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Li+ transport in lithium sulfonylimide-oligo(ethylene oxide) ionic liquids and oligo(ethylene oxide) doped with LiTFSI.

The Li+ environment and transport in an ionic liquid (IL) comprised of Li+ and an anion of bis(trifluoromethanesulfonyl)imide anion (TFSI-) tethered to oligoethylene oxide (EO) (EO(12)TFSI-/Li+) were determined and compared to those in a binary solution of the oligoethylene oxide with LiTFSI salt (EO(12)/LiTFSI) by using molecular dynamics (MD) simulations and AC conductivity measurements. The latter revealed that the AC conductivity is 1 to 2 orders of magnitude less in the IL compared to the oligoether/salt binary electrolyte with greater differences being observed at lower temperatures. The conductivity of these electrolytes was accurately predicted by MD simulations, which were used in conjunction with a microscopic model to determine mechanisms of Li+ transport. It was discerned that structure-diffusion of the Li+ cation in the binary electrolyte (EO(12)/LiTFSI-) was similar to that in EO(12)TFSI-/Li+ IL at high temperature (>363 K), thus, one can estimate conductivity of IL at this temperature range if one knows the structure-diffusion of Li+ in the binary electrolyte. However, the rate of structure-diffusion of Li+ in IL was found to slow more dramatically with decreasing temperature than in the binary electrolyte. Lithium motion together with EO(12) solvent accounted for 90% of Li+ transport in EO(12)/LiTFSI-, while the Li+ motion together with the EO(12)TFSI- anion contributed approximately half to the total Li+ transport but did not contribute to the charge transport in IL.

Journal Article↗

Evaluation of an ethylene oxide sterilizer.

Ethylene oxide gas can be used under controlled conditions to sterilize heat and moisture sensitive articles, particularly those which cannot be steam sterilized or immersed in disinfectants. The ethylene oxide process is essentially one of sterilization and all micro-organisms, including bacterial spores, are destroyed.

Equipment and Supplies, Hospital↗

Limitations of thioglycolate broth as a sterility test medium for materials exposed to gaseous ethylene oxide.

Although ethylene oxide is a reliable sterilizer, the process may be limited by diffusion. Thus, situations may exist where microorganisms are protected from the sterilizing gas. It is possible that the exterior of a substance may be sterilized, whereas the interior is not. We investigated three general types of materials in which this limitation of diffusion could occur: the bore of glass and plastic tubing, the center of cotton balls, and plastic adhesive film/paper backing interface. These materials were contaminated as close to their geometric center as possible with Bacillus subtilis var. niger spores occluded in crystals of sodium chloride. After exposure of the contaminated materials (except aluminum foil) to ethylene oxide, thioglycolate broth (a standard sterility-test medium) indicated sterility, whereas Trypticase Soy Broth indicated nonsterility. It is likewise possible that aerobic microorganisms, surviving in or on material after exposure to dry heat or steam sterilization processes, would not be recovered by thioglycollate broth. Entrapped aerobic organisms will probably not grow out in the low oxygen tension zone of an anaerobic medium such as thioglycollate broth. It is recommended than an aerobic medium such as Trypticase Soy Broth be used concurrently with thioglycolate broth for sterility testing.

Bacillus subtilis↗

Aeration time following ethylene oxide sterilization for reusable rigid sterilization containers: concentration of gaseous ethylene oxide in containers.

Because ethylene oxide (EO) gas is toxic to humans, restrictions have been imposed on its use for sterilization, specifying allowable levels of residual EO remaining in sterilized apparatus and materials. However, the aeration time that optimizes the removal of the remaining EO when a rigid sterilizing container is used for a vessel had not been identified. Therefore, polyvinyl chloride, which easily adsorbs EO, was placed in rigid sterilizing containers, and aeration was carried out after 1, 8, 12, 17, and 24 hours. After standard EO sterilization, the EO concentrations remaining in the air in the rigid containers were measured. The results indicate that a period of 17 hours of aeration is appropriate when a rigid sterilizing container is used.

Air↗

Microbiological aspects of ethylene oxide sterilization. 3. Effects of humidity and water activity on the sporicidal activity of ethylene oxide.

