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    IPCS INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY
    Health and Safety Guide No. 16

    ETHYLENE OXIDE
    HEALTH AND SAFETY GUIDE






    UNITED NATIONS ENVIRONMENT PROGRAMME

    INTERNATIONAL LABOUR ORGANISATION

    WORLD HEALTH ORGANIZATION




    WORLD HEALTH ORGANIZATION, GENEVA

    This is a companion volume to Environmental Health Criteria 55:
    Ethylene Oxide

    Published by the World Health Organization for the International
    Programme on Chemical Safety (a collaborative programme of the United
    Nations Environment Programme, the International Labour Organisation,
    and the World Health Organization)

    ISBN 92 4 154339 6
    ISSN 0259 - 7268

    (c) World Health Organization 1988

    Publications of the World Health Organization enjoy copyright
    protection in accordance with the provisions of Protocol 2 of the
    Universal Copyright Convention.  For rights of reproduction or
    translation of WHO publications, in part or  in toto, application
    should be made to the Office of Publications, World Health
    Organization, Geneva, Switzerland.  The World Health Organization
    welcomes such applications.

    The designations employed and the presentation of the material in this
    publication do not imply the expression of any opinion whatsoever on
    the part of the Secretariat of the World Health Organization
    concerning the legal status of any country, territory, city or area or
    of its authorities, or concerning the delimitation of its frontiers or
    boundaries.

    The mention of specific companies or of certain manufacturers'
    products does not imply that they are endorsed or recommended by the
    World Health Organization in preference to others of a similar nature
    that are not mentioned.  Errors and omissions excepted, the names of
    proprietary products are distinguished by initial capital letters.

    CONTENTS

    INTRODUCTION

    1. PRODUCT IDENTITY AND USES
        1.1. Identity
        1.2. Physical and chemical properties
        1.3. Composition
        1.4. Production and uses

    2. SUMMARY AND EVALUATION
        2.1. Human exposure to ethylene oxide
        2.2. Fate in the environment
        2.3. Uptake, metabolism, and excretion
        2.4. Effects on organisms in the environment
        2.5. Effects on animals
        2.6. Effects on human beings

    3. CONCLUSIONS AND RECOMMENDATIONS

    4. HUMAN HEALTH HAZARDS, PREVENTION AND PROTECTION, EMERGENCY ACTION
        4.1. Main human health hazards, prevention and
            protection, first aid
            4.1.1. Advice to physicians
            4.1.2. Health surveillance advice
        4.2. Explosion and fire hazards
            4.2.1. Explosion hazards
            4.2.2. Fire hazards
            4.2.3. Prevention
            4.2.4. Fire-extinguishing agents
        4.3. Storage
        4.4. Transport
        4.5. Spillage and disposal
            4.5.1. Spillage
            4.5.2. Disposal

    5. HAZARDS FOR THE ENVIRONMENT AND THEIR PREVENTION

    6. INTERNATIONAL CHEMICAL SAFETY CARD

    7. CURRENT REGULATIONS, GUIDELINES, AND STANDARDS
        7.1. Previous evaluations by international bodies
        7.2. Exposure limit values
        7.3. Specific restrictions
        7.4. Labelling, packaging, and transport
        7.5. Waste disposal
        7.6. Other measures

    BIBLIOGRAPHY
    

    INTRODUCTION

    The Environmental Health Criteria (EHC) documents produced by the
    International Programme on Chemical Safety include an assessment of
    the effects on the environment and on human health of exposure to a
    chemical or combination of chemicals, or physical or biological
    agents.  They also provide guidelines for setting exposure limits.

    The purpose of a Health and Safety Guide is to facilitate the
    application of these guidelines in national chemical safety
    programmes. The first three sections of a Health and Safety Guide
    highlight the relevant technical information in the corresponding EHC. 
    Section 4 includes advice on preventive and protective measures and
    emergency action; health workers should be thoroughly  familiar with
    the medical information to ensure that they can act efficiently in an
    emergency.  Within the Guide is an International Chemical Safety Card
    which should be readily available, and should be clearly explained, to
    all who could come into contact with the chemical.  The section on
    regulatory information has been extracted from the legal file of the
    International Register of Potentially Toxic Chemicals (IRPTC) and from
    other United Nations sources.

    The target readership includes occupational health services, those in
    ministries, governmental agencies, industry, and trade unions who are
    involved in the safe use of chemicals and the avoidance of
    environmental health hazards, and those wanting more information on
    this topic.  An attempt has been made to use only terms that will be
    familiar to the intended user.  However, sections 1 and 2 inevitably
    contain some technical terms.  A bibliography has been included for
    readers who require further background information.

