Amount Of Di-2-ethylhexyl Phthalate Research Articles

Quantitative determination of trace amounts of Diethylhexyl phthalate content in Dextrose injection proficiently by a simplistic Gas Chromatography Technique

The objective of present study was to analyze Diethylhexyl phthalate content in 5% Dextrose injection and other reconstituting diluents for pharmaceutical injectable formulations. Reconstituting diluents for pharmaceutical injectable formulations are mainly stored and supplied in polyvinyl chloride bags. This may lead to leaching of Diethylhexyl phthalate, a toxic content from polyvinyl chloride bags into reconstituting formulations. In the current study, a proficient and simple method by using a Gas Chromatograph was developed and validated for the quantitation of trace amounts of Diethylhexyl phthalate in 5% Dextrose injection. The method was optimized by using silica fused short capillary column (DB-1; USP G2 phase) with dimensions 5 m length x 0.53 mm inner diameter and 2.65µm film thickness. The method involves a simple extraction procedure for sample preparation by means of extraction with n-Hexane solvent and evaporation with a stream of nitrogen gas. An Internal standard (1-Phenydodecane) was added to standard and sample preparations by using n-Hexane as diluent. The method was validated as per the current regulatory guidance for analytical method validation.The projected methodology was found to be selective, accurate, precise, and linear in the test concentration range from 0.004 µg/mL to 5.065µg/mL for Diethylhexyl phthalate. The method was effectively used to analyze the Diethylhexyl phthalate content in 5% Dextrose Injection and other reconstituting diluents for pharmaceutical injectable formulations.

Potential environmental risk assessment of di-2-ethylhexyl phthalate emissions from a municipal solid waste landfill leachate.

BackgroundIn certain countries, including Poland, polyvinyl chloride (PVC) waste, together with di-2-ethylhexyl phthalate (DEHP) contained within (up to 60%), is mostly directed to municipal solid waste (MSW) landfills. From there, over time, it is released from the polymer matrix and can migrate with landfill leachate into the environment. The amount of DEHP placed on the Polish market since the start of industrial production and the prevalent landfilling disposal of PVC waste in Poland, indicate that DEHP pollution can increase risk factors in the future. The objective of this study was to determine the concentrations of DEHP in leachates from a chosen MSW landfill directed to a local sewage treatment plant (STP) and estimate the associated potential risks to the environment.ResultsDEHP concentrations in leachates ranged from < LOQ to 394.4 µg/L, depending on the sampling year and season. DEHP is a pervasive environmental contaminant present in all investigated landfill leachate samples. The results from The European Union System for the Evaluation of Substances (EUSES) modelling related to DEHP in leachate directed to STP indicated potentially unacceptable risk to freshwater organisms; and birds and mammals feeding on earthworms (where a sewage sludge applications in agriculture take place). The results indicated low risk for other environmental components including local fresh-water sediment, local soil and microorganisms of STP, and freshwater fish-eating birds and mammals.ConclusionsFuture DEHP emissions may occur after the technical lifetime of the landfill and/or decay its bottom sealing. To avoid contamination, the monitoring of landfills after closure should include DEHP concentrations and last longer than the recommended (inter alia in Poland) 30 years, or until emissions from PVC to leachate are eliminated. More research on leachate of DEHP and its potential risks should be conducted, utilising detailed modelling which can including other landfills and different routes of DEHP emissions in leachates.

Distributions, temporal trends and ecological risks of polyethylene terephthalate (PET) and di-(2-ethylhexyl) phthalate (DEHP) in sediments of Jiaozhou Bay, China

Spatiotemporal distribution and ecological risk of the polyethylene terephthalate (PET) plastic polymer and plasticizer di-(2-ethylhexyl) phthalate (DEHP) were investigated using both surface and core sediments in Jiaozhou Bay, China. The concentrations of PET and DEHP ranged 210.6–1929.7 μg/kg and 0–591.2 μg/kg, respectively. The depth profiles of PET and DEHP in the sediment cores indicated that PET and DEHP pollution increased since the 1970s, which is in accord with the regional PET and DEHP consumption history. The levels of PET in Jiaozhou Bay was found to represent low ecological risk based on the assessment models for Potential Ecological Risk factor and Potential Ecological Risk. The amounts of DEHP also posed a low risk to the aquatic organisms in the sediment phase as indicated by the Risk Quotient method.

