Diethyl phthalate, a plasticizer, induces adipocyte inflammation and apoptosis in mice after long-term dietary administration.

The incidence of metabolic diseases is increasing alarmingly in recent times. Parallel to nutritional excess and sedentary lifestyle, the random usage of several endocrine disrupting chemicals including plasticizers is reported to be closely associated with metabolic diseases. Diethyl phthalate (DEP) is a widely used plasticizer in a host of consumer and daily care products. Adipose tissue plays a central role in energy storage and whole-body metabolism. The impairment of adipose function is critically implicated in the pathogenesis of insulin resistance, diabetes, and related metabolic diseases. Recently, exposure to certain phthalate esters has been linked to the development of obesity and diabetes, although there are contradictions and the mechanisms are not clearly understood. In an effort to ascertain the metabolic consequences of chronic phthalate exposure and the underlying mechanism, the present study was designed to examine the effects of long-term dietary consumption of DEP in adipocytes. DEP-treated mice were hyperglycemic but nonobese; their body weight initially increased which subsequently was reduced compared to control. DEP exposure at lower levels impaired adipogenesis by downregulating the key transcription factor, peroxisome proliferator-activated receptor γ and its downstream insulin-sensitizing adipokine, adiponectin, thereby severely compromising adipocyte function. The activation of master regulator nuclear factor κB led to rise in proinflammatory cytokines. We found that DEP triggered intrinsic apoptotic pathways through activated cytochrome c-Apaf1-caspase 9-caspase 3 axis in adipocytes. Taken together, our data revealed that chronic administration of dietary DEP could unleash adverse metabolic outcomes by initiating oxidative stress, inflammation, and apoptosis in the adipocytes, thus leading to adipose tissue dysfunction.

Vanillic acid ameliorates diethyl phthalate and bisphenol S-induced oxidative stress and neuroinflammation in the hippocampus of experimental rats.

Long-term adverse effects on human health are caused by exogenous compounds that alter the functions of biological systems, especially neuroendocrine disruptors like diethyl phthalate (DEP) and bisphenol S (BPS). Although vanillic acid (VA) has pertinent neuropharmacological characteristics, its effect against DEP + BPS-induced neurotoxicity has not been explored. This study proposed that VA may offer protection against the neurotoxicity caused by DEP + BPS. Thirty male Wistar rats were randomly distributed across five groups: a control group receiving DMSO, a group exposed to a mixture of BPS and DEP, two BPS + DEP-exposed groups treated with VA at doses of 25 mg/kg or 50 mg/kg, and a nonexposed group treated with 50 mg VA/kg. After 21 days, the hippocampal tissues were processed for biochemical analyses. Our results indicate that exposure to DEP + BPS upregulated neurosignaling mediators (NTPDase, ADA, MAO-A, and Ca2+), inhibited others (AChE and Ca2+/Mg2+-ATPase), decreased hippocampus antioxidants (GSH, GPx, CAT, and SOD), and elevated markers of oxidative stress/damage (NO, H2O2, MDA, and AOPP). AR, BAX, TNF-α, BAK1, and IL-1ß expressions were upregulated, while IL-10 and BDNF expressions were downregulated. NF-κB and caspase-3/9 pathways were also upregulated. Co-treatment with vanillic acid remarkably precluded these neurotoxic outcomes by improving neurosignaling, augmenting antioxidant status, abrogating oxidative damage, inflammation (TNF-α, IL-1ß), and apoptosis (BAX, BAK1, caspase-3/9). Vanillic acid also restored IL-10 and BDNF levels, thereby exhibiting neuroprotective effects, corroborated by histological examinations. We posit vanillic acid as a safe and effective therapeutic agent against neurotoxicity occasioned by exposure to neuroendocrine disruptors.

Synthesis and functional mechanism evaluation of novel polymer-graphene oxide-biochar nanocomposite for efficient removal of diethyl phthalate.

