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.

    Environmental Health Criteria  193

    First draft prepared at the National Institute of Health Sciences,
    Tokyo, Japan, and the Institute of Terrestrial Ecology, Monk's Wood,
    United Kingdom

    Published under the joint sponsorship of the United Nations
    Environment Programme, the International Labour Organisation, and the
    World Health Organization, and produced within the framework of the
    Inter-Organization Programme for the Sound Management of Chemicals.

    World Health Organization
    Geneva, 1997

         The International Programme on Chemical Safety (IPCS) is a joint
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    WHO Library Cataloguing in Publication Data


    (Environmental health criteria ;193)

    1.Phosgene - toxicity              2.Phosgene - adverse effects
    3. Environmental exposure          I.Series

    ISBN 92 4 157193 4                 (NLM Classification: QV664)
    ISSN 0250-863X

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    1.   SUMMARY

         1.1    Identity, physical and chemical properties, and analytical
         1.2    Uses and sources of human and environmental exposure
         1.3    Environmental transport, distribution and transformation
         1.4    Environmental levels and human exposure
         1.5    Kinetics and metabolism
         1.6    Effects on experimental animals and  in vitro test systems
                1.6.1    Single and short-term exposures
                1.6.2    Non-pulmonary effects
         1.7    Effects on humans
         1.8    Effects on organisms in the environment


         2.1    Identity
         2.2    Physical and chemical properties
         2.3    Analytical methods
         2.4    Conversion factors


         3.1    Natural occurrence
         3.2    Anthropogenic sources
                3.2.1    Production levels and processes
                3.2.2    Environmental processes
                3.2.3    Uses


         4.1    Transport and distribution between media
         4.2    Abiotic degradation


         5.1    Environmental levels
                5.1.1    Air
                5.1.2    Water
                5.1.3    Soil
                5.1.4    Food and feed
         5.2    General population exposure
         5.3    Occupational exposure
                5.3.1    Manufacture and use
                5.3.2    Non-manufacturing occupations


         6.1    Absorption
         6.2    Distribution


         7.1    Single and short-term inhalation exposures
         7.2    Skin and eye irritation; sensitization
         7.3    Long-term exposure
         7.4    Reproductive and developmental toxicity
         7.5    Mutagenicity and related end-points
         7.6    Carcinogenicity
         7.7    Immunotoxicity
         7.8    Mechanism of toxicity.


         8.1    General population and occupational exposure
         8.2    Case reports - individual accidents
         8.3    Epidemiological studies



         10.1   Evaluation of human health risks
                10.1.1   Exposure
                10.1.2   Health effects
                  Evaluation of animal data
                  Evaluation of human data
                10.1.3   Guidance value
         10.2   Evaluation of effects on the environment


         11.1   Conclusions
         11.2   Recommendations for protection of human health







         Every effort has been made to present information in the criteria
    monographs as accurately as possible without unduly delaying their
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    Criteria monographs, readers are requested to communicate any errors
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    on Chemical Safety, World Health Organization, Geneva, Switzerland, in
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                                     * * *

         A detailed data profile and a legal file can be obtained from the
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                                     * * *

         This publication was made possible by grant number 5 U01 ES02617-
    15 from the National Institute of Environmental Health Sciences,
    National Institutes of Health, USA, and by financial support from the
    European Commission.

                                     * * *

         The Federal Ministry for the Environment, Nature Conservation and
    Nuclear Safety, Germany, provided financial support for this

    Environmental Health Criteria



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    Dr D. Anderson, British Industry Biological Research Institute (BIBRA)
    Toxicology International, Carshalton, Surrey, United Kingdom

    Dr R. Chhabra, Environmental Toxicology Program, Toxicology Branch,
    National Institute of Environmental Health Sciences,  Research
    Triangle Park, North Carolina, USA

    Dr H. Ellisa, Epidemiology Department, Rohm & Haas, Bristol,
    Pennsylvania, USA

    Dr  B. Gilbert, FarManguinhos, FIOCRUZ, Institute of Technology and
    Pharmacology, Ministry of Health, Manguinhos, Rio de Janeiro, Brazil
    ( Chairman)

    Professor M. Jakubowski, Occupational and Environmental Hygiene
    Division, Nofer Institute of Occupational Medicine, Lodz, Poland

    Dr S.K. Kashyap, National Institute of Occupational Health, Meghani
    Nagar, Ahmedabad, India ( Vice-chairman)

    Dr R. Liteplo, Environmental Health Directorate, Health Protection
    Branch, Environmental Health Centre, Tunney's Pasture, Ottawa,
    Ontario, Canada

    Dr  E. E. McConnell, Laurdane Estates, Raleigh, North Carolina, USA
    ( Co-rapporteur)

    Dr H. Naito, Ibaraki Prefecture University of Health Sciences,
    Amimachi, Inashikigun, Ibaraki, Japan


    a     Invited, but unable to attend.

