IPCS INCHEM Home

    IPCS INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY
    Health and Safety Guide No. 92

    MORPHOLINE
    HEALTH AND SAFETY GUIDE






    UNITED NATIONS ENVIRONMENT PROGRAMME

    INTERNATIONAL LABOUR ORGANISATION

    WORLD HEALTH ORGANIZATION




    WORLD HEALTH ORGANIZATION, GENEVA 1995

    This is a companion volume to Environmental Health Criteria 179:
    Morpholine

    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)

    This report contains the collective views of an international group of
    experts and does not necessarily represent the decisions or the stated
    policy of the United Nations Environment Programme, the International
    Labour Organisation, or the World Health Organization

    WHO Library Cataloguing in Publication Data

    Health and safety guide for Morpholine.

    (Health and safety guide ; no. 92)

    1.Morpholines - adverse effects
    2.Enviromental exposure I.Series

    ISBN 92 4 151092 7          (NLM Classification: QD 399)
    ISSN 0259-7268

    The World Health Organization welcomes requests for permission to
    reproduce or translate its publications, in part or in full. 
    Applications and enquiries should be addressed to the Office of
    Publications, World Health Organization, Geneva, Switzerland, which
    will be glad to provide the latest information on any changes made to
    the text, plans for new editions, and reprints and translations
    already available.

    (c) World Health Organization 1995

    Publications of the World Health Organization enjoy copyright
    protection in accordance with the provisions of Protocol 2 of the
    Universal Copyright Convention.  All rights reserved.

    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. Analysis
         1.4. Production and uses

    2. SUMMARY AND EVALUATION
         2.1. Exposure
         2.2. Uptake, metabolism, and excretion
         2.3. Effects on organisms in the environment
         2.4. Effects on experimental animals and in vitro test systems
         2.5. Effects on humans

    3. CONCLUSIONS AND RECOMMENDATIONS
         3.1. Recommendations for the protection of human health
         3.2. Recommendations for the protection of the environment

    4. HUMAN HEALTH HAZARDS, PREVENTION AND PROTECTION, EMERGENCY ACTION
         4.1. Human health hazards, prevention and protection, first aid
               4.1.1. Information for physicians
                       4.1.1.1   Signs and symptoms of exposure
                       4.1.1.2   First aid
                       4.1.1.3   Medical treatment
               4.1.2. Health surveillance advice
                       4.1.2.1   Initial medical screening
                       4.1.2.2   Periodic medical examination
         4.2. Explosion and fire hazards
               4.2.1. Reactivity data
               4.2.2. Explosion hazards
               4.2.3. Fire hazards
               4.2.4. Extinguishing media
               4.2.5. Special firefighting procedures
         4.3. Storage
         4.4. Transport
         4.5. Spillage
         4.6. Disposal

    5. HAZARDS FOR THE ENVIRONMENT AND THEIR PREVENTION
         5.1. Hazards

    6. SUMMARY OF CHEMICAL SAFETY INFORMATION

    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
               7.4.1. Labelling

    BIBLIOGRAPHY
    

    INTRODUCTION

    The Environmental Health Criteria (EHC) monographs 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 a Summary of Chemical Safety
    Information 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 Director
    International Programme on Chemical Safety
    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

    CAS/IUPAC name:          morpholine

    Chemical formula:        C4H9NO

    Chemical structure:      CHEMICAL STRUCTURE

    CAS registry number:     110-91-8

    EC number:               613-028-00-9

    EINECS number:           2038151

    UN number:               2054

    Synonyms:                1-oxa-4-azacyclohexane;
                             tetrahydro-2H-1,4-oxazine;
                             tetrahydro-1,4-oxazine;
                             tetrahydro-1,4-isoxazine; diethylene oximide;
                             diethyleneimide oxide; diethylene imidoxide

    Relative molecular       87.12
    mass:

    Morpholine is distributed as an anhydrous liquid and as 40% and 88%
    solutions with water. It is marketed as a product with approximately
    99% purity.

