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    TOLUENE DIISOCYANATE




    Mary-Jane Bennie

    National Poisons Information Service (London Centre)
    Medical Toxicology Unit
    Guy's & St Thomas' Hospital Trust
    Avonley Road
    London
    SE14 5ER
    UK


    This monograph has been produced by staff of a National Poisons
    Information Service Centre in the United Kingdom.  The work was
    commissioned and funded by the UK Departments of Health, and was
    designed as a source of detailed information for use by poisons
    information centres.

    Peer review group: Directors of the UK National Poisons Information
    Service.


    1  SUBSTANCE/PRODUCT NAME

    1.1  Origin of substance

    Toluene diisocyanates are not known to occur as natural products. They
    are manufactured by the reaction of diaminotoluenes with phosgene.

    1.2  Name

    1.2.1  Compound

    Toluene di-isocyanate

    1.2.2  Generic names

    Desmodur T100, Hylene-T, Mondur-TD, Mondur-TD-80, Nacconate-100, Niax
    isocyanate TDI, Rubinate TDI
    Rubinate TDI 80/20, T 100, TDI-80, TDI 80-20.

    1.2.3  Synonyms

    TDI, toluene diisocyanate, benzene 1,3 iisocyanatomethyl-, isocyanic
    acid, methyl phenylene ester, isocyanic acid, methyl-m-phenylene
    ester, methyl-meta-phenylene diisocyanate, methylphenylene isocyanate,
    methyl-m-phenylene isocyanate, toluene-1,3-diisocyanate,
    diisocyanates, diisocyanatotoluene, tolylene diisocyanate, tolylene
    isocyanate.

    1.2.4  Common names/street names

    Toluene diisocyanates are produced as 2 isomers: 2,4 toluene
    diisocyanate (2,4-TDI) and 2,6-toluene diisocyanate (2,6-TDI).
    They are commercially available in 3 isomer ratios:

    *  > 99.5% 2,4-TDI
    *  80% 2,4-TDI:20% 2,6-TDI, which is the most common and referred to
       in this document as 80:20 mixture
    *  65% 2,4-TDI:35% 2,6-TDI

    'Crude' TDI, with an unidentified isomer ratio, is also commercially
    available, but not widely used. By far the most widely used is the
    80:20 isomer mixture.

                                                   
    Chemical name               Common name
                                                   
    commercial mixture 
       2:4-, 2,6- isomers       TDI
    2,4-TDI                     TDI, 2,4-TDI
    2,6 -TDI                    2,6-TDI
                                                   

    1.3  Chemical group/family

    Isocyanates.

    1.4  Substance identifier and/or classification by use

    1.5  Reference numbers

                                                                        
    Number      2,4-TDI            2,6-TDI         Commercial mixture
                                                   (80:20)
    CAS         584-84-991-08-7    26471-62-5
    RTECS       CZ 6300000         CZ 6310000      CZ 6200000
    EINECS      2095445            2020390         2477224
    UN                                             2078
    CEC         615-006-00-4
                                                                        

    1.6  Manufacturer

    Data not found.

    1.7  Supplier/importer/agent/ licence holder

    Data not found.

    1.8  Presentation

    1.8.1  Form

    Colourless liquid or crystals with pungent odour; turn pale yellow on
    exposure to air.

    1.8.2  Formulation details

    No data available.

    1.8.3  Pack sizes available

    No data available.

    1.8.4  Packaging

    No data available.

    1.9  Physico-chemical properties

    Chemical structure
         TDIs are synthetic organic chemicals with a molecular formula of
         C9H6N2O2 and the following chemical structure (R = -N=C=O).

    Physical state
         At room temperature liquid or crystals.

    Colour
         Colourless to pale yellow.

    Odour
         Distinct pungent, sweet, fruity, odour detectable around
         0.7mg/m3.

    Solubility in water and organic solvents
         Soluble in acetone, alcohol, benzene, ethyl acetate, ether,
         carbon tetrachloride, chlorobenzene, kerosene, and various oils,
         e.g. corn oil. TDI reacts with water, releasing carbon dioxide
         (Lewis, 1992).

    Autoignition temperature
         620C

    Important chemical interactions
         They may react violently with compounds containing active
         hydrogen, such as alcohols, with the generation of enough heat to
         lead to self-ignition and subsequent release of toxic combustion
         products. Other solvents that must not be mixed with toluene
         diisocyanates include water, acids, bases, and strong alkaline
         materials (Hardy and Purnell, 1978) such as sodium hydroxide and
         tertiary amines. Toluene diisocyanates react with water and most
         acids to produce polymeric urea.

    Major products of combustion/pyrolysis
         When heated to decomposition TDI emits toxic fumes of oxides of
         nitrogen (Sax and Lewis, 1989).

    Explosion limits
    For 2,4 TDI
         Concentration (% v/v)
         lower          0.9%
         upper          9.5%

    Boiling point
         At 760mmHg     251 C
         At 10mmHg      120 C for 2,4-TDI
                        121 C for commercial mixture

    Density (g/cm3)
         2,4-TDI                                 1.22g/mL 25/15
         Commercial mixture(2,4-,2,6-isomers)    1.22 g/mL 25/15 (both
                                                 mixes)

    Vapour pressure
         Pa at 20 C : 1.3

    Relative vapour density
         6.0

    Flash point
         open cup       135 (2,4-TDI)
                        132 (commercial mixture-2,4-, 2,6-isomers)
         closed cup     127(2,4-TDI)

    Reactivity
         TDI forms potentially violent polymerisation reactions with bases
         or acyl chlorides, reaction with water liberates carbon dioxide
         (Lewis, 1992). TDI can react with alanine. The heat of this
         reaction may be sufficient to ignite surrounding combustibles and
         the material itself.

         It reacts violently with amines, alcohols, bases, and warm water,
         causing explosion hazards. Strong oxidizers, water, and acids
         cause foam and splatter. TDI is combustible when exposed to heat
         or flame. When heated to decomposition, TDI emits highly toxic
         fumes of oxides of nitrogen (Lewis, 1992). TDI polymerizes in the
         presence of alkali.

    1.10  Hazard/risk classification

    1.11  Uses

    Toluene diisocyanates are reactive intermediates that are used in
    combination with polyether and polyester polyols to produce
    polyurethane products. The production of flexible polyurethane foams
    represents the primary use of toluene diisocyanates (approximately 90%
    of the toluene supply). The 80:20 mixture is used in their production
    at an average of 30% by weight. Domestic consumption of flexible
    polyurethane foam in the USA in 1981, estimated at 499 x 106 kg, can
    be broken down into the following uses (in million kg): furniture
    (208.7), transportation (99.8), bedding (63.5), carpet underlay (72.6)
    and other uses (11.3). An estimated 27 x 106 kg of rigid polyurethane
    foams, used in refrigeration equipment was produced with 'crude' TDI
    in the USA in 1982 (US EPA 1984).

