What is ethylene oxide sterilization used for?

Environmental Fate and Behavior

Ethylene oxide released to the environment partitions primarily to the atmosphere due to its high volatility (vapor pressure 146 kPa at 20 °C). Although the high water solubility of ethylene oxide suggests it can be extracted from air by rainfall, its rapid volatilization from water (half-life of 1 h) argues against this process being a significant factor in its environmental fate. In the atmosphere, ethylene oxide reacts with hydroxyl radicals resulting in a half-life of 2–5 months. In freshwater, ethylene oxide is hydrolyzed to ethylene glycol (half-life ∼1 week); in salt water, it is hydrolyzed to ethylene glycol and ethylene chlorohydrin (half-life ∼2 weeks). In unacclimated aqueous media, ethylene oxide is also subject to biodegradation with estimated half-lives of 1–6 months (aerobic) and 4–24 months (anaerobic). However, in the presence of activated sludge, ethylene oxide is readily biodegradable. Due to its high volatility and water solubility, ethylene oxide is not expected to persist in soil or sediments. The low log Kow (−0.30) for ethylene oxide indicates little potential for bioaccumulation.

35.17.5.1 Ethylene Oxide

Ethylene oxide (C2H4O), sometimes called oxirane, is an organic alkylating gas with very potent and highly penetrating properties. Ethylene oxide is capable of destroying most viruses, bacteria, and fungi, including bacterial spores. It reacts with protoplasm, DNA, and proteins and deactivates enzymes and other biologically important components of a living organism. Ethylene oxide is more effective in killing microorganisms under dry conditions. The objective of the aeration period is to remove ethylene oxide residues and by-products, such as ethylene glycol (formed out of ethylene oxide and ambient humidity) and ethylene chlorohydrine (formed out of ethylene oxide and materials containing chlorine, eg, Polyvinyl Chloride (PVC)). Ethylene oxide does not cause changes to the physical and mechanical properties of the items treated (eg, no degradation of plastics occurs), however, negative aspects of ethylene oxide are toxic and explosive properties (Sandle, 2013b).

4.410.2.3.1 Ethylene oxide

EO is bactericidal, sporicidal, and virucidal, and has been widely used as a low-temperature sterilant since the 1950s. EO is a colorless gas that is flammable and explosive.

EO's microbiocidal activity is a result of alkylation of proteins, DNA, and RNA in microorganisms, which prevents normal cellular metabolism and replication and thus renders affected microbes nonviable.10–12 EO's high reactivity in combination with high diffusivity plays a major role in the inactivation of microorganisms.

In EO sterilization process, the major factors that affect the lethality of sterilization include EO concentration, temperature, humidity, and exposure time.12,13 The bioburden reduction increases with the increase of EO concentration, exposure time, and temperature. Humidity is another critical variable in EO sterilization. In the range of 30–90% humidity, the humidity does not have significant impact on lethality, and sterilization efficacy decreases markedly below 30% and above 90%. The commonly used operational ranges for EO concentration, temperature, humidity, and exposure time are 450–1200 mg l−1, 29–65 °C, 45–85%, and 2–5 h, respectively.12

Besides the major parameters mentioned above, other variables, such as product bioburden, device/package properties, load density, and configuration, should also be considered. In addition, the raw material composition, material diffusion properties, sensitivity to both negative and positive pressure changes, and maximum allowed heat and moisture as well as chemical tolerance to EO should be analyzed to determine if the EO is a suitable sterilization method for the material.

The potential hazards of EO to people and the environment, such as mutagenicity potential and risks associated with handling a flammable gas, have limited its use.14–16 However, if the recommended practices are followed and current Occupational Safety and Health Administration EO regulations are met, EO can be used safely.

In addition to EO toxicity concerns at work place, it should be noted that EO and EO derived residues in sterilized products also encounter toxicity issues. EO and its derivatives, such as ethylene chlorohydrin, formed in the presence of chloride ions, and ethylene glycol, formed by reaction of EO with water, are toxic residues. The allowable EO residual and its derivatives by categorization of products are specified by International Organization for Standardization.17 Removal of EO and its derivatives from the EO-sterilized biomaterials to the acceptable level is essential to ensure the safety of the medical device, and the removal process sometimes becomes a challenge.