    1.2  Physical and Chemical Properties

    Morpholine is a colourless, oily, hygroscopic, volatile liquid with a
    characteristic amine odour. It is heavier than air and, as a result,
    the vapour can travel a significant distance to a source of ignition
    and "flash back".

    Morpholine can undergo a diversity of chemical reactions. It is an
    amino ether. The ether function of the molecule is typically inert and
    most of the reactions involve the secondary amine group.

    The physical and chemical properties of morpholine are given in
    section 6.

    1.3  Analysis

    Methods suitable for measuring trace levels of morpholine include ion
    chromatography (IC), gas chromatography (GC) with packed and also
    capillary columns, high-performance liquid chromatography (HPLC)
    usually using reverse phase (RP) columns.

    The poor UV absorptivity of morpholine necessitates chemical
    derivatization to detect trace amounts. Detection methods include
    UV-detectors (HPLC) and flame ionisation (FID following GC) as well as
    thermal energy analysers (TEA). Photochemical methods are not specific
    for morpholine.

    1.4  Production and Uses

    At least 25 thousand tonnes of morpholine are produced throughout the
    world each year. The main process used (in the western world) is the
    reaction of diethylene glycol with ammonia in the presence of hydrogen
    and catalysts. Morpholine is a versatile chemical. It is important as
    a chemical intermediate in the rubber industry, as a corrosion
    inhibitor, and in the synthesis of optical brighteners, pharmaceutical
    products, crop protection agents, and dyes. Morpholine itself is a
    solvent for a large variety of organic materials, including resins,
    dyes, and waxes. It can be used as a catalyst. Morpholine is still
    used in some countries in toiletry and cosmetic products as a
    surfactant and emulsifier, at concentrations of up to 5%. It is used
    in some countries in several direct and indirect food additive
    applications.

    2. SUMMARY AND EVALUATION

    2.1  Exposure

    The general population can be exposed to morpholine in food,
    cosmetics, and tobacco. There is ample evidence that this substance
    can be nitrosated to the carcinogenic  N-nitrosomorpholine (NMOR) by
    reactions outside, or within, the human body.

    Food can become contaminated with morpholine in several ways:  a)
    through direct treatment of fruit with waxes containing morpholine for
    conservation purposes;  b) through steam treatment during processing,
    and  c) by use of packaging material containing morpholine.

    Morpholine is used in some countries in cosmetic preparations,
    particularly mascara eye makeup.  NMOR has been found in some toiletry
    articles and rubber articles including babies' pacifiers and bottle
    nipples.

    Morpholine and NMOR, probably from contact with waxed packaging and
    containers, have been detected in various tobaccos. Neither of these
    compounds has been detected in samples marketed in other packaging
    materials.

    Most countries recommend an 8-h TLV-TWA of 70 mg/m3 (skin notation)
    for occupational exposure to morpholine, and a 15-min, short-term,
    exposure limit (STEL) of 105 mg/m3.

    2.2  Uptake, Metabolism, and Excretion

    Morpholine is well absorbed after oral and dermal administration and
    inhalation. Distribution studies showed that, in rabbits, following
    inhalation or injection, the highest concentrations of morpholine were
    found in the kidney, whereas, in rats, high concentrations were found
    in muscle.

    In mice, rats, hamsters, guinea-pigs, and rabbits, almost all ingested
    or intravenously or intraperitoneally injected morpholine was excreted
    unchanged in the urine. In guinea-pigs, the metabolite 
     N-methylmorpholine- N-oxide was identified. Only 0.5% was
    eliminated as CO2.

    NMOR may be formed following concomitant administration of morpholine
    and nitrite or nitrous oxide under physiological conditions.

    2.3  Effects on Organisms in the Environment

    Morpholine has antibacterial and antimycotic properties, as has been
    demonstrated on pathogenic organisms. The toxicity threshold of
    morpholine for aerobic bacteria (after 16 h) was 310 mg/litre and for
    green-blue algae (after 193 h), 1.7 mg/litre. Inhibition of protozoa
    started at a morpholine concentration of 12 mg/litre, and growth of
    algae was inhibited from 4.1 mg/litre.