    Polyurethane coatings represent the second largest market for toluene
    diisocyanates. Toluene diisocyanates are also used in the production
    of polyurethane elastomeric casting systems, adhesives, sealants and
    other limited uses (Brandt, 1972; Granatek et al, 1975; Aragon et al,
    1980).

    TDI is one of the most common isocyanates employed in the manufacture
    of polyurethane foams, elastomeres, and coating. Foams are used in
    furniture, packaging, insulation and boat building. Flexible foams are
    made of TDI, whereas the rigid foams have the less volatile MDI
    (Finkle, 1983). Polyurethane coatings are used in leather, wire, tank
    linings, masonary, paints, floors and wood finishes. Elastomers are
    abrasion and solvent resistant, and are used in adhesives, coated 

    fabrics, films, linings, clay pipe seals, and in abrasive wheels, and
    other mechanical items.

    1.12  Toxicokinetics

    1.12.1  Absorption

    Absorption of toluene diisocyanates through the respiratory tract is
    suggested by their high acute toxicity for animals via inhalation and
    reports of systemic effects and antibody formation in individuals
    exposed to toluene diisocyanates primarily via inhalation (Sharonova
    and Kryzahanovskaya, 1976; Steinmetz et al, 1976; White et al, 1980).

    1.12.2  Distribution

    No information was found regarding the distribution of toluene
    diisocyanates in mammalian systems. Because of the wide distribution
    of water and other nucleophiles in tissues, it is likely that toluene
    diisocyanates will react with the tissues they initially contact and
    be transformed into various products.

    1.12.3  Metabolism

    Reaction of TDI with human serum albumin yields mono- or bisureido
    protein derivatives (ITIC/USEPA 1981).
    Hydrolysis of both isocyanate groups produce 2,4-toluene diamine, a
    carcinogen (ITIC/USEPA 1981).

    1.12.4  Elimination

    No data available.

    1.12.5  Half-life

    No data available.

    1.12.6  Special populations

    No data available.

    2  SUMMARY

    3  EPIDEMIOLOGY OF POISONING

    No data available.

    4  MECHANISM OF ACTION/TOXICITY

    4.1  Mechanism

    TDI exposure tends to have a cumulative effect in man. There are two
    classes of reaction to TDI :

    1. primary irritation or pharmacodynamic action to which all exposed
    persons are susceptible to some degree and
    2. sensitisation reaction or allergic response in those persons who
    have become sensitised to TDI during earlier exposure (Butcher et al,
    1977)

    TDI is a severe irritant to all living tissues with which it comes in
    contact in liquid or vapour form, especially the mucous membranes of
    the eyes, gastrointestinal and respiratory tract. It also has a marked
    inflammatory reaction on direct skin contact (Hathaway et al, 1988).

    Respiratory sensitisation occurs in susceptible persons after repeated
    exposure to TDI at levels of 0.002ppm and below (Elkins, 1962). A
    chronic syndrome consisting of coughing, wheezing, tightness or
    congestion in the chest and shortness of breath has been characterised
    with repeated exposures at such low concentrations (NIOSH, 1973).

    A sensitised individual in addition to the aforementioned instant
    reactions may be afflicted with marked tissue eosinophilia and acute
    pneumonitis with inflammatory oedema of the lungs (Fabbri, 1985;
    Fabbri, 1987; Zocca et al, 1990 ).

    Some individuals who have been reported to have an allergic response
    have been demonstrated to have circulating antibodies to TDI or to
    TDI-animal protein conjugates (Butcher et al, 1977; Fabbri, 1987;
    Finkel, 1983; Karol, 1980; Karol, 1981).

    Further evidence is the demonstration of lymphocyte transformation in
    TDI sensitised workers induced by TDI-conjugated proteins.

    TDI-induced late asthmatic reactions have been attributed to increased
    bronchovascular permeability caused by leukotriene B4 levels which
    also promote granulocyte adherence and leukocyte migration into
    tissues (Zocca et al, 1990).

    Because one micromole of TDI can stimulate methacholine-induced
    tracheal ring contractions, the pharmacological effect of TDI is
    believed to be due to an autonomic imbalance between cholinergic and
    beta-adrenergic neural control (Borm et al, 1989).

    Epithelial damage, thickening of basement membrane, and mild to
    moderate inflammatory reaction in the submucosa were demonstrated in
    TDI-sensitised patients who have ceased work within 4 to 40 months
    prior to bronchial biopsy (Paggiaro, 1990).

    4.2  Toxic dose

    In the UK and many other countries, a maximum permissible
    concentration of TDI in the atmosphere to which operatives may be
    exposed continuously has been laid down, the ceiling threshold limit
    value TLV(C), and it is 0.02 parts per million (0.01ppm in Sweden),
    but exposure to even lower concentrations than this may produce 

    asthmatic symptoms of varying intensity in sensitised persons. Ceiling
    Threshold Limit Value TLV(C), is defined as the maximum concentration
    of material in the atmosphere that can be tolerated throughout a 7 to
    8 hour working day, or a 40 hour working week. The TLV(C) is expressed
    in ppm (i.e. parts of vapour per million parts of contaminated air by
    volume at 25 C and 760mmHg pressure) and in mg/m3 (i.e. milligrams
    per cubic metre of air). It is important to note that on contact with
    water, TDI is converted to toluene diamine which is carcinogenic to
    both mice and rats (National Cancer Institute, 1979). Each
    diisocyanate on hydrolysis might produce breakdown products with
    different carcinogenic properties.

    Exposure to higher concentrations may cause symptoms in individuals
    who have not become allergic. In mild cases the affected individual
    usually experiences slight irritation of the eyes, nose and throat.
    There may be cough, particularly troublesome at night, and sense of
    tightening in the chest. In more severe cases the individual
    experiences acute bronchial irritation and difficulty in breathing.
    Detection of TDI by smell is an unreliable procedure since the minimum
    concentration of isocyanate vapour that can be detected by most people
    in this manner exceeds 0.1ppm. However with reasonable care
    concentrations can be kept below the permissible limit of 0.02ppm.

