ABSTRACT
The work explored the DEHP migration parameters in PVC infusion in clinic,based on the previous research on the test model of DEHP migrated from PVC infusion,to assess the safety of PVC infusion.The leaching solution samples in different conditions were evaluated by analysis of the DEHP in leaching solution using GC-MS under simulated clinical transfusion way.The release behavior of DEHP was significantly affected by the storage time,storage temperature,surrounding temperature,dripping speed,sterilization process,volume of the leaching solution,and the property of the leaching solution.
Subject(s)
Diethylhexyl Phthalate , Pharmacokinetics , Gas Chromatography-Mass Spectrometry , Plasticizers , Pharmacokinetics , Polyvinyl Chloride , Pharmacokinetics , TemperatureABSTRACT
OBJECTIVE@#Previous studies have indicated that the plasticizer di (2-ethylhexyl) phthalate (DEHP) affects lipid accumulation; however, its underlying mechanism remains unclear. We aim to clarify the effect of DEHP on lipid metabolism and the role of TYK2/STAT1 and autophagy.@*METHODS@#In total, 160 Wistar rats were exposed to DEHP [0, 5, 50, 500 mg/(kg•d)] for 8 weeks. Lipid levels, as well as mRNA and protein levels of TYK2, STAT1, PPARγ, AOX, FAS, LPL, and LC3 were detected.@*RESULTS@#The results indicate that DEHP exposure may lead to increased weight gain and altered serum lipids. We observed that DEHP exposure affected liver parenchyma and increased the volume or number of fat cells. In adipose tissue, decreased TYK2 and STAT1 promoted the expression of PPARγ and FAS. The mRNA and protein expression of LC3 in 50 and 500 mg/(kg•d) groups was increased significantly. In the liver, TYK2 and STAT1 increased compensatorily; however, the expression of FAS and AOX increased, while LPL expression decreased. Joint exposure to both a high-fat diet and DEHP led to complete disorder of lipid metabolism.@*CONCLUSION@#It is suggested that DEHP induces lipid metabolism disorder by regulating TYK2/STAT1. Autophagy may play a potential role in this process as well. High-fat diet, in combination with DEHP exposure, may jointly have an effect on lipid metabolism disorder.
Subject(s)
Animals , Female , Male , Adipose Tissue , Metabolism , Autophagy , Body Weight , Diet, High-Fat , Diethylhexyl Phthalate , Toxicity , Endocrine Disruptors , Toxicity , Lipid Metabolism , Lipid Metabolism Disorders , Liver , Metabolism , Rats, Wistar , STAT1 Transcription Factor , Metabolism , TYK2 Kinase , MetabolismABSTRACT
Phthalate derivatives cause a number of risks to human health and the environment. Essential oil and volatile fractions of some vegetables and herbal products were extracted by hydrodistillation and percolation methods to analyze using gas chromatography and mass spectrometry (GC-MS) for evaluation of phthalate contaminations. The results revealed that four vegetables and all aromatic waters were contaminated by phthalate derivatives including di-n-butyl phthalate (DBP), diisobutyl phthalate and di-(2-ethylhexyl) phthalate (DEHP) (0.1-7.95%). Butylated hydroxytoluene (BHT), a widely used synthetic antioxidant, was also found in the most of the aromatic waters in the range of 3.15-61.3%. In addition, three vegetable samples contained diazinon (0.36-4.61%), an organophosphorus insecticide. Plants and herbal preparations may be contaminated by the absorption of phthalates from contaminated water or soil or by the migration of phthalates from inexpensive recycled plastic. Regarding the widespread use and associated health risks of phthalates, effective quality and safety regulations for herbal products should be implemented with respect to their phthalate content.