    The 24-h EC50 values for  magna ranged from 100 to 119 mg/litre.
    The EC0 values ranged from 16 to 68 mg/litre. The lowest LC50 for
    freshwater fish (rainbow trout) was 180 mg/litre; the LC50 value for
    a marine fish (tidewater silversides) was 400 mg/litre.

    2.4  Effects on Experimental Animals and in vitro Test Systems

    Morpholine administered orally resulted in LD50 values of 1-2 g/kg
    body weight (rat) and 0.9 g/kg body weight (guinea-pig). Rats
    receiving neutralized morpholine (1 g/kg body weight) survived.

    In short-term oral administration of doses of half of the LD50 to
    rats and guinea-pigs, nearly all the animals died before 30 days, the
    principal symptoms being severe damage to the secreting tubules of the
    kidney, fatty degeneration of the liver, and necrosis of the stomach
    glandular epithelium. Long-term oral exposure to morpholine caused
    fatty degeneration of the liver in rats.

    Feeding up to 2.5% morpholine oleic acid salt (MOAS) resulted in
    reduced body weight and renal malfunction in the highest-dose group;
    otherwise, no effects were seen on physical appearance and general
    behaviour, and there were no changes in biochemical, pathological, and
    histological observations.

    Discrepancies in the reports of morpholine vapour saturation
    concentrations make an evaluation of inhalation data difficult.
    Probable LC50 values are 8 g/m3 for rats and 5-7 g/m3 for mice.

    In short-term inhalation studies, lung haemorrhage, and damage to the
    kidneys and liver were described.  At low concentrations (1.8 g/m3;
    6 h/day; 9 days), weight loss and eye irritation were reported.
    Long-term inhalation studies (up to 0.54 g morpholine/m3; 104 weeks)
    showed increased incidences of inflammation of the cornea, and
    inflammation and necrosis of the nasal cavity in rats.

    In rats exposed to morpholine levels of up to 0.5 g/m3, keratitis,
    oedema, abrasion, scarring, ulceration with or without
    neovascularization, and corneal endothelial hyperplasia were observed.
    The irritative action of morpholine was reduced on neutralization.

    In studies on rabbits treated with a mascara composite containing 1%
    morpholine, a slight redness of the conjunctiva was noted throughout
    the study, but this disappeared 24 h after treatment.

    No data are available on reproductive toxicity, embryotoxicity, and
    teratogenicity.

    Morpholine was reported to be non-mutagenic in microbial  (Salmonella
     typhimurium, Escherichia coli) gene mutation assays, with, and
    without, metabolic activation (with an exception at a relatively high
    concentration where there was also cytotoxicity), and in the
    host-mediated assay. In a DNA damage and repair assay on primary rat
    hepatocytes, no repair synthesis was induced. It did not produce point
    or chromosomal mutations in hamster embryos exposed  in utero.
    Morpholine did not cause a meaningful increase in sister chromatid
    exchanges in Chinese hamster ovary cells.  It did not induce
    unscheduled DNA synthesis.

    Morpholine was considered to be weakly mutagenic in the L5178Y mouse
    lymphoma assay. It induced increases in type III foci in the Balb/3T3
    malignant cell transformation assay, but, when this was conducted at a
    neutral pH, there was no significant induction of transformed foci.

    Morpholine can be easily nitrosated to form  N-nitrosomorpholine
    (NMOR), the mutagenicity of which is well documented. The intake of
    ascorbic acid can prevent the formation of nitrosamines. Morpholine,
    given sequentially with nitrite or nitrate, was mutagenic in a
    host-mediated mutagenicity assay using  Salmonella typhimurium TA1950
    as a genetic indicator system.

    In a long-term inhalation study for carcinogenicity in rats, there was
    no increase in the incidence of tumours at concentrations of
    morpholine of up to 0.54 g/m3.

