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PubMed2001

Two episodes of ethylene oxide poisoning--a case report.

Ethylene oxide is used as a sterilizer, a solvent, a plasticizer and in the manufacture of special solvents, antifreeze, polyester resins and non-ionic surfactants. Its toxicity is caused by an alkylating reaction with most organic substances in the body. Four workers, without any protection, managed the leakage of ethylene oxide from the collecting tank improperly on July 29, 2000. In the same factory, the overflow of ethylene oxide in process resulted in leakage of ethylene oxide again on Aug. 7, 2000. Two workers were poisoned despite wearing full-face respirators with ethylene oxide approved canisters. In these two events, the workers all smelled an ether-like odor. Six workers experienced nausea, vomiting, chest tightness, shortness of breath, dizziness, cough and ocular irritation. One worker had transient loss of consciousness. Oxygen therapy and supportive care were used. Patients were discharged in stable condition. The permissible exposure limit of ethylene oxide in air is 1 ppm as an eight hour TWA. Above 50 ppm, the odor threshold, a positive-pressure supplied air respirator is needed to protect the worker. Full-face respirators with ethylene oxide approved canisters could not protect our cases who smelled the odor and were exposed to an unknown concentration. It is important to wear positive-pressure self-contained breathing apparatuses equipped with full facepieces to clean up the contamination area and rescue the patients.

Adult↗
PubMed1992

[Parkinsonism secondary to ethylene oxide exposure: case report].

Ethylene oxide is a gas widely used in the production of industrial chemicals. It is also used to sterilize heat-sensitive medical supplies. Previous reports of acute and chronic exposure have described neurotoxic effects like peripheral neuropathy and cognitive impairment. We describe a pure parkinsonian syndrome following acute ethylene oxide intoxication. A 39-years-old male was referred to our Movement Disorders Clinic for evaluation of a parkinsonian syndrome. He was acutely exposed to ethylene oxide four years before and remained comatose for three days, and gradually regained consciousness. At that time he showed a global parkinsonian syndrome including bradykinesia, rigidity and rest tremor, with a severe motor disability; no other neurological disorders were found. The symptomatology was partially controlled with biperidene and levodopa plus carbidopa. Two years later he developed L-dopa induced dyskinesias. Four years after the intoxication he was evaluated at our clinic. General examination showed no abnormalities. Neurologic examination revealed a normal mental status. Motor evaluation disclosed moderate bradykinesia, rigidity and rest tremor, shuffling gait, poor facial mimic, stooped posture, and his speech was low and monotonous; deep tendon reflexes were brisk. The Hoehn-Yahr disability score was degree IV. Routine laboratory and radiological exams showed results within normal limits. The CSF examination was normal. Brain computed tomography and magnetic ressonance were normal. A trial with bromocriptine and levodopa plus carbidopa did not improve dyskinesia, and he was put on a schedule including amantadine and biperidene with improvement to grade III in Hoehn-Yahr scale. In the present case there was a clear relation between the acute exogenous intoxication and irreversible parkinsonism.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1982

Sister chromatid exchanges induced in rabbit lymphocytes by ethylene oxide after inhalation exposure.

Ethylene oxide, which is the simplest epoxide and an extremely important commercial compound, has been used by many investigators as a model compound to study mutagenicity by alkylation of DNA. Knowledge of in vivo dose-effect relations under experimental conditions may provide further insight into the dynamics of the sister chromatid exchange (SCE) response. It may also provide information on temporal aspects of sampling design for human worker populations. Groups of four male New Zealand white rabbits were exposed in inhalation chambers to 0, 10, 50, and 250 parts per million (ppm) ethylene oxide for 6 hr a day, 5 days a week, for 12 weeks. Peripheral blood samples were taken before the start of exposure, at intervals during exposure, and up to 15 weeks after the end of exposure to measure SCE rates in peripheral lymphocytes as well as standard hematological endpoints. Additionally, the level of reduced glutathione (GSH) in liver and blood was measured in a set of concurrently exposed animals at the end of the 12-week exposure. Results show that exposure to 10 ppm does not cause a detectable increase in SCE rates. However, exposure to 50 and 250 ppm does cause an increase in SCEs that decreases after exposure ends, but still remains above baseline levels 15 weeks after exposure. Hematological and GSH measurements did not differ between control and exposed groups. These results indicate that inhalation exposure to the mutagenic alkylating agent ethylene oxide results in a dose-related SCE effect, and that SCE is a more sensitive indicator of exposure than either standard hematological end points or GSH levels.