Phthalates, categorized as a main constituent of endocrine-disrupting chemicals (EDCs), are present in polymeric products. These substances can enter the environment through several pathways, including improper handling, which leads to their presence in toilet water, floor washings, surface runoff, and landfill leachate. This study focuses on the performance analysis of nanocomposite materials made of polymer (polypyrrole), quasi-metal (graphene oxide), and biochar (from palmyra seed) for the elimination of diethyl phthalates (DEP) from aqueous environments. Scanning electron microscope (SEM), X-ray diffraction (XRD), and Fourier-transform infrared spectroscopy (FTIR) were used to describe the nanocomposite characteristics. The experimental results supported a chemisorption process by agreeing well with the pseudo-second order. The Langmuir isotherm explained the DEP sorption data, which aligned to monolayer DEP adsorption on the nanocomposite surface. With a binding affinity of -13.36 (kcal/mol) and the highest docking score, Diethyl phthalates and graphene oxide interaction is validated. The produced nanocomposite is suggested as a possible alternative for the sorption of DEP. Future applications could benefit from the higher adsorption capacity, and environmental friendliness of nanocomposites.

Fabrication of novel glutathione-Fe3O4-loaded/activated carbon encapsulated sand bionanocomposites for enhanced removal of diethyl phthalate from aqueous environment in a vertical flow reactor.

The extensive use of plasticizers in various industries has made Diethyl phthalate (DEP), a serious threat to the environment and ecological water security, owing to its complex-structure and low-biodegradability. Thus, the present study aimed to design a sustainable sand-coated nano glutathione (GSH) -Fe3O4-loaded/activated carbon (AC) bionanocomposite (AC-GSH-Fe3O4@sand bionanocomposite) for effective removal of DEP from water. Characterization results suggested bionanocomposites' rough and irregular texture due to the uneven distribution of AC and Fe3O4 nanoparticles over the sand. The XRD spectra indicated high crystallinity of bionanocomposites, while the FTIR spectra confirmed the presence of all individual components, i.e., GSH, AC, Fe3O4, and sand. EDX-mapping, AFM, and TGA further verified its elemental composition, topographical changes and thermal stability. The influence of pH (3, 7, 9), bed height (2, 4, 6) cm, and flow rate (2.5, 3.5, 4.5) mL min-1 were studied in a dynamic system with an initial DEP concentration of 50 mg L-1 to investigate the removal behavior of the bionanocomposites. The best DEP removal efficiency (90.18 %) was achieved over 28-h at pH 9, bed-height-4 cm, and flow-rate-3.5 mL min-1, with an optimum qmax-200.25 mg g-1 as determined through Thomas-model. Breakthrough curves were predicted using various column models, and the corresponding parameters essential for column-reactor process design were calculated. The high reusability up to the 10th cycle (≥83.32%) and the effective treatment in complex matrices (tap-water: 90.11 %, river-water: 89.72 %, wastewater: 83.83%) demonstrated bionanocomposites' prominent sustainability. Additionally, the production cost at 6.64 USD per Kg, underscores its potentiality for industrial application. Phytotoxicity assessment on mung-bean revealed better root (5.02 ± 0.27 cm) and shoot (17.64 ± 0.35 cm) growth in the bionanocomposite-treated DEP samples over the untreated samples. Thus, AC-GSH-Fe3O4@sand bionanocomposites could be considered a highly-sustainable, low-cost technique for the effective removal of DEP and other phthalate-esters from contaminated matrices.

High concentrations of phthalates affect the early development of the sea urchin Paracentrotus lividus.

The toxicity of three phthalates (PAEs) - butylbenzyl phthalate (BBP), diethyl phthalate (DEP), and di-(2-ethylhexyl) phthalate (DEHP) - was tested on the Mediterranean sea urchin Paracentrotus lividus. Fertilized eggs were exposed to environmental and high PAE concentrations for 72 h. The potential toxic effects on larval development and any morphological anomalies were then assessed to estimate PAEs impact. Environmental concentrations never affected development, while high concentrations induced toxic effects in larvae exposed to BBP (EC50: 2.9 ×103 µg/L) and DEHP (EC50: 3.72 ×103 µg/L). High concentrations caused skeletal anomalies, with a slight to moderate impact for DEP/DEHP and BBP, respectively. PAE toxicity was: BBP>DEHP>DEP. In conclusion, the three PAEs at environmental concentrations do not pose a risk to sea urchins. However, PAE concentrations should be further monitored in order not to constitute a concern to marine species, especially at their early developmental stages.