    TDI levels of 0.3 to 0.7 ppm was associated with a high incidence of
    illness but no cases were observed from concentrations below 0.03 ppm
    (Hama, 1947). The maximum incidence of illnesses occurred when the
    average concentration of vapour was 0.1 ppm and very little trouble
    was reported at 0.01 ppm (Walworth and Virchow, 1959).

    No respiratory symptoms or changes in pulmonary function were noted
    among workers pouring and moulding polyurethane foam and breathing as
    much as 0.001 to 0.002 ppm TDI (Roper and Cromer, 1975). Occasional
    exposures to TDI beyond 0.02 ppm caused no significant deterioration
    in lung function (Erlicher and Brochhagen, 1976).

    A dose-response relationship was demonstrated between acute pulmonary
    function changes and exposure of 112 workers to 0.0035 to 0.06
    milligram TDI/cubic meter (IARC, 1979). Exposure of volunteers have
    shown that 0.05 to 0.1ppm TDI in the air can cause eye and nose
    irritation (Grant and Schuman 1993 ). A normal age- and smoking-
    related rate of decline forced expiratory volume in 1 second (FEV1)
    was demonstrated in subjects exposed to 0.001 to 0.0015 ppm TDI thus
    negating any effects of TDI at these levels (Musk et al, 1985).

    Permissible Exposure levels
    The threshold Limits Committee of the American Conference of
    Governmental Industrial Hygienists (ACGIH) adopted 0.1ppm as a
    tentative exposure limit in 1956. In 1959 this was changed from a
    tentative to a recommended value. In 1961 the recommended maximum
    allowable concentration of TDI was changed to 0.02ppm. A concentration
    of 0.01ppm was recommended in 1962 at the ACGIH Annual meeting and in
    1968 the ACGIH recommended a ceiling of 0.02ppm for TDI. In 1973 the 

    national institute for occupational safety and health recommended that
    TDI be controlled so that no workers be exposed to a time-weighted
    average (TWA) concentration of TDI more than 0.005ppm for any 8 hour
    work day or for any 20-minute period to more than 0.02ppm (NIOSH,
    1973).

    In 1978 it was recommended that the period of the TWA was extended to
    a 10-hour day (or 40-hour week) and that the ceiling level be 0.02ppm
    for any 10-minute period (NIOSH, 1978). The recommendations of the
    ACGIH in 1980 were for 0.005ppm as an 8-hour TWA with excursions to a
    ceiling of 0.02ppm for four 15-minute periods a day.

    5  FEATURES OF POISONING

    5.1  Acute

    Toluene diisocyanate are irritant to skin, lungs, the mucous membranes
    of the conjunctiva and the gastrointestinal tract. They may also cause
    euphoria, ataxia and mental aberrations. The signs and symptoms of
    acute exposure are non-specific and include, complaints of irritation
    of the nose and throat, shortness of breath, choking, coughing,
    retrosternal discomfort or pain, and gastrointestinal stress (e.g.
    nausea, vomiting and abdominal pain). The onset of signs and symptoms
    may be delayed following exposure, and may persist for several days,
    months, or years following exposure, and may persist for several days,
    months, or years following removal from the contaminated environment
    (Walworth and Virchow 1959; Munn 1960; NIOSH 1978).

    5.1.1  Ingestion

    There have been no reports of human ingestion. Necropsy of rats
    revealed corrosive action on stomach as well as possible toxic effects
    on the liver (ACGIH 1986).

    5.1.2  Inhalation

    This is the commonest route of exposure. TDI is a strong irritant of
    the eyes, mucous membranes, and skin. It is a potent sensitizer of the
    respiratory tract. A common respiratory system response to inhaled TDI
    is both acute and chronic diminution of ventilatory capacity, measured
    by a decrease in FEV1 even in the absence of other overt symptoms
    (Adams, 1970; Adams, 1975; Moller et al, 1986; Venables, 1985; Weill
    et al, 1981). Exposure of humans to sufficient concentrations causes
    irritation of the eyes, nose and throat, a choking sensation, and a
    productive cough of the paroxysmal type, often with retrosternal
    soreness and chest pain (NIOSH, 1973; Elkins et al, 1962). If the
    breathing zone concentration reaches 0.5 ppm, the possibility of
    respiratory response is imminent (Rye, 1973). Depending on the length
    of exposure and the level of concentration above 0.5 ppm, respiratory
    symptoms will develop with a latent period of 4 to 8 hours (Rye,
    1973). Higher concentrations produce a sensation of oppression or
    constriction of the chest. There may be bronchitis, severe 

    bronchospasm or pulmonary oedema. Nausea and vomiting and abdominal
    pain may complicate the presenting symptoms. Upon the subject's
    removal from exposure, the symptoms may persist for 3-7 days (Rye,
    1973).

    Although the acute effects may be severe, their importance is
    overshadowed by respiratory sensitisation in susceptible persons, this
    has occurred after repeated exposure to levels of 0.02 ppm TDI and
    below (Elkins 1962). This will be further discussed in the chronic
    exposure section.

    5.1.3  Dermal

    Dermal absorption is low but irritation and inflammation are common.

    5.1.4  Ocular

    Eye contact with toluene diisocyanates (vapour, aerosols, or liquids)
    causes mild irritation, characterised by itching and lacrimation,
    which may progress to conjunctivitis and keratoconjunctivitis (Brugsh
    and Elkins, 1963; Luckenbach and Kieler, 1980). Oculorhinitis may also
    occur and be delayed by a few hours (Paggiaro et al, 1985).

    Severe conjunctival irritation and lacrimation may occur following
    exposure of liquid or high vapour concentration (Axford et al, 1976).
    Burning or prickling sensations from lower concentrations have been
    reported (Grant and Schuman, 1993).

    Iridocyclitis and secondary glaucoma were noted in a workman who
    accidentally splashed TDI in one eye (Grant and Schuman 1993).

    5.1.5  Other routes

    No data available.

    5.2  Chronic toxicity

    5.2.1  Ingestion

    No data available.

    5.2.2  Inhalation

    The onset of symptoms of sensitisation may be insidious, becoming
    progressively more pronounced with continued exposure over a period of
    days to months. Initial symptoms are nocturnal dyspnoea and/or
    nocturnal cough with progression to asthmatic bronchitis (NIOSH 1973).
    Immediate, late and dual patterns of bronchospastic response to
    laboratory exposure to TDI in sensitised individuals have been
    observed, confirming the clinical findings of nocturnal symptoms in
    some exposed workers. The time from initial employment to the
    development of symptoms suggestive of asthma has been reported to vary
    from 6 months to 20 years.