Despite EO's toxicity and safety concerns, for some sensitive materials, EO is the only acceptable sterilization method.18 In contrast to irradiations and heat sterilizations that have deleterious effects on biological materials and polymers,19 EO is compatible with a wide range of materials, and its penetration properties make EO sterilization the most suitable process for the majority of heat- and/or moisture-sensitive medical products.20

Ethylene Oxide

Ethylene oxide (EO) is the most commonly used agent in chemical sterilization. Because it is a gas, it rapidly penetrates packaging and items to be sterilized at temperatures tolerated by almost all materials. However, its use is limited by the size of the equipment, the time requirement, and concerns about toxicity. It is recommended for use only for items unsuitable for steam sterilization, including laparoscopes, light cables, and camera heads.15,19 In fact, because of environmental concerns, EO sterilizers are now required by law to be retrofitted with abaters that reduce more of the exhausts to water vapor. Despite the use of abaters, the Environmental Protection Agency has outlawed the use of EO sterilizers altogether in some areas. Gas plasma sterilizers are a logical replacement choice (see later).

EO is an alkylating agent that kills microorganisms by inactivation of proteins, DNA, and RNA, and it is effective against vegetative bacteria, fungi, viruses, and spores.20 It is supplied as a gas mixed with a carrier agent (Freon or CO2) to reduce flammability.5 Mixed with air or oxygen, EO is explosive and flammable.5 Carbon dioxide is the preferred diluent because of environmental concerns about fluorinated hydrocarbon (Freon) release, although EO has a tendency to stratify from carbon dioxide in storage containers, which could affect sterilization.5

Sterilization by EO is influenced by gas concentration, temperature, humidity, and exposure time (Table 9-4).21 The more sophisticated equipment for EO sterilization includes methods for temperature elevation to shorten sterilization times.19 Spores require time for humidification to allow optimal killing by EO.10,20,21 The humidity should not be raised by wetting the materials to be sterilized, because EO forms condensation products with water that may damage rubber and plastic surfaces. Also, the effectiveness of EO sterilization may be reduced below the lethal point by moisture left in needles and tubing.22 Instruments need to be cleaned as described for steam sterilization.

Because EO penetrates materials more readily than steam, a wider variety of materials may be used in packaging items for sterilization and storage. Films of polyethylene, polypropylene, and polyvinyl chloride are commercially available, but nylon should not be used, because it is penetrated poorly by EO.10,20-22 Positioning of packs is less critical than with steam, but overloading and compression in the sterilizer can prevent adequate penetration.5

After sterilization by EO, materials must be aerated to allow dissipation of the absorbed chemical (Table 9-5), because residual EO can damage tissues.23,24 For example, inadequate aeration of endotracheal tubes sterilized by EO caused tracheal necrosis and stenosis in horses and dogs.25,26 Although some EO chambers are equipped with mechanical aeration systems to reduce aeration times, those commonly used in veterinary hospitals use natural aeration in well-ventilated areas.7 EO sterilization indicator strips should be used on the outside of surgery packs, and chemical or biologic indicators of EO exposure are used inside.22 The 3M Comply EO chemical integrators demonstrate a color change and migration on an absorptive strip in response to all the critical aspects of EO sterilization, such as EO concentration, relative humidity, time, and temperature. Safe storage times are 90 to 100 days for plastic wraps sealed with tape, and 1 year for heat-sealed plastic wraps.22

Exposure to EO can cause skin and mucous membrane irritation, nausea, vomiting, headache, cognitive impairment, sensory loss, reproductive failure, and increased incidence of chromosomal abnormalities.10,23 Ability to detect the gas by smell is lost after prolonged exposure.24 Ethylene chlorohydrin is a highly toxic degradation product of EO that is formed most readily in products that have been previously sterilized by radiation.10,20,21 This risk is greatest with polyvinyl chloride products.9

ETHYLENE OXIDE

EO is a gas at room temperature; it is water soluble and widely distributed to all organs shortly following inhalation exposure. EO is a powerful alkylating agent and reacts with virtually all cellular components, including DNA, and with histidine in hemoglobin.122 Its principal industrial use is in the synthesis of ethylene glycol. EO is an effective sterilant for medical supplies and fumigant for furs and some foods. Experimental and epidemiologic studies suggest EO to be a potential carcinogen and mutagen.134,147

