adults with daily fruit consumption in both males and females. DEHPs, measured by metabolite concentrations, may increase the risk of frailty among older men and women; further studies are necessary. The preventive effects of nutrition on DEHP risk should also be further investigated.

A mixture of diethylhexyl, diisononyl and dibutyl phthalate decreased anogenital distance, postnatal testosterone levels, and changed social behavior in Wistar rats.

Phthalates are chemicals interfering with the function of testosterone and are suspected to play a role in the emergence of neurodevelopmental diseases. This could be due to interference with brain development for which optimal testosterone levels are essential. We investigated the effect of prenatal and early postnatal exposure to a phthalate mixture on the anogenital distance (AGD), plasma testosterone levels and social behavior in rats. Pregnant rats were exposed to a mixture of diethylhexyl, diisononyl and dibutyl phthalate, each at a dose of 4.5 mg/kg/day, from gestational day 15 to postnatal day 4. A social interaction test was performed to assess sociability in the three ontogenetic stages (weaning, puberty, adulthood). AGD was measured in adulthood to assess changes in prenatal testosterone levels. Plasma testosterone levels were measured in adults by a radioimmunoassay. The total frequency and time of socio-cohesive interactions were decreased in phthalate exposed females in weaning, puberty and adulthood. Phthalate exposed males showed a decrease in the frequency of social interactions in weaning only. Shorter anogenital distance was observed in adult males exposed to phthalates. Decreased testosterone levels were observed in the exposed group in both sexes. Our results suggest that early developmental phthalate exposure may play an important role in the hormonal and behavioral changes associated with several neurodevelopmental diseases.

Seasonal distribution and ecological risks of phthalic acid esters in surface water of Taihu Lake, China

Phthalic acid esters (PAEs) are endocrine-disrupting compounds that are ubiquitous in surface water. However, early studies on PAEs only focused on six species on the priority contaminant list, and the seasonal variation in the PAE distribution in Taihu Lake, China is unclear. The present study investigated the occurrence, spatial distribution, and ecological risks of 16 PAEs in Taihu Lake during the dry, normal, and wet seasons. The results showed that dibutyl phthalate, diethylhexyl phthalate (DEHP), and diisobutyl phthalate (DIBP) were the major species detected in the surface water of Taihu Lake. The summed concentration of the six priority PAEs accounted for less than 50% of the total, indicating that the contamination of the other PAE congeners was non-negligible. Significant seasonal effects were observed that the total PAE concentration was higher in the wet season than in the dry season, and there were significant positive correlations between the total PAE concentration and rainfall, the water reserve, and the water level. In the dry season, a relatively high PAE level was detected in the area close to the inflow river estuary and the tourist island in the lake. The concentrations of PAEs in the lakeshore area were higher than those in the lake center in the normal season, and were generally high in the wet season. DEHP posed high risks for fish regardless of the season, while butyl benzyl phthalate, DIBP, dihexyl phthalate, and diphenyl phthalate also showed high risks in the normal and wet seasons. These results suggest that the contamination and risks of congeners other than the priority PAEs are also of necessary concern, and seasonal variation should be considered for a comprehensive understanding of PAE contamination in surface water.

Linking Diethylhexyl Phthalate (DEHP) to Gestational Diabetes Mellitus (GDM) via Adverse Outcome Pathways Using a Network-Based Approach

Several epidemiologic studies have revealed exposure to diethylhexyl phthalate (DEHP), a ubiquitous endocrine disruptor in the environment, might associate with gestational diabetes mellitus (GDM). However, the studies are few and demonstrated contradictory results. This study aims to investigate the causal relationship between DEHP and GDM using the adverse outcome pathway (AOP) framework, which can combine information from different sources to elucidate causal pathways between chemicals and adverse outcomes. We used a computational approach to construct and validate AOPs from DEHP to GDM based upon information from publicly available databases. Associations of DEHP to genes were extracted from the CTD and CompTox databases, interactions between genes and GDM were obtained from the DisGeNET and MalaCards databases. Based on these data, we developed a DEHP-Gene-Phenotype-GDM network, and then constructed a computational AOP (cAOP) network and verified the tumor necrosis factor (TNF)-initiated cAOP. The results demonstrated that TNF plays a significant role for exposure to DEHP in GDM via downregulating the glucose uptake process. This study illustrates the utility of computational methods in supporting AOP development, and so facilitating a better understanding of the toxic mechanism in the pathogenesis of chemicals on human health.