    Revision of the information in this Guide will take place in due
    course, and the eventual aim is to use standardized terminology. 
    Comments on any difficulties encountered in using the Guide would be
    very helpful and should be addressed to:

    The Manager
    International Programme on Chemical Safety
    Division of Environmental Health
    World Health Organization
    1211 Geneva 27
    Switzerland

    THE INFORMATION IN THIS GUIDE SHOULD BE CONSIDERED AS A STARTING POINT
    TO A COMPREHENSIVE HEALTH AND SAFETY PROGRAMME

    1.  PRODUCT IDENTITY AND USES

    1.1  Identity

    Common name:                Ethylene oxide

    Chemical formula:           C2H4O

    Chemical structure:                     O
                                          /   \
                                      H - C - C - H
                                          '   '
                                          H   H

    Common trade names:         Anprolene, Melgas, Merpal, Sterigas P
                                (pure products); Carboxide, Cartox, Etox,
                                Oxyfume 20, Oxyfume 30, Sterigas 90/10,
                                Steroxide 20, T-gas (formulations with
                                carbon dioxide); Oxyfume 12, Sterigas
                                12/88, Steroxide 12/88 (formulations with
                                fluorocarbons); Etoxiat (formulation with
                                methyl formate)

    Common synonyms:            dihydrooxirene, dimethylene oxide,
                                1,2-epoxyethane, ethene oxide, oxane,
                                alpha,beta-oxido-ethane, oxirane

    Abbreviations:              EO, ETO, EtO

    CAS registry number:        75-21-8

    RTECS registry number:      KX2450000

    UN number:                  1040 and 1041

    Conversion factors:         1 ppm = 1.80 mg/m3 air; 1 mg/m3 = 0.55
                                ppm at 25C and 101.3 kPa (760mmHg)

    1.2  Physical  and Chemical Properties

    Ethylene oxide is a colourless gas at room temperature and normal
    atmospheric pressure.  It condenses to a liquid at 10C.  It has an
    ethereal odour with reported odour thresholds of 470 mg/m3 for
    perception and 900-1260 mg/m3 for recognition. It is highly
    flammable and, in vapour form, is subject to explosive decomposition. 
    The liquid is stable to common detonating agents, but polymerization
    may be violent after initiation by acids, bases, or heat. 
    Polymerization is catalysed by certain metal chlorides and hydroxides. 
    Both liquid and gaseous ethylene oxide are very reactive.  It is
    relatively stable in aqueous solution, or when diluted with carbon
    dioxide or halocarbons.  Some physical and chemical properties of
    ethylene oxide are given on the International Chemical Safety Card on
    pp. 20-23.

    1.3  Composition

    Common impurities found in ethylene oxide during the production
    process involving the oxidation of ethene, include water, acetic acid,
    acetaldehyde, and inorganic chlorides. Common impurities found in
    ethylene oxide, produced by the chlorohydrin process, are vinyl
    chloride, 1,2-dichloroethane, chloroethane, and ethylene chlorohydrin. 
    Ethylene oxide, sold for fumigation or sterilization purposes, is
    often mixed with carbon dioxide (e.g., 10-30% ethylene oxide and
    70-90% carbon dioxide) or fluorocarbons (e.g., 12% ethylene oxide and
    88% fluorocarbons), as already indicated by the trade names in
    section 1.1.

    1.4  Production and Uses

    The global production of ethylene oxide in 1985 was estimated to have
    been greater than 5.5 million tonnes.  The substance is produced in
    many countries, the highest volume being produced in the USA.

    Its major use is as an intermediate in the production of various
    chemicals including: the antifreeze, ethylene glycol; polyethylene
    terephthalate polyester for fibres, films, and bottles; non-ionic
    surface active agents; glycol ethers; ethanolamines; and choline.  A
    small fraction of the total consumption (less than 1%) is used for the
    fumigation and sterilization of foodstuffs and medical equipment.

    2. SUMMARY AND EVALUATION

    2.1  Human Exposure to Ethylene Oxide

    Human exposure occurs mainly through inhalation in sterilization
    facilities and in production plants.  Residues in medical equipment
    that has been sterilized with ethylene oxide and insufficiently
    aerated can migrate into tissues and blood, producing primarily local
    effects.  Ingestion of ethylene oxide residues from most fumigated or
    sterilized foodstuffs is unlikely, as they dissipate through
    evaporation or reaction with food constituents.  A major conversion
    product in foodstuffs, pharmaceutical products, and medical equipment
    is 2-chloroethanol, which is more persistent than ethylene oxide. 
    Levels of 2-chloroethanol as high as several g/kg have been measured
    in food and levels of several hundred mg/kg in medical equipment.

    Most ethylene oxide is used as a reactive intermediate in the chemical
    plant in which it is produced.  Because of the explosion hazard,
    ethylene oxide is stored and handled in chemical process plants in
    closed, automated systems.  This equipment is often located outdoors,
    and, except during maintenance, the probability of exposure of the
    workers is minimal.  Air samples collected in the processing areas of
    chemical production plants have shown that ethylene oxide vapour
    concentrations are now generally less than 4 mg/m3, with occasional
    high peak values.  Occupational exposure to ethylene oxide tends to be
    much higher in health instrument manufacture and in hospital
    sterilizationa areas than in the chemical processing industries. 
    Air levels of ethylene oxide near malfunctioning or improperly
    designed equipment in industry may reach hundreds of mg/m3 for brief
    periods.  However, 8-h time-weighted average concentrations in the
    breathing zone in hospital sterilization areas are generally less than
    36 mg/m3.  It should be emphasized that the exposure of hospital
    workers to ethylene oxide tends to be of a short-term and intermittent
    nature during loading and unloading, with the likelihood of exposure
    to short-term (5-120 min) concentrations of about 100 mg/m3 and to
    peak concentrations of up to 1800 mg/m3 following the opening of
    sterilization chambers.

    Ambient air levels to which members of the general population are
    exposed at a distance from industrial point sources of emission have
    been estimated to be below the limit of detection.



              

    a   Patients undergoing haemodialysis may also be exposed to
        ethylene oxide from equipment sterilized with it.  Cases of
        anaphylaxis during dialysis have been ascribed to it.