    Dr W. Popp, Universitatsklinikum Essen, Institute for Health and
    Occupational Medicine, Essen, Germany

    Dr R. Sram, Laboratory of Genetic Ecotoxicology, Institute of
    Experimental Medicine, Videnska, Prague, Czech Republic

    Dr Shou-Zheng Xue, Toxicology Programme, Shanghai Medical University,
    Shanghai, People's Republic of China


    Dr G. C. Becking, Team Leader, IPCS/IRRU, World Health Organization,
    Research Triangle Park, North Carolina, USA

    Ms R. Gomes, Health Canada, Environmental Health Directorate, Tunney's
    Pasture, Ottawa, Ontario, Canada ( Co-rapporteur)


         A WHO Task Group on Environmental Health Criteria for Phosgene
    and Selected Chloroalkyl Ethers met at the British Industrial
    Biological Research Association (BIBRA) Toxicology International,
    Carshalton, Surrey, United Kingdom, from 18 to 23 March 1996.  Dr D.
    Anderson opened the meeting and welcomed the participants on behalf of
    the host institute.  Dr G.C. Becking, IPCS, welcomed the participants
    on behalf of Dr M. Mercier, Director of the IPCS, and the three
    cooperating organizations (UNEP/ILO/WHO).  The Task Group reviewed and
    revised the draft criteria monograph and made an evaluation of the
    risks for human health and the environment from exposure to phosgene.

         Financial support for this Task Group was provided by the United
    Kingdom Department of Health as part of its contribution to the IPCS.

         Dr E.E. McConnell, Raleigh, North Carolina, USA, prepared the
    first draft of this monograph.  The draft reviewed by the Task Group,
    which contained the comments received following circulation of the
    draft monograph to the IPCS Contact Points for Environmental Health
    Criteria monographs, was prepared by the Secretariat.

         Dr G.C. Becking (IPCS, Central Unit, Inter-regional Research
    Unit) and Dr P.G. Jenkins (IPCS, Central Unit, Geneva) were
    responsible for the overall scientific content and technical editing,

         The efforts of all who helped in the preparation of the document
    are gratefully acknowledged.


    CI             confidence interval
    L(CT)50        median lethal concentration-time product
    LFP            lavage fluid protein
    MDI            methylene-diphenyl diisocyanate
    Nk             natural killer
    OES            occupational exposure standard
    PMN            polymorphonuclear leukocyte
    ppb            parts per billion
    ppm            parts per million
    ppt            parts per trillion
    PVC            polyvinyl chloride
    SMR            standardized mortality ratio
    TDI            toluene diisocyanate
    TLV            threshold limit value
    TWA            time-weighted average

    1.  SUMMARY

    1.1  Identity, physical and chemical properties, and
         analytical methods

         Phosgene is a highly reactive colourless gas at room temperature
    and ambient pressure, and has a  suffocating odour similar to mouldy
    hay.  The odour may be detected between 1.6 and 6 mg/m3.

         Analytical methods are available for the detection of phosgene in
    air and for use in industrial hygiene programmes that measure total
    dose (e.g., paper tape monitors).

    1.2  Uses and sources of human and environmental exposure

         More than 99% of the phosgene produced is used on-site in closed
    systems.  It is produced by reacting equimolar amounts of anhydrous
    chlorine and carbon monoxide in the presence of a carbon catalyst. 
    World production has been estimated to be greater than 3 million
    tonnes.   Environmental phosgene levels arise from industrial
    emissions and thermal degradation of some chlorinated solvents and
    chlorinated polymers.  However, a significant source of environmental
    phosgene is the photochemical oxidation of chloroethylenes such a tri-
    and tetraethylene.

    1.3  Environmental transport, distribution and transformation

         Because of its high reactivity, inter-compartmental transport of
    phosgene is expected to be limited. Removal of phosgene from ambient
    air occurs by heterogeneous decomposition (surface catalysis) and slow
    gas-phase hydrolysis.  Long-range transport takes place and diffusion
    from the troposphere to the stratosphere is believed to lead to more
    rapid photolytic degradation of phosgene.

    1.4  Environmental levels and human exposure

         Human exposure in both the general population and occupational
    setting is primarily by inhalation.

         The average level of phosgene in ambient air may range from
    approximately 80 to 130 ng/m3 although few data are available.  In
    view of the varied industrial hygiene practices worldwide it is
    impossible to give an exposure figure for workers manufacturing or
    using phosgene or for  fire-fighters.  At present the Threshold Limit
    Values (time-weighted average) in 15 countries range from 0.4 and
    0.5 mg/m3.