Los derivados de ftalato causan una serie de riesgos para la salud humana y el medio ambiente. El aceite esencial y las fracciones volaÌtiles de algunos vegetales y productos a base de hierbas fueron extraiÌdos mediante hidrodestilacioÌn y meÌtodos de percolacioÌn y luego fueron analizados mediante cromatografiÌa de gases y espectrometriÌa de masas (GC-MS) con el propoÌsito de identificar contaminacioÌn con ftalatos. Los resultados revelaron que cuatro productos herbales y todas las aguas aromaÌticas analizadas estaban contaminadas con derivados de ftalato, incluyendo el ftalato de dibutulo (DBP), ftalato de diisobutilo y ftalato de bis(2-etilhexilo) (DEHP) (0.1-7.95%). El butilhidroxitolueno (BHT), un antioxidante sinteÌtico ampliamente utilizado, tambieÌn se encontroÌ en aguas aromaÌticas en el rango de 3.15- 61.3%. AdemaÌs, tres muestras vegetales conteniÌan diazinoÌn (0.36-4.61%), un insecticida organofosforado. Las plantas y las preparaciones herbales pueden ser contaminadas a partir de absorcioÌn de ftalatos del agua o el suelo contaminados o por la migracioÌn de ftalatos desde plaÌstico reciclado de bajo costo. Con respecto al uso generalizado y los riesgos asociados a la salud de los ftalatos, deben implementarse normas efectivas de calidad y seguridad para los productos a base de hierbas con respecto a su contenido de ftalato.
Subject(s)
Phthalic Acids/analysis , Water Pollutants, Chemical/analysis , Oils, Volatile/chemistry , Plant Preparations/chemistry , Gas Chromatography-Mass SpectrometryABSTRACT
As we all know, DEHP is seriously harmful to human health and consequently has been acquired critical attention. DEHP is able to migrate from PVC medical devices for the non-chemically bound to PVC, thus contact with user and patient. The DEHP migration is influenced by various parameters. In order to assess the security of PVC-tubes medical devices scientifically of DEHP migration, we develop an experimental model by analyzing the parameters comprehensively and systematically, taking into account the clinical practices. For example, assessing the security of DEHP migration from infusion sets by utilizing this model.
Subject(s)
Humans , Diethylhexyl Phthalate , Equipment and Supplies , Models, Theoretical , Plasticizers , Polyvinyl ChlorideABSTRACT
DEHP is largely used in soft PVC products as the plasticizer, which is also widely applied in medical devices. Due to its potential and widespread toxicity and medical devices' specific use, the safety of DEHP's application in medical devices has received extensive attention. In this paper, a comprehensive review of the application and potential toxicity of DEHP in PVC medical devices is made on the basis of the research results all over the world. Besides, the safety evaluation in medical devices is discussed and some possible coping strategies are explored.
Subject(s)
Diethylhexyl Phthalate , Equipment Safety , Equipment and Supplies , Plasticizers , Polyvinyl ChlorideABSTRACT
Phthalates widely used in the manufacture of plastics have deeply penetrated into our everyday lives. Recently, a concern over the toxicity of phthalates on thyroid, has been raised but in most of cases, the doses employed were unrealistically high. To investigate the effects of phthalates on thyroid, we investigated the effects of the repeated oral exposure to low to high doses (0.3, 3, 30 and 150 mg/kg) di-2-ethylhexylphthalate (DEHP) from weaning to maturity for 90 days in juvenile rats on the thyroid. The histological examination revealed that DEHP significantly induced hyperplasia in the thyroid from the doses of 30 mg/kg, which was confirmed with Ki67 staining. In line with this finding, increased mRNA expression of thyrotropin releasing hormone (Trh) was observed in the thyroid of female at 0.3 mg/kg and 150 mg/kg as determined by RNAseq analysis. Moreover, significantly increased expression of parathyroid hormone (Pth) in the female at 0.3 mg/kg, and thyroglobulin (Tg) and thyroid hormone responsive (Thrsp) in the male at 0.3 mg/kg were noted in the blood, of which changes were substantially attenuated at 150 m/kg, alluding the meaningful effects of low dose DEHP on the thyroid hormone regulation. Urinary excretion of mono-2-ethylhexyl-phthalate (MEHP), a major metabolite of DEHP was determined to be 4.10 and 12.26 ppb in male, 6.65 and 324 ppb in female at 0.3 and 30 mg/kg DEHP, respectively, which fell within reported human urine levels. Collectively, these results suggest a potential adverse effects of low dose phthalates on the thyroid.