A newly-constructed technology to remove and recover diethyl phthalate from wastewater by using the instant plasticization assembly ability of PVC.

Diethyl phthalate (DEP) is a typical environmentally organic pollutant, widely used in the production process of polyvinyl chloride (PVC) to improve the flexibility of plastic materials. Its interaction with living organisms can inflict considerable harm to reproductive system functions. This research aims to utilize tetrahydrofuran (THF) to selectively break the chemical bonds in PVC molecules to provide more adsorption sites. Then incorporates the plasticizing assembly process of PVC to instantly remove and recover DEP from wastewater, achieving waste utilization, and sustainable environmental development. The research found that PTFR with a concentration of around 75 mg/L shows the best DEP removal efficiency. Sequencing batch processing removes more DEP compared to direct processing under the same material usage conditions. Furthermore, the recovery rate of DEP can reach over 90%. The technology demonstrates notable enhancements in removal efficiency and adsorption duration when compared to conventional adsorption techniques. This research has established an instant and efficient method for DEP removal, providing a new idea and technology for plasticizer treatment in practical wastewater.

Fluorescence Signal Amplification: Red Carbon Dots@SiO2-Induced Ultra-sensitive Immunoassay for Diethyl Phthalate.

Carbon dots as new nanomaterials, have been widely used in rapid detection because of their nondestructive, real-time detection characteristics. Improving the sensitivity and selectivity of the method in complex real samples is new challenge and requirement for sensing technology. Here, we report an ultrasensitive fluorescence immunoassay (FIA) for trace diethyl phthalate (DEP) using red carbon dots@SiO2 (R-CDs@SiO2) as tags. SiO2 as a nanocarrier can effectively improve the bio-functionalization and utilization rate of carbon dots. Moreover, several R-CDs embedded in SiO2 nanospheres can magnify the fluorescence signal and improve sensitivity. R-CDs@SiO2 conjugate anti-DEP antibody (Ab) as fluorescent immunosensor, which can specifically recognize DEP. Under optimization conditions, the detection limit (LOD) of this FIA was calculated as 0.0011 ng/mL. In addition, the recoveries of this established FIA ranged from 96.8 to 108.5%, showing satisfactory accuracy. Compared with GC-MS/MS (LOD µg/mL), the sensitivity of the FIA was significantly improved. As a result, the FIA developed using R-CDs@SiO2 as tags has a high potential for determining trace DEP.

Contamination and ecological risk of microplastics and phthalates in the surface water of the Tha Dee Sub-River basin, Nakhon Si Thammarat Province, Thailand.

Plastic waste has become a significant source of water pollution worldwide, releasing microplastics (MPs) and hazardous chemicals into aquatic environments. The purpose of this study was to determine the occurrence and ecological risk of MPs and phthalates (PAEs) in the surface water of the Tha Dee Sub-River basin in Nakhon Si Thammarat Province, Thailand. MPs, PAEs, and water quality parameters, including turbidity, pH, conductivity, dissolved oxygen, and salinity, were investigated simultaneously at 26 sampling stations. The average number of MPs per liter was 0.5 ± 0.4. Filaments were the most common MPs (59%), and transparent/white was the most prevalent color (51%). Four PAEs were found, with an average total concentration of 25.78 ± 93.87 µg/L, and diethyl phthalate was observed in the highest concentrations. Although there was no association between PAEs and other parameters, there was a significant correlation among particular PAEs (P < 0.05), indicating that they came from the same source. The pollution load index of MPs indicated a minor risk, but PAEs posed a medium risk to fish in the study area. This study's findings suggest that further research into the sources of PAEs and their contamination of aquatic life is needed.

Inhibition of biofilm formation and quorum sensing mediated virulence in Pseudomonas aeruginosa by marine sponge symbiont Brevibacterium casei strain Alu 1.