    Similarly, in a long-term oral study on mice, administration of
    morpholine oleate in the drinking-water did not result in any increase
    in the incidence of tumours.  The results of a long-term study in
    which morpholine (1000 mg/kg) was fed in the diet showed a marginal
    increase in tumours of the liver and lung in rats, but not in
    hamsters.  Morpholine fed to rats at a dietary concentration of
    1000 mg/kg caused an increase in tumours (mostly hepatocellular
    carcinomas and sarcomas of the liver and lungs), probably because of
    the endogenous formation of NMOR.

    2.5  Effects on Humans

    There are no data on acute toxicity or the effects of short- or
    long-term exposure to morpholine in the general public.

    The phenomenon known as blue vision or glaucopsia, as well as some
    instances of skin and respiratory tract irritation, have been
    described in older reports of occupational exposure to morpholine.

    When applied to human finger tips, undiluted morpholine  causes
    cracking of the eponychium and hyponychium about the nail. The intense
    stinging sensation makes it impossible to tolerate it on the fingers
    for a sufficient length of time to allow absorption. Diluted
    morpholine (1:40) is also a mild irritant.

    In a cytogenetic analysis of the lymphocytes in the peripheral blood,
    24 workers (16 men, 8 women) with 3-10 years exposure to morpholine
    (0.54-0.93 mg/m3, the maximum single concentration being
    0.74-2.14 mg/m3) during production were compared with a control
    group of the same size, from the same town, having no contact with
    chemicals at work. There was no significant increase in the number of
    cells with chromosome aberrations.

    3. CONCLUSIONS AND RECOMMENDATIONS

    Morpholine does not present a toxic risk for humans at the usual
    levels of exposure, but its potential for conversion to the
    carcinogenic compound  N-nitrosomorpholine should be noted.

    There is no evidence that, at present levels of exposure, morpholine
    poses a substantial risk for biota in the environment.

    3.1  Recommendations for the Protection of Human Health

    Human exposure to morpholine should be avoided as far as possible.

    Contamination of food through food packaging and food processing
    should be avoided.

    Morpholine should not be used in rubber products intended for direct
    contact with humans.

    Morpholine should not be used in toiletry or cosmetic preparations.

    Industrial effluents should be rigorously treated to avoid entry of
    morpholine into drinking-water.

    In the light of the formation of carcinogenic  N-nitrosomorpholine,
    the present occupational exposure limits should be reconsidered.

    3.2  Recommendations for the Protection of the Environment

    The addition of spills and shock loads to effluent-treatment plants
    should be avoided.

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

    4.1  Human Health Hazards, Prevention and Protection, First Aid

    Morpholine is a corrosive liquid and is a severe irritant for the
    skin, eyes, and respiratory tract. It is toxic through skin absorption
    and via inhalation. Thus, it is essential that the correct precautions
    should be observed during handling and use.

    4.1.1  Information for physicians

    4.1.1.1  Signs and symptoms of exposure

    Contact of undiluted product with eyes or skin causes severe
    irritation and pain and may cause burns, necrosis, and permanent
    injury. Burns of the eye may cause blindness. Morpholine is readily
    absorbed and can cause malaise, discomfort, injury, and death, unless
    treated promptly.

    The vapour in low concentrations can cause lacrimation,
    conjunctivitis, and corneal oedema. Inhalation of vapour causes
    irritation of the respiratory tract; there may be coughing and chest
    pain.

    Repeated and/or prolonged exposure to morpholine at low levels may
    damage the respiratory tract, produce adverse skin effects, or blue
    vision (glaucopsia).

    Medical conditions generally aggravated by exposure to irritant
    agents, including morpholine, are:

    - asthma
    - skin disorders and allergies
    - chronic respiratory disease, e.g., bronchitis, emphysema
    - eye disease.

    4.1.1.2  First aid

     Eye contact:  Eyes should be flushed immediately and gently with
    large volumes of water for 15 min. Prompt medical assistance is
    necessary.

