Toxicology and Poisoning Ethylene Oxide Ethylene Oxide ((CH(2))(2)0) CAS: 75-21-8; UN 1040 Synonyms of ethylene oxide include dimethylene oxide, epoxy ethane, oxirane, oxacyclopropane, amprolene, and anprolene. Victims exposed to only ethylene oxide gas do not pose a significant risk of secondary contamination; however, victims whose clothing or skin is contaminated with ethylene oxide liquid or solution can secondarily contaminate personnel by direct contact or through off-gassing vapor. Ethylene oxide is a flammable, explosive, and highly penetrating gas; its odor does not provide sufficient warning of dangerous concentrations. Ethylene oxide is rapidly absorbed after inhalation or skin contact. Description -- Ethylene oxide is a colorless gas at room temperature and a colorless liquid below 51 degrees F. It is shipped as a liquefied, compressed gas. Both the gas and liquid are potential fire and explosion hazards. Ethylene oxide has an ether-like odor at air concentrations of 500 ppm and above. Inhalation - Most ethylene oxide exposures occur by inhalation or skin contact, both of which may cause or contribute to systemic effects. Odor is not a reliable indicator of ethylene oxide's presence and may not provide adequate warning of dangerous concentrations. The gas is heavier than air and may cause asphyxiation in enclosed, poorly ventilated, or low-lying areas. Skin/Eye Contact - Ethylene oxide vapors are absorbed readily through the skin and eyes, which can cause or contribute to systemic effects. Contact with solutions of ethylene oxide or high vapor concentrations may cause chemical burns. Contact with liquid anhydrous ethylene oxide may result in burns and frostbite injury. Ingestion - Ethylene oxide is used commonly as a gas at room temperature, so ingestion is unlikely to occur. Sources/Uses -- Ethylene oxide is produced by catalytically reacting ethylene (a hydrocarbon) and oxygen. It ranks 26th in volume among the major industrial chemicals produced in the United States. About 65% of ethylene oxide is used for synthesis of ethylene glycol, an anti-freeze product. Ethylene oxide also is used as a cold sterilizing agent for foods and medical equipment and supplies; as a fumigant and fungicide in the manufacture of medical products and foodstuffs; and as a solvent, plasticizer, and chemical intermediate. Properties of Ethylene Oxide -- Appearance: Colorless gas with a sweet, ether-like odor Warning properties: Inadequate; odor is detectable at about 500 ppm, and many sensitized persons experience symptoms below the odor threshold. OSHA PEL (Permissible Exposure Limit) = 1 ppm (averaged over an 8-hour workshift) OSHA STEL (Short Term Exposure Limit) = 5 ppm (15-minute sample) NIOSH IDLH (Immediately Dangerous to Life or Health) = 800 ppm Molecular weight -- 44.1 Boiling point (760 mm Hg) = 51 degrees F (10.7 degrees C) Vapor pressure (67 degrees F) = > 760 mm Hg Vapor density = 1.49 (air = 1) Miscible with water Flammable gas between 3% and 100% (concentration in air); extremely flammable liquid; may be ignited by heat, sparks, or flames. Vapors may travel to a source of ignition and flash back. Health Effects Ethylene oxide gas may produce immediate local irritation of the skin, eyes, and upper respiratory tract. At high doses, it may cause immediate or delayed pulmonary edema, CNS depression, and respiratory paralysis. Ethylene oxide inhalation or skin contact may result in allergic or immune-mediated sensitization. Acute Exposure -- Systemically, ethylene oxide is a highly reactive alkylating agent that forms adducts with cellular macromolecules, such as DNA and hemoglobin, causing cellular dysfunction and death. Because ethylene oxide is highly water soluble, it may produce immediate local irritation of skin and mucous membranes. At high concentrations, it can produce CNS depression and respiratory paralysis. Respiratory - Initially, ethylene oxide affects the nasopharynx. Concentrations as low as 200 ppm produce rapid onset of nose and throat irritation. Higher concentration may cause inflammation of the trachea and bronchi, bronchoconstriction, and atelectasis. Acute pulmonary edema may evolve up to 12 hours or more after exposure. Neurologic - Ethylene oxide is a CNS depressant. High-dose exposures can result in diverse neurologic manifestations including seizures and coma. Onset of neurologic signs and symptoms may be delayed up to 6 hours or more after exposure. Respiratory paralysis and delayed peripheral neuropathy have been reported after massive exposure. Gastrointestinal - Exposure to even low vapor concentrations of ethylene oxide can result in nausea