The alternative antimicrobial strategies that mitigate the threat of antibiotic resistance is the quorum-sensing inhibition (QSI) mechanism, which targets autoinducer dependent virulence gene expression in bacterial pathogens. N-acyl homoserine lactone (AHL) acts as a key regulator in the production of virulence factors and biofilm formation in Pseudomonas aeruginosa PAO1 and violacein pigment production in Chromobacterium violaceum ATCC 12472. In the present study, the marine sponge Haliclona fibulata symbiont Brevibacterium casei strain Alu 1 showed potential QSI activity in a concentration-dependent manner (0.5-2% v/v) against the N-acyl homoserine lactone (AHL)-mediated violacein production in C. violaceum (75-95%), and biofilm formation (53-96%), protease (27-82%), pyocyanin (82-95%) and pyoverdin (29-38%) productions in P. aeruginosa. Further, the microscopic analyses validated the antibiofilm activity of the cell-free culture supernatant (CFCS) of B. casei against P. aeruginosa. Subsequently, the biofilm and pyoverdin inhibitory efficacy of the ethyl acetate extract of B. casei CFCS was assessed against P. aeruginosa. Further, the gas chromatography-mass spectrometry (GC-MS) analysis revealed the presence of variety of components in which diethyl phthalate was found to be a major active component. This phthalate ester, known as diethyl ester of phthalic acid, could act as a potential therapeutic agent for preventing bacterial biofilm and virulence associated infectious diseases.

Associations of dermal diethyl phthalate level with changes in lung function test value mediated by absolute eosinophil count: A panel study of adults in southern Taiwan.

Phthalate concentrations in indoor and outdoor dust are associated with respiratory disease. Both immunoglobulin E (IgE) and eosinophil count are associated with airway inflammation from exposure to environmental allergens. Dermal phthalate level can be used as a matrix for assessing personal exposure through direct absorption from the air, particle deposition, or contact with contaminated products. However, the association between dermal phthalate level and changes in lung function test values, as mediated by immunological response, remains unclear. In total, 237 adults in southern Taiwan were recruited. Spirometry measurements (in L) of forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were taken on visits 1 (2016-2018) and 2 (2019). Dermal phthalate level, absolute eosinophil count, and IgE level were recorded on visit 1. Mean changes in FVC and FEV1 decrease pear year, as determined through pairwise comparisons, were significant (diffFVCper year: -0.46, 95% CI: -0.51, -0.41; p < 0.001; diffFEV1per year: -0.37, 95% confidence interval [CI]: -0.41, -0.34; p < 0.001). For FEV1 decrease, log-unit increases in dermal diethyl phthalate (DEP) were positively associated with diffFEV1per year (ß = 0.096; 95% CI: 0.042, 0.150; p = 0.001) and negatively associated with absolute eosinophil count (ß= -0.201; 95% CI: -0.380, -0.023; p= 0.027). Log-unit increases in absolute eosinophil count were negatively associated with diffFEV1per year (ß= -0.109; 95% CI: -0.150, -0.068; p < 0.001). Absolute eosinophil count mediated 19.70% of the association between dermal DEP level and diffFEV1per year. For FVC decrease, log-unit increases in dermal DEP were positively associated with diffFVCper year (ß = 0.095; 95% CI: 0.035, 0.155; p = 0.002) and negatively associated with absolute eosinophil count (ß = -0.243; 95% CI: -0.427, -0.060; p = 0.010). Log-unit increases in absolute eosinophil count were negatively associated with diffFVCper year (ß= -0.122; 95% CI: -0.168, -0.076; p < 0.001). Absolute eosinophil count mediated 29.98% of the association between dermal DEP level and diffFVCper year. The results suggest that dermal DEP level is positively associated with changes in lung function test values and is mediated by absolute eosinophil count.

Risk assessment for humans using physiologically based pharmacokinetic model of diethyl phthalate and its major metabolite, monoethyl phthalate.