    5.2.3  Dermal

    Skin sensitisation on repeated exposure to toluene diisocyanates may
    occur. Urticaria, dermatitis, and allergic contact dermatitis have
    been reported in workers exposed to toluene diisocyanates-based
    photopolymerised resins (Brugsch and Elkins, 1963; Calas et al, 1977).
    The dermatological symptoms included skin lesions of an eczematous,
    and also, of an irritant, pruriginous and erythematous nature. Studies
    on experimental animals have shown that skin application of TDI can
    lead to pulmonary sensitisation thus, it is prudent to avoid repeated
    skin contact.

    5.2.4  Ocular

    Evidence of microcystic corneal oedema and conjuctival infection in
    both eyes in a polyurethane foam worker has been reported (Luckenbach
    and Kieler, 1980).

    5.2.5  Other routes

    Data not available.

    5.3  Systematic description of clinical effects

    5.3.1  Cardiovascular

    Data not available.

    5.3.2  Respiration

    Peters and Murphy (1970) identified four general patterns of airway
    response to TDI in man :
    1. chemical bronchitis (following high doses)
    2. isocyanate asthma (in "sensitised" subjects)
    3. acute asymptomatic deterioration in airway function during a long
    shift and
    4. chronic deterioration in airway function with prolonged low levels
    of exposure.
    Later, a fifth pattern of airway response was observed:
    5. failure of asthma to clear in sensitised subjects whose exposure to
    isocyanates has ceased (Paggiaro et al, 1984; Peters and Wegman,
    1975).

    In high enough concentrations isocyanates have a primary irritant
    effect on the respiratory tract producing complaints of dry throat and
    cough. In addition they may give rise to acute pulmonary oedema some
    hours after exposure which may be fatal. An asthmatic attack may
    result at these levels as well as at levels devoid of an immediate
    irritant effect. When asthmatic attacks occur immediately on exposure
    and cease shortly after exposure ceases, cause and effect are readily
    associated. Asthmatic attacks may occur at an interval of hours after
    cessation of exposure, presenting as nocturnal cough and dyspnoea, 

    when the association may be less obvious. The natural history of
    continued exposure in the latter presentation may be the development
    of symptoms during, as well as after cessation of exposure.

    Even if the affected worker transfers from isocyanate work, recovery
    may be protracted. Cough may be the dominant feature.
    Characteristically it is dry, only producing a small amount of sputum
    after a severe protracted bout of coughing. Dyspnoea may dominate and
    vary from gross acute airway obstruction with cyanosis and distress to
    dyspnoea only on effort. Sensitised workers may develop asthma at
    atmospheric levels of isocyanate below the control limit. Interstitial
    pulmonary fibrosis has been reported as a long term hazard.

    Burning or irritation of nose and throat, choking sensation, cough
    which may or may not produce blood-streaked sputum, laryngitis,
    retrosternal soreness and chest pain have been reported (Elkins et al,
    1962; NIOSH, 1973).

    Depending upon the length of exposure and level of concentration above
    0.5ppm, respiratory symptoms will develop with a latent period of 4 to
    8 hours (Rye, 1973) and based on the onset of symptoms, asthmatic
    reactions to isocyanate challenge have been classified as immediate,
    late or dual (Fabbri, 1990). At the end of a few days to two months of
    exposure, lacrimation and irritation of the conjunctivae and pharynx
    occur and are later coupled with dry nocturnal cough and sternal pain.
    The symptoms worsen in the evening and disappear in the morning with
    minimal mucus production. Symptoms diminish after a few days rest but
    recur upon return to work. The characteristic substernal pain may be
    due to the paroxysmal or persistent cough often associated with
    inhalation. Asthmatic syndrome, chronic bronchitis, emphysema and cor
    pulmonale have been noted with high exposures (Axford et al, 1976).

    The onset of symptoms experienced by the TDI sensitised individual may
    be insidious, becoming progressively more pronounced with continued
    exposure over days to months. The initial symptoms of dyspnoea and
    cough can progress to severe asthma and bronchitis (ACGIH, 1986;
    Bruckner et al, 1968; Porter et al, 1975; Weill et al, 1981;
    Williamson, 1965).

    Workers exposed to low TDI levels may also experience sudden acute and
    severe asthmatic reactions (Banks et al, 1986). Late asthmatic
    reactions have been documented in sensitised workers in association
    with early elevations of the neutrophils, eosinophils, leukotrienes
    B4, and albumin in bronchoalveolar lavage fluid (Fabbri 1990; Fabbri
    et al, 1985; Fabbri et al, 1987; Zocca et al, 1990).

    Susceptibility to TDI-induced asthma does not require a prior history
    of atopy or allergic conditions, and sensitisation may not be
    especially common in atopics (Bernstein 1982). Given sufficient
    exposure, it appears that virtually any person may become sensitised.
    The proportion of individuals with TDI asthma in working populations
    has varied from 4.3% to 25% (ACGIH 1986). There is some evidence that

    this percentage has decreased with decreasing air concentrations.
    Exposure to spills of TDI appears to increase the risks of
    sensitisation. The pathophysiology of TDI-induced asthma is unknown.
    Both immunological and non-immunological pharmacological mechanisms
    have been postulated. Amines may play a causative role in TDI-induced
    asthma (Berlin et al, 1983). It is clear however, that TDI-induced
    asthma is not solely mediated by a type I hypersensitivity response
    associated with IgE antibody (Bernstein, 1982).

    Several studies have provided evidence of cross-shift and progressive
    annual declines in FEV1 of 25% to 75% among asymptomatic workers
    without evidence of TDI asthma when exposed to low levels of TDI
    (below 0.02ppm and as low as 0.003ppm). The annual declines were
    two-to threefold greater than expected, appeared dose related, and
    correlated with observed cross-shift declines. Workers, in general,
    exhibited no acute or chronic symptoms or pulmonary function
    decrements related to these exposures (Diem et al, 1982; Wegman et al,
    1982).

    The diagnosis of TDI-induced asthma relies primarily on the clinical
    history in a worker with known exposure, recognising that symptoms
    such as wheezing, dyspnoea and cough develop at night long after the
    end of the shift. Serial measurement of peak flow rates by the worker
    may help one to make the diagnosis (Burge et al, 1979). Non-specific
    bronchial hyperreactivity to histamine or methacholine is frequently,
    but not invariably present in patients with TDI-induced asthma. Its
    absence may indicate that the asthma is quiescent owing to no recent
    exposure, and re-exposure may lead to hyperreactivity. Failure to
    demonstrate non-specific hyperreactivity on a single test does not
    exclude the diagnosis of TDI-induced asthma (Burge et al, 1982). RAST
    testing for IgE antibodies against p-tolyl monoisocyanate antigens
    probably is not useful because of the occurrence of false positive (in
    exposed but asymptomatic workers) and false negative results (Butcher
    et al, 1983).