An investigation determined the effects of environmental moisture content or water activity (Aw), exposure humidity, and sterilant concentration on the resistance of microbial spores. Decimal reduction values [expressed as D values at 54.4 C-specified concentration (milligrams per liter) of ethylene oxide] were determined from spore destruction curves of Bacillus subtilis var. niger dried on hygroscopic and nonhygroscopic surfaces. Four groups of spore preparations were preconditioned in one of four Aw environments (<0.1, 0.1, 0.5, 0.95) for 2 weeks or longer and were exposed to 500 mg of ethylene oxide per liter at 54.4 +/- 3 C and 10, 50, and 95% relative humidity in a specially designed thermochemical death rate apparatus. A fifth group did not receive any preconditioning treatment and was exposed immediately after preparation, in the same apparatus at the same temperature, to ethylene oxide concentrations of 200, 400, 600, 800, and 1,200 mg/liter and relative humidities of 15, 30, 50, 60, and 90%. The resistance of the spores on both types of surfaces to ethylene oxide increased proportionately with the Aw of the conditioning environment. The study also showed that moisture in the exposure system was not as critical a variable as the ethylene oxide concentration. The spore destruction rates, irrespective of the carrier types at all concentrations and at different humidities, varied little from one another. The decimal reduction values were reduced as the ethylene oxide concentration increased, and no optimal exposure humidity concentration was observed.

Bacillus subtilis↗

Effect of cast solvent on the electron transfer reaction for poly(ethylene oxide)-modified myoglobin on the electrode in poly(ethylene oxide) oligomers.

Myoglobin from horse skeletal muscle was modified with poly(ethylene oxide) (PEO) with an average molecular weight of 2000 or 5000. Myoglobin was soluble after this modification in several organic solvents and PEO oligomers. The electron transfer reactions of PEO-modified myoglobin cast on the indium tin oxide (ITO) glass electrode were investigated by cyclic voltammetry. The PEO-modified myoglobin, cast on the electrode from water or a methanol solution, showed quasi-reversible redox reactions in PEO (average MW of 400). On the other hand, no redox response was seen in PEO-modified myoglobin cast on it using chloroform or benzene as a casting solvent. A clear redox response of the PEO-modified myoglobin was observed after methanol treatment of these layers cast from chloroform or a benzene solution. This suggests that the conformational change of the adsorbed PEO-modified myoglobin layer on the ITO electrode cast from chloroform or a benzene solution was not irreversible. The cast condition of PEO-modified myoglobin on the ITO glass electrode was revealed to affect the electron transfer reaction for protein considerably in PEO oligomers.

Animals↗

Physico-chemical and toxicologo-hygienic aspects of using ethylene oxide for the sterilization of medical appliances. Part I. Sorption and diffusion of ethylene oxide in polymeric materials.

Sorption ability of polymeric materials for medical purposes was studied with respect to the sterilizing gas - ethylene oxide - at 23, 35 and 55 degrees C. Sorption coefficients of ethylene oxide (EO) for the materials under study were calculated on the basis of results. Investigation of the kinetics of desorption of EO from the polymeric materials for medical purposes has shown that its content changes exponentially depending on the time of degassing. However, the lines in the 1g Q/Q0 - tau coordinates show a sharp break which testifies to a change in the mechanism of the process determining the character of the mentioned dependence. In the first region, corresponding to high concentrations and short periods of time, the determining process is diffusion while in the second region (low concentrations, long time intervals) - it is desorption of EO molecules most firmly bound to the polymer. Diffusion coefficients were calculated for the first region. The possibility of predicting the time periods of removing ethylene oxide from the polymeric materials was demonstrated for both stages on the basis of calculated diffusion coefficients and kinetic curves of degassing. Recommendations were given for the use of polymers for medical appliances and apparatuses.

Diffusion↗

Pharmacokinetics of ethylene in man; body burden with ethylene oxide and hydroxyethylation of hemoglobin due to endogenous and environmental ethylene.