Diethyl phthalate (DEP) belongs to phthalates with short alkyl chains. It is a substance frequently used to make various products. Thus, humans are widely exposed to DEP from the surrounding environment such as food, soil, air, and water. As previously reported in many studies, DEP is an endocrine disruptor with reproductive toxicity. Monoethyl phthalate (MEP), a major metabolite of DEP in vivo, is a biomarker for DEP exposure assessment. It is also an endocrine disruptor with reproductive toxicity, similar to DEP. However, toxicokinetic studies on both MEP and DEP have not been reported in detail yet. Therefore, the objective of this study was to evaluate and develop physiologically based pharmacokinetic (PBPK) model for both DEP and MEP in rats and extend this to human risk assessment based on human exposure. This study was conducted in vivo after intravenous or oral administration of DEP into female (2 mg/kg dose) and male (0.1-10 mg/kg dose) rats. Biological samples consisted of urine, plasma, and 11 different tissues. These samples were analyzed using UPLC-ESI-MS/MS method. For DEP, the tissue to plasma partition coefficient was the highest in the kidney, followed by that in the liver. For MEP, the tissue to plasma partition coefficient was the highest in the liver. It was less than unity in all other tissues. Plasma, urine, and fecal samples were also obtained after IV administration of MEP (10 mg/kg dose) to male rats. All results were reflected in a model developed in this study, including in vivo conversion from DEP to MEP. Predicted concentrations of DEP and MEP in rat urine, plasma, and tissue samples using the developed PBPK model fitted well with observed values. We then extrapolated the PBPK model in rats to a human PBPK model of DEP and MEP based on human physiological parameters. Reference dose of 0.63 mg/kg/day (or 0.18 mg/kg/day) for DEP and external doses of 0.246 µg/kg/day (pregnant), 0.193 µg/kg/day (fetus), 1.005-1.253 µg/kg/day (adults), 0.356-0.376 µg/kg/day (adolescents), and 0.595-0.603 µg/kg/day (children) for DEP for human risk assessment were estimated using Korean biomonitoring values. Our study provides valuable insight into human health risk assessment regarding DEP exposure.

The Genome Analysis of Methylobacterium populi YC-XJ1 with Diverse Xenobiotics Biodegrading Capacity and Degradation Characteristics of Related Hydrolase.

Methylobacterium populi YC-XJ1 isolated from desert soil exhibited a diverse degrading ability towards aromatic oxyphenoxypropionic acid esters (AOPPs) herbicide, phthalate esters (PAEs), organophosphorus flame retardants (OPFRs), chlorpyrifos and phoxim. The genome of YC-XJ1 was sequenced and analyzed systematically. YC-XJ1 contained a large number of exogenous compounds degradation pathways and hydrolase resources. The quizalofop-p-ethyl (QPE) degrading gene qpeh2 and diethyl phthalate (DEP) degrading gene deph1 were cloned and expressed. The characteristics of corresponding hydrolases were investigated. The specific activity of recombinant QPEH2 was 0.1 ± 0.02 U mg-1 for QPE with kcat/Km values of 1.8 ± 0.016 (mM-1·s-1). The specific activity of recombinant DEPH1 was 0.1 ± 0.02 U mg-1 for DEP with kcat/Km values of 0.8 ± 0.02 (mM-1·s-1). This work systematically illuminated the metabolic versatility of strain YC-XJ1 via the combination of genomics analysis and laboratory experiments. These results suggested that strain YC-XJ1 with diverse xenobiotics biodegrading capacity was a promising candidate for the bioremediation of polluted sites.

Exposure to phthalate-containing prescription drugs and the risk of colorectal adenocarcinoma: A Danish nationwide case-control study.

PURPOSE: Some drug products contain phthalates as excipients, and in vitro studies have demonstrated that phthalates interfere with cellular mechanisms involved in colorectal cancer development. We therefore examined the association between cumulative phthalate exposure from drug products and risk of colorectal adenocarcinomas. METHODS: We used the Danish Cancer Registry to identify all patients with incident colorectal adenocarcinoma from 2008 to 2015 (n = 25 814). Each cancer case was matched to ten population controls. Linking information from Danish registers, we quantified cumulative phthalate exposure to the ortho-phthalates diethyl phthalate (DEP) and dibutyl phthalate (DBP) as well as enteric phthalate polymers from orally administered drugs. The association between cumulative phthalate exposure and colorectal cancer was estimated using conditional logistic regression. RESULTS: Cumulative exposure to ortho-phthalates exceeding 500 mg was associated with lower odds of colorectal cancer diagnosis (ORadj  = 0.89; 95% CI, 0.81-0.96). Similar associations were observed for all DEP exposure exceeding 500 mg. Subgroup analysis excluding NSAID users, demonstrated that ortho-phthalate exposure was positively associated with colorectal cancer (ORadj  = 1.26; 95% CI, 1.05-1.51). CONCLUSION: We found an apparent overall protective effect of cumulative phthalate exposure from drug excipients for colorectal adenocarcinoma. Omitting NSAID users reversed the signal and suggested a slightly increased risk associated with high cumulative ortho-phthalate exposure.