and vomiting, often delayed. Dermal - Skin contact with concentrated vapor or aqueous solutions of ethylene oxide may cause inflammation with erythema, blistering, and crusted ulcerations. Initially, lesions are painless but later can become painful and pruritic. Skin reactions may be delayed up to 5 hours or more after exposure. Exposure to anhydrous ethylene oxide liquid may cause burns and frostbite injury. Ocular - Exposure to high concentrations of vapor or splashes of concentrated solutions can cause eye irritation, conjunctivitis, and corneal injury. Cardiovascular - Dysrhythmias may occur after a severe inhalation exposure. Immunologic - Inhalation and skin exposure may cause allergic and immune-mediated sensitization leading to contact dermatitis, urticaria, and anaphylactic reactions. Potential Sequelae - Survivors of severe inhalation injury may suffer residual chronic lung disease. Skin burns may result in scarring or hyperpigmentation. Cataracts may develop after serious eye exposure. Chronic Exposure -- Chronic ethylene oxide exposure may cause delayed peripheral nerve damage resulting in denervation atrophy, especially in the lower extremities. Although the results are inconclusive, some data suggest that chronic ethylene oxide exposure causes impairment of cognitive function. It also may damage the liver and kidneys. Skin allergy can result from exposure and some persons can become sensitized to the chemical. Data suggest that repeated exposure to ethylene oxide causes an increased risk of leukemia in humans. It has been shown to cause leukemia and abdominal cavity cancer in animals. IARC states that there is limited evidence of carcinogenicity in humans and sufficient evidence of carcinogenicity in animals. Ethylene oxide is on NTP's list of substances that may reasonably be anticipated to be carcinogens. Shepard's Catalog of Teratogenic Agents describes one study of in which the spontaneous abortion frequency in hospital workers exposed to ethylene oxide during pregnancy was 16.7% (average for the general population); however, the frequency for appropriate hospital controls was 5.6% (below average for the general population). A 1991 Report (Reproductive and Developmental Toxicants) published by the US General Accounting Office (GAO) lists 30 chemicals of concern because of their reproductive and developmental consequences; ethylene oxide is on this list. Prehospital Management Ethylene oxide can produce immediate eye, skin, and respiratory irritation; CNS depression and respiratory paralysis. There is no antidote for ethylene oxide intoxication. Treatment is supportive. Potential for Secondary Contamination. Victims exposed to only ethylene oxide gas do not pose a significant risk of secondary contamination to personnel outside the Hot Zone. However, victims whose clothing or skin is contaminated with ethylene oxide liquid or solution can secondarily contaminate personnel by direct contact or through off-gassing vapor. Hot Zone -- Rescuers should be trained and appropriately attired before entering the Hot Zone. If the proper equipment is not available, or if rescuers have not been trained to use it, call for assistance from a local or regional hazmat team or other properly equipped response organization. Rescuer Protection - Rescuers in the Hot Zone should wear self-contained breathing apparatus (SCBA). Chemical-protective clothing and gloves are required if contact with liquid ethylene oxide or its concentrated vapors is possible. ABCs - Quickly establish a patent airway. Stabilize the cervical spine with a collar if trauma is suspected. Administer supplemental oxygen and assist ventilation with a bag-valve-mask device if necessary. Victim Removal- If victims can walk, lead them out of the Hot Zone to the Decontamination Zone. If a victim is unable to walk, remove him or her on a backboard or gurney. If there is no means of transport, carefully drag the victim out. Decontamination Zone -- Victims with exposure to only ethylene oxide gas and with no skin or eye irritation do not need decontamination. They may be transferred immediately to the Support Zone. For all others see Basic Decontamination. Rescuer Protection - Rescuers in the decontamination zone should wear self-contained breathing apparatus (SCBA) and chemical-protective clothing and gloves if they will be caring for victims with ethylene oxide-soaked clothing or skin. If the proper equipment is not available, or if rescuers have not been trained to use it, call for assistance from a local or regional hazmat team or other properly equipped response organization. If the decontamination area