Glutathione peroxidase 6 from Arabidopsis thaliana as potential biomarker for plants exposure assessment to di-(2-ethylhexyl) phthalate.

As a most abundant plasticizer, Di-(2-ethylhexyl) phthalate (DEHP) has been widely used in agriculture with an associated potential toxicity to many species including plants via the production of the excessive reactive oxygen species (ROS). However, the potential toxic mechanisms of the plasticizer DEHP-induced oxidative damage to plants remain unknown. The antioxidant enzyme glutathione peroxidase has been suggested as biomarkers to reflect over excessive oxidative stress. In this study, the effect of DEHP on AtGPX6 was evaluated by multi-spectroscopic techniques and molecular docking method. The fluorescence intensity of AtGPX6 was reduced by the static quenching mechanism upon the addition of DEHP. The predominant forces in complex formation was mainly impelled by hydrogen bonding and Van der Waals forces based on the negative ΔH and ΔS, which was in accordance with the molecular docking results. In addition, the secondary structural changes resulted from the complex formation were investigated in presence of different amounts of DEHP by the combination of fluorescence, UV-vis absorption and Circular dichroism spectra, which revealed the loosening and unfolding of the framework of AtGPX6 accompanied with the enhancement of the hydrophilicity around the tryptophan residues. The exploration of the interaction mechanism of DEHP with AtGPX6 at molecular level would help to evaluate the toxicity of the plasticizers and forecast the related adverse effects on plants.

Uptake of Di(2-ethylhexyl) Phthalate (DEHP) by the Plant Benincasa hispida and Its Use for Lowering DEHP Content of Intercropped Vegetables

Uptake of di(2-ethylhexyl) phthalate (DEHP) by the plant Benincasa hispida and its use for topical phytoremediation were investigated by cultivation of plants in DEHP-contaminated environments. The results showed that major plant organs of B. hispida , including leaves, stems, and fruits, readily absorbed DEHP from the air. The amount of DEHP that accumulated in leaves, stems, and fruits was mainly dependent upon exposure time, and most DEHP accumulated in their inner tissues. A single plant of B. hispida with a gourd was able to absorb more than 700 mg of DEHP when it was exposed to DEHP-contaminated air for 6 week. B. hispida reduced air DEHP concentration by 65-76% as the air DEHP concentration ranged from 2351 to 3955 μg/m³ (high DEHP level) and 85-92% as the air DEHP concentration ranged from 35.1 to 65.3 μg/m³ (low DEHP level) in greenhouse experiments. When intercropping of B. hispida and Brassica chinensis or Brassica campestris , B. hispida reduced more than 87% of DEHP accumulation in the latter, which indicates that B. hispida has excellent use potential for lowering the DEHP content of intercropped vegetables.

Effect of UV Irradiation on the Migration of DEHP from Food-Grade PVC Film into Packaged Ground Meat

Effect of UV irradiation on the migration of di-2-ethylhexyl phthalate (DEHP) plasticizers from food-grade PVC film into packaged ground meat that had various levels of fat content (i.e. 10%, 20%, 30%, and 40%) was studied. After 20 h of UV irradiation (intensity 900µW cm-2)，the amount of migrated DEHP had a dramatic increase by 2.55, 2.75, 2.18 and 2.16 times in comparison to that in control samples having a fat content of 10%, 20%, 30% and 40%, respectively. The migration was intensified greatly by the UV irradiation of 8 to 12 h. There were 220.10 mg kg-1, 245.88 mg kg-1, 291.18 mg kg-1, and 357.40 mg kg-1 DEHP migrating from the PVC film into the ground meat during these periods, which contributed a large proportion to the final total amounts of DEHP, being 66.6%, 57.5%, 60.6% and 68.7% of 20 h of UV irradiation, for the ground meat of fat content of 10%, 20%, 30% and 40%, respectively. These results indicate that safety risk of packaged food will increase when the packaged food is under UV irradiation.