Use of dietary supplements in relation to urinary phthalate metabolite concentrations: Results from the National Health and Nutrition Examination Survey.

BACKGROUND: Research suggests that dietary supplements may be a source of exposure to phthalates, given that diethyl phthalate (DEP) or di-n-butyl phthalate (DBP) can be components of coatings that facilitate extended release or encapsulate dietary supplements. METHODS: Using nationally representative data on a population of 12,281 adults ages 20 y + surveyed between 1999 and 2014 from the National Health and Nutrition Examination Survey (NHANES), we evaluated the association between dietary supplement use in relation to urinary phthalate metabolites of DEP (monoethyl phthalate, MEP) and DBP (mono-n-butyl phthalate, MBP). We examined associations pertaining to regular use of multivitamin/multimineral (MVMM) supplements, as well as regular use of any other non-MVMM supplement products, the number of non-MVMM supplement products used, as well as individual supplements potentially containing phthalates (exclusive of MVMM). For each urinary phthalate metabolite, results are presented as the minimally-adjusted and multivariable-adjusted ratio, comparing the geometric mean among users to non-users. RESULTS: In multivariable models, we observed a significant positive association between regular use of MVMM use and MEP, with persons using MVMM supplements having 11% higher geometric mean MEP than non-users (Ratio: 1.11; 95% CI: 1.04-1.20); no association was observed for MVMM in relation to MBP. No other significant multivariable-adjusted associations were observed, although power was limited in analyses of individual supplements. Associations did not markedly vary by gender; however, the associations of garlic supplement use with MEP and MBP varied by calendar time, with statistically significant positive associations observed in later years. CONCLUSIONS: A modest significant association was observed between MVMM use and MEP. No other significant associations were observed in our overall multivariable models. Follow-up on the positive association observed between garlic and urinary phthalate metabolite concentrations observed in later years in a well-powered, prospective study would further clarify study findings.

Analysis of phthalate esters in two different baby care products available in United Arab Emirates.

Phthalates are used as plasticizers in a wide range of products and are known to affect the human health adversely. Hence, the present study was carried out to identify and quantify the presence of four phthalates namely dimethyl phthalate (DMP), dibutyl phthalate (DBP), and diethyl phthalate (DEP), di (2-ethylhexyl) phthalate (DEHP) in the two baby products i.e. baby oils and baby lotions. The daily exposure levels and hazard index of each phthalate were also calculated. It was an analytical study where two different brands of samples of baby oil and baby lotion each, from the date of manufacturing of 3, 10, and 20 months were collected. The extraction of phthalates from different samples was done and analyzed using HPTLC. Results showed the presence of all four phthalates, although some phthalates were not present in 3 M samples. The maximum concentration of all the phthalates was found in 20 M samples. Their concentration increased with the storage time indicating the possibility of leaching and migration of phthalates from the container into the product. The hazard indices for phthalates estimated for baby oil and baby lotion were found below 1, which denotes that the daily phthalate exposures are within the regulatory limits. It is important to consider that the exposure to phthalates can occur not only by dermal contact of these baby products but also through other routes. Hence, the study signifies the importance of phthalates concentration in such regularly used products.

Effects of iron (hydr)oxides on the degradation of diethyl phthalate ester in heterogeneous (photo)-Fenton reactions.