EO clearly causes a distal symmetrical polyneuropathy in humans and in experimental animals following chronic or intermittent peak exposure at levels in excess of 250 ppm.58,122,124 Prolonged extreme low-level exposure may also be hazardous to the nervous system; one study suggests that residual EO in dialysis tubing may contribute to peripheral neuropathy in patients on long-term hemodialysis.172 Another report implicates potential neurotoxicity of EO in the solvent vehicle for cyclosporine.173 It is also alleged that sterilizer workers may develop overt or subclinical, EO-induced CNS and PNS dysfunction.

Humans with symptomatic polyneuropathy initially experience symptoms of distal extremity numbness and weakness, accompanied by evidence of diminished sensation in the feet and hands.60 Tendon reflexes are diminished throughout and ankle jerks are absent. Motor and sensory nerve conduction velocities are mildly diminished. Encephalopathic symptoms and cognitive impairment may accompany peripheral neuropathy. Sural nerve biopsies exhibit axonal degeneration. There are no reports of postmortem findings in humans with EO intoxication. Gradual recovery from peripheral neuropathy commences following withdrawal from exposure. One report of three individuals describes normalization of motor and sensory nerve conductions and improved neurologic function at a 4-year follow-up examination.58

Experimental animals chronically exposed to 250 ppm of EO develop widespread sensory nerve fiber degeneration in the distribution of a central-peripheral distal axonopathy,71,124 as do rats chronically dosed with 1500 ppm of propylene oxide, a chemically similar substance.123 Intact animal studies demonstrate that EO exposure causes impaired fast axoplasmic transport.118 An in vitro report describes degeneration in dorsal root ganglion cell neurite extensions following EO exposure.172

The pathogenesis and biochemical basis of EO neurotoxicity are unknown.

Ethylene oxide [SED-15, 1296; SEDA-29, 242; SEDA-34, 379; SEDA-36, 341; SEDA-37, 273; SEDA-38, 214]

Ethylene oxide is used directly in the gaseous form to sterilize drugs, hospital equipment, disposable and reusable medical items, packaging materials, foods and other items [SEDA-36, 341; SEDA-37, 273; SEDA-38, 214]. A new method for biomonitoring of ethylene oxide was developed based on liquid chromatography and tandem mass spectrometric analysis of N-(2-hydroxyethyl) adduct at the N-terminal valine in globin [41E].

EO and LTSF sterilization

EO and LTSF are alkylating agents that destroy microorganisms, including spores, by denaturing protein, enzymes and nucleic acids(92). They are toxic, inflammable and explosive, and the Control of Substances Hazardous to Health (COSHH) Regulations 1999 limits exposure to these chemicals (Table 20.7)(93). Design of facilities, installation and operation of an EO or LTSF sterilizer must strictly follow Health and Safety regulations and environmental regulations, standard and guidance. BS EN 1422(94) and BS EN 14180(95) provide the requirements and tests for EO and LTSF sterilizers, respectively.

Table 20.7. Maximum exposure limits for atmospheric formaldehyde and ethylene oxide

GasShort-term exposure limitsLong-term exposure limits(ppm)(mg m−3)(ppm)(mg m−3)Formaldehyde22.522.5Ethylene oxide1530510

The short-term maximum exposure limit (STMEL) is the average exposure over any 15-min period.

The long-term maximum exposure limit (LTMEL) is the exposure over any 24-hour period expressed as a single uniform exposure over an 8 hour period.

COSHH does not specify a STMEL for EO. In the above table the STMEL is deemed to be three times the LTMEL in accordance with the recommendations of the Health and Safety Executive.

Source: COSHH Regulations 1999(95), HSE Guidance Note EH40/2005: Workplace exposure limits.

It is recommended to check the compatibility with the instrument load and packaging to be used. Due to the complex operation, health and safety and environmental concern, the use of the EO sterilizer is better dealt with in a separate unit. For the same reasons, EO sterilizers and LTSF are not commonly used in the UK hospital.

What can be sterilized by ethylene oxide?

Why is ethylene oxide used for sterilization?

What is ethylene oxide used for in hospitals?