    2.2  Fate in the Environment

    The main pathway of entry of ethylene oxide into the environment is
    through evaporation or by venting gases during production, handling,
    storage, transport, or use (e.g., sterilization procedures).

    The removal of ethylene oxide from the atmosphere is slow, but may be
    accelerated through washout by rain.

    Ethylene oxide is highly soluble in water, but will evaporate to a
    great extent.  Degradation of ethylene oxide in neutral water is slow,
    even in the presence of aerobic microorganisms, but more rapid under
    acidic or basic conditions due to catalysis.  Because of its limited
    lipid solubility, it is unlikely that ethylene oxide and it conversion
    products will bioaccumulate.

    2.3  Uptake, Metabolism, and Excretion

    Inhaled ethylene oxide is readily absorbed into the blood, distributed
    throughout the body, and rapidly metabolized.  The half-life in the
    tissues of man and rodents is approximately 10 min; clearance from the
    blood of dogs occurred with a half-life of 33 min.  Marked nausea and
    profuse vomiting following dermal exposure of man to aqueous solutions
    of ethylene oxide indicate that absorption can occur through the skin. 
    Two metabolic pathways have been identified including hydrolysis to
    1,2-ethanediol and conjugation with glutathione. Excretion is
    primarily via the urine.

    2.4  Effects on Organisms in the Environment

    The toxicity of ethylene oxide for aquatic organisms is low. 
    Concentrations lethal for half the number of various aquatic organisms
    in populations tested for 1-4 days were approximately 90 mg/litre
    (LC50) or higher. 2-Chloroethanol, a degradation product in saline
    water, is equally toxic, but, 1,2-ethanediol, a major degradation
    product, is less toxic.   Thus, the probable effects of ethylene oxide
    on the aquatic environment are considered negligible.  There are no
    data concerning the toxicity of ethylene oxide for terrestrial
    organisms.

    2.5  Effects on Animals

    Single oral doses of 330 mg/kg body weight (LD50) and exposure to
    vapour concentrations of 2630 mg/m3 (LC50) for 4 h have been shown
    to be lethal for half the number of exposed rats.  The compound is
    moderately toxic in acute exposures, according to the scale of Hodge &
    Sterner.

    Ethylene oxide directly alkylates proteins and DNA and is mutagenic in
    microorganisms, plants, insects, mammalian cells in vitro, and mammals
    in vivo, inducing both gene mutations and chromosomal abnormalities. 
    Sister chromatid exchanges and chromosomal aberrations have also been
    observed in the blood lymphocytes of monkeys exposed by inhalation.

    The potential of ethylene oxide to cause teratogenic or adverse
    reproductive effects has been examined in four animal species (mouse,
    rat, rabbit, and monkey) by two routes of administration.  Results
    from these studies show that ethylene oxide induces toxic effects on
    the reproductive function in both males and females.  The levels
    needed to produce fetal effects approach or equal the dose needed to
    produce maternal toxicity.

    In experimental animal studies, it has been clearly demonstrated that
    ethylene oxide is carcinogenic via different routes of exposure
    (intragastric, subcutaneous injection, and inhalation).  Ethylene
    oxide induced forestomach carcinomas in rats following oral
    administration and subcutaneous fibrosarcomas in mice following
    subcutaneous injection. In two inhalation studies, confirmatory data
    demonstrated dose-related increases in the incidences of leukaemia,
    peritoneal mesothelioma, and cerebral glioma.

    2.6  Effects on Human Beings

    No ambient air monitoring data are available from which the effects of
    ethylene oxide on the health of man and the environment can be
    assessed.   However,  the risk of adverse health effects from exposure
    to ethylene oxide in the ambient air, apart from point-source
    emissions and accidental spillage, is likely to be negligible.

    Case reports indicate that headache, nausea, vomiting, dyspnoea, and
    respiratory tract irritation are common effects of acute inhalation
    exposure to ethylene oxide.  Respiratory tract irritation increases
    with inhaled vapour concentration and may result in severe
    life-threatening pulmonary disease after a latency period of several
    hours.  Cardiovascular collapse and renal failure have been attributed
    to residues of ethylene oxide in medical equipment.a  Case reports
    and the results of animal studies indicate that sensorimotor
    neuropathies may follow repeated exposure to concentrations of
    ethylene oxide recognizable by its odour (approximately 900 mg/m3 or
    more).  Because of its high odour threshold (900-1260 mg/m3),
    sensory recognition does not offer adequate warning of a health
    hazard.


              

    a   Anaphylactic reactions have been reported during haemodialysis,
        when using equipment sterilized with ethylene oxide.

    Dermatological effects in man following skin contact with aqueous
    ethylene oxide include erythema, oedema, and vesiculation, in that
    order.  The severity of the skin injury is related to concentration (a
    50% solution (500 g/litre) being most hazardous) and duration of
    contact.  When liquid ethylene oxide vapourizes, it can result in a
    freeze burn.  On repeated exposure, ethylene oxide may cause allergic
    contact dermatitis.  Aqueous solutions of ethylene oxide and its
    conversion products are irritating to the eyes and can produce corneal
    injury.  Ethylene oxide vapour or residues in medical equipment have
    also been observed to produce irritant effects on the eyes and the
    respiratory tract.  The irritant effects on the eyes and skin are
    often delayed.  Cataracts have occurred following repeated exposure to
    concentrations of the vapour recognizable by its odour (approximately
    900 mg/m3).

