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SECTION 1. CHEMICAL IDENTIFICATION

CHEMINFO Record Number: 119
CCOHS Chemical Name: Ethylene Oxide

Synonyms:
Dihydrooxirene
Dimethylene oxide
EO
ETO
1,2-Epoxyethane
Epoxyethane
Ethene oxide
Oxacyclopropane
Oxane
Oxidoethane
Oxirane

Chemical Name French: Oxyde d'éthylène
Chemical Name Spanish: Oxido de etileno
CAS Registry Number: 75-21-8
UN/NA Number(s): 1040
RTECS Number(s): KX2450000
EU EINECS/ELINCS Number: 200-849-9
Chemical Family: Organic oxide / aliphatic oxirane / aliphatic epoxide / cyclic ether
Molecular Formula: C2-H4-O
Structural Formula: -O-CH2-CH2- (3 member ring structure)

SECTION 2. DESCRIPTION

Appearance and Odour:
Colourless gas with a sweet, ether-like odour; colourless liquid below 10 deg C (50 deg F).(45-47)

Odour Threshold:
Wide range reported; 0.82 to 690 ppm. The range of acceptable values is 257 to 690 ppm (detection); 493 ppm (recognition).(48)

Warning Properties:
POOR - odour threshold is more than 400 times the TLV.

Composition/Purity:
Ethylene oxide (EO) is a high purity chemical (99.7% or higher). Impurities may include acetaldehyde, acetic acid, acetylene, and inorganic and organic chlorides.(1,6,45) It is also available as an non-flammable mixture with nitrogen or carbon dioxide. Historically, mixtures with dichlorodifluoromethane (Fluorocarbon 12) were available, but environmental concerns have led to the use of other flame retardant diluent gases.(49,50) Ethylene oxide it is not available commercially in aqueous solutions, although it is used in aqueous solution in some reactions.(46,50) EO is shipped as a liquid under its own vapour pressure of 50 kPa at 21.1 deg C in compressed gas cylinders, special containers, such as insulated steel drums, portable tanks or insulated single-unit tank cars.(45,50,51)

Uses and Occurrences:
The major use is as a chemical intermediate for the manufacture of other chemicals. As a non-explosive mixture with nitrogen or carbon dioxide, it is used as a sterilizing agent for medical devices and surgical instruments in hospitals, as a disinfectant and as a fumigant.(46,50,52)


SECTION 3. HAZARDS IDENTIFICATION

EMERGENCY OVERVIEW:
Colourless gas with a sweet odour; colourless liquid below 10 deg C. EXTREMELY FLAMMABLE GAS above 10 deg C or EXTREMELY FLAMMABLE LIQUID below 10 deg C. Solutions of EO in water, unless extremely dilute, are flammable. Gas is slightly heavier than air and may spread long distances. Distant ignition and flashback are possible. Mist can accumulate static charge by splashing or spraying. Can decompose explosively. Cylinders and closed containers may rupture violently if heated. COMPRESSED GAS. DANGEROUSLY REACTIVE. May polymerize or decompose violently when exposed to high temperatures or contaminants (e.g. acids and metals). VERY TOXIC. May be fatal if inhaled. Irritating to the respiratory tract. Central nervous system depressant. High concentrations may cause headache, nausea, dizziness, drowsiness, and incoordination. Solutions are CORROSIVE to the skin and eyes. Severe skin burns may not be immediately painful or visible. Can cause permanent scarring of the skin or blindness. CANCER HAZARD - can cause cancer, based on human information. POSSIBLE REPRODUCTIVE HAZARD - may harm reproductive capability, based on animal information. MUTAGEN - may cause inheritable genetic damage.



POTENTIAL HEALTH EFFECTS

Effects of Short-Term (Acute) Exposure

Inhalation:
Ethylene oxide (EO) gas mainly causes irritation of the nose, throat and respiratory tract, as well as central nervous system effects such as headache, nausea, and vomiting. With high exposures, drowsiness, headache, weakness, irregular gait and loss of consciousness may occur.(1,2)
A review of 41 case reports found the main symptom was vomiting, recurring periodically for hours, accompanied by nausea and headache.(3) Another report described nausea and vomiting in 3 employees who became drenched with a 1% EO solution for 2 hours.(4) Exposure of a nurse to 500 ppm (estimated) for 2 or 3 minutes caused nausea, stomach spasms, lightheadedness, temporary unconsciousness and seizures. Random twitching of the muscles, nausea and tiredness occurred over the next 24 hours. Full recovery occurred within 3 weeks.(5) Exposure of 2 employees to greater than 700 ppm (estimated) for up to 30 minutes caused headache and diarrhea, which disappeared in 70 hours. Irritation of the throat, mouth dryness, itching, dizziness and weakness was observed 3 other employees. These symptoms disappeared within 21 days.(6)
Persistent non-allergic asthma (reactive airways syndrome) developed in an employee exposed to EO above 700 ppm 4 hours/day for 4 days. Symptoms included coughing, wheezing and shortness of breath. This individual developed impaired lung function due to scarring of the lungs (pulmonary fibrosis). Similar effects were not observed in 5 other employees similarly exposed.(7)
Four men were exposed to over 700 ppm EO intermittently for 2 to 8 weeks due to accidental leakage of a sterilizer. Three men developed peripheral neuropathy with headache, weakness in the extremities, incoordination and irregular gait.(8)

Skin Contact:
EO gas is expected to cause moderate to severe skin irritation, mainly on wet or oily parts of the skin.(1,9) EO residues on sterilized face masks, gloves and surgical gowns have also been reported to cause severe irritation.(1,9,11) The evaporation of liquid EO from skin may cause frosting of the tissue if large quantities are involved. Blisters may develop later. Small amounts produce no effects.(1,10)
EO solutions are corrosive, based on animal information. Corrosive materials are capable of producing severe burns, blisters, ulcers and permanent scarring. The degree of irritation caused by EO solutions is determined by the concentration of the solution and the length of exposure. The most harmful concentrations are in the 50% range. More concentrated solutions evaporate quickly while more dilute solutions are less irritating. Typical effects included a tingling and chilling sensation as EO evaporates, followed by swelling, redness and sometimes hives 1-5 hours after exposure. Blisters, when they occur, appear after 6-12 hours.(4,10)