         Levels of phosgene in water, soil and food have not been

    1.5  Kinetics and metabolism

         There are very few data on the absorption, metabolism,
    distribution and fate of phosgene. The primary route of exposure is by
    inhalation, the gas penetrates into the tissues of the respiratory
    tract, and  so only minimal amounts of phosgene are distributed in the
    body.  The very short half-life (0.026 seconds) in aqueous solutions
    precludes a significant retention of phosgene in the body.  No
    information on the metabolism of phosgene has been reported.  The
    hydrolyic products of phosgene, i.e. hydrochloric acid and carbon
    dioxide, are disposed of by the body through normal physiological

         Phosgene exerts its toxicity through acylation of proteins, as
    well as through the production of hydrochloric acid.  The amino,
    hydroxyl and sulfhydryl groups in the proteins appear to be the target
    for acylation leading to marked inhibition of several enzymes related
    to energy metabolism and a breakdown of the blood:air barrier.

    1.6  Effects on experimental animals and in vitro test systems

    1.6.1  Single and short-term exposures

         In all species studied, the lung is the major target organ.  The
    L(CT)50 varies from 900 mg/m3-min (225 ppm-min) in the mouse to
    1920 mg/m3-min (480 ppm-min) in the guinea-pig.  An L(CT)50 of
    1000 mg/m3-min (250 ppm-min) was reported in the monkey.  In all
    species the characteristic pathological feature is the delayed
    clinical manifestation of pulmonary oedema, which is dose-dependent. 
    Pathological changes in the terminal bronchioles and alveoli at low
    concentrations are typical of a pulmonary irritant, whereas at higher
    exposures pulmonary oedema occurs, leading to interference with gas
    exchange and death.

         No long-term exposure studies of phosgene have been reported.

         One study in rats showed that a single phosgene exposure of
    2 mg/m3 for 4 h can result in decreased pulmonary immunocompetence as
    measured by the natural killer activity of pulmonary cells.  No
    effects were seen at an exposure level of 0.4 mg/m3 for 4 h.

         Two other studies of the effects of single exposures of phosgene
    on pulmonary immunocompetence in rats and mice have been reported.  In
    rats infected with influenza virus after a 4-h exposure to 4 mg
    phosgene/m3, there was a 10-fold increase in viral titre 1 day
    post-infection, which remained significantly elevated for 4 days. 
    Furthermore, in rats exposed to phosgene levels between 0.2 and
    4 mg/m3 for 4 h, a marked decrease in prostaglandin E2 and
    leukotrienes was noted at exposure levels of 0.4 mg/m3 or more, with
    a decrease in the number of alveolar macrophages and an increase in
    the number of neutrophils observed at 0.4 mg/m3.  In a host-
    resistance assay, where mice were exposed to levels of phosgene
    between 0.04 and 0.4 mg/m3 for 4 h, an increase in mortality from

     Streptococcus zooepidemicus infection or an increased number of
    B16/BL6 melanoma lung tumours was noted at levels of 0.1 mg/m3 or
    more.  Pulmonary bacterial clearance was reduced in rats exposed to
    0.4 mg/m3 (0.1 ppm) phosgene for 6 h or to 0.4 mg/m3 (0.1 ppm) for
    6 h/day, 5 days/week for 4 to 12 weeks.  This effect was reversible
    following termination of exposure.

    1.6.2  Non-pulmonary effects

         Phosgene exposure can result in eye and skin irritation.  Studies
    concerning the sensitization potential of phosgene have not been found
    in the literature.

         No data are available on the reproductive and developmental
    effects of phosgene.

         No adequate data are available for the assessment of the
    mutagenicity or carcinogenicity of phosgene.

    1.7  Effects on humans

         The target organ in humans, as in experimental animals, is the
    lung.  After exposure to phosgene levels between 120 and
    1200 mg/m3-min, three distinct clinicopathological phases have been
    reported.  The initial phase consists of pain in the eyes and throat
    and tightness in the chest, often with shortness of breath, wheezing
    and coughing; hypotension, bradycardia and rarely sinus arrhythmias
    can occur.  The second or latent phase, which is often asymptomatic,
    can last as long as 24 h depending upon the level and duration of
    exposure.  In the third phase, pulmonary oedema may develop, leading
    to death in some cases.

         Populations exposed to phosgene after industrial accidents have
    reported a wide variety of symptoms, including headache, nausea,
    cough, dyspnoea, fatigue, pharyngeal pain, chest tightness and pain,
    intense pain in the eye and severe lacrimation.  In one study
    pulmonary oedema occurred after a latent phase of 48 h.

         The effects of long-term exposure to phosgene have been studied
    in three groups of workers at two facilities, i.e., a phosgene
    production plant and an uranium processing facility.  In both
    facilities, only limited air sampling or personal monitoring was
    carried out, and worker exposures were only estimates.