    In man, ethylene oxide may induce chromosomal aberrations and  sister
    chromatid exchanges in lymphocytes and micronuclei in erythroytes at
    air concentrations that can be found in the work place.  Tissue
    distribution studies have provided evidence that ethylene oxide
    reaches the  gonads, supporting the findings of heritable mutations in
    insects and rodents.  Therefore, ethylene oxide may be considered a
    potential human mutagen for both somatic and germ cells.

    The results of animal studies suggest possible reproductive impairment
    in human males, but are inadequate for assessing the fetal risk.  Data
    on the reproductive effects in human beings are insufficient.  The
    results of one study suggest an increase in spontaneous abortion rate
    in pregnant women occupationally exposed to ethylene oxide at an 8-h
    time-weighted average of 0.18-0.90 mg/m3, with peak concentrations
    of up to 450 mg/m3.  However, exposure data are limited and this
    prevents the establishment of a relationship between abortion rates
    and exposure levels.

    Two epidemiological studies have shown an association between ethylene
    oxide exposure and an excess risk of cancer, but both studies have
    limitations.  Airborne concentrations of ethylene oxide in the two
    studies were reported to be time-weighted averages of 3618 mg/m3
    and 10-50 mg/m3, with occasional brief exposures in excess of the
    odour threshold (900-1260 mg/m3). Although the evidence for the
    carcinogenicity of ethylene oxide alone in man is inadequate, these
    two studies indicate that exposure to ethylene oxide increases the
    risk of malignancies.

    Taking into account available data concerning the alkylating nature of
    ethylene oxide, the demonstration of DNA adducts, the overwhelming
    positive  in vivo responses in mutagenic and clastogenic assays, the
    reproducible positive carcinogenic findings in animals, and the
    epidemiological findings suggesting an increase in the incidence of
    human cancer, ethylene oxide should be considered as a probable human
    carcinogen, and its levels in the environment should be kept as low as
    feasible.

    3. CONCLUSIONS AND RECOMMENDATIONS

    The risks for the health of the general population from exposure to
    ethylene oxide in the ambient air, apart from point-source emissions
    and accidental spillage, are likely to be negligible.

    Common effects of single inhalation exposures are headache, nausea,
    vomiting, dyspnoea, and respiratory tract irritation, which may result
    in lung oedema.  Sensorimotor neuropathies and eye cataracts may
    follow repeated exposure to a concentration of ethylene oxide
    recognizable by its odour.  Odour recognition does not offer adequate
    warning of a health hazard.  Ethylene oxide solutions in water are
    irritating to the skin and eyes. The pure liquid can cause a freeze
    burn.  Absorption through the skin, even from dilute solutions, may
    cause systemic effects.  On repeated exposure of the skin, ethylene
    oxide solutions may cause allergic contact dermatitis.

    Taking into account all the available data, ethylene oxide should be
    considered as a mutagen and a probable human carcinogen.  It may pose
    a reproductive hazard.  Its levels in the environment should be kept
    as low as possible.

    From: Environmental Health Criteria 55: Ethylene Oxide (WHO, 1985).

    4.  HUMAN HEALTH HAZARDS, PREVENTION AND PROTECTION, EMERGENCY
        ACTION

    4.1  Main Human Health Hazards, Prevention and Protection, First Aid

    The human health hazards associated with certain types of exposure to
    ethylene oxide, together with preventive and protective measures and
    first aid recommendations are listed on the International Chemical
    Safety Card on pp. 20-23.

    4.1.1  Advice to Physicians

    No specific antidote is known. Treat symptomatically.  If skin
    sensitization has developed following exposure to ethylene oxide,
    further exposure should not be allowed.  Be aware of the possibility
    of neuropathies.

    4.1.2  Health Surveillance Advice

    Human beings potentially exposed to ethylene oxide should undergo
    periodic medical examination with particular emphasis given to the
    pulmonary, haematological, neurological, and reproductive systems, and
    to the eyes and skin.  The physician should be aware of increased risk
    of cancer and reproductive effects associated with exposure to
    ethylene oxide.

    Exposure to ethylene oxide should be checked regularly by general
    and/or personal monitoring.

    4.2  Explosion and Fire Hazards

    4.2.1  Explosion hazards

    Ethylene oxide-air mixtures containing 2.7% by volume or more of
    ethylene oxide may be explosive (the flash point is -57C and
    autoignition occurs at 429C) and can be ignited by sources of heat or
    ignition.  The vapour of ethylene oxide is subject to explosive
    decomposition above 425C.  The vapour, which is heavier than air, may
    travel along the ground and be ignited from a distance.

    The liquid may polymerize violently after initiation by acids, bases,
    or heat.   The polymerization is catalysed by certain metal chlorides
    and metal hydroxides.  Ethylene oxide reacts violently with many
    compounds, including oxidizing agents, acids, organic bases, ammonia,
    amines, alcohols, mercaptans, alkane thiols, and bromoethane.

    4.2.2  Fire hazards

    Ethylene oxide is a flammable gas.  In the vapour form, it will burn
    without the presence of air or other oxidizing agents.

    4.2.3  Prevention

    Use closed systems, ventilation, explosion-proof electrical equipment
    and lighting, and spark-proof hand tools.  Do not use ethylene oxide
    near sources of heat or ignition.  Do not smoke.  Do not use
    compressed air for filling, discharging, or handling.  Purge air from
    unloading system before unloading.  Avoid contact of the compound with
    incompatible materials (section 4.2.1).