is outdoors and has good natural ventilation, a lesser level of respiratory protection may suffice. ABCs - Quickly establish a patent airway. Stabilize the cervical spine with a collar if trauma is suspected. Supplemental oxygen can be administered if available. Evaluate the need for an intravenous line, cardiac monitor, and life support. Basic Decontamination - If the exposure involved liquid ethylene oxide (ambient temperature below 51 degrees F) and there is evidence of wet clothing, remove and double-bag the contaminated clothing. Patients who are able and cooperative may remove their own clothing and assist with basic decontamination. Flush exposed skin and hair with plain water for 3 to 5 minutes. Flush exposed or irritated eyes with plain water or saline for 3 to 5 minutes. Remove contact lenses if present. In case of ingestion, do not induce emesis. If the patient is conscious and able to swallow, administer 1 to 2 glasses of water to dilute stomach contents. The effectiveness of activated charcoal in cases of ethylene oxide ingestion is not known. Transfer to Support Zone - As soon as basic decontamination is completed, move the patient to the Support Zone. Support Zone -- Be certain that patients have undergone basic decontamination (see Decontamination Zone). Patients who have undergone proper decontamination or have been exposed to only vapors pose no serious risk of causing secondary contamination. Support Zone personnel require no specialized protective gear in such cases. ABCs - Quickly establish a patent airway. Stabilize the cervical spine with a collar if trauma is suspected. Administer supplemental oxygen and assist ventilation with a bag-valve-mask device, if necessary. Evaluate the need for an intravenous line, cardiac monitor, and life support. Advanced Treatment - Intubate the trachea if indicated (severe respiratory distress or apnea). When endotracheal intubation cannot be performed due to airway obstruction, perform cricothyroidotomy if equipped and trained to do so. Treat bronchospasm with aerosolized bronchodilators. Treat coma, seizures, and ventricular dysrhythmias according to ALS protocol. Additional Decontamination - If skin or eyes remain irritated, continue rinsing with water or saline. Remove contact lenses if present and irrigate the eyes with saline via IV tubing for 10 to 15 minutes or until pain and irritation have resolved. In case of ingestion, do not induce emesis. Administer 1 to 2 glasses of water to dilute stomach contents if it was not administered in the decontamination zone and if the patient is conscious and able to swallow. The effectiveness of charcoal in cases of ethylene oxide ingestion is not known. Transport to Medical Facility - Report to the base station and receiving medical facility the condition of the patient, treatment given, and estimated time of arrival at the medical facility. If a patient has ingested ethylene oxide solution, prepare the ambulance for possible vomiting of toxic material. Have ready several towels and opened plastic bags to quickly clean up and isolate vomitus. Multi-Casualty Triage -- If possible, consult with the base station physician or regional poison control center for advice regarding triage of multiple victims. Because effects may be delayed for up to several hours after exposure, it is prudent to refer all patients with a potential exposure to a medical facility. Emergency Department Management Ethylene oxide can produce immediate eye, skin, and respiratory tract irritation; CNS depression; and respiratory paralysis. There is no specific antidote for ethylene oxide poisoning. Treatment is supportive. Potential for Secondary Contamination. Victims exposed to only ethylene oxide gas do not pose a significant risk of secondary contamination to personnel outside the Hot Zone. However, victims whose clothing or skin is contaminated with ethylene oxide liquid or solution can secondarily contaminate personnel by direct contact or through off-gassing vapor. Decontamination Area -- Patients with exposure to only ethylene oxide gas and with no skin or eye irritation do not need decontamination. They can be transferred immediately to the Critical Care Area. Other patients will require decontamination as described below. ABCs - Evaluate and support airway, breathing, and circulation. Watch for signs of airway compromise. Monitor cardiac rhythm. Treat bronchospasm with aerosolized bronchodilator. Seizures, coma, hypotension, renal failure, and apnea may complicate serious exposure. Treat in the conventional manner. Basic Decontamination - If the patient has not been decontaminated, perform