The inhalation pharmacokinetics and the endogenous production of ethylene has been determined in healthy volunteers with respect to the formation of the carcinogen ethylene oxide. Ethylene showed a low degree of accumulation in the body determined in six subjects, the thermodynamic partition coefficient "body/air" being 0.53 +/- 0.23 (mean +/- SD) and the accumulation factor "body/air" at steady-state being 0.33 +/- 0.13 (mean +/- SD). The rate of metabolism was directly proportional to the exposure concentration. Only 2% of ethylene inhaled was metabolized to ethylene oxide, whereas 98% of ethylene was exhaled unchanged. The rate of the endogenous production of ethylene was 32 +/- 12 nmol/h (mean +/- SD), as calculated from exhalation data from 14 subjects. The resulting body burden was 0.44 +/- 0.19 nmol/kg (mean +/- SD). By analyzing published data on ethylene oxide in man its half-life was estimated to be 42 min. Using the pharmacokinetic parameters of ethylene and ethylene oxide, the body burden of ethylene oxide due to the sum of the exposure to environmental ethylene of about 15 ppb and to endogenous ethylene exposure of 0.44 nmol/kg was predicted to be 0.25 nmol/kg. In the blood of five non-smokers and one smoker the hemoglobin adduct resulting from the reaction of ethylene oxide with the N-terminal valine, N-(2-hydroxyethyl)valine, was quantified by gas chromatography/mass spectrometry. The value of 20 +/- 5 pmol/g Hb (mean +/- SD) found in the non-smokers corroborated the steady-state level of 18 +/- 3 pmol/g Hb (mean +/- SD) calculated from the pharmacokinetic approach.

Adult↗

Detection and quantitation of ethylene oxide, 2-chloroethanol, and ethylene glycol with capillary gas chromatography.

A procedure is described for detection and quantitation of ethylene oxide and two major reaction products. Detection of ethylene oxide residuals extracted from alcohol pads (cellulose) and plastic material is illustrated. Quantitation of the three compounds can be obtained with a single gas chromatographic (GC) analysis. A DB-Wax-30N, 0.25 mm i.d. column is used with 1:50 split injections with dimethylformamide as the solvent and 1:100 split injections with water as the solvent. A DB-Wax-30W, 0.32 mm i.d. column is used for on-column injections and 1:100 split water injections. Linearity of the three compounds is demonstrated.

Chromatography, Gas↗

Control of medicine release from solid dispersion composed of the poly(ethylene oxide)-carboxyvinylpolymer interpolymer complex by varying molecular weight of poly(ethylene oxide).

Solid dispersion composed of the poly(ethylene oxide) (PEO)-carboxyvinylpolymer (CP) interpolymer complex containing phenacetin (PHE) was prepared by using nine grades of PEO having different molecular weights from 2000 to 4500000. We attempted to control the medicine release from the PEO-CP solid dispersion by varying the molecular weight of PEO. The physicochemical properties of the solid dispersion were analyzed by powder X-ray diffractometry and thermal analysis. The interaction between PEO and CP was analyzed by IR spectroscopy. Transmittance of the polymer solution was measured to study the complexation between PEO and CP. The release profile of PHE varied depending on the molecular weight of PEO. The minimum release rate was observed at the PEO molecular weight of 35000. It was found that the amount of the PEO-CP complex formation by hydrogen bonding changed depending on the molecular weight of PEO. These results indicate that it is feasible to control the medicine release from the PEO-CP solid dispersion by varying the molecular weight of PEO.

Analgesics, Non-Narcotic↗

Evaluating the formulae for integrated lethality in ethylene oxide sterilization using six different endospore forming strains of bacteria, and comparisons of integrated lethality for ethylene oxide and steam systems.

Bacterial endospores from six different species of bacteria were exposed to a spectrum of ethylene oxide (EtO) sterilizing conditions. Temperature was varied from 40 to 60 degrees C and the ethylene oxide concentration was varied from 300 to 750 mg/L. Relative humidity was maintained at 60+/-10% RH. The fraction negative procedure was used to determine the D value for each of the test conditions. Bacterial species tested included Bacillus atrophaeus ATCC # 9372, Bacillus smithii ATCC # 51232, Bacillus subtilis "5230" ATCC # 35021, Bacillus subtilis, DSM # 4181, Bacillus pumilus ATCC # 27142, and Geobacillus stearothermophilus ATCC # 7953. All spore preparations were inoculated on filter paper strips packaged in blue, sterilizable glassine pouches. G. stearothermophilus was the least resistant organism tested. The most resistant organisms tested were B. atrophaeus and B. subtilis "5230". The B. subtilis "5230" strain was slightly more resistant than B. atrophaeus at conditions of 54C and EtO concentrations of 400, 600, and 750 mg/L, as well as at 60C/750mg/L EtO. The other species were between these extremes. This empirical data allowed the application of the recently published formula for converting D values from one set of conditions to another and evaluations of accuracy. The measured D values also allowed the determination of Z values based on temperature variations. These formulae, when applied to process temperatures independent of gas concentration, result in a Z value of approximately 32 degrees C that appears to be similar for all species tested. These data support the application of the previously published formulae 1-6 and allow the same approach to integrated lethality for ethylene oxide processes as is commonly applied to steam sterilization. A review of steam sterilization and related principles was conducted for comparison of integrated lethality for these two methods of sterilization. Errors associated with D values, Z values, extrapolation, and integrated lethality for both methods of sterilization are discussed.