Eye Contact:
A review of cases of exposure to EO gas showed that slight irritation was occasionally reported.(3) Exposure to 500 ppm (estimated) for 2-3 minutes was not reported to cause eye effects.(5) Following a blast of EO into the eye, there was no immediate discomfort. However, within 2-3 hours the eye became uncomfortable. Within 24 hours, the eye was completely normal.(12)
EO solutions are considered corrosive based on evidence of skin corrosion in a well-conducted animal study. Permanent injury including blindness could result. Limited animal studies have shown effects ranging from moderate irritation to corrosive effects. EO solution squirted directly into the eye of a person and flushed immediately with water caused irritation that lasted 1 day.(12) A case report describes a corneal burn in a person exposed to EO. The burn healed within 48 hours.(63)

Ingestion:
EO is a gas at normal room temperature and pressure. There are no reports of human ingestion of EO solutions. Animal information suggests that EO solutions are toxic following ingestion. Symptoms of central nervous system depression, as described for inhalation exposure, would be expected. Ingestion is not a typical route of occupational exposure.

Effects of Long-Term (Chronic) Exposure

In many long-term exposures situations, particularly in hospital employees involved in sterilizing instruments, some tasks which involve fairly high exposure may only be performed occasionally. Thus, relatively low time-weighted average exposure concentrations may mask incidental, higher exposures.
Three studies of employees with exposure ranging from less than 0.25 ppm to 10 ppm (time-weighted average) for 6 months to 14 years have not shown significant blood, liver, kidney or immune system changes. Changes in kidney function, as evidenced by protein in the urine, were increased in one study.(6,13) Other studies have shown similar results.(14)

Nervous System:
Several studies have reported nervous system effects in employees exposed to less than 1 to 4.7 ppm (8-hour time-weighted average), with daily short-term peaks of 250 to 700 ppm for 0.5 to 20 years. Damage to the nerves which provide feeling and movement in the extremities (peripheral neuropathy) is most commonly observed. Symptoms include numbness in the feet and fingers, muscular weakness in the lower limbs, reduced hand-eye coordination, reduced nerve velocity in the calf muscle, and nerve fibre affects.(6,8,14-16) Many of the studies are limited by factors such as the small number of employees studied and incomplete exposure information.
No conclusions can be drawn from a case report of long-term low-level exposure (4.2 ppm, 8-hour time-weighted average; 10 years) involving sterilization of equipment with EO. This report suggested EO exposure was related to impaired thinking ability and sensory loss.(17,18)

Respiratory Sensitization:
EO may be a respiratory sensitizer but no firm conclusions can be drawn based on the available information. Occupational asthma has been reported among seven medical staff exposed to EO.(6) In most of the cases, there was also exposure to other chemicals which have also been associated occupational asthma, e.g. latex and formaldehyde. In general, it is not possible to conclude that EO alone caused the asthmatic symptoms and/or that pre-existing conditions did not contribute to the effect.(20,54-57)

Skin:
Dry, red, itchy skin (dermatitis) and burns may result from residues in gloves, clothing or footwear that has been sterilized with EO.(9,11,14)

Skin Sensitization:
EO may cause allergic skin reactions, but no firm conclusions can be drawn based on the available information. A case report describes a nurse who developed an allergic reaction to an EO sterilized rubber glove. The authors indicated that the reaction may have been to EO or to an EO- glove reaction product.(11) No other details are available. One historical report described a "sensitivity" reaction in 3/8 volunteers repeatedly exposed to EO.(10) A few other case reports describe sensitivity developing following non-occupational EO contact.(14,19) Some of the reports do not describe a typical allergic reaction. Reports of severe allergic reactions developing in dialysis patients after being exposed to medical equipment sterilized with EO are not relevant to occupational exposures.(6)

Eyes/Vision:
Limited evidence suggests that there may be an increased risk of developing cataracts in employees exposed to relatively high EO levels.(21,22)

Carcinogenicity:

EO is known as a human carcinogen. In humans exposed to EO, the most frequently reported association has been with lymphatic and hematopoietic cancer. These studies have examined two groups - hospital employees using EO as a sterilant and chemical employees manufacturing or using EO.(6) Hospital employees generally have clearly identified EO exposure. A large mortality study of this group observed significantly more deaths from hematopoietic cancer and leukemia among men.(24) In a follow-up study, there was a positive trend in all lymphatic and hematopoietic cancer mortality for cumulative EO exposure.(25) In another study, the only significant increase in mortality was caused by non-Hodgkin's lymphoma in men.(26) Studies of chemical industry employees are more difficult to interpret because often there is exposure to other chemicals. Nevertheless, the observations are compatible with the small but consistent excesses of lymphatic and hematopoietic cancer observed in hospital employees.(6) In one study, chemical workers licensed to handle EO experienced increased mortality due to lymphosarcoma, reticulosarcoma and hematopoietic tissue cancers.(27)

The International Agency for Research on Cancer (IARC) has concluded that this chemical is carcinogenic to humans (Group 1).

The American Conference of Governmental Industrial Hygienists (ACGIH) has designated this chemical as a suspected human carcinogen (A2).

The US National Toxicology Program (NTP) has listed this chemical as a known human carcinogen.

Teratogenicity and Embryotoxicity:
No firm conclusions can be drawn from a limited study which suggests that EO exposure may be related to increased miscarriages in hospital employees. Exposures were estimated to be 0.1-0.5 ppm (time-weighted average) with peaks up to 250 ppm.(28) Employees were exposed to EO, glutaraldehyde and formaldehyde, information was gathered by questionnaire which may have led to reporting biases, exposure information was limited and only a small number of employees were studied. No conclusions can be drawn from another poorly conducted study in which pregnant women exposed to EO had more pregnancy complications and a higher rate of miscarriages.(1) Animal information suggests that EO can cause reduced birth weight, but maternal toxicity was not fully evaluated. It is toxic to animal germ cells (sperm and fertilized eggs).