Structural Control of SiOx Coatings and their Migration-Resistance Properties

Diethylhexyl phthalate (DEHP) is a kind of plasticizers which is generally used in plastics packaging materials to provide the flexibility. Especially in PVC films, a large amount of DEHP used makes it possibility of the widespread usage of PVC in the fresh food packaging market. But recent researches proved that DEHP can be easily migration into food and food stimulant. It causes reproductive disorders, mutation, carcinogenicity, and other genetic toxicity to all mammals. Hence blocking the migration of DEHP from the plastic to the foods becomes very important issue for the food safety. In this work, the migration kinetics of DEHP was explored. We achieved that the migration of DEHP can be well controlled through coated nano-scale SiOxbarrier layer on the surface of PVC films, and the plasma enhanced chemical vapor deposition (PECVD) process is a very efficient way to prepare SiOxcoatings on the plastic surface. It is also noticed that there is a relationship between the migration-resistance properties and coating structure through Fourier transform infrared spectroscopy (FTIR) for the chemical composition analysis, scanning electron microscope (SEM) for the topography investigation of the coating surfaces, surface profilemeter for the thickness measurement of coatings, and high-performance liquid chromatography (HPLC) for the barrier property evaluation of coatings at last. We conclude that the coatings can perfectly block the migration of the DEHP from plastics to their contents. When the deposition conditions of SiOxcoatings were optimized, i.e. 50W of the discharge power, 4:1 of ratio of O2: HMDSO, and ca.100 nm thickness of SiOx, the 71.2% DEHP, compared to the control PVC film, was effectively barriered.

Materials Degradation in PVC Medical Devices, DEHP Leaching and Neonatal Outcomes

Polymeric materials play a key role in the production of medical and clinical devices thanks to their special features such as flexibility, easy processing and good price/performance ratio. Among the different polymeric matrixes, one of the most used is Poly(vinyl chloride) (PVC). At room temperature PVC is hard and brittle, thus great amounts (40-50%) of phthalate esters that act as plasticizers are added to the polymer to make it flexible and appropriate for medical use. Di-(2-ethylhexyl)-phthalate (DEHP) is the most widely used plasticizer in PVC medical devices. However, DEHP is not chemically bound to PVC and migrates from medical devices with time and use. The potential for DEHP to produce adverse effects in humans has been the subject of considerable discussion and debate in the scientific community. In particular, newborns in the new environment have to be considered at particularly increased risk, because of their small body size and the multiple medical device-related to the DEHP exposure. The major factors determining the degree to which DEHP migrates from medical devices are temperature, amount of DEHP in the device, storage time, shaking of the device while in contact with the medical solutions and degree of PVC degradation.

Plasticizer, Di(2-ethylhexyl)Phthalate (DEHP), exposure in neonatal ECMO vs. near-miss ECMO patients

Objective: The plastic used in many medical devices is composed primarily of the plastic polyvinyl chloride (PVC). PVC is made flexible by treating it with chemical compounds ca lled plasticizers. The most commonly used plasticizer is di(2-ethylhexyl) phthalate (DEHP). The general population is exposed daily to DEHP and one of its many metabolites, mono(2- ethylhexyl) phthalate (MEHP), primarily through food and aerosolization of environmental exposure. Exposure rises dramatically in premature or ill neonates, who are exposed to medical devices including enteral, blood and infusion bags, tubes and infusion devices. The rate of leaching of DEHP depends on many factors, including contact with lipophilic solutions and the amount of DEHP found in the product. Highly lipophilic substances readily extract plasticizers from PVC bags and tubes. Our objective was to determine the concentration of DEHP and MEHP in the urine of infants undergoing extracorporeal membrane oxygenation (ECMO) and near-miss ECMO to determine if ECMO results in increased concentrations of DEHP and MEHP in the urine. Study design: Using an in vivo prospective comparative study design, we evaluated 12 term or near-term neonates requiring ECMO. Our control population included 17 neonates with similar underlying diagnoses, referred to our NICU for ECMO but who ultimately responded to maximal medical therapy without ECMO. Two baseline urine samples were collected on admission to the NICU for DEHP and MEHP analysis on both the ECMO and near-miss populations. Daily urine samples were collected sequentially for five days in both populations. Urine sample s were collected prior to discharge/transfer for both popul ations. Urinary DEHP and MEHP analysis was performed using tandem mass spectroscopy. Demographic data was collected for each patient. Results: We enrolled a total of twenty-nine patients in the study. All patients were transported to our NICU from outside birthing centers. Twelve neonates required ECMO support. The other seventeen patients responded to maximal medical therapy without

Presence of Plasticizer Di-2(ethylhexyl)phthalate in Primed Extracorporeal Circulation Circuits