    In case of fire, shut off the supply.  If this is impossible and there
    is no risk to the surroundings, let the fire burn itself out.  Cool
    fire-exposed containers by spraying with water from a safe distance. 
    Fire-fighters should be equipped with self-contained breathing
    apparatus, eye protection, and full protective clothing.

    4.2.4  Fire-extinguishing agents

    Dilution of ethylene oxide with 23 volumes of water raises its flash
    point, thereby reducing the possibility of ignition at ambient
    temperature. Dry chemical powder can be used to extinguish small
    fires.  Alcohol resistant foam should be used on large fires. 
    However, in all cases of fire, the prime requirement before
    extinguishing the fire should be to attempt to shut off the vapour
    escape.

    4.3  Storage

    Ethylene oxide should be stored in a cool, well-labelled,
    well-ventilated, fire-proof area, preferably away from other chemicals
    and outdoors.  The storage area should be surrounded by a retaining
    wall or a sill.  Keep away all sources of ignition and heat as well as
    incompatible materials (section 4.2.1).  Containers for ethylene oxide
    can be made of stainless steel, aluminium 3003, zinc, nickel, copper,
    teflon, ceramics, or glass.  Storage vessels should contain a positive
    pressure layer of inert nitrogen.  A pressure vessel check programme
    should be made.  Storage pressure and temperature ranges are
    240-410 kPa and 10-15C, respectively.  When long storage times are
    anticipated, a lower temperature range is recommended to minimize
    polymerization.  Prolonged storage in small containers where there is
    a high surface to volume ratio should be avoided, because the
    polymerization rate is increased by the presence of any metal. 
    Mixtures of ethylene oxide and water should not be left dormant for
    any length of time, and the temperature and pressure of vessels
    containing these mixtures should be carefully monitored.

    4.4  Transport

    In case of accident, stop the engine.  Remove all sources of ignition. 
    Keep bystanders at a distance, mark the roads and keep upwind. 
    Evacuate the area endangered by poison gas. Wear full protective
    clothing and self-contained breathing apparatus.  In case of spillage

    or fire, use the methods advised in sections 4.5 and  4.2,
    respectively.  In case of poisoning, follow the advice in section 4.1. 
    Notify the police and fire brigade immediately.

    4.5  Spillage and Disposal

    4.5.1  Spillage

    Remove all ignition sources and evacuate the danger area.  Provide
    optimum ventilation, which should be explosion-proof. Spilled liquid
    should be washed away with water.  Avoid run-off into drains or sewers
    (explosion hazard). Ensure personal protection by use of
    self-contained breathing apparatus and full protective clothing.

    4.5.2  Disposal

    Ethylene oxide can be disposed of by evaporation in a open area or by
    burning, after ignition from a safe distance.  Burning in an
    incinerator can cause difficulties, unless a gas feed can be arranged,
    as ethylene oxide boils at 10C.  It is soluble in water or alcohol,
    and these solutions can be incinerated.

    5.  HAZARDS FOR THE ENVIRONMENT AND THEIR PREVENTION

    Ethylene oxide will evaporate from water.  Degradation of ethylene
    oxide in the atmosphere and in neutral water is slow, but it is more
    rapid in acidic or basic solutions.  Bioaccumulation of ethylene oxide
    and its conversion products is unlikely.

    The toxicity of ethylene oxide for aquatic organisms is low.  The
    effects of ethylene oxide on the aquatic environment are considered to
    be negligible.

    Contamination of soil, water, and the atmosphere can be avoided by
    proper methods of storage, transport, handling, and waste disposal. 
    In cases of spillage, apply methods recommended in section 4.5.1.

    6.  INTERNATIONAL CHEMICAL SAFETY CARD

     This card should be easily available to all health workers concerned
     with, and users of, ethylene oxide. It should be displayed at, or
     near, entrances to areas where there is potential exposure to
     ethylene oxide, and on processing equipment and containers.  The card
     should be translated into the appropriate language(s).  All persons
     potentially exposed to the chemical should also have the instructions
     on the chemical safety card clearly explained.  Space is available on
     the card for insertion of the National Occupational Exposure Limit,
     the address and telephone number of the  National Poison Control
     Centre, and for local trade names. 


    
    ETHYLENE OXIDE

    (EO, ETO, 1,2-epoxyethane, ethene oxide, oxirane)

                                                                                                                                         

    PHYSICAL PROPERTIES                                              OTHER CHARACTERISTICS
                                                                                                                                         

    Relative molecular mass                 44.05                    Colourless gas with ethereal odour; the gas is heavier
    Appearance                              colourless gas           than air, may travel along the ground, and be ignited
    Odour                                   ethereal                 from a distance; it is subject to explosive decomposition
    Odour perception threshold (mg/m3)      470                      above 425C; the liquid may polymerize violently
    Melting point (C)                      -111                     after initiation by acids, bases, or heat;
    Boiling point (C)                      10.4                     polymerization is catalysed by metal chlorides and
    Solubility in water (20C)              infinite                 metal hydroxides; ethylene oxide reacts violently with
    Density (20C) (g/ml)                   0.87                     many compounds, including oxidizing agents, acids,
    Relative vapour density                 1.5                      organic bases, ammonia, amines, alcohols, mercaptans,
    Vapour pressure (20C) (kPa)            146                      alkane thiols, and bromoethane; it can induce adverse
    Flash point (C) (open cup)             -57C                    effects at levels well below the odour threshold
    Flammable (explosive) limits (vol %)    2.7-100
    Autoignition (C)                       429
    log  n-octanol/water partition
       coefficient                          -0.30