Reproductive Toxicity:
In a small study, 37 male employees exposed to 5-10 ppm EO for an average of 10.7 years did not have more reproductive disorders compared to non-exposed employees. However, reproductive capacity was not evaluated.(2) No conclusions can be drawn from a few studies which showed disturbances in menstrual cycle because of design limitations.(2) EO has produced harmful effects on the reproductive capability of male and female animals by directly affecting the germ cells (sperm and the fertilized egg).

Mutagenicity:
Studies of employees exposed to EO in hospitals and in EO manufacturing and processing plants consistently show chromosomal damage in peripheral blood lymphocytes. Some of the effects have persisted for up to 2 years after exposure has stopped.(6,29) Positive results, including somatic cell mutations and gene mutations and heritable translocations in germ cells, have also been obtained in numerous animal studies.

Toxicologically Synergistic Materials:
There is no information available.

Potential for Accumulation:
EO is readily absorbed by inhalation (retention 75-80%). Once absorbed, EO is rapidly distributed throughout the body. EO is metabolized by 2 different routes. Excretion of metabolites takes place in the urine generally within 24 hours following exposure. A small amount is excreted as carbon dioxide and unchanged ethylene glycol in the exhaled air or as metabolites in the feces.(1,6,9)


SECTION 4. FIRST AID MEASURES

Inhalation:
This is chemical is extremely flammable and very toxic. Take proper precautions to ensure your own safety before attempting rescue (e.g. remove any sources of ignition and wear appropriate protective equipment, use the buddy system). Remove source of contamination or move victim to fresh air. If breathing has stopped, trained personnel should begin artificial respiration (AR) or, if the heart has stopped, cardiopulmonary resuscitation (CPR) or automated external defibrillation (AED) immediately. Avoid mouth-to-mouth contact by using mouth guards or shields. Quickly transport victim to an emergency care facility.

Skin Contact:
GAS: If irritation occurs, flush with lukewarm, gently flowing water for 5 minutes or until the chemical is removed. If irritation persists, obtain medical attention. SOLUTIONS: Avoid direct contact. Wear chemical protective clothing, if necessary. As quickly as possible, remove contaminated clothing, shoes and leather goods (e.g. watchbands, belts). Immediately flush with lukewarm, gently flowing water for 15-20 minutes. Quickly transport victim to an emergency care facility. Double bag, seal, label and leave contaminated clothing, shoes and leather goods at the scene for safe disposal.

Eye Contact:
GAS: If irritation occurs, remove source of contamination or move victim to fresh air. If irritation persists, obtain medical attention. SOLUTIONS: Avoid direct contact. Wear chemical protective gloves, if necessary. Immediately flush the contaminated eye(s) with lukewarm, gently flowing water for 15-20 minutes, while holding the eyelid(s) open. If a contact lens is present, DO NOT delay irrigation or attempt to remove the lens until flushing is done. Take care not to rinse contaminated water into the unaffected eye or onto the face. Quickly transport victim to an emergency care facility.

Ingestion:
GAS: Ingestion is not an applicable route of exposure for gases. SOLUTIONS: NEVER give anything by mouth if victim is rapidly losing consciousness, is unconscious or is convulsing. Have victim rinse mouth thoroughly with water. DO NOT INDUCE VOMITING. If vomiting occurs naturally, have victim rinse mouth with water again. Quickly transport victim to an emergency care facility.

First Aid Comments:
Provide general supportive measures (comfort, warmth, rest).
Consult a doctor and/or the nearest Poison Control Centre for all exposures.
All first aid procedures should be periodically reviewed by a doctor familiar with the material and its conditions of use in the workplace.

Note to Physicians:
Many jurisdictions have specific regulations for EO. These regulations may include requirements for medical surveillance programs, including pre- employment and pre-placement examinations, periodic medical examinations, clinical tests, health education and record keeping. Obtain detailed information from the appropriate government agency in relevant jurisdictions.



SECTION 5. FIRE FIGHTING MEASURES

Flash Point:
-20 deg C (-4 deg F) (closed cup) (pure ethylene oxide).(47,53)). 41.5 deg C (107 deg F) (0.5 wt% EO in water) (closed cup); -2 deg C (28 deg F) (5 wt%) (closed cup); -45 deg C (-49 deg F) (60 wt%); -53 deg C (-63 deg F) (80 wt%) (open cup).(46,59)

Lower Flammable (Explosive) Limit (LFL/LEL):
3.0% (47,50)

Upper Flammable (Explosive) Limit (UFL/UEL):
100% (47,50)

Autoignition (Ignition) Temperature:
429 deg C (804 deg F) (46,47); 570 deg C (1058 deg F) in the absence of air (47)

Electrical Conductivity:
4 X 10(6) pS/m at -25 deg C (50)

Minimum Ignition Energy:
Approximately 1000 millijoules (mJ) (gas); 0.06 mJ (gas air mixtures) (50)

Combustion and Thermal Decomposition Products:
Toxic and/or irritating gases or vapours.

Flammable Properties:

Specific Hazards Arising from the Chemical:
The heat of a fire may cause spontaneous polymerization, which can cause containers to rupture violently. EO can burn in sealed containers if ignited. Under fire conditions, an EO pipeline may undergo internal decomposition.(50) Explosions will occur if gas or vapours are ignited in a confined area.