         An examination of the medical records of all 326 workers in the
    phosgene production facility who were potentially exposed to phosgene
    (up to 0.5 mg/m3, with some excursions above this value;  average
    0.01 mg/m3) did not yield any chronic lung problems or increased
    mortality from respiratory disease compared to a group of 6228
    controls.  However, the lack of detail in the report on both exposure
    and effects makes it difficult to draw firm conclusions from this

         Two groups of workers were studied at the uranium processing
    plant: a cross-section of 699 workers from the over 18 000 employed
    during the period, with potential exposure to phosgene  levels below
    0.4 mg/m3 (and 4 or 5 daily short-term excursions to > 4 mg/m3);
    and a group of 106 workers known to have been involved in accidents
    and exposed to levels above 200 mg/m3-min.  In the group exposed
    chronically to low levels of phosgene, an examination of death
    certificates did not indicate an increased mortality from all causes
    or from respiratory disease or lung cancer.  In the group involved in
    chemical accidents no increase in deaths from all causes was reported. 
    There were no lung cancer deaths but there was a slight increase in
    the number of deaths from respiratory diseases.  In view of the lack
    of exposure data and the methodological characteristics of this study
    the conclusions regarding the chronic effects of phosgene that  can be
    drawn are limited.

    1.8  Effects on other organisms in the laboratory and field

         No information concerning the effects of phosgene on organisms in
    the environment has been reported.


    2.1  Identity

    Molecular formula:        COC12

    Chemical structure:       CI
                                  C = O

    Common Synonyms:          carbonic acid dichloride, carbonyl chloride,
                              chloroformyl chloride, carbon oxychloride

    IUPAC and CAS names:      carbonic dichloride

    CAS Registry number:      CAS 75-44-5

    RTECS Registry number:    SY5600000

    UN Transport number:      1076

    2.2  Physical and chemical properties

         Phosgene is a colourless nonflammable gas at room temperature and
    ambient pressure.  It has a suffocating odour and a smell reminiscent
    of mouldy hay (Budavari, 1996).  The recognition of the odour of
    phosgene occurs at levels > 6 mg/m3 (1.5 ppm), although  some
    trained workers are capable of perceiving the odour at a level of
    0.4 mg/m3 (0.1 ppm).  The physical and chemical properties are
    summarized in Table 1.

    Table 1.  Physical and chemical properties of phosgenea


    Colour                                     colourless

    Relative molecular mass                    98.92

    Physical state                             gas

    Melting point                              -127.8°C

    Boiling point                              7.56°C

    Vapour pressure (20°C)                     161.6 kPa

    Relative vapour density (air = 1)3.42

    Relative density, 20°C (water = 1)1.4

    Solubility in water                        slight, reacts with water

    Solubility in organic solvents             reacts with ethanol, very
                                               soluble in benzene,
                                               toluene, acetic acid,
                                               and most liquid

    a    From:  Schneider & Diller (1989); Verschueren (1983);
         Budavari (1996)
    2.3  Analytical methods

         A number of techniques may be used to determine phosgene
    concentrations in air.  These include passive dosimetry (Moore &
    Matherne, 1981; Mathern et al., 1981), manual colorimetry (NIOSH,
    1976), automated colorimetry (US EPA, 1986; Dangwal, 1994), gas
    chromatography (Singh, 1976; Tuggle et al., 1979), infrared
    spectroscopy (Esposito, 1977) and ultraviolet spectrophotometry
    (Crummett & McLean, 1965).  In addition, paper tape monitors capable
    of detecting 5 µg/m3 have been described (Hardy, 1982).  A summary of
    these methods is presented in Table 2.

        Table 2.  Sampling and analysis of phosgene in aira


    Sampling             Analytical methodb          Limit of detection   Sample          Comments              Reference
    methodb                                              (range)          size

    Passive              Direct reading              (8-400 mg/m3-min)        -           Concentration-        Moore &
    dosimetry            colorimetric reaction                                            time relationship     Matherne 
                         with NBP                                                         in breathing zone     (1981)

    Air through          Measure colour at           (0.2 - 100 mg/m3)    1 litre/min     Too slow              NIOSH (1976)
    impinger             475 nm                                           for 25 min      response for
    containing DEP                                                                        continuous
    solution of NBP                                                                       monitoring
    and BA

    Air bubbled into     Automated colorimetry       0.004 mg/m3          1 litre/min     Response time of      US EPA (1986)
    flowing stream of    at reagent flow rate of     (0-4 mg/m3)          for 20 min      20 min too long
    NBP-BA-DEP           0.2 ml/min                                                       for continuous

    Air through          Derivative determined       0.04 mg/m3           1 litre air     Extremely             Wu & Gaind
    impinger             by reverse-phase HPLC                            sample          sensitive but         (1993)
    containing                                                                            needs highly
    tryptamine                                                                            trained staff and

    Table 2 (contd).