                                                                                                                                         

    HAZARDS/SYMPTOMS                        PREVENTION AND PROTECTION                 FIRST AID
                                                                                                                                         

    SKIN: Irritation by solutions           Wear clean protective impervious          Remove contaminated clothing (not in case
    in water; concentrated liquid           gloves and boots and clean impermeable    of frost bite) and shoes immediately; rinse
    may cause freeze burn with              body-covering clothing; do not wear       with water for at least 15 minutes; treat
    redness and pain                        leatherware                               for inhalation exposure; seek medical
                                                                                      attention

    EYES: Irritation by vapour and          Wear safety face shield or eye            Rinse open eyes with plenty of water for
    liquid; pure liquid may cause           protection in combination with            at least 15 minutes; treat for inhalation;
    freeze burn with redness, pain,         breathing protection                      seek medical attention
    and blurred vision

    INHALATION: Irritation of               Use explosion-proof general or            Remove victim to fresh air; keep victim
    respiratory tract; dyspnoea;            exhaust ventilation, and, for             quiet and warm; if breathing has stopped,
    effects on the central nervous          non-routine activities, use               apply artificial respiration; transport
    system, such as headache, nausea,       self-contained breathing                  to hospital: pulmonary oedema may occur
    and vomiting                            apparatus                                 after a latent period

    INGESTION: Irritation of mouth,         Do not eat, drink, or smoke during        Rinse mouth; give plenty of water to drink;
    throat, and stomach; see                work                                      do not induce vomiting; transport to
    inhalation                                                                        hospital

    REPEATED EXPOSURE: Ethylene             Exposure should be kept as low as
    oxide should be considered              feasible
    as a probable human mutagen
    and carcinogen; it may pose
    a reproductive hazard; and may
    cause allergic contact
    dermatitis

    ENVIRONMENT: Low toxicity               Apply proper methods of storage,
    for aquatic life                        transport, waste disposal, and
                                            handling of spills (see below)

                                                                                                                                         

    SPILLAGE                                STORAGE                                   FIRE AND EXPLOSION
                                                                                                                                         

    Remove all ignition sources;            Store in well-labelled, cool, well-       Flammable; vapour-air mixtures may be
    evacuate area; provide optimum          ventilated, fire-proof area,              explosive; use closed systems, ventilation,
    explosion-proof ventilation;            preferably separated and outside; store   and explosion-proof equipment; do not use
    wash spilled liquid away with           away from incompatible substances;        compressed air for filling, discharging, or
    water; ensure personal                  storage vessels should have a positive    handling; no source of ignition or heat; in
    protection by use of self-              pressure layer of nitrogen                case of fire, keep containers cool by
    contained breathing apparatus                                                     spraying with water; extinguish fire with
    and full protective clothing                                                      carbon dioxide, dry chemical, powder,
                                                                                      water, or foam

                                                                                                                                         

    WASTE DISPOSAL
                                                                                                                                         

    Evaporate in an open area;              National Occupational Exposure Limit:     UN: 1040 and 1041
    burn after ignition from a
    safe distance; incinerate               National Poison Control Centre
    after dissolution in water
    or alcohol                              Local Trade Names:

    FIGURE 1
    

    7.  CURRENT REGULATIONS, GUIDELINES, AND STANDARDS

    The information given in this section has been extracted from the
    International Register of Potentially Toxic Chemicals (IRPTC) legal
    file and other UN sources.  Its intention is to give the reader a
    representative but non-exhaustive overview of current regulations,
    guidelines, and standards.

    The reader should be aware that regulatory decisions about chemicals
    taken in a certain country can only be fully understood in the
    framework of the legislation of that country.a

    7.1  Previous Evaluations by International Bodies

    An International Agency for Research on Cancer Working Group (IARC,
    1985) evaluated the carcinogenicity of ethylene oxide and concluded
    that:

    "There is sufficient evidence for the carcinogenicity of ethylene
    oxide to experimental animals; there is limited evidence for the
    carcinogenicity to humans of exposures to ethylene oxide in
    combination with other chemicals; there is inadequate evidence for the
    carcinogenicity to humans of exposures to ethylene oxide alone.  Taken
    together, the data  indicate that ethylene oxide is probably
    carcinogenic to humans."  This conclusion was confirmed in 1987.

    The FAO/WHO Joint Meeting on Pesticide Residues (JMPR) reviewed
    residues and toxicity data on ethylene oxide in 1965, 1968 and 1971. 
    It concluded that the data available were insufficient to establish an
    acceptable daily intake (ADI) for man for either ethylene oxide or
    ethylene chlorohydrin and other reaction products.

    7.2  Exposure Limit Values

    Some exposure limit values are given in the table on pp. 26-28.

    When no effective date appears in the IRPTC legal file, the year of
    the reference from which the data are taken is indicated by (r).

              

    a    The regulations and guidelines of all countries are subject to
         change and should always be verified with the appropriate
         regulatory authorities before application.

    7.3  Specific Restrictions

    The European Community legislation prohibits the putting on the market
    of cosmetics containing ethylene oxide.

    The European Community legislation prohibits the putting on the market
    and use of plant protection products containing ethylene oxide. 
    Nevertheless, the Member States may temporarily agree derogations for
    some minor uses until 31 December, 1989.