Extinguishing Media:
Carbon dioxide, dry chemical powder, "alcohol resistant" foam, or water spray or fog. Use flooding quantities of water as fog. Water may be ineffective. (47)

Fire Fighting Instructions:
Evacuate area and fight fire from a safe distance or protected location. Approach fire from upwind to avoid extremely hazardous gas and toxic decomposition products.
It is best to stop the flow of gas before attempting to extinguish the fire. To extinguish the fire, while allowing continued flow of the gas, is extremely dangerous. The gas could form an explosive mixture with air and reignite, which may cause far more damage than if the original fire had been allowed to burn. In some cases, extinguishing the fire with carbon dioxide or dry chemical powder may be necessary to permit immediate access to shut-off valves. However, this must be done carefully.
If it is not possible to stop the flow of gas and if there is no risk to the surrounding area, it is preferable to allow continued burning, while protecting exposed materials with water spray until the flow of gas can be stopped. Isolate materials not yet involved in the fire and protect personnel.
Gas clouds may be controlled by water spray or fog. Water spray may be used to dilute a liquid spill to a nonflammable mixture. Water solutions are no longer flammable in open areas when diluted with at least 22 parts of water by volume. In confined areas, such as sewers, the dilution must be increased to 100 parts of water.(47,59) Dike fire control water for appropriate disposal. NOTE: The addition of water to pools of liquefied EO may increase evolution of toxic gas.
Move cylinders or containers from the fire area if this can be done without risk. Otherwise, fire-exposed containers, tanks or pipelines should be cooled by application of hose streams and this should begin as soon as possible (within the first several minutes) and should concentrate on any unwetted portions of the container. If this is not possible, use unmanned monitor nozzles and immediately evacuate the area. No part of a cylinder or container should be subjected to a temperature higher than 52 deg C (approximately 125 deg F). The heat generated by the fire can cause polymerization and explosive decomposition may occur.
For a massive fire in a large area, use unmanned hose holder or monitor nozzles; if this is not possible withdraw from fire area and allow fire to burn. Stay away from ends of tanks, but be aware that flying material from ruptured tanks may travel in any direction. Withdraw immediately in case of rising sound from venting safety device or any discolouration of tank due to fire. After the fire has been extinguished, explosive and toxic atmospheres may linger. Before entering such an area especially confined areas, check the atmosphere with an appropriate monitoring device.

Protection of Fire Fighters:
EO is very toxic and a suspected human carcinogen. Do not enter fire area without wearing specialized protective/equipment suitable for the situation. Firefighter's normal protective clothing (Bunker Gear) will not provide adequate protection. A full-body encapsulating chemical resistant suit with positive pressure self-contained breathing apparatus (NIOSH approved or equivalent) may be necessary.



NATIONAL FIRE PROTECTION ASSOCIATION (NFPA) HAZARD IDENTIFICATION

NFPA - Health: 3 - Short exposure could cause serious temporary or residual injury.
NFPA - Flammability: 4 - Will rapidly or completely vaporize at atmospheric pressure and normal ambient temperature, or readily disperse in air and burn readily.
NFPA - Instability: 3 - Capable of detonation or explosive decomposition or explosive reaction, but requires a strong initiating source or must be heated under confinement before initiation, or reacts explosively with water.

SECTION 9. PHYSICAL AND CHEMICAL PROPERTIES

Molecular Weight: 44.05

Conversion Factor:
1 ppm = 1.80 mg/m3; 1 mg/m3 = 0.556 ppm at 25 deg C (calculated)

Physical State: Gas
Melting Point: -112.5 deg C (-170.5 deg F) (pure EO) (45,46,51) 5.6 deg C (42.1 deg F) (10 wt%); 9.3 deg C (48.8 deg F) (50 wt%); 3.7 deg C (38.7 deg F) (80 wt%).(50,59)
Boiling Point: 10.4 deg C (50.7 deg F) (pure EO).(1,45,50) 42.4 deg C (108.5 deg F) (10 wt%); 19 deg C (66.2 deg F) (50 wt%); 13 deg C (55.4 deg F) (80 wt%).(50,59)
Relative Density (Specific Gravity): Not applicable (gas)
Solubility in Water: Soluble in all proportions.(45,50)
Solubility in Other Liquids: Soluble in all proportions with ethanol, diethyl ether and most organic solvents.(45,50,51)
Coefficient of Oil/Water Distribution (Partition Coefficient): Log Poct = -0.30 (1,6,49)
pH Value: Not available.
Viscosity-Dynamic: 0.325 mPa.s (0.325 centipoise) at 0 deg C; 0.26 mPa.s (0.26 centipoise) at 20 deg C (liquid) (50)
Surface Tension: 27.6 mN/m (27.6 dynes/cm) at 0 deg C; 24.3 mN/M (24.3 dynes/cm) at 20 deg C (liquid) (46,50)
Vapour Density: 1.52 (air=1) (45)
Vapour Pressure: 146 kPa (1095 mm Hg or 1.44 atm) at 20 deg C (45,46,50)
Vapour Pressure at 50 deg C: 391-392 kPa (2933-2940 mm Hg or 3.86-3.87 atm) (46,50)
Saturation Vapour Concentration: Not applicable (gas)
Evaporation Rate: Not available.
Critical Temperature: 195.8 deg C (384.4 deg F) (45,50,51)
Critical Pressure: 7190 kPa (70.95 atm) (45,50,51)

SECTION 10. STABILITY AND REACTIVITY

Stability:
Normally stable. EO can decompose at high temperatures (approx. 500 deg C). The decomposition temperature decreases with increased volume and pressure.(50)

Hazardous Polymerization:
May undergo slow polymerization in storage. High temperatures or contamination with impurities (e.g. acids, water, metals) can cause violent polymerization. If traces of polymerization initiators are present, polymerization may start slowly and then accelerate.(46,50)

Incompatibility - Materials to Avoid:

NOTE: Chemical reactions that could result in a hazardous situation (e.g. generation of flammable or toxic chemicals, fire or detonation) are listed here. Many of these reactions can be done safely if specific control measures (e.g. cooling of the reaction) are in place. Although not intended to be complete, an overview of important reactions involving common chemicals is provided to assist in the development of safe work practices.