Subject(s)
Animals , Female , Humans , Male , Rats , Diethylhexyl Phthalate , Hyperplasia , Parathyroid Hormone , Plastics , RNA, Messenger , Thyroglobulin , Thyroid Gland , Thyrotropin-Releasing Hormone , WeaningABSTRACT
Di-(2-ethylhexyl) phthalate (DEHP) is an ubiquitous environmental contaminant because of its extensive use in plastics and its persistence. As an environmental endocrine disruptor, it is suspected to interfere with neurodevelopment in people. However, evidence of the effects of maternal DEHP exposure on cerebellar development in offspring is scarce. The objective of this study was to investigate maternal exposure to DEHP and its effect on apoptosis of cerebellar granule cells (CGCs) and related mechanisms. Pregnant Wistar rats were administrated DEHP (0, 30, 300 and 750 mg/kg/d) by gavage from gestational day (GD) 0 to postnatal day (PN) 21. Primary CGCs were also exposed to mono-(2-ethylhexyl) phthalate (MEHP), the main metabolite of DEHP, for 24 h with concentrations of 0, 25, 100 and 250 µM. The CGCs of male offspring from 300 and 750 mg/kg/d DEHP exposure groups showed significantly increased apoptosis. In addition, the PI3K/AKT signaling pathway was inhibited in the male offspring of the 300 and 750 mg/kg/d DEHP exposure groups. However, effects on female pups were not obvious. Apoptosis was also elevated and the PI3K/AKT signaling pathway was inhibited after primary CGCs were exposed to MEHP. Furthermore, apoptosis was reduced after treatment with the PI3K/AKT signaling pathway activator, insulin-like growth factor (IGF) 1, and increased after treatment with LY294002, an inhibitor of the PI3K/AKT signaling pathway. These results suggested that maternal DEHP exposure induced apoptosis in the CGCs of male pups via the PI3K/AKT signaling pathway, and the apoptosis could be rescued by IGF1 and aggravated by LY294002.
Subject(s)
Female , Humans , Male , Apoptosis , Diethylhexyl Phthalate , Maternal Exposure , Plastics , Rats, WistarABSTRACT
Wide spread use of Di-(2-ethylhexyl) phthalate (DEHP) has made it a ubiquitous contaminant in today’s environment, responsible for possible carcinogenic and endocrine disrupting effects. In the present investigation an integrative toxico-proteomic approach was made to study the estrogenic potential of DEHP. In vitro experiments carried out with DEHP (0.1-100 μM) induced proliferations (E-screen assay) in human estrogen receptors-α (ERα) positive MCF-7 and ERα negative MDA-MB-231 breast cancer cells irrespective of their ERα status. Further, DEHP suppressed tamoxifen (a potent anti-breast cancer drug) induced apoptosis in both cell types as shown by flowcytometric cell cycle analysis. Label-free quantitative proteomics analysis of the cell secretome of both the cell lines indicated a wide array of stress related, structural and receptor binding proteins that were affected due to DEHP exposure. The secretome of DEHP treated MCF-7 cells revealed the down regulation of lactotransferrin, an ERα responsive iron transport protein. The results indicated that toxicological effects of DEHP did not follow an ERα signaling pathway. However, the differential effects in MCF-7 and MDA-MB-231 cell lines indicate that ERα might have an indirect modulating effect on DEHP induced toxicity.