     Skin contact:  The affected area should be flushed promptly with
    large quantities of water for 15 min. With the exception of minor
    cases, the affected area should be covered with a sterile dressing or
    clean sheeting and the patient transported for medical care. Greases
    or ointments should not be applied. When necessary, treat for shock.
    Clothes should be laundered prior to reuse and contaminated leather
    wear discarded.

     Inhalation:  The affected person should be moved to an
    uncontaminated atmosphere. If breathing has stopped or is impaired,
    assisted respiration (e.g., mouth to mouth) and/or supplemental oxygen
    should be given. The air passages should be kept free of vomited
    material and mucous. Medical attention should be sought.

     Ingestion:  In the event of ingestion, vomiting should not be
    induced.  Medical care and hospital treatment are essential, as soon
    as possible.

    4.1.1.3  Medical treatment

    The main health effects of morpholine are similar to those of strongly
    irritating agents, i.e., it is injurious to tissues. Chemical
    pneumonitis, pulmonary oedema, laryngeal oedema, and delayed scarring
    of the airways or other affected organs may occur following exposure.
    There is no specific treatment. Clinical management is based upon
    supportive treatment, which is similar to that for thermal burns.

    Victims with major skin contact should be kept under medical
    observation for at least 24 h.

    4.1.2  Health surveillance advice

    Each employee exposed to morpholine at potentially hazardous levels
    should undergo an initial medical screening for history of certain
    medical conditions (listed below) that might place the employee at
    increased risk from morpholine exposure.

    4.1.2.1  Initial medical screening

     (a) Chronic respiratory disease: Morpholine causes respiratory tract
    irritation. In persons with impaired pulmonary function, especially
    those with obstructive airway diseases, the breathing of morpholine
    may cause exacerbation of symptoms, because of its irritant
    properties.

     (b) Liver/kidney disease:  Morpholine causes liver and kidney damage
    in animals. This should therefore be considered before exposing
    persons with impaired liver or renal function.

     (c) Eye disease:  Morpholine is an eye irritant and has caused
    corneal oedema in exposed workers. Persons with pre-existing eye
    disorders may be more susceptible to the effects of this agent.

     (d) Skin disease:  Morpholine is a primary skin irritant. Persons
    with pre-existing skin disorders may be more susceptible to the
    effects of this agent.

    4.1.2.2  Periodic medical examination

    Any employee developing the above-listed conditions should be referred
    for further medical examination.

    4.2  Explosion and Fire Hazards

    4.2.1  Reactivity data

    The product is chemically stable and insensitive to light.

    However, violent reaction and fire may result when the product is
    mixed with oxidizing agents, such as perchlorates, nitrates,
    permanganates, chromates, nitric acid, halogens, peroxides, and some
    cleaning solutions containing acids.

    A reaction accompanied by great heat release occurs when the product
    is mixed with acids. The heat generated may be sufficient to cause
    vigorous boiling, creating a hazard because of the splashing or
    splattering of hot material.

    The product corrodes copper, aluminium, zinc, and galvanized surfaces.
    Materials for containment should be constructed of iron or steel.

    The combustion of morpholine in the presence of sufficient oxygen may
    result in harmful concentrations of carbon monoxide, carbon dioxide,
    and nitrogen oxide gases. Nitrogen oxide can react with water vapours
    to yield corrosive nitric acid.

    Combustion of morpholine under oxygen-starved conditions can be
    expected to produce numerous toxic products including carbon monoxide,
    hydrogen cyanide, nitriles, cyanic acid, isocyanates, cyanogens,
    nitrosamines, amides, and carbamates.

    Liquid morpholine attacks some forms of plastic and rubber.

    Caution:  N-nitrosomorpholine, known to be a potent carcinogen in
    experimental animals, may be formed when the product comes in contact
    with nitrous acid, nitrites, or atmospheres with high nitrogen oxide
    concentrations.