    In Czechoslovakia, as a suspected carcinogen, the use and handling of
    ethylene oxide must be reported by the user to the authorities. 
    Requirements and restrictions on handling, labelling, packaging,
    storage, and transport are listed (1985).

    Denmark prohibits the manufacture, marketing, and importation of
    foodstuffs or food ingredients treated with ethylene oxide (1986).

    In the Federal Republic of Germany, handling of ethylene oxide is
    prohibited or restricted for adolescents and pregnant and nursing
    women (1980).

    In Kenya, the compound is permitted for the fumigation of specified
    food products, and maximum levels of use are listed (1982 (r)).

    In the USSR, the pesticide ethylene oxide is prohibited in specified
    food products (1983).

    In the USA, in the occupational environment, an "action level" of
    0.5 ppm (8-h time-weighted average) has been established as the level
    above which employers must initiate certain compliance activities such
    as periodic monitoring of employee exposure and medical surveillance
    (1984).

    In Canada, application is restricted to licenced commercial
    applicators only and residues on food must be below 0.1 ppm (1987).



    
    EXPOSURE LIMIT VALUES

                                                                                                                                         

    Medium      Specification       Country/            Exposure limit descriptiona                Value                Effective
                                    organization                                                                          date
                                                                                                                                         

    AIR         Occupational        Australia           Threshold limit value (TLV)                                       1985 (r)
                                                        - Time-weighted average (TWA)                90 mg/m3

                                    Czechoslovakia      Maximum allowable concentration (MAC)                             1985
                                                        - Time-weighted average (TWA)                1 mg/m3b
                                                        - Ceiling value                              5 mg/m3              1985

                                    Denmark             Threshold limit value (TLV)                                       1985
                                                        - Ceiling value                              1.8 mg/m3

                                    Finland             Maximum allowable concentration                                   1981
                                                        - Time-weighted average (TWA)                20 mg/m3             1981
                                                        - Short-term exposure limit (STEL)           40 mg/m3
                                                          (15-min time-weighted average)

                                    Germany,            Maximum work-site concentration              withdrawn            1986 (r)
                                      Federal                                                        (carcinogenicity)
                                      Republic of

    AIR         Occupational        Germany,            Technical reference value                    5 mg/m3              1986
                                      Federal
                                      Republic of

                                    Hungary             Maximum allowable concentration (MAC)                             1985 (r)
                                                        - Time-weighted average (TWA)                1 mg/m3
                                                        - Short-term exposure limit (STEL)           1 mg/m3
                                                          (30-min time-weighted average)
                                                                                                                                         

                                                                                                                                         

    Medium      Specification       Country/            Exposure limit descriptiona                Value                Effective
                                    organization                                                                          date
                                                                                                                                         

                                    Japan               Maximum allowable concentration (MAC)        90 mg/m13            1982 (r)

                                    Netherlands         Maximum limit                                                     1982 (r)
                                                        - Time-weighted average (TWA)                90 mg/m3

                                    Romania             Maximum permissible concentration                                 1985 (r)
                                                        - Time-weighted average (TWA)                30 mg/m3
                                                        - Ceiling value                              60 mg/m3

                                    Sweden              Threshold limit value (TLV)                                       1985
                                                        - Time-weighted average (TWA)                9 mg/m3c
                                    Sweden              - Short-term exposure limit                  18 mg/m3
                                                          (15-min time-weighted average)

    AIR         Occupational        United Kingdom      Threshold limit value (TLV)                  10 mg/m3             1985 (r)

                                    USA (OSHA)          Permissible exposure limit (PEL)                                  1984
                                                        - Time-weighted average (TWA)                2 mg/m3

                                    USA (ACGIH)         Threshold limit value                                             1986
                                                        - Time-weighted average                      2 mg/m3

                                    USSR                - Ceiling value                              1 mg/m3              1977

    AIR         Ambient             USSR                Maximum allowable concentration (MAC)                             1984
                                                        - Once per day                               0.3 mg/m3
                                                        - Average per day                            0.03 mg/m3

                                                                                                                                         

    a  TWA = time-weighted average over one working day (usually 8 h).
    b  Suspected carcinogenic potential for man.
    c  Carcinogenic; for new and renovated plants, a TWA of 1.8 mg/m3 is desired.
    

    7.4  Labelling, Packaging, and Transport

    The European Community legislation requires labelling as a dangerous
    substance using the symbol(s):

    FIGURE 2

    FIGURE 3

    The label must read:

          may cause cancer; may cause heritable genetic damage; extremely
          flammable liquified gas; toxic by inhalation; irritating to
          eyes, respiratory system and skin; not recommended for interior
          use onlarge surface areas; keep container tightly closed, in a
          cool, well-ventilated place; keep away from sources of ignition
          -- no smoking; take precautionary measures against static
          discharges; if you feel unwell, seek medical advice (show the
          label where possible).

    The European Community legislation on labelling of pesticide
    preparations classifies ethylene oxide in Class I/a for the purpose of
    determining the label for preparations containing ethylene oxide and
    other active ingredients.

    The International Maritime Organization classifies ethylene oxide as 
    a flammable, slightly poisonous (liquified) gas (Hazard Class 2(3,
    6.1).

    The recommended label is:

    FIGURE 4

    In the USA, certain specified vessels carrying ethylene oxide in bulk
    and bound for, or departing from, US ports must notify the captain of
    the port at least 24 h in advance and must give him certain
    information (1983 (r)).