    Sampling             Analytical methodb          Limit of detection   Sample          Comments              Reference
    methodb                                              (range)          size

    Direct sample        Gas-chromatography                               0.5 ml          Extremely             Singh (1976)
    injection,           - electron capture          < 0.08 mg/m3         injection       sensitive, needs      Tuggle et al.
    continuous           - aluminium columns         < 0.08 - 20 mg/m3                    highly trained        (1979)
    sampling             didecyl phthalate on                                             staff and
                         chromosorb p                                                     equipment

    Air is drawn         Infrared spectroscopy,      0.1 mg/m3            2 to 5          Can be used as a      Esposito et al.
    directly into        comparison of               (0.1 to 1200         litre/min       continuous            (1977)
    spectrophotometer    absorbance at 11.8 µm       mg/m3)                               monitor for
                         and reference                                                    ambient levels of
                         wavelength of 11.2 µmn                                           phosgene
                         using 20 m variable
                         path length cell

    a    Proper medical treatment for those exposed to phosgene will depend on the concentration and length of exposure. Therefore,
         any procedure used for monitoring ambient and workplace levels must give information on both parameters, preferably on a
         continuous basis, since a latent period of 2-24h may occur between exposure and any warning symptoms.

    b    NBP = 4,4 -nitrobenzyl pyridine
         DEP = diethyt phthalate
         BA = N-benzylalanine
         HPLC = high performance

    2.4  Conversion factors

    1 ppm   = 4.05 mg/m3

    1 mg/m3 = 0.25 ppm

    at 25°C and 101.3 kPa


    3.1  Natural occurrence

         Phosgene is not known to occur naturally.

    3.2  Anthropogenic sources

    3.2.1  Production levels and processes

         Phosgene is produced by reacting equimolar amounts of anhydrous
    chlorine and carbon monoxide in the presence of a carbon catalyst
    (Schneider & Diller, 1989).  The great majority is used directly in a
    closed system.

         It is difficult to give accurate production figures because more
    than 99% of phosgene production is for on-site use (Schneider &
    Diller, 1989).  However, phosgene is manufactured in most
    industrialized countries.  Approximately 37% of the world's production
    is in the USA (about 1 million tons); in 1989 European phosgene
    production was approximately 1.2 million tonnes (Schneider & Diller,

    3.2.2  Environmental processes

         Phosgene in ambient air may arise from three sources:

    a)  direct emissions during its manufacture, handling, use and

    b)  thermal decomposition, in the presence of air, of chlorinated
    hydrocarbons, e.g., solvents such as chloroform, methylene chloride
    (Snyder et al., 1992) and 1,2-dichloropropane (IPCS, 1993) and
    polymers such as polyvinyl chloride (PVC); 

    c)  photooxidation of chlorinated hydrocarbons, particularly
    chloroform and the chloroethylenes (Rinzema, 1971; Singh, 1976; Gay et
    al., 1976; Birgesson, 1987).

         The thermal degradation of chlorinated hydrocarbons can occur as
    a result of combustion of these materials during waste disposal, in
    fires, and during welding in situations where PVC plastics are
    degraded (Rinzema, 1971; Birgesson, 1982).  Firefighters and welders
    are at particular risk from these sources of phosgene.

         A significant contribution to ambient air levels of phosgene is
    the photooxidation of chloroethylenes, particularly tri- and tetra-
    chloroethylene (Singh, 1976; Gay et al. 1976).  It has been estimated
    that such reactions may result in the worldwide formation of 350 000
    tonnes of phosgene per year (Singh, 1976).

    3.2.3  Uses

         Initially important as an agent of chemical warfare, phosgene is
    now widely used as a chemical intermediate, most often at the point of
    production.  The major use is in the production of aromatic
    diisocyanates such as methylene diphenyl diisocyanate (MDI) and
    toluene diisocyanate (TDI), which are used to produce polyurethane
    foams and other polymers.  Worldwide about 80% of phosgene is used for
    TDI and MDI production.  Other major uses of phosgene include the
    production of polycarbonate, aliphatic diisocyanates, monoisocyanates
    and chloroformic esters and urethanes (Schneider  & Diller, 1989;
    Borak, 1991).  Phosgene is also used in the manufacture of some
    agrochemicals, in the pharmaceutical industry, and metallurgy (US NLM,


    4.1  Transport and distribution between media

         Phosgene can enter the atmosphere in the form of  industrial
    emissions or from the degradation of chlorohydrocarbons (section
    3.2.2).  Detectable levels have been found in ambient air (section
    5.1.1).  However phosgene is unlikely to be detectable in soil and
    vegetation owing  to heterogeneous decomposition (section 4.2).

         In water, phosgene is rapidly degraded to hydrochloric acid and
    carbon dioxide (Butler & Snelson., 1979), the half-life in aqueous
    solution being 0.026 seconds (Manogue and Pigford, 1969).