    4.2.2  Explosion hazards

    If the product is heated to temperatures above 35C, explosive
    air-vapour mixtures may form.

    4.2.3  Fire hazards

    Flash-point (anhydrous): 35C (closed cup); 38C (open cup)

         88% solution:       42C

    Flammability limits (%) (anhydrous):

         Lower:              1.8%
         Upper:              10.8%

    Ignition temperature:    310C
    (anhydrous)

    4.2.4  Extinguishing media

    Water spray, carbon dioxide, dry chemical, and "alcohol" foam are
    recommended as extinguishing agents. Water may be ineffective on
    flames, but should be used to cool fire-exposed containers and to
    disperse vapours.

    4.2.5  Special firefighting procedures

    Firefighters should wear self-contained breathing apparatus to prevent
    inhalation of toxic ammonia, carbon monoxide, or nitrogen oxide gases,
    which may form when the product is burned or is heated.

    Suits, gloves, and boots, impervious to chemicals (e.g., butyl
    rubber), should be worn.

    4.3  Storage

    Morpholine should be protected from atmospheric moisture and carbon
    dioxide. As morpholine corrodes copper, aluminium, zinc, and
    galvanized surfaces, the compound should be stored in iron or steel
    containers, preferably located outdoors, above ground, and surrounded
    by dykes to contain spills or leaks.

    4.4  Transport

    Local requirements regarding movements of hazardous goods should be
    complied with.

    UN Classification: Class 3; Number 2054

    4.5  Spillage

    All sources of ignition should be removed and, if possible, the leak
    stopped. Spills should be contained and covered with sodium bisulfate
    to neutralize the product. The spillage should then be sprayed with
    water and scooped up into steel containers for proper disposal.

    The spilled product must be prevented from entering drinking-water
    supplies or streams. Morpholine is completely miscible with water.

    4.6  Disposal

    Incineration is acceptable and the preferred method of disposal;
    however, nitrogen oxide emission controls may be required to meet
    environmental regulations.  Morpholine is also broken down by
    activated sludge and this is a possible method of disposal under
    controlled conditions.

    5.  HAZARDS FOR THE ENVIRONMENT AND THEIR PREVENTION

    5.1  Hazards

    As morpholine is an important industrial chemical with a wide range of
    applications, the presence of the compound or its derivatives is to be
    expected in many industrial effluents.

    Morpholine has a very low bioaccumulation potential. The compound is
    inherently biodegradable. Biotic decomposition is possible in adapted
    industrial treatment plants.  In natural waters, biodegradation of
    morpholine is probably not significant. It is acutely toxic for
    aquatic organisms from 1.7 mg/litre (see section 2.3).

    6. SUMMARY OF CHEMICAL SAFETY INFORMATION

     This summary should be easily available to all health workers
     concerned with, and users of, morpholine. It should be displayed at,
     or near, entrances to areas where there is potential exposure to
     morpholine, and on processing equipment and containers. The summary
     should be translated into the appropriate language(s).  All persons
     potentially exposed to the chemical should also have the instructions
     in the summary clearly explained.

     Space is available for insertion of the National Occupational Exposure
     Limit, the address and telephone number of the National Poison Control
     Centre, and local trade names.


        MORPHOLINE

    CAS chemical name: morpholine
    Synonyms: tetrahydro-1,4-oxazine; diethylene oximide
    CAS registry number: 110-91-8: RTECS registry number: QD6475000
    UN number: 2054; EC number: 613-028-00-9
    Chemical formula: C4H9NO; Relative molecular mass: 87.1
                                                                                                                                                