    7.5  Waste Disposal

    In the Federal Republic of Germany, the emission into the air of
    organic compounds in Class I, which includes ethylene oxide, must not
    exceed (as the sum of all compounds in this class) a mass
    concentration of 20 mg/m3 at a mass flow of greater than 0.1 kg/h.
    If compounds of different classes are present, the mass concentration
    must not exceed 30 mg/m3 (1982 (r)).

    In the USA, any solid waste (except domestic) that contains ethylene
    oxide must be listed as hazardous waste (subject to handling,
    transport, treatment, storage and disposal regulation, and permit and
    notification requirements) unless it is found that the waste cannot
    pose a threat to human health or the environment when improperly
    managed.  If ethylene oxide is a commercial chemical product, it is
    identified as "toxic waste" subject to handling, transport, treatment,
    storage and disposal regulation and permit and notification
    requirements (1980).  An owner or operator of a hazardous waste
    incinerator must achieve 99.99% destruction and removal efficiency for
    this substance, if it is designated as a principal organic hazardous
    constituent in its EPA permit (1981).  Under the Comprehensive
    Environmental Response, Compensation, and Liability Act of 1980
    (CERCLA), unless in compliance with a specified permit or procedure,
    owners/operators of vessels or on- or offshore facilities must notify
    the US government (National Response Center) of any release of the
    hazardous substance in or on navigable waters, adjoining shorelines,
    the contiguous zone or beyond the contiguous zone or to any other
    environmental media (air, land and ground water) in an amount equal to
    or greater than 0.454 kilogram in any 24-h period (1985 (r)).

    7.6  Other Measures

    The European Community legislation concerning the major accident
    hazards of certain industrial activities foresees that the
    manufacturer must take all necessary measures to prevent accidents and
    to limit their consequences for man and the environment, when
    processing ethylene oxide or when storing it in quantities equal to,
    or over, 50 tonnes.

    Furthermore, when ethylene oxide is processed in quantities equal to,
    or over, 50 tonnes, or is stored in quantities equal to, or over,
    300 tonnes, notification has to be made to the competent authorities
    including information on the substance, on the installation,
    information on possible major accident situations, and emergency
    plans.

    BIBLIOGRAPHY

    BRETHERICK, L. (1981)   Hazards in the chemical laboratory, 3rd ed.
    London, The Royal Society of Chemistry.

    CEC  (1984)   Classification and labelling of dangerous substances.
    Brussels, Commission of the European Communities.

    DUTCH CHEMICAL INDUSTRY ASSOCIATION  (1980)   Handling chemicals
     safely, 2nd ed. Dutch Association of Safety Experts, Dutch Safety
    Institute.

    GOSSELIN, R.E., SMITH, R.P., HODGE, H.C., & BRADDOCK, J.E  (1976) 
     Clinical toxicology of commercial products, 5th ed. Baltimore,
    Maryland, Williams and Wilkins Company.

    HOMMEL, G.  (1987)   [Handbook of dangerous goods.] 2nd ed. Berlin,
    Springer Verlag (in German).

    IARC  (1972 - present)   IARC Monographs on the Evaluation of
     Carcinogenic Risk of Chemicals to Man. Lyons, International Agency
    for Research on Cancer.

    IRPTC  (1985)   IRPTC file on treatment and disposal methods for waste
     chemicals. Geneva, International Register for Potentially Toxic
    Chemicals, United Nations Environment Programme.

    IRPTC  (1987)   IRPTC legal file 1986. Geneva, International Register
    of Potentially Toxic Chemicals, United Nations Environment Programme.

    IRPTC  Data profile on individual chemical substances. Geneva,
    International Register of Potentially Toxic Chemicals, United Nations
    Environment Programme (unpublished file).

    SAX, N.I.  (1984)  Dangerous properties of industrial materials. New
    York, Van Nostrand Reinhold Company, Inc.

    UNITED NATIONS  (1986)  Recommendations on the transport of dangerous
     goods. 4th ed. New York, United Nations.

    US NIOSH   Current intelligence bulletins. Washington, DC, US
    Department of Health, Education and Welfare.

    US NIOSH  (1976)  A guide to industrial respirator protection.
    Cincinnati, Ohio, US National Institute for Occupational Safety and
    Health, pp. 76-189.

    US NIOSH/OSHA  (1981)   Occupational health guidelines for chemical
     hazards. 3 Vols, Washington DC, US Department of Health and Human
    Services, US Departmnent of Labor (Publication No. DHSS(NIOSH)
    01-123).

    US NIOSH/OSHA  (1985)   Pocket guide to chemical hazards. Washington
    DC, US Department of Health, Education and Welfare, US Department of
    Labor (Publication No. 85.114).

    WHO (1985)   EHC No. 55: Ethylene oxide. Geneva, World Health
    Organization, 78pp.

    


    See Also:
       Toxicological Abbreviations
       Ethylene oxide (EHC 55, 1985)
       Ethylene oxide (ICSC)
       ETHYLENE OXIDE (JECFA Evaluation)
       Ethylene oxide (FAO Meeting Report PL/1965/10/2)
       Ethylene oxide (FAO/PL:1968/M/9/1)
       Ethylene oxide (WHO Pesticide Residues Series 1)
       Ethylene oxide (CICADS 54, 2003)
       Ethylene Oxide (IARC Summary & Evaluation, Volume 60, 1994)