    Specific bronchoprovocation challenge with TDI is a definitive way to
    make the diagnosis, but often is not practical because of the need for
    prolonged observation for late reactions and the risk of severe
    reactions.

    Following removal from exposure, some patients have had resolution of
    symptoms and findings suggestive of asthma.

    Long term respiratory symptoms with slightly impaired ventilatory
    function have been reported and in some, irreversible damage has been
    documented (Adams, 1970; Adams, 1975; Banks et al, 1990; Innocenti et
    al, 1981; Luo et al, 1990; Mapp et al, 1988; Moller et al, 1986;
    Paggiaro et al, 1984; Venables et al, 1985; Weill et al, 1981).
    Lozewicz et al (1987) reported that 82% of 50 patients followed up,
    continued to have respiratory symptoms four or more years after
    avoidance of exposures, and nearly one half of these patients required
    treatment at least once per week.

    A 43 year old male with a 6 year history of TDI induced asthma
    developed a fatal asthma attack while mixing 2 components of a
    polyurethane paint. Despite advice to change jobs he continued to work
    while taking anti-asthmatic drugs at home and work to control his
    symptoms of asthma (Fabbri et al, 1988).

    Haemorrhagic pneumonia was diagnosed in a 34 year old spray painter
    who presented with haemoptysis, dyspnoea, bilateral pulmonary
    opacities, respiratory failure and high levels of IgG and IgE
    antibodies against HDI-HSA (hexamethylene diisocyanate human serum
    albumin) and TDI-HSA (Patterson et al, 1990). He was declared normal
    after 2 days of assisted ventilation and 11 days of steroids.

    Hypersensitivity pneumonitis was confirmed by biopsy in a 41 year old
    automobile paint sprayer who presented with dyspnoea, cyanosis, fever,
    crepitant rales, reticulonodular radiographic infiltrates, restrictive
    pulmonary function, and elevated TDI-specific IgG (Yoshizawa et al,
    1989). He improved markedly with prednisolone and oxygen.

    A 53 year old steel plant maintenance worker who occasionally glued
    pipes together presented with cough, fever, malaise interstitial
    pneumonitis, eosinophilia, and elevated IgG antibody levels specific
    for diphenylmethane diisocyanate (MDI) (Walker et al, 1989).

    5.3.3  Neurological

    Firefighters exposed to TDI and possibly other substances experienced
    neurological complaints of euphoria, loss of co-ordination and loss of
    consciousness. Long-lasting symptoms of personality change,
    irritability, depression, and loss of memory (confirmed by
    psychometric testing) were also reported (Le Quesne et al, 1976;
    McKerrow et al, 1970; O'Donoghue 1985). Whether these complications
    are a result of neurotoxic or hypoxaemic effects of diisocyanates is
    not known.

    5.3.4  Gastrointestinal

    Inhalation of vapour or aerosol may produce vomiting and abdominal
    pain (Axford et al, 1976). Epigastric and substernal pain may be
    secondary to the paroxysmal or persistent cough associated with
    inhalation.

    5.3.5  Hepatic

    No data available.

    5.3.6  Urinary

    No data available.

    5.3.7  Endocrine and reproductive system

    Possible impotence. Fire-fighters exposed to TDI and possibly other
    substances suffered from impotence for some time after exposure. This
    was thought to be due to an indirect neurological effect rather than
    to direct toxicity to the male genitalia (Le Quesne et al, 1976).

    5.3.8  Dermatological

    Skin sensitisation on repeated exposure to toluene diisocyanates may
    occur. Urticaria, dermatitis, and allergic contact dermatitis have
    been reported in workers exposed to toluene diisocyanates-based
    photopolymerised resins (Brugsch and Elkins, 1963; Calas et al, 1977).
    The dermatological symptoms included skin lesions of an eczematous,
    and also, of an irritant, pruriginous and erythematous nature. A 21
    year old female developed a rash following direct skin contact with
    toluene diisocyanates. The urticaria or maculopapular lesions occurred
    primarily over exposed areas, but occasionally spread to covered areas
    and lasted for up to 10 days after exposure. Titres of specific Ig E
    antibodies gradually declined over the period of observation from a
    high level after occupational exposure ceased. The low level
    corresponded to those found in non-sensitised toluene diisocyanates
    workers (Karol et al, 1978).

    5.3.9  Eye, ears, nose and throat

    Burning and irritation of the nose and throat and laryngitis have been
    reported. Severe conjunctival irritation and lacrimation from liquid
    or high vapour concentrations is likely. Lower concentrations may
    produce a burning or prickling sensation. Glaucoma and iridocyclitis
    have been reported with a splash incident.

    5.3.10  Haematological

    No data available.

    5.3.11  Immunological

    Elevated specific IgE and IgG antibodies have been noted among
    sensitised and exposed workers. Positive skin test reactions to
    TDI-conjugates with human serum albumin and positive TDI-specific IgE
    and IgG antibodies have been reported but the exact mechanism involved
    is still unknown (Butcher et al, 1977; Cartier et al, 1989; Finkel,
    1983; Karol et al, 1979; Karol, 1980; Keskinen et al, 1988; Wass and
    Berlin, 1989).
    Serum chemotaxis factor - Release of a serum chemo-attracting factor
    for normal neutrophils and activation of asthmatic were demonstrated
    among workers with late asthmatic reaction to TDI (Valentino et al,
    1988).
    HDI-specific Ig G antibodies were elevated in a car painter who had 3
    episodes of hypersensitivity pneumonitis-like disease after exposure
    to acrylic lacquers with hexamethylene diisocyanate (HDI) as the
    curing agent (Selden et al, 1989).

    5.3.12  Metabolic

    5.3.12.1  Acid-base disturbances

    No data available.

    5.3.12.2  Fluid and electrolyte disturbances

    No data available.

    5.3.12.3  Other

    5.3.13  Allergic reactions

    5.3.14  Other clinical effects

    5.4  At risk groups

    5.4.1  Elderly

    No data available.

    5.4.2  Pregnancy

    No data available.

    5.4.3  Children

    No data available.

    5.4.4  Enzyme deficiencies

    No data available.

    5.4.5  Enzyme induced

    No data available.