the decontamination procedure immediately. Patients exposed to only vapors do not require decontamination unless they have skin or eye irritation. Since touching clothing or skin wet with ethylene oxide may cause burns, ED staff should don chemical-resistant jumpsuits (e.g., of Tyvek, Saranex*) or butyl rubber aprons, rubber gloves, and eye protection. After the patient has been decontaminated, no special protective clothing or equipment is required for ED personnel. If the patient's clothing is wet with ethylene oxide, quickly remove and double-bag the contaminated clothing and all personal belongings while flushing the skin. Flush exposed skin with copious water (preferably under a shower). Remove contact lenses and irrigate exposed eyes with water for at least 5 minutes. An ophthalmic anesthetic, such as 0.5% tetracaine, may be necessary to alleviate blepharospasm, and lid retractors may be required to allow adequate irrigation under the eyelids. Critical Care Area -- Be certain that appropriate decontamination has been carried out. See Basic Decontamination above. ABCs - Evaluate and support airway, breathing, and circulation. Continuously monitor cardiac rhythm. Treat hypotension, seizures, and ventricular arrhythmias in the conventional manner. Patients with significant and persistent CNS depression should be evaluated for the presence of other underlying disorders (e.g., trauma, hypoglycemia, and drug intoxication). Inhalation Exposure - Administer supplemental oxygen by mask to patients with respiratory complaints. Observe patients in respiratory distress for up to 12 hours and periodically reexamine them using chest examinations and other appropriate studies. Follow-up as clinically indicated. Treat bronchospasm with aerosolized bronchodilators. Skin Exposure - If ethylene oxide was in contact with the skin, chemical burns may result. Eye Exposure - If eye irritation or injury is evident, test visual acuity and examine the eyes for corneal damage using a magnifying device or a slit lamp and fluorescein staining. Small corneal defects may be treated with topical ophthalmic antibiotic ointment or drops and analgesic medication. Immediately consult an ophthalmologist for patients with severe corneal injury. Ingestion - Do not induce emesis. Offer the alert patient water or milk to dilute the ethylene oxide and minimize corrosive injury. Perform gastric lavage and consider endoscopy to evaluate esophageal or gastric injury. The effectiveness of charcoal in cases of ethylene oxide ingestion is unknown. Antidotes and Other Medications - There is no antidote for ethylene oxide poisoning; treatment is supportive. Laboratory Tests - Depending on the initial evaluation, useful tests might include CBC, glucose, electrolytes, renal function tests (urinalysis, BUN, creatinine), liver function tests, and ECG monitoring. Chest radiography and ABGs also are recommended for severe inhalation exposure. Disposition and Follow-up -- Hospitalization should be considered for patients with evidence of systemic toxicity from any route of exposure. Delayed Effects - Patients with a history of significant ingestion exposure, severe respiratory distress, or extensive skin burns should be admitted to an intensive care unit. Because neurologic and respiratory signs and symptoms may not be evident for as long as 12 hours after exposure, patients with a suspected serious exposure should be observed and reexamined periodically. Patients with bronchospasm or pulmonary edema should be admitted and watched for signs of impending respiratory failure and managed accordingly. Patient Release - Patients with mild exposure and those who initially are asymptomatic should be observed for 4 to 6 hours, then discharged if no symptoms occur during this period. Advise discharged patients to seek medical care promptly if symptoms develop. (For a list of symptoms, see the reverse side of Ethylene Oxide--Patient Information Sheet.) Follow-up - Patients requiring ophthalmic care should be reevaluated in 24 hours. Reporting -- If a work-related incident has occurred, you may be legally required to file a report; contact your state or local health department. Other persons may still be at risk in the setting where this incident occurred. OSHA may be contacted for assistance in evaluating workplace conditions, or an appropriate public agency can be notified if a public health risk exists. If appropriate, inform patients that they may request an evaluation of their workplace from the Hazard Evaluation Division at NIOSH. Ethylene Oxide-- Patient Information Sheet This handout provides information and follow-up instructions