Animals↗
PubMed1984

Inhalation pharmacokinetics based on gas uptake studies. VI. Comparative evaluation of ethylene oxide and butadiene monoxide as exhaled reactive metabolites of ethylene and 1,3-butadiene in rats.

When ethylene oxide or butadiene monoxide is added to the atmosphere of a closed inhalation chamber occupied by Sprague-Dawley rats, a first-order elimination pattern is observed. When either of these compounds is IP injected into rats which are subsequently placed in the closed chamber, the course of epoxide in the atmosphere follows Bateman exponential functions. From the experimental data, the kinetic parameters for distribution and metabolic elimination of ethylene oxide and butadiene monoxide can be derived. When ethylene or 1,3-butadiene was added to the closed exposure systems and kept at atmospheric concentrations which assured maximal metabolic turnover of the olefin (i.e., concentrations above 1,000 ppm ethylene or 1,500 ppm 1,3-butadiene), exhalation of the appropriate epoxide occurred and led finally to a constant (plateau) concentration of the reactive metabolite in the system's atmosphere. Although the initial time-course was different between butadiene monoxide and ethylene oxide (with a high initial increase of ethylene oxide and a subsequent decrease) an analysis at steady-state (plateau concentrations) revealed that only 29% of the amounts of both epoxides which in theory are formed as primary metabolites from the parent olefins are systematically available (i.e., distributed in the entire organism). The discrepancy is probably related to first pass elimination of the epoxide.

Animals↗
PubMed1977

Simple GLC determination of ethylene oxide and its reaction products in drugs and formulations.

Convenient rapid GLC methods for the estimation of residual ethylene oxide, ethylene chlorohydrin, and ethylene glycol in ethylene oxide-sterilized bulk drugs and formulations prepared therefrom are described. Ethylene oxide was chromatographed using a porous polymer column; ethylene chlorohydrin and ethylene glycol were chromatographed using either polyethylene glycol 400 or a porous polymer column. All three residuals were determined from the same sample preparation for each type of drug or formulation examined. Recoveries of each of the three residuals were greater than 95% for all samples examined. Detection limits, at moderate electrometer sensitivities, were 2 microgram/g or ml for ethylene oxide and ethylene chlorohydrin and 5 microgram/g or ml for ethylene glycol. The most likely interferences are discussed.

Chromatography, Gas↗
PubMed1995

Ethylene oxide sterilization update.

Ethylene oxide (EtO) sterilization technology faced an uncertain future a few years ago, but this situation has now changed. The factors involved and the advantages offered by the latest technically sophisticated EtO technology are reviewed in this article.

Chlorofluorocarbons↗
PubMed1990

Preparation of electrophoric derivatives of N7-(2-hydroxyethyl)guanine, an ethylene oxide DNA adduct.

Ethylene oxide, a potential human carcinogen, mainly damages DNA by reacting at guanine sites to form N7-(2-hydroxyethyl)guanine. In order to determine this DNA adduct with high sensitivity by gas chromatography, we have prepared, for comparison purposes, four electrophoric derivatives. The two that are most promising to date are bis- and tris-pentafluorobenzyl products prepared by first chemically transforming the N7-(2-hydroxyethyl)guanine to a corresponding xanthine, and then reacting the latter with pentafluorobenzyl bromide. These two derivatives are obtained in good yields and give molar responses of 0.6 and 0.5, respectively, relative to that of lindane by gas chromatography with electron-capture detection.

Chromatography, Gas↗
PubMed1991

Ultrastructural changes produced in dorsal root ganglia in vitro by exposure to ethylene oxide from hemodialyzers.