Many centers advocate the use of a standby wet-primed extracorporeal membrane oxygenation (ECMO) circuit for rapid deployment during cardiopulmonary resuscitation. However, concerns with regard to the potential health hazards associated with the release of the plasticizer di-2(ethylhexyl)phthalate (DEHP) from the polyvinyl chloride (PVC) tubing exist. The purpose of this study was to determine the time course of DEHP release from a preprimed ECMO circuit and to evaluate the effect of PVC tubing coatings on DEHP release. Seven circuits including three uncoated (Medtronic, Medtronic with albumin, and Medtronic Super Tygon) and four attenuated surfaces (Carmeda, COBE Smart, Medtronic Trillium, and Terumo x-coated) were primed with Plasmalyte A. Samples of the circuit prime were collected over a period of 2 weeks and were analyzed for DEHP, using gas chromatography. Results were compared by using a two-tailed t test. One coated (Carmeda) and all three uncoated circuits leached DEHP. The greatest amount of leaching occurred in the uncoated Medtronic tubing with albumin. The COBE Smart, Medtronic Trillium, and Terumo x-coated circuits had undetectable amounts of DEHP (p = 0.006 vs Medtronic uncoated). Prepriming an ECMO circuit composed of uncoated PVC tubing is associated with DEHP release. Using coated PVC tubing appears to eliminate DEHP release over a 2-week period.

Transport of di(2-ethylhexyl)phthalate (DEHP) applied with sewage sludge to undisturbed and repacked soil columns.

Municipal sewage sludge is often used on arable soils as a source of nitrogen and phosphorus, but it also contains organic contaminants that may be leached to the ground water. Di(2-ethylhexyl)phthalate (DEHP) is a priority pollutant that is present in sewage sludge in ubiquitous amounts. Column experiments were performed on undisturbed soil cores (20-cm depth x 20-cm diameter) with three different soil types: a sand, a loamy sand, and a sandy loam soil. Dewatered sewage sludge was spiked with 14C-labeled DEHP (60 mg kg(-1)) and bromide (5 g kg(-1)). Sludge was applied to the soil columns either as five aggregates, or homogeneously mixed with the surface layer. Also, two leaching experiments were performed with repacked soil columns (loamy sand and sandy loam soil). The DEHP concentrations in the effluent did not exceed 1.0 microg L(-1), and after 200 mm of outflow less than 0.5% of the applied amount was recovered in the leachate in all soils but the sandy loam soil with homogeneous sludge application (up to 3.4% of the applied amount recovered). In the absence of macropore flow, DEHP in the leachate was primarily sorbed to mobilized dissolved organic macromolecules (DOM, 30.3 to 81.3%), while 2.4 to 23.6% was sorbed to mobilized mineral particles. When macropore flow occurred, this changed to 16.5 to 37.4% (DOM) and 36.9 to 40.6% (mineral particles), respectively. The critical combination for leaching of considerable amounts of DEHP was homogeneous sludge application and a continuous macropore structure.

経腸経管栄養療法時におけるポリ塩化ビニル製チューブからのフタル酸ジ‐２‐エチルヘキシルの溶出

Di-2-ethylhexyl Phthalate (DEHP) was reported to dissolve from a polyvinyl chloride (PVC) administration tube during the infusion of an injection fluid containing a solvilizing agent, soybean oil or lecithin, etc. This paper describes the behavior of DEHP dissolution from PVC tubes during enteral tube feeding. The DEHP concentration was determined using HPLC. After the passage the ENSURE LIQUID® (EL) solution through the PVC tube, DEHP was dissolved in the EL solution. The EL solution is one type of enteral nutrition. This dissolution pattern was similar to that of injection fluid containing a solvilizing agent, in which the DEHP concentration in the EL solution increased linearly over time at first and thereafter reached a plateau. 170 μg of the DEHP was dissolved after 200mL of the EL solution had passed through the PVC administration set (the drip conditions were 25°C, 100mL/hr, tube length 115cm and inner diameter 0.3cm). The amount of DEHP which dissolved into the solution depended on the temperature (25-40°C), and no clear difference was observed between the PVC tubes (administration tube, feeding tube). In addition, the amount of DEHP that dissolved into the solution varied depending on the type of enteral nutrition.