EO is extremely reactive, gives off heat in its reactions and can explode.(46)
ACIDS, COVALENT HALIDES (e.g. anhydrous aluminum, iron and tin chlorides), BASES (e.g. alkali metal hydroxides, ammonia and amines), ALKALI METALS (e.g. potassium) or CATALYTICALLY ACTIVE SOLIDS (e.g. aluminum oxide, iron oxide or rust) - can cause violent, explosive polymerization or reaction.(47,53)
COPPER, SILVER, MERCURY, MAGNESIUM or their ALLOYS - may react with traces of acetylene in EO to form unstable acetylides, which can detonate.(53)
POROUS REFRACTORY INSULATION (e.g mineral wool or calcium silicate) - EO can react with the water contained in insulation to form low molecular weight polyglycols, which can accumulate, self-heat and may lead to a fire.(50)
ALCOHOLS, ALKANETHIOLS, MAGNESIUM PERCHLORATE or 3-NITROANILINE - can explode.(47,53)
DINITROGEN PENTAOXIDE - react to form the explosive 1,2-denitrate ester.(53)

Hazardous Decomposition Products:
None reported.

Conditions to Avoid:
Sparks, static discharge, open flames, heat, other ignition sources and contamination (including air, oxygen or reactive impurities).

Corrosivity to Metals:
EO is not corrosive to carbon steel and stainless steel.(45,50) Take care to prevent rust formation when using steel.(46) Do not use copper, silver, mercury, magnesium or their alloys.(45,52,53)

Stability and Reactivity Comments:
EO attacks most organic materials.(50)
Decomposition of ethylene oxide in water is slow under neutral conditions, but becomes more rapid under acidic or basic conditions, with the generation of heat.(46,50) In a closed container, the heat released from the reaction of ethylene oxide and water can build up resulting in an accelerating or "runaway" reaction and rupture of the container.(59)


SECTION 11. TOXICOLOGICAL INFORMATION

LC50 (rat): 1460 ppm (4-hour exposure) (30)
LC50 (mouse): 835 ppm (4-hour exposure) (30)

LD50 (oral, rat): 330 mg/kg (dissolved in water) (31); a lower value of 72 mg/kg cannot be confirmed and the vehicle is unknown.(32)
LD50 (oral, guinea pig): 270 mg/kg (dissolved in water) (31)

Eye Irritation:

Limited studies with ethylene oxide (EO) show effects ranging from moderate irritation to corrosive effects.

Application of a single drop of EO solution (concentration not specified) caused intense inflammation in rabbits that cleared in 4 days.(33) No effects were observed in rabbits following application of 2.0% in water, but repeated application of a lower concentration produced irritation.(1,2) An unpublished report indicates that application of the liquid caused great damage in rabbits with tissue death and loss of sight.(34) Clouding of the cornea has been observed in guinea pigs exposed to high airborne concentrations.(2)

Skin Irritation:

EO solutions are corrosive.

Application of 0.5 mL of undiluted ethylene oxide (concentration not specified), under a patch to intact skin for 4 hours, caused irreversible chemical burns in rabbits (average score for 24 and 72 hours: edema 4/4; erythema 4/4; primary irritation score based on intact and abraded skin 7.8/8).(62) Application of 10% or 50% water solutions (EO 97-98.6%), under cover, caused swelling in rabbits if contact was longer than 6 minutes. Longer exposures (up to 60 minutes) caused scarring.(34)

Effects of Short-Term (Acute) Exposure:

Short-term exposure mainly affects the respiratory and central nervous systems.

Inhalation:
In studies with several animal species, longer exposures or higher concentrations produced deaths. Concentrations of 14000 ppm and above were lethal to guinea pigs after 10-60 minutes exposure, while 280 ppm caused some deaths after 48 hours. In general, exposure to 1000 ppm and above irritated the respiratory system and depressed the central nervous system (CNS). Early signs included nose irritation and discharge, and salivation followed by gasping and laboured breathing. In survivors, recovery appeared to be complete until delayed effects, including nausea, vomiting, diarrhea, paralysis of the hind quarters, convulsions and death occurred. Autopsy showed the lungs were filled with fluid.(2,30)

Ingestion:
Rats given oral doses of 100 mg/kg dissolved in olive oil for 21 days experienced body weight loss, stomach irritation, and slight liver damage. Animals fed lower doses for 30 days did not show similar effects.(34) The olive oil may have increased EO's toxicity. Ingestion of lethal doses of EO solutions has produced incoordination, difficult respiration, and, occasionally, convulsions.(2)

Effects of Long-Term (Chronic) Exposure:

Repeated inhalation exposure may harm the peripheral nervous system with symptoms such as reduced sensation and reflexes and paralysis of the hind limb muscles. These effects may be gradually reversible. Changes in nerve fibres are visible following exposure to 50 to 100 ppm, while physical signs and symptoms are evident at higher concentrations.

Inhalation:
Several long-term exposure studies have been conducted with several animal species. Concentrations of 100 ppm have produced irritation of the respiratory tract, with lung damage at higher concentrations. Changes in organ weights and enzyme levels have been observed at 250 ppm and above for 4-17 weeks. Exposures above 200 ppm have affected the lumbar and sacral nerves with weakness, tremors, muscle degeneration, decreased pain perception, decreased reflexes, and some paralysis in the hind limbs.(1,2,6,9,29,30,34,35) Monkeys exposed to 50 or 100 ppm for 2 years showed no symptoms of nerve damage, but demyelination was observed in 1/2 animals in both exposure groups. Axonal dystrophy was observed in 2/2 animals at 50 ppm and 1/2 animals at 100 ppm.(36) When animals were followed after exposure, a slow but apparent recovery within 3 to 6 months was generally observed.(2)

Skin Sensitization:
Sensitization was not produced win guinea pigs hen EO was administered on or under the skin.(14)

Carcinogenicity:
The International Agency for Research on Cancer (IARC) has concluded that there is sufficient evidence in experimental animals for the carcinogenicity of EO.(6)
EO was tested for carcinogenicity in rats exposed orally, in rats and mice exposed by inhalation and in mice exposed by skin application. In rats orally exposed, EO produced tumours in the forestomach. In mice exposed by inhalation, lung tumours and tumours of the Harderian gland were produced in both sexes and uterine and mammary carcinomas and malignant lymphomas in females. In rats exposed by inhalation, mononuclear cell leukemia and brain tumours were observed in both sexes. Abdominal mesotheliomas and subcutaneous fibromas were observed in males. In a limited study, no tumours were observed in mice following skin application.(6,36,37)