Ethylene oxide (EO) gas, used to sterilize hemodialysis equipment, is a known neurotoxin and residual gas remains in dialyzers after airing. If tissue culture medium is incubated in dialyzers and then rat dorsal root ganglion (DRG) cultures are exposed to this medium, characteristic changes occur. These include axonal swellings and the death of neurons after five days. Electron microscope findings were compared between DRG grown in control medium containing 10% calf serum, DRG incubated in the same medium exposed to the blood compartment of capillary flow or plate dialyzers and DRG grown in medium supplemented with 10% dialysis patient serum. Electron microscope findings included frequent axonal swellings with the accumulations of membrane bound vesicles and the apparent disruption of microtubules. There were also conspicuous accumulations of membrane bound vesicles, dense bodies, myeloid figures, and areas of vesicular degeneration in Schwann cells. These changes were seen with dialyzer exposed medium or with medium containing patient serum but not with controls or with medium incubated in plate dialyzers. The changes were similar to those reported in nerve biopsy specimens from patients with known EO neuropathy.

Animals↗
PubMed1993

Molecular dosimetry of DNA and hemoglobin adducts in mice and rats exposed to ethylene oxide.

Experiments involving ethylene oxide (ETO) have been used to support the concept of using adducts in hemoglobin as a surrogate for DNA adducts in target tissues. The relationship between repeated exposures to ETO and the formation of N-(2-hydroxyethyl)valine (HEtVal) in hemoglobin and 7-(2-hydroxyethyl)guanine (7-HEG) in DNA was investigated in male rats and mice exposed by inhalation to 0, 3, 10, 33, or 100 ppm ETO for 6 hr/day for 4 weeks, or exposed to 100 ppm (mice) or 300 ppm (rats) for 1, 3, 5, 10, or 20 days (5 days/week). HEtVal was determined by Edman degradation, and 7-HEG was quantitated by HPLC separation and fluorescence detection. HEtVal formation was linear between 3 and 33 ppm ETO and increased in slope above 33 ppm. The dose-response curves for 7-HEG in rat tissues were linear between 10 and 100 ppm ETO and increased in slope above 100 ppm. In contrast, only exposures to 100 ppm ETO resulted in significant accumulation of 7-HEG in mice. Hemoglobin adducts were lost at a greater rate than predicted by normal erythrocyte life span. The loss of 7-HEG from DNA was both species and tissue dependent, with the adduct half-lives ranging from 2.9 to 5.8 days in rat tissues (brain, kidney, liver, lung, spleen, testis) and 1.0 to 2.3 days in all mouse tissues except kidney (t1/2 = 6.9 days). The concentrations of HEtVal were similar in concurrently exposed rats and mice, whereas DNA from rats had at least 2-fold greater concentrations of 7-HEG than DNA from mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1999

Occupational exposure to ethylene oxide of hospital staff.

Occupational exposure to ethylene oxide was assessed among the workers remaining in direct contact with ethylene oxide or with ethylene oxide-sterilized instruments in 13 hospitals located in the city of Lódź and its suburbs. Individual dosimetry and stationary sampling methods were employed. The samples collected from the occupational environment were analysed by gas chromatography with mass detection. The analytical method enabled determination of low ethylene oxide concentrations in the presence of the accompanying chemicals, such as ethyl alcohol, isopropyl alcohol, ethyl ether and isoflurene. In total, 227 determinations were made, and ethylene oxide at concentrations above 0.01 mg/m3 (which was the detection limit of the method) was found to be present in 164 samples. The ethylene oxide levels were found to vary widely, from lower than 0.01 TLV to several hundred times the TLV value.

Air↗
PubMed1995

Effectiveness of ethylene oxide for sterilization of dental handpieces.

Ethylene oxide gas has been utilized as an alternative method for sterilization of dental handpieces, as it is less corrosive than steam. However, its effectiveness for sterilization of the internal components of dental handpieces has not been established. The objective of this study was to compare the effectiveness of ethylene oxide and steam for sterilization of dental handpieces. Unused handpieces and handpieces which had been exposed to clinical dental procedures ('clinical') were contaminated with Streptococcus mutans, exposed to steam or ethylene oxide, and flushed with sterile saline. Washings were plated on mitis-salivarius agar, and colonies identified and counted. No viable colonies could be established from washings from 'clinical' or 'unused' handpieces exposed to steam. However, viable colonies could be established from 'clinical' handpieces exposed to ethylene oxide. This data suggests that a substance entrapped within 'clinical' handpieces (possibly the biofilm) may protect bacteria from ethylene oxide gas, preventing adequate sterilization.