This work studied the structural effects of hematite (α-Fe2O3), 2-line ferrihydrite (HFO) and goethite (α-FeOOH) on diethyl phthalate ester (DEP) degradation. The results showed that the degradation of DEP was faster under 365 nm light irradiation than in the dark in the presence of iron (hydr)oxides. The apparent kinetic rates of DEP degradation followed the order HFO > goethite ≈ hematite in the dark and HFO > hematite > goethite under 365 nm light irradiation. Two pathways governed H2O2 decomposition efficiency on iron (hydr)oxide surfaces: (1) forming OH on inherent surface hydroxyl groups (Fe-OH) and (2) producing O2 and H2O on the surface oxygen vacancies. X-ray photoelectron spectroscopy (XPS) analyses indicated that HFO not only has high Fe-OH content but also has high Vo content, resulting in its low H2O2 utilization efficiency (η). DEP was degraded through hydrogen abstraction and de-esterification, and the major products were (OH)2-DEP, mono-ethyl phthalate (MEP), OH-MEP, and phthalate acid (PA). The study is important in understanding the transformation of phthalate esters in top surface soils and surface waters under ultraviolet light.

[Effects of phthalate on pulmonary allergy of offspring during intrauterin and lactating exposure].

OBJECTIVE: To investigate the effects of exposure to diethyl phthalate(DEHP) during pregnancy and lactation in respiratory allergy of offspring Wistar rats. METHODS: To establish the maternal DEHP exposure model: 36 healthy 2-month-old female Wistar rats were divided into three different dose groups. From GD0, each group of pregnant mice were given different concentrations of DEHP(0, 30, 300 mg/(kg·d)) until to the newborn weaning(PND21). After birth, one of offspring was selected from each cage in different dose groups. At PND21 and PND28 the offspring were sensitized by intraperitoneal injection(i. p. ) OVA and continuous nasal sensitization at PND32, PND33, PND34. Bronchoalveolar lavage fluid(BALF) and lung tissue were collected at PND35 with non-sensitized groups. ELISA detected the secretion of Th2 cytokine interleukin(IL)-4, IL-5 and IL-13 in BALF, and the pathological changes of allergic inflammation in lung tissues were observed by HE and PAS staining. Expression of epithelium-derived factor IL-33 detected by immunohistochemistry. RESULTS: In BALF, compared with the control group, the total number of inflammatory cells and eosinophils in the DEHP0+OVA group increased to(131. 500±25. 548)×10~4, (32. 000±10. 079)×10~4(P<0. 05); The total number of inflammatory cells and eosinophils in the DEHP30+OVA group increased to(156. 167±17. 994)×10~4, (16. 331±6. 667)×10~4(P<0. 05); and the total number of inflammatory cells and eosinophils in the DEHP300+OVA group increased to(172. 167±19. 994)×10~4, (55. 000±17. 018)×10~4(P<0. 05). After adding different doses of DEHP and OVA, compared with the control group, The expression levels of IL-4, IL-5, IL-13 in DEHP0+OVA group increased to(38. 401±6. 594) pg/mL(P>0. 05), (30. 026±2. 756) pg/mL(P<0. 05), (13. 806±4. 355) pg/mL(P<0. 05); The expression levels of IL-4, IL-5 and IL-13 in DEHP30+OVA group increased to(57. 733±7. 293) pg/mL(P<0. 05) and(31. 544±1. 043) pg/mL(P>0. 05), (18. 068±1. 497) pg/mL(P<0. 05); The expression levels of IL-4, IL-5 and IL-13 in DEHP300+OVA group increased to(54. 943±6. 049) pg/mL(P>0. 05) and(32. 377±3. 739)pg/mL(P>0. 05), (20. 168±0. 939) pg/mL(P<0. 05), respectively. The tissue section of all the DEHP+saline groups could be observed that no obvious allergic inflammatory reaction, meanwhile all the DEHP+OVA groups had a relatively obvious allergic reaction and were severe with the increase of DEHP dose. Immunohistochemistry showed no significant increase in the expression of IL-33 in the DEHP+saline groups, while the expression of IL-33 in the DEHP+OVA groups increased with a certain dose response. CONCLUSION: Exposure to DEHP during pregnancy and lactation will aggravate the sensitization reaction of offspring, the possible mechanism that DEHP increase the Th2 type of immune response may be the overexpression of IL-33 in the epithelial cells.