Teratogenicity, Embryotoxicity and/or Fetotoxicity:
EO may be fetotoxic but no firm conclusions can be drawn from the available information. It does not appear to be teratogenic or embryotoxic, but does harm germ cells. Refer to "Reproductive Toxicity" below.
EO produced fetotoxicity (reduced weight) in rats exposed to 100 ppm on days 6-15 of pregnancy. No treatment-related adverse effects were noted in the mothers. However, this study cannot be evaluated because a complete evaluation of maternal toxicity was not conducted. No significant effects were observed at lower concentrations.(38) In an unconventional study, EO was administered to rats by inhalation during days 6-15 of pregnancy. Animals were exposed to up to 1200 ppm for 0.5 hours once/day or 0, 200 or 400 ppm or 0, 800 or 1200 ppm 3 times/day for 0.5 hours. The only observed effect was reduced fetal weight at 800 and 1200 ppm 3 times/day. Maternal toxicity (decreased weight gain) was observed as 1200 ppm, but not 800 ppm.(39) Other studies did not use relevant routes of exposure, showed effects on the offspring in the presence of significant maternal toxicity or did not evaluate maternal toxicity.(1,2,6,29,40)

Reproductive Toxicity:
EO has produced harmful effects on the reproductive capability of male and female animals by directly affecting the germ cells (sperm and the fertilized egg).
Rats were exposed to up to 100 ppm 12 weeks prior to mating and during mating. Females were then exposed during pregnancy and nursing of pups. There were no significant differences in male or female fertility indices. In the 100 ppm group, there were fewer implantation sites and fewer pups born/litter.(41) The pre- and post-implantation loss of eggs, mainly indicating a mutagenic effect, may have masked effects on fertility.(2) Other studies have shown that high inhalation exposure to EO around the time of fertilization can produce cell death and malformations in the fetuses. Exposure of female mice to 1200 ppm for 1, 6, 9 or 25 hours following mating produced fetal deaths with exposure at 1 and 6 hours. A large number of the fetuses that survived were malformed. Few such effects were observed at 9 hours and none at 25 hours. These effects are due to a direct effect on the fertilized egg (zygote).(6,42,43) EO has produced dominant lethal effects in rodents. Monkeys exposed to 50 or 100 ppm for 2 years had reduced sperm counts and motility.(36) Male rats exposed to 250 ppm for 13 weeks showed slight degeneration in some seminiferous tubules, reduced sperm count and increased sperm head abnormalities. An increase in malformed sperm heads was observed in all treated groups (50-250 ppm).(44) Other studies with rats, mice and guinea pigs have also shown testicular effects, but some of these effects may have been secondary to other toxicity.(34,35)

Mutagenicity:
Extensive testing has shown that EO is a powerful mutagen. Positive results, including somatic cell mutations and gene mutations and heritable translocations in rodent germ cells, have been obtained in numerous studies. EO is often used as a positive control in mutagenicity tests. It is regarded as a direct mutagen, which means that metabolic activation is not required.(1,2,6,9,29)