Biofilms↗
PubMed1996

Synthesis and characterization of peptide adducts for use in monitoring human exposure to acrylonitrile and ethylene oxide.

Human exposure to ethylene oxide and acrylonitrile may be monitored by determination of the products that these electrophilic compounds form with the amino terminal of hemoglobin. The procedure involves a modified Edman degradation, using the reagent pentafluorophenyl isothiocyanate, which cleaves the adducted N-terminal amino acid from the protein chain as a substituted pentafluorophenyl thiohydantoin. This may then be quantitated using selected ion monitoring gas chromatography-mass spectrometry (GC-MS). To overcome problems arising from the lack of an ideal internal standard for this analysis, we have now synthesized adducts of ethylene oxide and acrylonitrile with the N-terminal tripeptide of the alpha-chain of human globin (Val-Leu-Ser). These adducts should behave analogously to the protein adduct in the Edman degradation. The adducts were characterized by nuclear magnetic resonance and fast atom bombardment and electrospray MS and tandem MS. Additionally, an analogous stable isotope-labeled standard was synthesized for the acrylonitrile adduct using a d8-labeled tripeptide. Quantitative calibration lines for analysis of the adducts have been established and the validity of the assays established by the detection of acrylonitrile adducts in the globin of acrylonitrile-exposed workers and of cigarette smokers.

Acrylonitrile↗
PubMed1982

[Cytogenetic effects of ethylene oxide poisoning].

Mutagenic effects of ethylene oxide have been demonstrated by short-term testing in vitro and in vivo in several organisms. Oncogenic activity in human has been suspected and recently supported by experiments in mice. Exposure can occur during ethylene oxide gas sterilization of medical materials. We have tested effects on chromosomes by evaluative sister chromatids exchange frequency. A statistically significant increase in the rate of SCE has been observed in workers exposed occupationally to ethylene oxide, compared with controls.

Adult↗
PubMed1982

Carcinogenicity of ethylene oxide and 1,2-propylene oxide upon intragastric administration to rats.

Ethylene oxide and 1,2-propylene oxide were each administered intragastrically by gavage at 2 dosages (30 and 7.5 mg/kg body wt; 60 and 15 mg/kg body wt respectively) to groups of 50 female Sprague-Dawley rats twice weekly for a period of nearly 3 years using salad oil as the solvent. Both compounds induced local tumours, mainly squamous-cell carcinomas of the forestomach, dependent on the dosage. The first tumour occurred in the 79th week both in the group treated with ethylene oxide and in that treated with 1,2-propylene oxide. The following tumour rates resulted: ethylene oxide 62 and 16%; 1,2-propylene oxide 40 and 4%. In addition carcinomata in situ, papillomas and reactive changes of the squamous epithelium of the forestomach were observed in other animals, but neither ethylene oxide nor 1,2-propylene oxide induced tumours at sites away from the point of administration.

Animals↗
PubMed1993

[Measurement of ethylene oxide at a medical sterilization site].

Although ethylene oxide gas is widely used as a sterilizing agent for medical instruments because of its disinfection property, the effects of its use in medical settings have not been clarified. In the present study, we measured the ethylene oxide gas concentration (EOGC) within a hospital sterilization unit and in the ambient air near the unit. Before the sterilizer was turned on (about 9:00), the ambient air EOGC was below the detection limit (0.1 ppm). When the door was opened to place the instruments in the sterilizer, the maximum EOGC near the door of the sterilizer was 1.71 ppm. Before the sterilizer door was opened, the residual EOGC within the sterilizer was 0.10-24.56 ppm. During the operation of the sterilizer (9:00-17:00), ethylene oxide gas could not be detected in the air near the unit. When the sterilizer door was opened at the end of the routine operation of the sterilizer (about 17:00), EOGC near the door was 2.10-2.73 ppm. After the door was closed, the ambient air EOGC level was 0.5-0.57 ppm. These findings indicate that the personnel near the unit were exposed to ethylene oxide gas for about 15 min during the transfer. However, no ethylene gas could be detected by the ethylene oxide gas monitor (3M Co., #3551). The finding that EOGC in sterilized medical instruments after 24 h of aeration was about 2 ppm also suggests that the personnel using these instruments were exposed to ethylene oxide gas.(ABSTRACT TRUNCATED AT 250 WORDS)

Air↗
PubMedDate not supplied

Differences in the adsorption behaviour of poly(ethylene oxide) copolymers onto model polystyrene nanoparticles assessed by isothermal titration microcalorimetry correspond to the biological differences.