Subject(s)
Apoptosis/drug effects , Breast Neoplasms/pathology , Cell Cycle/drug effects , Cell Division/drug effects , Cell Line, Tumor/drug effects , Cell Line, Tumor/metabolism , Diethylhexyl Phthalate/toxicity , Environmental Pollutants/toxicity , Estrogen Receptor alpha/drug effects , Estrogen Receptor alpha/physiology , Estrogens , Female , Gene Expression Regulation, Neoplastic/drug effects , Humans , Lactoferrin/biosynthesis , Lactoferrin/genetics , Lactoferrin/metabolism , MCF-7 Cells/drug effects , MCF-7 Cells/metabolism , Mass Spectrometry/instrumentation , Microchemistry/instrumentation , Neoplasm Proteins/drug effects , Neoplasm Proteins/physiology , Neoplasm Proteins/metabolism , Neoplasms, Hormone-Dependent/pathology , Proteomics , Tamoxifen/antagonists & inhibitors , Tamoxifen/pharmacologyABSTRACT
<p><b>OBJECTIVE</b>To estimate the daily intake of DEHP among workers in flavoring factories.</p><p><b>METHODS</b>71 workers in two flavoring manufacturers, 27 administrators in those factories and 31 laboratory technicians in a research institute were recruited and assigned to exposure group, control group 1 and control group 2 respectively. Their urinary DEHP metabolites, mono(2-ethylhexyl) phthalate (MEHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), were detected by isotope dilution-ultra performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS). The urinary metabolites concentrations were converted into DEHP intake levels using two pharmacokinetic models: the urine creatinine-excretion (UCE) one and the urine volume (UV) one.</p><p><b>RESULTS</b>No significant differences were found among the three groups. Based on the urinary concentrations of Σ₃MEHP, we got a median daily DEHP intake of 3.22 or 1.85 μg/kg body-weight/day applying the UV or UCE models respectively. Depending on the UV model, three subjects (2.34%) exceeded the RfD value given by US EPA and the P₅₀ of estimate daily DEHP intakes accounted for 16.10% of the RfD value. No subjects exceeded the limitation depending on the UCE model.</p><p><b>CONCLUSION</b>The workers in flavoring factories were not supposed to be the high DEHP exposure ones and their exposure level remained at a low risk.</p>
Subject(s)
Adult , Humans , Young Adult , Diethylhexyl Phthalate , Urine , Flavoring Agents , Occupational ExposureABSTRACT
OBJECTIVE: To develop GC/MS method in detect plasticizers in compound aluminum hydroxide tablets adsorbed from pharmaceutical packaging. METHODS: The column: HP-5MS silica capillary column (30 m × 0.25 μm, 0.25 mm) was used; Ion source temperature was 230°C; Quadrupole temperature was 150°C; The total ion scanning rang: m/z 50~500. RESULTS: The diethylhexyl phthafate linearity was in the range of 0.5 -20.0 μg · mL-1 with a regression coefficient of 0.9990. The average recovery of this method was 98.8%, and RSD was 1.4%. The RSD of intra-day and inter-day was 2.8% and 3.1% respectively. CONCLUSION: This method is specificity, sensitive, and can be applied to detect and research DEHP which may be adsorbed or penetrated into drugs. Copyright 2012 by the Chinese Pharmaceutical Association.
ABSTRACT
OBJECTIVES: In most DEHP exposure assessment studies, single spot urine sample was used. It could not compare the exposure level among studies. Therefore, we are going to represent the necessity of selection of proper sampling time of spot urine for assessing the environmental DEHP exposure, and the association urinary DEHP metabolites with steroid hormones. METHODS: We collected urine and plasma from 25 men. The urine sampling times were at the end of the shift (post-shift) and the next morning before the beginning of the shift (pre-shift). Three metabolites of DEHP {mono(2-ethylhexyl) phthalate [MEHP], mono-(2-ethyl-5-hydroxyhexyl)phthalate [MEHHP], and mono(2-ethyl-5-oxohexyl)phthalate [MEOHP]} in urine were analyzed by HPLC/MS/MS. Plasma luteinzing hormone, follicle stimulating hormone, testosterone, and 17beta-estradiol were measured at pre-shift using a ELISA kit. A log-transformed creatinine-adjusted urinary MEHP, MEHHP, and MEOHP concentration were compared between the post- and pre-shift. The Pearson's correlation was calculated to assess the relationships between log-transformed urinary MEHP concentrations in pre-shift urine and hormone levels. RESULTS: The three urinary metabolite concentrations at post-shift were significantly higher than the concentrations in the pre-shift (p<0.0001). The plasma hormones were not significantly correlated with log-transformed creatinine - adjusted DEHP metabolites. CONCLUSIONS: To assess the environmental DEHP exposure, it is necessary to select the urine sampling time according to the study object. There were no correlation between the concentration of urinary DEHP metabolites and serum hormone levels.