SECTION 16. OTHER INFORMATION

Selected Bibliography:
(1) International Programme on Chemical Safety (IPCS). Ethylene oxide. Environmental health criteria; 55. World Health Organization, 1985
(2) Toxicity of ethylene oxide and its relevance to man. Technical report no. 5. European Chemical Industry Ecology & Toxicology Centre (ECETOC), Sept. 20, 1982
(3) Theiss, A.M. Observations on the health hazards of ethylene oxide. {English translation}. Archiv fur Toxicologie. Vol. 20 (1963). p. 127-140. (NIOSHTIC Control Number: 00133777)
(4) Sexton, R.J., et al. Dermatological injuries of ethylene oxide. Journal of Industrial Hygiene and Toxicology. Vol. 31, no. 5 (1949). p. 297-300
(5) Salinas, E., et al. Acute ethylene oxide intoxication. Drug Intelligence and Clinical Pharmacology. Vol. 15 (May, 1981). p. 384-386
(6) International Agency for Research on Cancer. Ethylene oxide. In: IARC monographs on the evaluation of carcinogenic risks to humans. Vol. 60. Some industrial chemicals. World Health Organization, 1994. p. 73-159
(7) Deschamps, D., et al. Persistent asthma after accidental exposure to ethylene oxide. British Journal of Industrial Medicine. Vol. 49 (1992). p. 523- 525
(8) Gross, J.A., et al. Ethylene oxide neurotoxicity: report of four cases and review of the literature. Neurology. Vol. 29, no. 7 (July 1979). p. 978-983
(9) Gardiner, T.H., et al. Epoxy compounds. In: Patty's industrial hygiene and toxicology. 4th ed. Edited by G.D. Clayton, et al. Vol. II. Toxicology. Part A. John Wiley and Sons, Inc., 1993. p. 338-349
(10) Sexton, R.J., et al. Experimental ethylene oxide human skin injuries. Archives of Industrial Hygiene and Occupational Medicine. Vol. 2 (Nov. 1950). p. 549-564
(11) Fisher, A.A. Contact Dermatitis. 3rd ed. Lea and Febiger, 1986. p. 473-475, 631-633
(12) Grant, W.M., et al. Toxicology of the eye. 4th ed. Charles C. Thomas, 1993. p. 669-672
(13) Joyner, R.E. Chronic toxicity of ethylene oxide. Archives of Environmental Health. Vol. 8 (May 1964). p. 700-710
(14) Haines, T., et al. Health effects of ethylene oxide. A report submitted to the Ontario Ministry of Labour, 1983
(15) Fukushima, T., et al. Chronic ethylene oxide poisoning in a factory manufacturing medical appliances. Journal of the Society of Occupational Medicine. Vol. 36, no. 4 (1986). p. 118-123
(16) Estrin, W.J., et al. Evidence of neurologic dysfunction related to long- term ethylene oxide exposure. Archives of Neurology. Vol. 44, no. 2 (Dec. 1987). p. 1283-1286
(17) Crystal, H.A., et al. Cognitive impairment and sensory loss associated with chronic low-level ethylene oxide exposure. Neurology. Vol. 38, no. 4 (1988). p. 567-569
(18) Dretchen, K.L., et al. Cognitive dysfunction in a patient with long-term occupational exposure to ethylene oxide. Journal of Occupational Medicine. Vol. 34, no. 11 (1992). p. 1106-1113
(19) Shupack, J.L., et al. Human skin reactions to ethylene oxide. Journal of Laboratory and Clinical Medicine. Vol. 98, no. 5 (1981). p. 723-729
(20) Verraes, S., et al. Occupational asthma induced by ethylene oxide. Lancet. Vol. 346, no. 8987 (Nov. 1995). p. 1434-1435
(21) Deschamps, D., et al. Toxicity of ethylene oxide on the lens and on leukocytes: an epidemiological study in hospital sterilisation installations. British Journal of Industrial Medicine. Vol. 47 (1990). p. 308-313
(22) Jay, W.M., et al. Possible relationship of ethylene oxide exposure to cataract formation. American Journal of Ophthalmology. Vol. 93 (1982). p. 727- 732
(23) Report on Carcinogens. 11th ed. US Department of Health and Human Services, Public Health Service, National Toxicology Program
(24) Steenland, K., et al. Mortality among workers exposed to ethylene oxide. New England Journal of Medicine. Vol. 324, no. 20 (May 1991). p. 1402-1407
(25) Stayner, L., et al. Exposure-response analysis of cancer mortality in a cohort of workers exposed to ethylene oxide. American Journal of Epidemiology. Vol. 138, no. 10 (1993). p. 787-798
(26) Wong, O., et al. An epidemiological study of workers potentially exposed to ethylene oxide. British Journal of Industrial Medicine. Vol. 50 (1993). p. 308-316
(27) Bisanti, L., et al. Cancer mortality in ethylene oxide workers. British Journal of Industrial Medicine. Vol. 50 (1993). p. 317-324
(28) Hemminki, K., et al. Spontaneous abortions in hospital staff engaged in sterilising instruments with chemical agents. British Medical Journal. Vol. 285 (1982). p. 1461-1463
(29) Ethylene oxide toxicity and its relevance to man: an up-dating of ECETOC technical report no. 5. Technical report no. 11. European Chemical Industry Ecology & Toxicology Centre (ECETOC), Mar. 1984
(30) Jacobson, K.H, et al. The toxicity of inhaled ethylene oxide and propylene oxide vapours. Archives of Industrial Health. Vol. 13, no. 3 (1956). p. 237-244
(31) Smyth, H.F., Jr. et al. The single dose toxicity of some glycols and derivatives. Journal of Industrial Hygiene and Toxicology. Vol. 23, no. 6 (1941). p. 259-268
(32) RTECS database record for ethylene oxide. Last updated: 1997-10
(33) Walker, W.J.G., et al. Toxicity of ethylene oxide. Journal of Hygiene. Vol. 32 (July 1932). p. 409-416
(34) Hollingsworth, R.L., et al. Toxicity of ethylene oxide determined on experimental animals. A.M.A. Archives of Industrial Health. Vol. 13, no. 3 (1956). p. 217-227
(35) Snellings, W.M., et al. A sub-chronic inhalation study on the toxicologic potential of ethylene oxide in B6C3F1 mice. Toxicology and Applied Pharmacology. Vol. 76, no. 3 (1984). p. 510-518
(36) Lynch, D.W., et al. Effects on monkeys and rats of long-term inhalation exposure to ethylene oxide: major findings of the NIOSH study. Association for Advancement of Medical Instrumentation, Technology Assessment Report No. 8-84. In-hospital ethylene oxide sterilization. Current Issues in EO Toxicity and Occupational Exposure, 1984. p. 7-10
(37) Snellings, W.M., et al. A two-year inhalation study of the carcinogenic potential of ethylene oxide in Fischer 344 rats. Toxicology and Applied Pharmacology. Vol. 75, no. 1 (1984). p. 105-117
(38) Snellings, W.M., et al. Teratology study in Fisher 344 rats exposed to ethylene oxide by inhalation. Toxicology and Applied Pharmacology. Vol. 64, no. 3 (1982). p. 476-481
(39) Saillenfait, A.M., et al. Developmental toxicity of inhaled ethylene oxide in rats following short-duration exposure. Fundamental and Applied Toxicology. Vol. 34 (1996). p. 223-227
(40) Hardin, B.D, et al. Reproductive-toxicologic assessment of the epoxides ethylene oxide, propylene oxide, butylene oxide, and styrene oxide. Scandinavian Journal of Work, Environment and Health. Vol. 9, no. 2 (special issue) (Apr. 1983). p. 94-102
(41) Snellings, W.M., et al. Effects on reproduction in Fischer 344 rats exposed to ethylene oxide by inhalation for one generation. Toxicology and Applied Pharmacology. Vol. 63, no. 3 (1982). p. 382-388
(42) Rutledge, J.C., et al. Developmental anomalies derived from exposure to zygotes and first-cleavage embryos to mutagens. Mutation Research. Vol. 296, nos. 1/2 (1992). p. 167-177
(43) Rutledge, J.C., et al. Fetal pathology by ethylene oxide treatment of the murine zygote. Teratology. Vol. 39, no. 6 (1989). p. 563-572
(44) Mori, K., et al. Dose dependent effects of inhaled ethylene oxide on spermatogenesis in rats. British Journal of Industrial Medicine. Vol. 48, no. 4 (1991). p. 270-274
(45) Ethylene oxide. In: Compressed Gas Association. Handbook of compressed gases. 3rd ed. Van Nostrand Reinhold Company, 1990. p. 346-351
(46) Rebsdat, S., et al. Ethylene oxide. In: In: Ullmann's encyclopedia of industrial chemistry. 7th ed. John Wiley and Sons, 2005. Available at: <www.mrw.interscience.wiley.com/ueic/ueic_search_fs.html> {Subscription required}
(47) Fire protection guide to hazardous materials. 13th ed. Edited by A.B. Spencer, et al. National Fire Protection Association, 2002. NFPA 49; NFPA 491
(48) Odor thresholds for chemicals with established occupational health standards. American Industrial Hygiene Association, 1989
(49) HSDB record for ethylene oxide. Last revision date: 97/03/27
(50) Dever, J.P.,et al. Ethylene oxide. In: Kirk-Othmer encyclopedia of chemical technology. John Wiley and Sons, 2005. Available at: <www.mrw.interscience.wiley.com/kirk/kirk_search_fs.html> {Subscription required}
(51) Ethylene oxide. In: Braker, W., et al. Matheson gas data book. 6th ed. Matheson Gas Products, 1980. p. 322-329
(52) Emergency action guide for ethylene oxide. Association of American Railroads, Sept. 1992
(53) Urben, P.G., ed. Bretherick's handbook of reactive chemical hazards. 5th ed. Vol. 1. Butterworth-Heinemann Ltd., 1995
(54) Meurice, J.-C., et al. Allergenes professionnels en milieu hospitalier (latex - trypsine - oxyde d'ethylene) et allergies alimentaires associees. Revue Francaise d'Allergologie. Vol. 30, no. 4 (1990). p. 247-249
(55) Jacson, F., et al. Allergie au formol, latex et oxyde d'ethylene: triple allergie professionnelle chez une infirmiere. Revue Francaise d'Allergologie. Vol. 31, no. 1 (1991). p. 41-43
(56) Balland, S., et al. Allergie a l'oxyde d'ethylene et au latex. Abstract. Revue Francaise d'Allergologie. Vol. 30, no. 4 (1990). p. 263
(57) Dugue, P., et al. Asthme professionnel a l'oxyde d'ethylene chez une infirmiere. Lettres. La Presse Medicale. Vol. 20, no. 30 (Sept. 28, 1991). p. 1455
(58) Emergency response planning guidelines. American Industrial Hygiene Association Journal. Vol. 56, no. 3 (1995). p. 297
(59) Ethylene oxide: users guide. 2nd ed. Celanese Ltd., Dow Chemical Company, Shell Chemical Company, Sunoco, Inc, and Equistar Chemical, LP, Aug. 1999. Available at: <www.ethyleneoxide.com>
(60) Forsberg, K., et al. Quick selection guide to chemical protective clothing. 4th ed. Van Nostrand Reinhold, 2002
(61) European Economic Community. Commission Directive 93/72/EEC. Sept. 1, 1993
(62) Industrial Bio-Test Labs Inc. Primary skin irritation tests with eighteen materials in albino rabbits with cover letter dated 061589. Date produced: July 28, 1972. Hoechst Celanese Corp. EPA/OTS 86-890001277. NTIS/OTS0520783.
(63) McLaughlin, R.S. Chemical burns of the human cornea. American Journal of Ophthalmology. Vol. 29, no. 11 (Nov. 1946). p. 1355-1362
(64) Occupational Safety and Health Administration (OSHA). Ethylene Oxide. In: OSHA Analytical Methods Manual. Revision Date: Oct. 31, 2001. Available at: <www.osha-slc.gov/dts/sltc/methods/toc.html>
(65) National Institute for Occupational Safety and Health (NIOSH). Ethylene Oxide. In: NIOSH Manual of Analytical Methods (NMAM(R)). 4th ed. Edited by M.E. Cassinelli, et al. DHHS (NIOSH) Publication 94-113. Aug. 1994. Available at: <www.cdc.gov/niosh/nmam/nmammenu.html>
(66) National Institute for Occupational Safety and Health (NIOSH). Ethylene Oxide by Portable GC. In: NIOSH Manual of Analytical Methods (NMAM(R)). 4th ed. Edited by M.E. Cassinelli, et al. DHHS (NIOSH) Publication 94-113. Aug. 1994. Available at: <www.cdc.gov/niosh/nmam/nmammenu.html>