for persons who may have been exposed to ethylene gas or solution. What is ethylene oxide? Ethylene oxide is a colorless liquid below 51 degrees F and a colorless gas at room temperature. It is used in the sterilization of hospital supplies, foods, and cosmetics; as a fumigant for spices, tobacco, furs, bedding, etc.; and in the manufacture of antifreeze and other chemicals. At toxic air concentrations, ethylene oxide may have a sweet, ether-like odor. However, odor is not a reliable warning of the seriousness of the exposure. What immediate health effects may result from ethylene oxide exposure? Most exposures to ethylene oxide occur from breathing the gas. Exposure to small amounts can cause eye, nose, and throat irritation; and skin rash. More serious exposure can cause severe breathing difficulty, skin burns, weakness, twitching, convulsions, and coma. What is the treatment for ethylene oxide poisoning? There is no antidote for ethylene oxide poisoning, but its effects can be treated and most exposed persons do recover fully. Persons who have had a serious exposure may need close medical observation for 12 hours or more. Are any future health effects likely to occur? After a single, small exposure, no delayed or long-term health effects are likely to occur. After a severe exposure, symptoms may be delayed up to 12 hours. The reverse side of this page lists some signs and symptoms to watch for--if any of them occur, seek medical care. Ethylene oxide is suspected of causing cancer of the blood, and birth defects may occur in offspring of mothers who were repeatedly and excessively exposed at work. What tests can be done if a person has been exposed to ethylene oxide? There are no specific blood and urine tests that can indicate a recent exposure to ethylene oxide. Generally, the severity of irritation symptoms is the best indicator of the seriousness of the exposure. However, blood, urine, and other tests may show if there has been any serious effect on the blood, heart, lungs, liver, or kidneys. Where can more information about ethylene oxide be found? More information about ethylene oxide may be obtained from your regional poison control center;, your state, county, or local health department; the Agency for Toxic Substances and Disease Registry (ATSDR); your doctor; or a clinic in your area that specializes in occupational and environmental health. If the exposure happened at work, you may wish to contact the Occupational Safety and Health Administration (OSHA) or the National Institute for Occupational Safety and Health (NIOSH). Ask the doctor who gave you this form for help in locating these telephone numbers. Ethylene Oxide Follow-up Instructions -- ( ) Call your doctor or the Emergency Department if you develop any of the following symptoms within the next 24 hours: * difficulty breathing or shortness of breath * chest pain * increased pain or discharge from your eyes * increased redness, pain, or pus-like discharge in the area of a skin burn * fever * unexplained drowsiness, fatigue, headache * belly pain, vomiting, diarrhea ( ) No follow-up appointment is necessary unless you develop any of the symptoms described above. ( ) Call for an appointment with Dr. _________ in the practice of_________. When you call for your appointment, please tell the receptionist/nurse that you were treated in the Emergency Department at__________________ Hospital by __________ and were advised to be seen again in __ days. ( ) Return to the Emergency Department/__________Clinic on (date)__________ at____ AM/PM for a follow-up examination. ( ) Do not perform vigorous physical activities for __ days. ( ) You may resume everyday activities including driving and operating machinery. ( ) Do not return to work for __ days. ( ) You may return to work on a limited basis. See instructions below. ( ) Avoid exposure to cigarette smoke for 24 hours since smoke may worsen injury to your lungs. ( ) Avoid drinking alcoholic beverages or taking aspirin for 24 hours since these substances may aggravate injury to your stomach lining or may have other effects. ( ) You may continue taking the following medication(s) that your doctor(s) prescribed for you:____________________________________________________ _______________________________________________________________________ ( ) Other instructions:____________________________________________________ _______________________________________________________________________ Signature of patient _______________________ Date _________________________ Signature of physician _____________________ Date _________________________ Above courtesy of C.D.C.