Peculiar effect of polyethylene glycol in comparison with triethyl citrate or diethyl phthalate on properties of ethyl cellulose microcapsules containing propranolol hydrochloride in process of emulsion-solvent evaporation.

Plasticizers play a crucial role in various process of microencapsulation. In this study, the effect of incorporation of plasticizer in process of emulsion solvent evaporation was investigated on properties of ethyl cellulose (EC) microcapsules containing propranolol hydrochloride. The effect of plasticizer type and concentration were investigated on characteristics of microcapsules prepared from different viscosity grades of EC. Product yield, encapsulation efficiency, mean particle size, shape, surface characteristics, solid state of drug, and drug release profiles were evaluated. Product yield and encapsulation efficiency were not dependent on plasticizer type and concentration. However, encapsulation efficiency decreased with increase in EC viscosity grade in the most of the cases. The mean particle size was in the range of 724-797 µm and was not dependent on plasticizer type. Microcapsules formed in the presence of PEG had a very smooth surface with few pores. XRD and DSC studies revealed a reduction of drug crystallinity after microencapsulation especially in presence of PEG. The results showed that the presence of TEC and DEP with different concentrations had no marked effect on drug release from microcapsules containing different viscosity grades of EC. This was not the case when PEG was used, and despite its water solubility it reduced the drug release rate noticeably. The reduction in the drug release in the presence of PEG was concentration-dependent. The use of PEG as a plasticizer in process of emulsion solvent evaporation highly improved the EC microcapsule structure and retarded the drug release rate and therefore is recommended.

[Determination of diethyl phthalate in the air of workplace by gas chromatography].

Objective: To establish a method for the determination of diethyl phthalate by gas chromatography in the air of workplaces. Methods: Diethyl phthalate in the air of workplace was collected throµgh glass fiber filter, eluted with methylbenzene, and detected by gas chromatography coupled with FID detectors. Results: The linear range of diethyl phthalate determined by this method was 14.0~1 400 µg/ml, y=2.09801x-3.66229, and the coefficient correlation was 0.999 99. The detection limit was 1.10 µg/ml, and the minimum detection concentration was 0.18mg/m(3) (collected sample volume was 30 L) . The within-run precisions were 1.04%~2.75%, and the between-run precisions were 0.34%~1.30%. The recovery rates were 98.72%~103.21%, and sampling efficiency was 97.2%~100.0%. The elution efficiencies were 97.25%~98.68%. The samples could be stored at room temperature for 15 days. Conclusion: The indicators established in this study were conformed with the requirements of GBZ/T210.4-2008, "The Guidelines for the Development of Occupational Hygiene Standards Methods Part 4: Determination of Chemical Substances in the Air of Workplaces" . Diethyl phthalate in the workplace air could be rapidly collected, accurate separated and determinated. This method is applicable to the determination of diethyl phthalate in the workplace air.

Migration of phthalates on culture plates - an important challenge to consider for in vitro studies.

Phthalates are endocrine disruptors of the reproductive system and suspected to influence many other organ and hormone systems. They are also semi-volatile organic compounds present in the gas phase in the environment. Their mode of action has been investigated in numerous in vitro studies. Multi-well culture plates are typically used to study phthalates in cell cultures. In a pilot study, we observed evidence of phthalate migration in 24-well culture plates. As this has not previously been described, we investigated the phenomenon in more detail. Primary human thyroid epithelial cell cultures (n = 8 cultures) were exposed to either di-ethyl phthalate (DEP), di-n-butyl phthalate (DnBP), mono-n-butyl phthalate (MnBP) or di-(2-ethylhexyl) phthalate (DEHP). Measurement of phthalate metabolites by mass spectrometry demonstrated that the short-branched DEP was able to migrate to adjacent wells when added to cell culture plates. DnBP also seemed to be able to migrate, unlike the long-branched DEHP or the monoester MnBP which did not seem to have this ability. High background levels of phthalate metabolites were also observed, which might compromise results from low dose phthalate studies. In conclusion, the migration of phthalates which is probably caused by their volatile properties might lead to false interpretation of study results.