         In the atmosphere, even at high humidity levels, phosgene is only
    slowly decomposed (Noweir et al., 1973; US EPA, 1986).  The half-life
    by homogeneous gas-phase hydrolysis of 4 g /m3 phosgene (1 ppb) in
    nitrogen (at sea-level pressure, 25 œC and with water vapour at a
    pressure of 10 Torr) has been calculated to be 113 years (range 20 to
    630 years) (Butler & Snelson, 1979).  Reaction rates with activated
    oxygen and hydroxyl radicals are also slow (Singh, 1976).  Phosgene
    is, therefore, likely to be persistent in the atmosphere and subject
    to long-range transport.  Diffusion to the stratosphere leads to more
    rapid degradation by photolysis (Singh, et al., 1977).

    4.2  Abiotic degradation

         Reaction with molecules having an active hydrogen atom (e.g.,
    water, primary and secondary alcohols, thiols and amines) does occur,
    forming hydrochloric acid, carbon dioxide, and carbonic acid
    derivatives (Butler & Snelson, 1979; Schneider & Diller, 1989), but
    phosgene reacts very slowly in the gas phase with photochemically
    produced hydroxyl radicals (Singh, 1976).Removal of phosgene from
    ambient air occurs by two major pathways, i.e. heterogeneous
    decomposition (Noweir et al., 1973) and liquid-phase hydrolysis (Singh
    et al., 1977).  At normal ambient temperatures the gas-phase
    hydrolysis is the major pathway for phosgene degradation (Singh et
    al., 1977).  However, even contact with soil particles and vegetation
    at ambient temperatures enhances the rate of phosgene degradation
    (Noweir et al., 1973).


    5.1  Environmental levels

    5.1.1  Air

         It has been suggested that the primary source of atmospheric
    levels of phosgene is from the thermal degradation and photo-
    degradation of chlorinated solvents such as tri- and
    tetrachloroethylene and PVC (Singh, 1976).  Direct emissions from the
    production and use of the chemical play a minor role and would most
    likely affect the air levels only near the factory.  Phosgene levels
    in ambient air at four locations in California, USA, were reported by
    Singh et al. (1977).  Multiple samples (10 to 257) were taken on a
    24-h basis from a single location in each area.  In one rural area an
    average level of 87 ng/m3 (21.7 ppt) was reported.  The average
    levels found in three urban areas were 117 ng/m3 (29.3 ppt), 
    121 ng/m3 (30.3 ppt) and 129 ng/m3 (31.8 ppt), with a peak level 
    in one sample of 244 ng/m3 (61.0 ppt).  In three other cities in the 
    USA the average level of phosgene in ambient air was reported to be less 
    than 80 ng/m3 (20 ppt) (Singh et al., 1981).

    5.1.2  Water

         There are no data on levels of phosgene in water, since
    hydrolysis precludes significant accumulation in this medium.

    5.1.3  Soil

         Data on levels of phosgene in soil are not available, since rapid
    breakdown on contact with solid surfaces and moisture prevents a
    significant accumulation in this medium (Noweir et al., 1973).

    5.1.4  Food and feed

         Although no data are available, the lack of stability in the
    presence of liquid-phase water, solid surfaces, and alcohols and or
    amines in foods makes contamination of food by phosgene unlikely (see
    sections 4.1 and 4.2).

    5.2  General population exposure

         The general population is exposed to only very low levels (in the
    ng/m3 range) of phosgene and this is almost entirely via contaminated
    urban air.  The origin of this phosgene is from decomposition of other
    chlorinated compounds or, in isolated circumstances, from the
    emissions of an industrial enterprise making or using phosgene without
    carrying out appropriate industrial hygiene practices.  Based on the
    range of average concentrations (< 80-129 ng/m3) given in section
    5.1.1, the estimated total daily intake of phosgene may range from

    < 1.6 to 2.6 œg, assuming a daily respiratory intake of 20 m3 air. 
    Much higher levels of phosgene exposure are possible during home use
    of chemicals such as methylene chloride under conditions where the
    temperature is sufficiently high to lead to degradation of this
    chemical (Snyder et al., 1992).

    5.3  Occupational exposure 

    5.3.1  Manufacture and use

         Occupational exposure limits (8- or 10-h TLV) in some 15
    countries range between 0.4 and 0.5 mg/m3 (ILO, 1991).  Based upon
    animal data, the United Kingdom has proposed an OES (8-h TWA) of
    0.08 mg/m3 (0.02 ppm) and an STEL of 0.24 mg/m3 (0.06 ppm) (HSE,
    1995).  It is difficult to report actual values in individual
    factories worldwide since levels will vary greatly depending upon the
    level of industrial hygiene practiced in any particular factory. 
    However, even early monitoring reports indicated that exposures were
    generally below the recommended TLV.  In a few cases exposure levels
    above 0.4 mg/m3 have been reported (Levina et al., (1966).  In a
    factory manufacturing phosgene, personal samplers detected levels up
    to 0.08 mg/m3 (average 0.012 mg/m3), whereas fixed position samplers
    (total of 56) showed levels between non-detectable and 0.52 mg/m3 in
    51 samples, with excursions in  a few samples to about 71 mg/m3
    (NIOSH, 1976).  More recent monitoring data are lacking.