Information on chemicals reviewed in the CHEMINFO database is drawn from a number of publicly available sources. A list of general references used to compile CHEMINFO records is available in the database Help.


Review/Preparation Date: 1998-06-24

Revision Indicators:
Carcinogenicity 2000-06-01
TDG 2002-05-29
Extinguishing media 2003-04-18
Flash point 2003-05-05
Sensitivity to static charge 2003-05-05
Electrical conductivity 2003-05-05
Minimum ignition energy 2003-05-05
Fire hazard summary 2003-05-05
TLV basis 2004-01-04
PEL-TWA final 2004-01-29
PEL-STEL final 2004-01-29
PEL final comments 2004-01-29
PEL-TWA transitional 2004-01-29
WHMIS classification comments 2004-03-15
Resistance of materials for PPE 2004-04-06
Passive Sampling Devices 2005-04-07
Sampling/analysis 2005-04-07
ERPG-1 2005-07-01
Bibliography 2006-02-22
Toxicological info 2006-03-17
Short-term skin contact 2006-03-17
Short-term eye contact 2006-03-17
WHMIS detailed classification 2006-03-17
WHMIS proposed classification 2006-03-17
WHMIS health effects 2006-03-17
Emergency overview 2006-03-17
First aid skin 2006-03-17
First aid eye 2006-03-17
First aid inhalation 2006-03-17
Eye/face protection 2006-04-05
Handling 2006-04-05
Stability/reactivity comments 2006-04-07
Melting point 2006-04-07
Boiling point 2006-04-07
Relative density 2006-04-07
Composition/purity 2006-04-07
Fire hazard summary 2006-04-07
Flash point 2006-04-07
Bibliography 2006-04-07
Disposal 2006-04-07
Relative density 2006-09-28



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