Influence of Plasticizer-Free CAPD Bags and Tubings on Serum, Urine, and Dialysate Levels of Phthalic Acid Esters in CAPD Patients

To evaluate the impact of a plasticizer-free device on exposure to di-(2-ethylhexyl) phthalate (DEHP) and its major metabolites in patients on continuous ambulatory peritoneal dialysis (CAPD). DEHP is the most commonly used plasticizer in polyvinyl chloride (PVC) products; it is added to CAPD bags in order to improve the flexibility of the material. Since DEHP leaches out of the plastic matrix, patients on CAPD are exposed to considerable amounts of DEHP and its metabolites. A prospective cross-over study. Department of nephrology in a teaching hospital. Six patients (4 female, 2 male) stable on peritoneal dialysis (PD) for at least 6 months. Patients were switched from a plasticizer-containing PVC CAPD system (A.N.D.Y. Plus, Fresenius Medical Care, Bad Homburg, Germany) to a polyolefine-made plasticizer-free system (stay-safe, Fresenius). Prior to and 42 days after the switch, 24-hour effluent dialysate and urine collections were performed and 10 mL blood was drawn. Concentrations of DEHP, mono-(2-ethylhexyl) phthalate (MEHP), phthalic acid (PA), and 2-ethylhexanol (2-EH) in urine, dialysate, and serum were determined using gas chromatography/mass spectrometry. Complete data were obtained from 5 patients. Serum levels of PA decreased significantly during the study period (0.137 +/- 0.078 mg/L vs 0.124 +/- 0.049 mg/L, p = 0.04), and the respective levels of DEHP decreased insignificantly (0.097 +/- 0.076 mg/L vs 0.069 +/- 0.046 mg/L, p = 0.07), whereas the concentrations of MEHP and 2-EH remained unchanged. Urine concentrations of PA were high (0.81 +/- 0.69 mg/L) but did not change substantially (0.70 +/- 0.50 mg/L). Effluent dialysate concentrations of MEHP and PA decreased significantly (0.0176 +/- 0.004 mg/L vs 0.0040 +/- 0.0007 mg/L, p = 0.043 and 0.158 +/- 0.056 mg/L vs 0.111 +/- 0.051 mg/L, p = 0.043, respectively). Although PD patients seem to be exposed to other sources of phthalates in addition to dialysis, use of plasticizer-free devices may help to reduce potentially immunosuppressive exposure to phthalate esters.

Uraemic pruritus and exposure to di(2-ethylhexyl) phthalate (DEHP) in haemodialysis patients.

Uraemic pruritus is a frequent and disabling symptom in patients on dialysis. The pathogenesis of uraemic pruritus is nevertheless still obscure. We investigated whether di(2-ethylhexyl)phthalate (DEHP), the most commonly used plasticizer in polyvinylchloride (PVC) haemodialysis tubings, is a possible pathogenetic factor in uraemic pruritus. Serum concentrations of DEHP and its major derivatives mono-(2-ethylhexyl)phthalate (MEHP), 2-ethylhexanol (2-EH) and phthalic acid (PA) were determined in uraemic patients before and after a haemodialysis session and compared with the occurrence and intensity of pruritus in these patients. Twenty-one patients on regular haemodialysis for at least 6 months were examined. The severity of uraemic pruritus was assessed using a standard questionnaire (pruritus score). The quantitative analysis of DEHP and its derivatives was carried out by GC/selected ion monitoring mass spectrometry. Fourteen out of 21 patients (66%) complained about uraemic pruritus to a variable degree. The post-dialysis serum concentrations of DEHP, MEHP and 2-EH were significantly higher than the corresponding pre-dialysis values, whereas the post-dialysis concentrations of PA (0.122 +/- 0.078 microgram/microliter) were significantly lower than pre-dialysis levels (0.194 +/- 0.101 microgram/microliter, P = 0.00068). Neither pre- nor post-dialysis serum concentrations of DEHP, MEHP, PA or 2-EH were correlated with the severity of uraemic pruritus. Additionally, serum concentrations of DEHP and its metabolites did not differ significantly in patients with and without pruritus. These findings suggest that patients on haemodialysis are regularly exposed to considerable amounts of DEHP and metabolites. Phthalic acid, one of the presumed end products of DEHP metabolism, might be eliminated at least in part by haemodialysis. The exposition to DEHP and metabolites during haemodialysis, as assessed by measuring serum concentrations, bears no immediate relation to the occurrence or intensity of uraemic pruritus.