    5.3.2  Non-manufacturing occupations 

         Firefighters and workers engaged in welding and building trades
    are at risk from the phosgene formed by the thermal degradation of
    chlorinated hydrocarbons and PVC.  The pyrolysis of Freon present in
    commercial refrigeration units (Birgesson, 1982), tri- and
    tetrachloroethylene (Rinzema, 1971; Andersson et al., 1975), PVC
    (Brown & Birky, 1980) and methylene chloride (Snyder et al., 1992)
    have all been shown to result in toxic levels of phosgene.  However,
    actual levels in the area of work or the breathing zone were not
    quantified in these studies.


         Because of the physico-chemical properties of phosgene, the
    kinetics and metabolism of phosgene in animals should be similar if
    not identical to those found in humans.  However, because of the
    highly toxic nature of phosgene, human experimental data appropriate
    for use in this monograph does not exist.

    6.1  Disposition of phosgene

         There are very few data on absorption, metabolism, distribution
    and fate of phosgene.  The primary route of exposure is by inhalation. 
    The gas penetrates into the tissues of the respiratory tract,  and so
    only minimal amounts of phosgene are distributed in the body.  The
    very short half-life (0.026 seconds) in aqueous solutions precludes a
    significant retention of phosgene in the body.  No information on the
    metabolism of phosgene has been reported.  The hydrolytic products  of
    phosgene, i.e. hydrochloric acid and carbon dioxide, are disposed of
    by the body through normal physiological processes (Manogue & Pigford,
    1960; Thienes & Haley, 1972).

    6.2 Reaction with body components

         Apart from the formation of hydrochloric acid on contact, Cessi
    et al. (1966) showed marked acylation of  in vitro poly-L-lysine and
    human albumin by phosgene.  The reaction of phosgene with cysteine
    yields 2-oxothiazolidine-4-carboxylic acid (Mansuy et al., 1977).  The
    same product is formed when chloroform (Pohl et al., 1977) or carbon
    tetrachloride (Shah et al., 1979) is incubated with hepatic


    7.1  Single and short-term inhalation exposures

         For some end-points (e.g., death, lung damage), the effects of
    phosgene exposure are dependent upon both the concentration and
    duration of exposure; considered as a product of CœT=K as stated in
    Haber's law (the product of the concentration and time of exposure
    required to produce a specific physiological effect is a constant).

         Early workers validated this relationship using death as the
    physiological end-point following acute and short-term exposures.  The
    validity of this concept for phosgene was tested in cats (Flury, 1921;
    Flury & Zernick, 1931).  Twenty cats were exposed to phosgene at
    levels between 5 and 500 mg/m3 for periods of time between 0.5 and
    120 min (CœT values varied from 37.5 to 562 ppm-min).  A plot of K
    (death or survival) against T (abscissa) and C (ordinate) resulted in
    an hyperbolic plot with marked deviations at both high and low
    concentrations (Long & Hatch (1961).  Similar results were obtained in
    rats when the physiological effect was impaired gas exchange (Rinehart
    & Hatch, 1964).

         Based on reviews of available information (Coman et al., 1947;
    Atherley, 1985) it was concluded that, for phosgene, effects
    associated with the product of CœT were reasonable constant only
    within the middle range of concentrations (i.e., between 4 and
    800 mg/m3), and for exposure times that negated the effect of an
    animal holding its breath.  Under these conditions and for these
    effects, it was considered appropriate to express the actual dose of
    phosgene, assuming equivalent respiratory volume, as CœT.  The CœT
    relationship probably does not apply to potential effects resulting
    from long-term exposure to low levels of phosgene.

         Single and short-term exposures are described together because of
    the similar biological responses observed.  Most of the numerous
    animals studied are summarized elsewhere (US EPA, 1986) and
    representative examples are shown (Table 3, Table 4).

         In inhalation studies the lung is the primary target organ in all
    species, and the characteristic pathological feature is the delayed
    clinical manifestation of pulmonary oedema, which is dose dependent. 
    Other mucous membranes such as the eye can also be affected. 
    Underhill (1919, 1920) exposed dogs for 30 min to phosgene
    concentrations between 176 and 480 mg/m3.  At the lower
    concentrations he reported that phosgene exposures resulted in
    pathological lesions in the terminal bronchioles and alveoli, typical
    for a pulmonary irritant.  However, at the higher exposure levels
    phosgene resulted in oedema leading to interference with gas exchange,
    cyanosis and eventually death.