Subject(s)
Adult , Humans , Male , Middle Aged , Diethylhexyl Phthalate/analogs & derivatives , Estradiol/blood , Follicle Stimulating Hormone/blood , Laboratories, Dental , Luteinizing Hormone/blood , Occupational Exposure/analysis , Phthalic Acids/urine , Specimen Handling/methods , Testosterone/blood , Time FactorsABSTRACT
Acyl-CoA synthetase 4 (ACS4) is an arachidonate-preferring enzyme abundant in steroidogenic tissues. We examined ACS4 in rat liver, which contains a variety of pathways that use acyl-CoAs, in order to determine subcellular locations. We demonstrate that ACS4 protein was present most abundantly in the mitochondria and to a much lesser extent in the peroxisomes and microsomes. To determined the dietary effects on the level of ACS4 mRNA, northern blotting was carried out using total RNA from the livers of adult male rats fed various diets. Fasting, high fat diet, and fat-free high sucrose diet increased the hepatic level of ACS4 mRNA approximately 2-fold. Furthermore, the levels of ACS4 mRNA were induced by DEHP[Di- (2-ethylhexyl) phthalate]. These data suggest that ACS4 expression in the liver is regulated with a variety of pathways, including beta-oxidation, hormone, and insulin.
Subject(s)
Adult , Animals , Humans , Male , Rats , Arachidonic Acid , Blotting, Northern , Blotting, Western , Diet , Diet, High-Fat , Fasting , Insulin , Ligases , Liver , Microsomes , Mitochondria , Peroxisomes , RNA , RNA, Messenger , SucroseABSTRACT
OBJECTIVE:To investigate the dissolution of DEHP in PVC infusion set and the packaged infusion sets of the Paclitaxel injection so as to evaluate the safety of clinical infusion sets for paclitaxel.METHODS:The packaged infusion sets of Paclitaxel injection were collected from 9 Three-A grade hospitals in Chongqing.Paclitaxel injections were prepared as per actual concentration needed by the clinic and dripped through eight different infusion sets(in which 7 were packaged infusion sets) for 3 h.The peak area of the collected solution was measured and its content was determined by HPLC,and the effect of infusion time on the dissolution of DEHP was investigated as well.RESULTS:The dissolution of DEHP dripped through eight infusion sets were 1 408,9 393,6 576.5,2 412.6,8 194.4,0,8 477.2,and 8 037.4 ?g,respectively.The dissolution increased with the prolonging of infusion time.CONCLUSION:At present,the majority of packaged infusion sets of Paclitaxel injection were made form PVC materials.The safe medication of Paclitaxel can't be ensured for the dissolved DEHP can enter the blood directly,thus its hazardness should be given great attention.
ABSTRACT
Objective To study the effects of di-(2-ethylhexyl) phthalate(DEHP) on the organs of rats.Methods Male Wister rats were divided into five groups,four exposure groups and one control group,10 in each.The exposure groups were given with DEHP at the doses of 1 500 mg /kg,3 000 mg /kg,4 500 mg /kg,6 000 mg /kg respectively,by gavage,28 consecutive days.The rats were weighed every 4 days,after 28 days,the rats were killed and the organ coefficients were calculated and the pathological examination was done.Results The weight of four exposure groups reduced significantly(P