    5.4.6  Occupations

    In the USA, it is estimated that 40,000 workers are involved in the
    manufacture or processing of toluene diisocyanate. As far as the
    general population is concerned, intake of toluene diisocyanates,
    apart from their use in the form of polyurethane lacquers and paints,
    is of a very low order, because of the short persistence of TDI.

    5.4.7  Others

    6  MANAGEMENT

    6.1  Decontamination

    Ingestion
    No applicable.

    Inhalation exposure

    Monitor patient for respiratory distress. If a cough or difficulty in
    breathing develops, evaluate for respiratory tract irritation,
    bronchitis and pneumonia. Sensitised individuals should be cautioned
    to avoid further exposure as serious allergic reactions may result.
    Move patient to fresh air. Monitor for respiratory distress. If cough
    or difficulty in breathing develops, evaluate for respiratory tract
    irritation, bronchitis, or pneumonitis. Administer 100% humidified
    supplemental oxygen with assisted ventilation as required.

    Eye exposure

    Exposed eyes should be irrigated with copious amounts of tepid water
    for at least 15 minutes. If irritation, pain, swelling, lacrimation,
    or photophobia persist, the patient should be seen by an
    ophthalmologist.

    Dermal exposure

    Wash exposed areas thoroughly with soap and water. A physician may
    need to examine the area if irritation or pain persists.

    6.2  Supportive care

    Monitor patient for respiratory distress. Bronchodilators and oxygen
    may be resorted to in an acute attack. If necessary consider
    endotracheal intubation and ventilation.

    6.3  Monitoring

    Monitor patients for respiratory distress and bronchospasm.

    6.4  Antidotes

    None available.

    6.5  Elimination techniques

    No data available.

    6.6  Investigations

    Perform respiratory function tests to assess degree of bronchospasm
    induced by inhalation of TDI. In acute exposure arterial blood gases
    should also be performed if the patient exhibits respiratory distress.

    6.7  Management controversies

    Several placebo-controlled randomized double-blind crossover studies
    have been conducted to investigate the efficacy of varying
    bronchodilators. Theophylline (6.5mg/kg twice a day) has only partial

    effect (Mapp et al, 1987). Prednisolone and aerosolised beclomethasone
    (1mg twice daily) have been shown to prevent late asthmatic reactions
    or increased airway responsiveness in TDI-sensitized patients (De
    Marzo et al, 1988, Fabbri et al, 1985).

    7  CASE DATA

    Case 1 - Neurological complications after a single severe
    exposure.

    Le Quesne et al, (1976) reported on a group of fireman who were
    heavily exposed to toluene di-isocyanate while fighting a fire in a
    factory where polyurethane foam was manufactured. During the course of
    the fire a total of 4500 litres of TDI leaked from 2 storage tanks and
    the men were exposed intermittently over 8 hours to TDI in the air and
    some of them by direct contact with TDI which soaked their clothing
    and equipment. Other chemicals were also used at the plant but with
    the massive leakage of TDI it was felt that their symptoms were most
    likely to be due to that chemical. During and after the fire 31 out of
    35 men complained of respiratory symptoms and 16 out of 35 men of
    gastrointestinal symptoms. In 23 cases, the men complained of
    neurological symptoms such as difficulty in concentrating, poor
    memory, headache, irritability or depression. In the 5 of these cases
    there had been acute onset of euphoria, ataxia, and loss of
    consciousness. Amongst the various neurological abnormalities observed
    up to 3 weeks after a fire, there were 2 complaints of impotence for 2
    weeks. One of the cases was one of the 5 men who suffered from loss of
    consciousness during the fire and he still shows signs of ataxia and
    had an abnormal EEG at 3 weeks with persistent neurological symptoms
    including prominent depression up to 4 years after a fire. In the
    other case, there was confusion in the first three weeks and ataxia
    and abnormal EEG at 3 weeks with persistent memory difficulties up to
    4 years after the fire. Of the 23 complaining of neurological effects,
    18 were re-examined 4 years after the fire and 13 were found to be
    still clinically affected with difficulty in concentration,
    irritability and depression. Psychometric testing also confirmed a
    selective memory deficit in long term recall in those still affected.
    Thus, from the spectrum of effects observed it seems likely that the
    reported temporary impotence in 2 of the exposed individuals was
    probably secondary to neurological impairment following heavy exposure
    to TDI.

    Case 2

    A 43 year old male with a 6 year history of TDI-induced asthma
    developed a fatal asthma attack while mixing 2 components of a
    polyurethane paint. Despite advice to change jobs he continued to work
    while taking anti-asthmatic drugs at home and work to control his
    symptoms of asthma (Fabbri et al, 1988)

    Case 3

    Haemorrhagic pneumonia was diagnosed in a 34 year old spray painter
    who presented with haemoptysis, dyspnoea, bilateral pulmonary
    opacities, respiratory failure and high levels of IgG and IgE
    antibodies against HDI-HSA (hexamethylene diisocyanate human serum
    albumin) and TDI-HSA (Patterson et al, 1990). He was declared normal
    after 2 days of assisted ventilation and 11 days of steroids..

    Case 4

    Hypersensitivity pneumonitis was confirmed by biopsy in a 41year old
    automobile paint sprayer who presented with dyspnoea, cyanosis, fever,
    crepitant rales, reticulonodular radiographic infiltrates, restrictive
    pulmonary function, and elevated TDI-specific IgG (Yoshizawa et al,
    1989). He improved markedly with prednisolone and oxygen.

    Case 5

    A 53 year old steel plant maintenance worker who occasionally glued
    pipes together presented with cough, fever, malaise, interstitial
    pneumonitis, eosinophilia and elevated IgG antibody levels specific
    for diphenylmethane diisocyanate (MDI) (Walker et al, 1989).

    8  ANALYSIS

    8.1  Agent/toxin/metabolite

    No data available.

    8.2  Sample containers to be used

    No data available.

    8.3  Optimum storage conditions

    Storage of toluene diisocyanate in polyethylene containers is
    hazardous due to absorption of water through the plastic (Lewis,
    1992). Containers should remain closed as much as possible (OHM/TADS
    1993). Inside storage should be in a dry, fire-resistant,
    well-ventilated storage room (OHM/TADS 1993). If stored in tanks, it
    should be blanketed with inert gas, such as nitrogen, or with dry air
    (HSBD, 1993). Storage Temperature - 75 to 100 degrees F (HSDB 1993).
    Store separate from amines, alcohols, bases and acids (HSDB, 1993).

    8.4  Transport of samples

    No data available.