Modern approaches to infusion therapy in pediatrics and chemotherapy

Background. Systems for intravenous administration of blood products and drugs are divided into the systems for transfusion (pore diameter – 114-200 μm) and systems for infusion (pore diameter – 15-75 μm). Gravity delivery systems consist of a drip chamber, an infusion rate regulator, a needle connector, a system tube, an injection needle, and a system fixation patch.
 Objective. To describe modern approaches and devices for infusion therapy.
 Materials and methods. Analysis of the literature on this issue.
 Results and discussion. If the needle is integrated into a drip chamber, it should contain two channels at different levels: a channel for the drug and an air channel with a built-in antibacterial filter. This is important because air is always considered a non-sterile environment. The use of antibacterial filter systems for injection of drugs into the vial is prohibited. Filter materials are able to absorb on its surface from 10 to 90 % of the drug. In addition, drying of some solutions make the filter impermeable to air. Another important filter in infusion systems is the drip chamber filter, which prevents insoluble particles of the drug, particles of ampoule glass, plastic or rubber stopper from entering the bloodstream. Typical characteristic of infusion from plastic vials is the absence of need for an air needle or opening of the ventilating chamber. During the infusion, air does not enter the vial, so it deforms. On an additional inverted scale you can see the amount of drug infused. The main materials for the systems are polyvinyl chloride, diethylhexyl phthalate, and thermoplastic elastomers. The most modern and safe systems are made of thermoplastic elastomers or neutral polyurethane, however, imperfect cheap systems made of polyvinyl chloride and diethylhexyl phthalate are still widespread in Ukraine. Parenteral uptake of phthalates has antiandrogenic, antiestrogenic, antithyroid, carcinogenic, and mutagenic effects. This increases the risk of reproductive problems, diabetes, obesity. Special care should also be taken when using latex-containing systems, as 3-17 % of inpatients are allergic to latex. Anaphylactic shock can develop even 4 hours after surgery. Ukrainian company “Yuria-Pharm” produces modern phthalate-free systems, including a system for the introduction of light-sensitive solutions. There are also closed non-drop level systems designed for both gravity infusion and use with volumetric infusion pumps of open type. Automatic filling of the system due to the use of a purge filter with a hydrophobic membrane allows to reduce drug losses when filling the system, to reduce the risk of chemical contamination, and significantly save time to fill the system. The nurse also does not have to look for a drain tray when filling the system. The drip system filter with non-drop level function allows not to lose the required fluid level during massive infusion therapy, significantly save the nurse’s time spent on monitoring the fluid level in the vial and refilling the system, reduce the number of “alarm” staff calls, reduce risk and chemical contamination of the vial. In turn, closed systems with a graduated regulator are designed for the infusion of drugs that require accurate dosing and careful rate control throughout the infusion period (Flow Set).
 Conclusions. 1. Systems for intravenous administration are divided into systems for transfusion and systems for infusion. 2. The most modern and safe systems are made of thermoplastic elastomers or neutral polyurethane. 3. There are closed systems with non-drop level, designed for both gravity infusion and the use with volumetric infusion pumps. 4. Closed systems with a graduated regulator are designed for the infusion of drugs that require accurate dosing and careful rate control throughout the infusion period.

Endocrine Disruption: Structural Interactions of Androgen Receptor against Di(2-ethylhexyl) Phthalate and Its Metabolites.

Diethylhexyl phthalate (DEHP) is a commonly used plasticizer in the manufacture of polyvinyl chloride plastics for household and commercial use. DEHP is a ubiquitous ecocontaminant and causes developmental and reproductive problems in children and adults. After exposure, DEHP is metabolized by endogenous hydrolysis and oxidation into the primary metabolite, mono-(2-ethylhexyl) phthalate (MEHP), and the secondary metabolites, mono-(2-ethyl-5-hydroxhexyl)phthalate (5-OH-MEHP), mono-(2-ethyl-5-oxohexyl) phthalate (5-oxo-MEHP), mono-(2-ethyl-5-carboxypentyl) phthalate (5-cx-MEPP), and mono-[(2-carboxymethyl)hexyl] phthalate (2-cx-MMHP). Very few studies have been reported on the adverse effects of DEHP metabolites, and the available information indicates that the metabolites might also be equally or more active as compared to the parent compound. In the present study, induced fit docking was used for structural binding characterization of the above five DEHP metabolites with androgen receptor (AR) to predict the potential endocrine-disrupting effects of these metabolites in AR signaling. All the DEHP metabolites interacted with the ligand-binding pocket of AR forming amino-acid residue interactions, hydrogen bonding, and pi-pi interactions. The binding energy of DEHP with AR was similar to that of native ligand testosterone. The amino-acid residue interactions of DEHP metabolites had 91–100% similarity compared to that of testosterone. In addition, all the DEHP metabolites and testosterone showed a common hydrogen bonding interaction with amino-acid Arg-752 of AR. Taken together, the structural binding data in the present study suggested the potential for DEHP metabolites to disrupt AR signaling, which may lead to androgen-related reproductive dysfunction.