    PHYSICAL PROPERTIES                                               OTHER CHARACTERISTICS
                                                                                                                                                

    Boiling point at 101.3 kPa                  129C                 Morpholine is a colourless hygroscopic liquid, with characteristic
    Melting point                                -5C                 odour; the substance decomposes on heating, producing toxic
    Relative density (water=1)                    1.0                 gases (nitrous oxides); it is a base, reacts violently with acid and is
    Solubility in water                         miscible              corrosive to aluminium, zinc and copper; morpholine reacts with
    Vapour pressure, kPa at 20C                1.06                  oxidants and nitrites; the carcinogenic N-nitrosomorpholine can
    Relative vapour density (air=1)             3.00                  be formed from nitrosation of morpholine
    Relative density of the vapour/
    air mixture at 20C (air=1)                 1.01
    Flash point (open cup)                      38-43C
    Autoignition temperature                    310C
    Explosive limits, vol% in air               1.8-15.2
    Octanol/water partition
    coefficient as log Pow                      -0.86 (at pH 5)
                                                                                                                                                

                                                                                                                                                

    HAZARDS/SYMPTOMS                           PREVENTION AND PROTECTION                 FIRST AID
                                                                                                                                                

    GENERAL: The substance is strongly
    irritant to the eyes, the skin, and the
    respiratory tract; inhalation of the
    substance may cause lung oedema;
    exposure to high concentrations may
    result in death; long-term exposure
    may affect the liver and kidneys

    SKIN: MAY BE ABSORBED;                     Wear protective gloves,                   Remove contaminated clothes, rinse skin with
    redness, skin burns, pain                  protective clothing                       plenty of water or shower, and refer for 
                                                                                         medical attention

    EYES: Redness, pain, blurred               Face shield                               First rinse with plenty of water for several
    vision                                                                               minutes (remove contact lenses if easily
                                                                                         possible); refer for medical attention

    INHALATION: Cough, laboured                PREVENT GENERATION                        Fresh air, rest, half-upright position, artificial
    breathing, shortness of breath,            OF MISTS; use ventilation, local          respiration, if indicated, and refer for medical
    sore throat                                exhaust, or breathing protection          attention

    INGESTION: Abdominal pain,                 Do not eat, drink, or                     Rinse mouth, give large amounts of water to
    cough, diarrhoea, vomiting                 smoke during work                         drink, and refer for medical attention

    ENVIRONMENT: This substance may be hazardous for the environment; special attention should be given to water
                                                                                                                                                

                                                                                                                                                

    SPILLAGE                                   STORAGE                                   FIRE AND EXPLOSION
                                                                                                                                                

    Consult an expert, collect leaking         Dry, fireproof storage is necessary;      Morpholine is flammable; above 38C
    and spilled liquid in sealable             keep separate from oxidants,              explosive vapour/air mixtures may be formed;
    containers as far as possible, absorb      nitrites, and, acids                      above 38C use closed system, ventilation,
    remaining liquid in sand or inert                                                    and explosion-proof electrical equipment; in
    absorbent and remove to safe place                                                   case of fire, use powder, alcohol-resistant
    (extra personal protection:                                                          foam, water spray, carbon dioxide; keep
    self-contained breathing apparatus)                                                  drums, etc., cool by spraying with water
                                                                                                                                                

    WASTE DISPOSAL                             NATIONAL INFORMATION
                                                                                                                                                

    Incineration                               National Occupational      National Poison Control Centre:
    Controlled activated sludge                Exposure Limit:            Local trade names:
    treatment
                                                                                                                                                
        7.  CURRENT REGULATIONS, GUIDELINES, AND STANDARDS

    7.1  Previous Evaluations by International Bodies

    The carcinogenic risks were evaluated by an International Agency for
    Research on Cancer  ad hoc expert group in 1989. It was concluded
    that there was inadequate evidence for assessing the carcinogenicity
    of morpholine in experimental animals. No data were available from
    studies on humans on the carcinogenicity of morpholine.

    The overall evaluation was that morpholine was not classifiable as to
    its carcinogenicity to humans (Group 3).

    7.2  Exposure Limit Values

    Most countries recommend an 8-h TLV-TWA of 70 mg/m3 for skin, and a
    15-min, short-term, exposure limit (STEL) of 105 mg/m3 for
    occupational exposure to MORP (ILO, 1991).