Uraemic pruritus and exposure to di(2-ethylhexyl)phthalate (DEHP) in haemodialysis patients

Uraemic pruritus is a frequent and disabling symptom in patients on dialysis. The pathogenesis of uraemic pruritus is nevertheless still obscure. We investigated whether di (2-ethylhexyl ) phthalate (DEHP), the most commonly used plasticizer in polyvinyichloride (PVC) haemodialysis tubings, is a possible pathogenetic factor in uraemic pruritus. Serum concentrations of DEHP and its major derivatives mono-(2-ethylhexyl ) phthalate (MEHP), 2-ethylhexanol (2-EH) and phthalic acid (PA) were determined in uraemic patients before and after a haemodialysis session and compared with the occurrence and intensity of pruritus in these patients. Twenty-one patients on regular haemodialysis for at least 6 months were examined. The severity of uraemic pruritus was assessed using a standard questionnaire (pruritus score). The quantitative analysis of DEHP and its derivatives was carried out by GC/selected ion monitoring mass spectrometry. Fourteen out of 21 patients (66%) complained about uraemic pruritus to a variable degree. The post-dialysis serum concentrations of DEHP, MEHP and 2-EH were significantly higher than the corresponding pre-dialysis values, whereas the post-dialysis concentrations of PA (0.122±0.078 μg/ml) were significantly lower than pre-dialysis levels (0.194±0.101 μg/ml, P=0.00068). Neither pre- nor post-dialysis serum concentrations of DEHP, MEHP, PA or 2-EH were correlated with the severity of uraemic pruritus. Additionally, serum concentrations of DEHP and its metabolites did not differ significantly in patients with and without pruritus. These findings suggest that patients on haemodialysis are regularly exposed to considerable amounts of DEHP and metabolites. Phthalic acid, one of the presumed end products of DEHP metabolism, might be eliminated at least in part by haemodialysis. The exposition to DEHP and metabolites during haemodialysis, as assessed by measuring serum concentrations, bears no immediate realtion to the occurence or intensity of uraemic pruritus.

Stability of fluorouracil administered through four portable infusion pumps

The stability of fluorouracil in four portable infusion pumps under simulated infusion conditions was studied. Three commercially available fluorouracil aqueous solutions (50 mg/mL) were used. Samples adjusted to six pH levels were examined for precipitate. Drug reservoirs of four different portable infusion pumps were filled with 70 mL of each fluorouracil injection. Under conditions simulating actual use, the reservoirs were attached to the pumps and the solutions were pumped at a rate of 10 mL/24 hours over a seven-day period at 25 degrees C and 37 degrees C. Samples at the distal end of the extension tubing were collected hourly for the first 10 hours and at 12-hour intervals thereafter. Visual observations and pH determinations were made immediately. Drug concentrations were determined by reverse-phase high-performance liquid chromatography. Diethylhexylphthalate (DEHP) concentrations (the result of leaching from the plastic tubing and container) were determined by gas chromatography. In the pH study, precipitate appeared immediately in all fluorouracil injections below pH 8.52; precipitate was observed after two to four hours at pH 8.60-8.68. Under simulated infusion conditions, no apparent changes in concentration or pH were detected with any of the brands of drugs or portable infusion devices. At 25 degrees C, a fine white precipitate was observed in the extension tubing of all devices with the Roche brand of fluorouracil 48 to 96 hours after the pumping cycle began. The amount of DEHP leached from the drug reservoirs over the seven-day period was less than 1 ppm at both temperatures. All tested brands of fluorouracil injection were found to be stable under simulated infusion conditions over a seven-day period at 37 degrees C.

Leaching of diethylhexyl phthalate from polyvinyl chloride bags into intravenous cyclosporine solution

The release of diethylhexyl phthalate (DEHP) from flexible polyvinyl chloride containers into intravenous cyclosporine solutions was studied. Intravenous cyclosporine solution or solutions containing the vehicle Cremophor EL and alcohol in dextrose were prepared in an all-glass system and stored in polyvinyl chloride (PVC) bags. Four samples were obtained at different time intervals, and DEHP content was analyzed by gas chromatography. The amount of DEHP that was leached into solutions stored in the PVC bags increased as storage time increased. By 48 hours, nearly 33 mg of DEHP had leached into the solution. Intravenous cyclosporine solutions should be prepared in glass containers to minimize patient exposure to DEHP. If plastic bags are used for preparing cyclosporine injections, the injections must be used immediately after preparation.