    8.5  Interpretation of data

    No data available.

    8.6  Conversion factors

    At 25C and 750mmHg :

         1mg/m3 = 0.14 ppm in air
         1mg/litre = 140.5 ppm

    8.7  Other recommendations

    There is sufficient knowledge about TDI to classify it as a very toxic
    compound, when inhaled, and it should be treated as a potential human
    carcinogen and as a known animal carcinogen. Consequently, the
    greatest priority should be given to safe methods of use, and the
    education, training, and supervision of operatives, together with
    state enforcement of legislation by an effective inspectorate. Special
    attention should be paid to the prevention and adequate treatment of
    unscheduled releases and spills.

    Normal protective equipment should be provided for all workers and a
    stock of decontaminants always available. Containers should be kept
    closed to prevent escape of vapour and entry of moisture. TDI must
    always be handled in a properly ventilated area. Machines should be
    equipped with enclosed ventilation hoods and benchwork done only in
    properly designed fume cupboards. The efficacy of the ventilation must
    be such that concentrations greater than the TLV do not arise in the
    general working area. Whenever products containing TDI are handled in
    inadequately ventilated areas, breathing apparatus must also be worn.

    Workers exposed to airborne isocyanate merit:
    1. pre-employment examination
    2. periodic examination routinely
    3. re-examination on return to work following sickness absence
    4. instruction in the first-aid treatment of accidental exposures and
       contamination

    Pre-employment examination

    The aim is to identify and to establish base line of fitness.
    Examination should include a history taking based on the MRC
    respiratory questionnaire (1976), spirometry (minimally FEV1 and FVC)
    and physical examination of the respiratory system.

    Where appropriate, a chest X ray may be included. By extrapolation
    from analogous conditions, it was earlier believed that atopic
    subjects might be hypersusceptible to sensitisation, so skin testing
    with common allergens was used for their identification. This
    hypotheses has not been substantiated.

    Workers suffering from hayfever, recurrent acute bronchitis,
    interstitial pulmonary fibrosis, occupational chest disease and
    impaired lung function should not risk exposure to isocyanates and
    prepolymers. Where there is the potential for exposure to a 

    significant skin hazard, workers identified as being at special risk
    from existing conditions should be informed and provision made for
    their protection.

    Periodic examination

    In the absence of significant sickness the questionnaire should be
    repeated annually. It is believed at present that a significant
    proportion of subjects who become sensitised do so in the first two
    months. Tests of ventilatory capacity should be carried out two weeks,
    six weeks and six months after engagement and subsequently six
    monthly. Significant departures from normal should lead to suspicion
    and reconsideration of environmental hygiene.

    After absence with respiratory disease lasting two weeks or more, or
    after repeated lesser absences at short intervals, it would be prudent
    for the doctor to re-examine the worker by questioning, examination
    and spirometry to determine if there has been significant departure
    from previous values and the relation to occupational exposure.

    Medical surveillance

    The available evidence presented indicates that serial measurements of
    the FEV1 is a useful means of identifying acute and long term effects
    of isocyanates in a workforce. The results of lung function tests may
    complement exposure measurements in indicating the presence of a
    problem in an industry. A change in FEV1 in an individual during the
    course of a workshift or over a longer period of time would be
    suggestive of an adverse effect, as would "asthma" (with or without
    "sensitisation") or progressive chronic impairment of lung function.
    An annual decrement in FEV1 of 0.02 litres in an adult non-smoker
    would be anticipated from ageing alone. The frequency of lung function
    testing of exposed subjects is arbitrary but it is suggested that all
    subjects should have preemployment measurements and subsequent
    measurements at least annually or more often if symptoms arise. It is
    difficult to be certain what work of workshift or annual loss of FEV1
    in an individual should signal the need for action. However, workshift
    decrements of 0.3 litres or greater and annual decrements of 5% or 0.2
    litres should be cause for evaluation and more frequent testing since
    the evidence presented suggests that these decrements may be
    associated with eventual chronic airflow obstruction or may be
    representative of asthma which may become intractable.

    For the foreseeable future, exposed workers require health monitoring
    by systemic symptom enquiry and by standardised measurement of
    ventilatory function, with subsequent analysis of trends in
    individual, and group mean, values.

    9  OTHER TOXICOLOGICAL DATA

    9.1  Carcinogenicity

    IARC (1979) evaluated the data on the carcinogenicity of TDI and found
    insufficient experimental animal or human data on which to base an
    evaluation. An evaluation of additional data by IARC (1986) led to the
    conclusion that there is sufficient evidence for the carcinogenicity
    of TDI for experimental animals.

    In the absence of adequate case reports or epidemiological studies,
    there is insufficient data to assess the carcinogenicity of TDI for
    human beings (IARC, 1986). No epidemiological studies of mortality or
    cancer incidence among workers exposed to toluene diisocyanate were
    available.

    One case report of adenocarcinoma in a 47 year old non-smoking spray
    painter has been published. The subject had been exposed to toluene
    diisocyanate and 4,4-methylene diisocyanate for 15 years. The level of
    exposure to isocyanates were not reported and neither were other
    chemicals to which the subject may have been exposed (Mortillaro and
    Schiaron, 1982).

    Inhalation experiments with TDI cited in one study (Laskin et al,
    1972) did not result in tumour production. However the evidence
    concerning the possible respiratory carcinogenicity of polyurethane
    foam dust appears to be conflicting (Laskin et al, 1972; Stemmer et
    al, 1975; Thyssen et al, 1978). Commercial grade TDI administered by
    gavage to mice has produced haemangiomas in the spleen and
    subcutaneous tissues, haemangiosarcomas in the liver, ovaries and
    peritoneum, and hepatocellular adenomas in female mice. All of these
    tumours showed a dose-response relationship (National Toxicology
    Program, 1986).

    9.2  Genotoxicity

    No data available.

    9.3  Mutagenicity

    There are conflicting reports about the mutagenicity of TDI. Anderson
    and Styles (1978) reported that TDI of unknown purity was
    non-mutagenic in a study of 120 chemicals tested but the fact that
    several known mutagens failed to give positive results means that the
    original report was suspect. Anderson et al (1980) later optimised the
    procedures to test the reactive isocyanates and showed that a mixture
    of 2,4- and 2,6-toluene diisocyanate caused a dose-dependent mutagenic
    response, using S-9 activation, in  S. typhimurium strains TA 98,
    TA100, and TA 1538. The positive control for these mutagen tests was
    the hydrolysis product of 2,4-TDI, 2,4-diaminotoluene, reported by
    Ames et al (1975) to be mutagenic. The NTP has also tested toluene
    diisocyanates using the  Salmonella test system and found that both
    2,6-TDI and a mixture of 2,4- and 2,6-TDI (80:20) were mutagenic in 

     S. typhimurium strains TA 98 and TA 100 in the presence (but not the
    absence) of Aroclor 1254-induced male Sprague Dawley or Syrian hamster
    liver S9. Neither sample was mutagenic in  S. typhimurium strains TA
    1535 or TA 1537, with or without metabolic activation.