Endospore-Forming Bacteria↗

Phase separation in the mixture of schizophyllan and poly(ethylene oxide) in aqueous solution driven by a specific interaction between the glucose side chain and poly(ethylene oxide).

We found that the mixture of schizophyllan and poly(ethylene oxide) in aqueous solution underwent phase separation at around 3-4 degrees C, and this temperature was independent of both polymer concentration and the difference in poly(ethylene oxide) molecular weight (Mw 6000 and 70,000). The phase-separation took place at the same temperature at which the optical rotation changed. Since the optical rotation change is ascribed to the difference in the nature of hydrogen bonding between the schizophyllan side chain and water, the phase separation is also considered to be due to an interaction between poly(ethylene oxide) and schizophyllan. The phase-separation temperature increased on changing H2O to D2O in accordance with a change in the optical rotation, confirming the specific interaction essential for the phase separation.

Chemical Phenomena↗

Ethylene oxide sterilization of medical devices--with special reference to the sporicidal activity and residual concentration of ethylene oxide and its secondary products.

For the sterilization of disposable medical devices, ethylene oxide gas is used in most cases. When this sterilization method is used, ethylene oxide (EO) and its secondary products, i.e., ethylene chlorohydrin (ECH) and ethylene glycol (EG), remain in the medical devices after sterilization. If their concentration is high, these residues are liable to cause hemolytic activity and dermal or mucous membrane irritability in the human body. For this reason, in 1978 the FDA announced a proposal to regulate the residual limits of EO, ECH and EG. Our studies were done to examine the conditions of EO sterilization from the viewpoints of the sterilization effect and the residual chemical substances and to find the optimum conditions for sterilization. Further, the aerator was fabricated for the exclusive purpose of reducing, within a brief period, the concentration of EO and other substances remaining in the medical devices after sterilization and we examined the condition of aeration by using this aerator. As the result, it was found that a satisfactory sterilization effect could be obtained under the sterilization conditions of an EO gas concentration of 500 mg/liter, a sterilizing temperature of 55 to 60 degrees C and a sterilizing time of two hours, and under these conditions the concentration of the residual substances such as the EO could be made comparatively lower. It was also clarified that the minimum required aeration conditions by using the exclusive-use aerator were a temperature of 55 to 60 degrees C and an aeration time of 24 hours and over.

Equipment and Supplies↗

[The effect of gas concentration on ethylene oxide sterilization].

Ethylene oxide (EO) gas is widely used for sterilization of medical instruments and supplies. The gas being used in our hospital consists of 20% EO and 80% carbon dioxide and is packed in a cylinder as liquefied gas. We investigated the relationship between the composition of the gas and the amount of EO gas used by measuring the EO concentration in a sterilizer. The concentration of EO was increased as the amount of gas increased, and it decreased sharply when the remaining gas in the cylinder decreased up to about 12% of its initial value. This value agreed with the calculated one by gas-liquid equilibrium when all of the liquefied gas was consumed and only saturated gas remained in the cylinder.

Ethylene Oxide↗

Poly(ethylene oxide sulfide): new poly(ethylene glycol) derivatives degradable in reductive conditions.

Poly(ethylene oxide sulfide) (PEOS), polymers consisting of an internal ethylene oxide oligomer and disulfide linkage, were synthesized and characterized. The degree of polymerization was dependent upon temperature, dimethyl sulfoxide condition, and monomer hydrophobicity. The stability of PEOS was measured by the size exclusion chromatography method after the incubation both with and without 5 mM glutathione. The disulfide bond was stable in the extracellular condition but completely degraded in 2 h in the reductive cytosolic condition. Hydrophilic PEOS polymers showed no cytotoxicity on the HepG2 cell line. On the basis of these properties, PEOS can be applied in many drug delivery fields.

Cell Line, Tumor↗