Exposure of newborn infants to plasticizers. Plasma levels of di-(2-ethylhexyl) phthalate and mono-(2-ethylhexyl) phthalate during exchange transfusion.

The exposure of newborn infants to the plasticizer di-(2-ethylhexyl) phthalate (DEHP) and its primary metabolite mono-(2-ethylhexyl) phthalate (MEHP) was studied during exchange transfusions by measuring their contents in the infused blood. Plasma concentrations of DEHP and MEHP in the blood withdrawn from the infants during the transfusions also were determined. The amounts of DEHP and MEHP inadvertently infused varied from 1.7 to 4.2 and 0.2 to 0.7 mg per kg body weight, respectively. Immediately after the transfusions, the plasma levels of DEHP in the individual infants varied between 3.4 and 11.1 micrograms per ml. MEHP in the corresponding samples ranged from 2.4 to 15.1 micrograms per ml. Judging from plasma concentrations of DEHP and MEHP during and after transfusion, there was no gradual accumulation of these substances in the plasma during the course of the transfusion. In the two infants who underwent a second exchange transfusion, significant levels of phthalates were found at 16 and 23 hours, respectively, after the first transfusion. Plasma concentrations of DEHP in these infants declined at a faster rate than those of MEHP, thus pointing to the importance of examining the pharmacokinetics of this potentially toxic metabolite.

Compatibility of plastic infusion devices with diluted N-methylformamide and N,N-dimethylacetamide

Leaching of the plasticizer di-2-ethylhexyl phthalate (DEHP) from i.v. sets and polyvinyl chloride bags was studied with solutions of a new anticancer drug, N-methylformamide (NMF), and N,N-dimethylacetamide (DMA), a structurally related solvent used in the formulation of some anticancer drugs. Solutions of 0.9% sodium chloride, 5 and 10% DMA in 0.9% sodium chloride, and 20, 40, and 60% NMF in 0.9% sodium chloride were used to fill i.v. administration sets ( Venoset -60, Abbott Laboratories) and polyvinyl chloride bags ( Viaflex -500, Travenol Laboratories). The solutions were kept in the containers for 20 hours at ambient temperature. Simulated infusions were also studied using 0, 20, and 40% NMF plus 5 and 10% DMA in 0.9% sodium chloride; both glass bottles and Viaflex -500 bags were used with the i.v. administration sets. DEHP was assayed using gas chromatography. Very small or unmeasurable amounts of DEHP were leached into 0.9% sodium chloride and 5 or 10% DMA solutions during 20-hour storage. DEHP concentrations increased exponentially with increasing NMF concentrations after 20-hour storage in both the i.v. sets and bags. Similar results were found in the simulated-infusion portion of the study. DEHP extraction from i.v. sets and polyvinyl chloride bags containing NMF and DMA in 0.9% sodium chloride is related directly to the concentrations of these organic compounds. The amount of DEHP leached into solutions is important only for solutions containing 60% NMF.

Recent progress in safety evaluation studies on plasticizers and plastics and their controlled use in Japan.

Recent experimental studies in Japan on the evaluation of potential health hazards from phthalate esters used in manufacturing poly (vinyl chloride) as well as several plastics for medical devices and for food containers and packages were introduced. Development of pulmonary granuloma formation after intravenous injection of diethylhexyl phthalate was assumed to be dependent on the particle size of the phthalate in vehicle used. Dietary administration of large amount of diethylhexyl phthalate and dibutyl phthalate produced renal cysts in mothers and in descendants in reproduction studies in mice. Cytotoxicity and mutagenicity of the phthalates and several plastics and resins were also examined by in vivo and in vitro studies. Hematological parameters examined in rabbits after repeated intravenous injection of diethylhexyl phthalate and after implantation of plastics in aorta for 3--6 months did not show any significant change. A slow decrease of radioactivity was observed in adipose tissue of rats following oral administration of 14C-labeled diethylhexyl phthalate. tthe administrative action on phthalates by the Japanese Ministry of Health and Welfare is briefly reviewed.