The adsorption behaviour of a tetrafunctional copolymer of poly (ethylene oxide)-poly (propylene oxide) ethylene diamine (commercially available as Poloxamine 908) and a diblock copolymer of poly (lactic acid)-poly (ethylene oxide) (PLA/PEG 2:5) onto a model colloidal drug carrier (156 nm sized polystyrene latex) is described. The adsorption isotherm, hydrodynamic thickness of the adsorbed layers and enthalpy of the adsorption were assessed. The close similarity in the conformation of the poly (ethylene oxide) (PEO) chains (molecular weight 5,000 Da) in the adsorbed layers of these two copolymers was demonstrated by combining the adsorption data with the adsorbed layer thickness data. In contrast, the results from isothermal titration microcalorimetry indicated a distinct difference in the interaction of the copolymers with the polystyrene colloid surface. Poloxamine 908 adsorption to polystyrene nanoparticles is dominated by an endothermic heat effect, whereas, PLA/PEG 2:5 adsorption is entirely an exothermic process. This difference in adsorption behaviour could provide an explanation for differences in the biodistribution of Poloxamine 908 and PLA/PEG 2:5 coated polystyrene nanoparticles observed in previous studies. A comparison with the interaction enthalpy for several other PEO-containing copolymers onto the same polystyrene colloid was made. The results demonstrate the importance of the nature of the anchoring moiety on the interaction of the adsorbing copolymer with the colloid surface. An endothermic contribution is found when an adsorbing molecule contains a poly (propylene oxide) (PPO) moiety (e.g. Poloxamine 908), whilst the adsorption is exothermic (i.e. enthalpy driven) for PEO copolymers with polylactide (PLA/PEG 2:5) or alkyl moieties.

Adsorption↗
PubMed2005

Toward an easy access to dendrimer-like poly(ethylene oxide)s.

Dendrimer-like poly(ethylene oxide)s (PEOs) were synthesized by an iterative divergent approach combining anionic polymerization of ethylene oxide from multi-hydroxylated precursors and branching reactions of PEO chain ends. Partial deprotonation of the hydroxyls (< 30%) and use of dimethyl sulfoxide as solvent proved crucial for a "controlled/living" polymerization of ethylene oxide at room temperature. These sequences of reactions allowed us to prepare a dendrimer-like PEO up to the eighth generation with a molar mass of 900 000 g mol(-1) and 384 external hydroxyl functions. All samples from generation 1 to 8 were characterized by 1H NMR spectroscopy, light scattering, and viscometry. The evolution of the intrinsic viscosity versus the generation number of these dendrimer-like PEO is similar to that of regular dendrimers.

Magnetic Resonance Spectroscopy↗
PubMed2005

Solid-state stability and characterization of hot-melt extruded poly(ethylene oxide) films.

Poly(ethylene oxide) (PEO) was used to prepare thin polymer films containing clotrimazole (CT) utilizing hot-melt extrusion (HME) technology. Films containing PEOs of two different molecular weights and the drug were investigated for solid-state characteristics, moisture-sorption, bioadhesivity, mechanical properties, release characteristics, and physical and chemical stability of the drug within the HME films. The solid-state characterization of the drug and the polymer were performed utilizing differential scanning calorimetry and X-ray diffractometry. A Texture analyzer was utilized to study the bioadhesive and mechanical properties of the HME films. Physical and chemical stability of the films, stored at 25 degrees C/60% RH, was studied for up to 12 months. XRD profiles indicated that the drug was physically unstable (recrystallization of the drug occurred) after storage for 3 months at 25 degrees C/60% RH. Based on the DSC studies, it has been proposed that the recrystallization of the drug may be due to the folding (due to HME) and unfolding (upon storage) of the linear PEO chains. Desirable bioadhesive, mechanical, and thermoplastic properties of PEO qualify it as a promising and potential drug carrier. However, further investigation is necessary to enhance the physical stability of these PEO-drug systems.

Antifungal Agents↗