    9.4  Reprotoxicity

    No published data were found on the effects of toluene diisocyanates
    on reproduction, or on the embryotoxicity or teratogenicity of these
    compounds. No relevant studies were found except for a report of
    transient impotence in two grossly exposed men.

    9.5  Teratogenicity

    Data not available.

    9.6  ADI acceptable daily intake

    9.7  MRL

    9.8  AOEL

    9.9  TLV

    9.10  Relevant animal data

    No relevant data found.

    9.11  Relevant  in vitro data

    Toluene diisocyanates were negative in two in-vitro cell
    transformation assays using human and hamster kidney cells (Styles
    1978).

    10  ENVIRONMENTAL DATA

    10.1  Ecotoxicological data

    No data found.

    10.2  Behaviour

    Adsorption onto soil

    If spilled on wet land TDI is rapidly degraded. In one experiment
    simulating a spill, 5.5% of the original material remained after 24
    hours, and in a field situation, the concentration of toluene
    diisocyanate had declined to the ppm levels in 12 weeks (HSDB 1993)

    10.3  Biodegradation

    Environmental fate

    There are very few studies on the overall environmental fate of
    toluene diisocyanates in the published literature. It has been
    demonstrated in environmental chambers that in the gaseous phase, TDI
    vapour and water vapour do not react to form diaminotoluenes, since
    not even trace amounts of these compounds were detected (Holdren et
    al, 1984). A rate of loss of about 20% of TDI-vapour per hour could be
    explained by surface adsorption. This rate of loss was much higher and
    more rapid when simultaneously present in the chamber. Again, no
    hydrolysis products of TDI could be detected.

    In most industrial situations, toluene diisocyanates are hydrolysed by
    water to give the corresponding polymeric ureas and carbon dioxide
    (Chadwick et al, 1981). However, when toluene diisocyanates come into
    contact with water without agitation, as in spills, a hard crystalline
    crust of polymeric ureas forms slowing down further degradation of the
    toluene diisocyanates, unless the crust is mechanically broken. The
    solid reaction products are insoluble and biologically inert
    (Brochhagen and Grieveson, 1984).

    A computerised partitioning model proposed by Mackay (1979) indicated
    that toluene diisocyanates released into the environment will tend to
    partition into water. However, in making this prediction, the
    reactivity of the compounds was not taken into consideration.

    Photolysis

    In the atmosphere TDI reacts with photochemically produced hydroxyl
    radicals and is also removed by dry deposition (HSDB, 1993).

    Half-life in water, soil and vegetation

    The half life for toluene diisocyanate in the atmosphere is 3.3 hours
    by reaction with photochemically produced hydroxyl radicals (HSDB,
    1993).

    10.4  Environmentally important metabolites

    No information on the environmental toxicity of TDI was found in
    available references at the time of this review. TDI may be released
    to the environment as fugitive emissions and from stack exhaust during
    the production, transport, and use of toluene diisocyanate in the
    manufacture of polyurethane foam products and coatings, as well as
    from spills (HSDB, 1993). If released into water, a crust forms around
    the liquid toluene diisocyanate and less than 0.5% of the original
    material remains after 35 days. Low concentrations of toluene
    diisocyanate disappears from the aqueous environment in approximately
    a day (HSDB, 1993).

    10.5  Hazard warnings

    An evaluation of the hazards for non-human targets from environmental
    levels of TDI is not possible on the basis of available data.

    10.5.1  Aquatic life

    Data not available.

    10.5.2  Bees

    Data not available.

    10.5.3  Birds

    Data not available.

    10.5.4  Mammals

    Data not available.

    10.5.5  Plants

    Data not available.

    10.5.6  Protected species

    Data not available.

    10.6  Waste disposal data

    At the time of this review, criteria for land treatment or burial
    (sanitary landfill) disposal practices are subject to significant
    revision. Prior to implementing land disposal of waste residue
    (including waste sludge), consult with environmental regulatory
    agencies for guidance with environmental regulatory agencies for
    guidance on acceptable disposal practices (HSDB 1993). Toluene
    diisocyanate is a waste chemical stream constituent which may be
    subjected to ultimate disposal by controlled incineration. Oxides of
    nitrogen are removed from the effluent gas by scrubbers and/or thermal
    devices (HSDB 1993). Toluene diisocyanate is a potential candidate for
    liquid injection incineration, rotary kiln incineration, and fluidized
    bed incineration (HSDB 1993).

    This compound should be susceptible to removal from waste water by air
    stripping (HSDB 1993).

    The re-use and the disposal of uncleaned empty drums and containers is
    not permissible because of the hazards associated with isocyanate
    remaining on the walls of the drums. As a matter of principle all
    residues of isocyanates in containers must be decontaminated in an
    appropriate way.

    There are three basic methods for disposal of isocyanate wastes, the
    choice will depend in part on the scale on the scale of operation i.e.
    amount of waste to be treated and in part on the availability of the
    'neutralising' agent

    1. Reaction with waste polyol
    React with excess waste polyol to make a low quality foam which may be
    incinerated, tipped or otherwise disposed of in an authorised waste
    disposal area.
    2. Reaction with liquid decontaminant
    React with excess liquid decontaminant by adding the isocyanate slowly
    and with stirring to liquid decontaminant in a fully opening drum.
    Leave for 48 hours, close the drum and dispose of by tipping or
    otherwise.
    3. Incineration
    Incineration should be done in properly supervised equipment specially
    designed for the disposal of noxious chemical wastes.

    Author

    Mary-Jane Bennie

    National Poisons Information Service (London Centre)
    Medical Toxicology Unit
    Guy's & St Thomas' Hospital Trust
    Avonley Road
    London
    SE14 5ER
    UK

    This monograph was produced by the staff of the London Centre of the
    National Poisons Information Service in the United Kingdom. The work
    was commissioned and funded by the UK Departments of Health, and was
    designed as a source of detailed information for use by poisons
    information centres.
     Peer review was undertaken by the Directors of the UK National
    Poisons Information Service.

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