    7.3  Specific Restrictions

    The use of morpholine in cosmetics has been forbidden in EU countries
    since 1986.  In Germany, the use of morpholine in water-repellent food
    packaging material is forbidden (BUA, 1991).

    7.4  Labelling, Packaging, and Transport

    7.4.1  Labelling

    The United Nations Committee of Experts on the Transport of Dangerous
    Goods classifies morpholine as: 

         Hazard - Class 3 - Flammable
         Packing Group III
         UN Number 2054

    The European Union legislation on classification and labelling
    requires supply labelling as a corrosive substance and gives the
    following risk and safety phrases:

         R 10:          Flammable
         R 20/21/22:    Harmful by inhalation, in contact with skin, and
                        if swallowed
         R 34:          Causes burns
         S 23:          Do not breathe fumes/vapour
         S 36           Wear suitable protective clothing

    The US Department of Transportation (DOT) specifies the Proper
    Shipping Name for anhydrous morpholine as Morpholine, Flammable
    Liquid, UN 2054. The DOT Proper Shipping Name for morpholine solutions
    is Morpholine, aqueous mixture, Corrosive Material, NA 1760.

    The US Occupational Safety and Health Agency (OSHA) Hazard
    Communication Standard (29CFR1910.1200) hazard classification for
    anhydrous morpholine is:

         -toxic by absorption through skin and inhalation,
         -corrosive,
         -flammable.

    The US Environmental Protection Agency (EPA) Title III hazard class
    is:
         -fire hazard
         -immediate health hazard.

    BIBLIOGRAPHY

    ACGIH (1986)  Documentation of the threshold limit values and
    biological exposure indices. Cincinnati, American Conference of
    Governmental Industrial Hygienists Inc. (ACGIH), p. 417.

    Air Products and Chemicals Inc. (1989) Material safety data sheet.
    Allentown, 10 pp.

    BUA (1991) GDCh-Advisory Committee on Existing Chemicals of
    Environmental Relevance. Morpholine.  Weinheim, VCH, 181 pp.
    (BUA Report 56) (in German).

    CEC (1987) Legislation on dangerous substances. Classification and
    labelling in the European Communities, Vol. 2.  Brussels, Commission
    of the European Communities.

    CEC/IPCS (1991) International chemical safety cards. Industrial Health
    and Safety EUR 12561/6 Fifth Series ILO.

    Clayton GD & Clayton FE, ed. (1982)  Patty's industrial hygiene and
    toxicology, 3rd. revised ed. Volume 2A, New York, Wiley-Interscience
    Publications, pp. 2276, 2693-2696.

    ILO (1991) Occupational exposure limits for airborne toxic substances,
    3rd ed., Geneva, International Labour Office, pp. 282-283
    (Occupational safety and health series, No. 37).

    IPCS (in preparation) Environmental Health Criteria: Morpholine.
    Geneva, World Health Organization.

    IRPTC (1991) Data profile on morpholine. International Register of
    Potentially Toxic Chemicals, United Nations Environment Programme.

    OSHA (1981)  Occupational health guidelines for chemical hazards:
    Occupational health guideline for morpholine. Cincinnati, Ohio, Hazard
    Evaluation and Technical Assistance Branch, Occupational Safety and
    Health Agency, pp. 962-966.

    Sittig M (1985) Handbook of toxic and hazardous chemicals and
    carcinogens, 2nd ed. Park Ridge, New Jersey, Noyes Publications,
    pp. 626-627.

    SORBE (1990) Sicherheitstechnische Kenndaten. Gefahrenindex chemischer
    Stoffe.  Ecomed-Verlag (in German).

    United Nations (1989) Recommendations on the transport of dangerous
    goods, 6th rev. ed. New York, United Nations, p. 2054.
    


    See Also:
       Toxicological Abbreviations
       Morpholine (EHC 179, 1996)
       Morpholine (ICSC)
       Morpholine  (IARC Summary & Evaluation, Volume 47, 1989)
       Morpholine  (IARC Summary & Evaluation, Volume 71, 1999)