        Table 3.  Effects of phosgene after single exposure by inhalation


    Speciesa                        Exposure                                Effects                     Reference

                       C x T           C            T
                    (mg/m3-min)     (mg/m3)       (min)

    Rat             100             0.4           250           Widening of pulmonary intestices        Diller et al. (1985)

    Rat             144             144           0.4-380       Reduced pulmonary bacterial             Yang et al. (1995)

    Cat             150             10            15            Slight illness                          Flury (1921)

    Mice, rats,     192             0.8           240           Increase in levels of lavage fluid      Hatch et al.
    hamsters                                                    protein                                 (1986)

    Rat             200             0.24          500           Increase in protein levels in           Diller et al. (1985)
                                    20            10            pulmonary lavage fluid

    Rat             200             20            10            Initiation of pulmonary oedema          Diller et al. (1985)

    Rats (male)     240             1             240           Increase in levels of lavage fluid      Currie et al.
                                                                protein. Increase in the percentage     (1987a)
                                                                of polymorpho-nuclear leukocytes

    Table 3 (contd).


    Speciesa                        Exposure                                Effects                     Reference

                       C x T           C            T
                    (mg/m3-min)     (mg/m3)       (min)

    Cat             440             44            10            L(CT)minimum                            Flury & Zernick

    Cat             450             10            45            L(CT)mimimum                            Flury & Zernick

    Guinea-pigs,    480             2.0           240           Increase in levels of lavage fluid      Hatch et al.
    rabbits                                                     protein                                 (1986)

    Rat             480             2             240           Increase of wet and dry lung weight     Currie et al.

    Rat             480             2             240           Decrease in pulmonary natural killer    Burleson & Keys
                                                                activity (NK)                           (1989)

    Cat             660             44            15            L(CT)100                                Flury (1921)

    Cat             720             12            60            L(CT)100                                Flury (1921)

    Mouse           900             60            15            L(CT)50                                 Cameron & Foss

    Table 3 (contd).


    Speciesa                        Exposure                                Effects                     Reference

                       C x T           C            T
                    (mg/m3-min)     (mg/m3)       (min)

    Monkey          1000            1000          1             L(CT)50                                 Diller & Zante

    Rat             1200            16            75            L(CT)50                                 Rinehart & Hatch

    Monkey          1320            440           3             L(CT)100                                Winternitz et al.

    Dog             1800            180           10            L(CT)50                                 Diller & Zante

    Guinea-Pig      1920            128           15            L(CT)50                                 Underhill (1920)

    Rat             4000            400           10            Ultrastructural changes in the          Pawlowski &
                                                                bronchoalveolar region of lungs;        Frosolono (1977)
                                                                cellular disruption and necrosis

    Guinea-pig      6160            308           20            L(CT)100                                Ong (1972)

    Dog             8808            2936          3             L(CT)99                                 Coman et al.

    Table 3 (contd).


    Speciesa                        Exposure                                Effects                     Reference

                       C x T           C            T
                    (mg/m3-min)     (mg/m3)       (min)

    Sheep           13 300          1330          10            L(CT)50                                 Keeler et al.

    Rabbit          21 140          604           35            L(CT)99                                 Coman et al.

    a    In most cases the sex of the animals was not specified

         Necropsy of dogs that died shortly after single exposure to
    phosgene showed frothy material around the mouth, engorgement of the
    visceral vasculature (shock-like syndrome), and heavy wet congested
    lungs (Winternitz et al., 1920).  Microscopically, the lungs were
    characterized by congestion and severe oedema.  Proteinaceous fluid,
    strands of fibrin, and leukocytes filled the alveoli.  In dogs that
    died 4 or more days after dosing, pulmonary infection (inflammation)
    was the primary cause of death.  Oedema, congestion and emphysema of
    lesser severity were still present but there was also evidence of an
    attempt to repair tissue.  In dogs that died or were killed later (11
    to 129 days), necropsy revealed varying degrees of lung collapse and
    emphysema suggesting obliterative bronchiolitis.  The epithelium of
    the larger airways (trachea and bronchi) did not show evidence of
    damage.  The authors  stated that the pathology of phosgene exposure
    was similar in the goat, dog, monkey, rabbit, guinea-pig, rat and
    mouse (Winternitz et al., 1920).

         Concurrent studies in a different laboratory confirmed the above
    results (Meek & Eyster, 1920).  These authors documented a well-marked
    succession of events after exposure of dogs for 30 min to phosgene
    levels of 320-400 mg/m3.  In the initial stage of exposure there is
    direct damage to the epithelial cells lining the pulmonary airways,
    with the distal ones showing the most damage. The cells are killed
    (necrosis) and sloughed.  This is immediately followed  by effusion of
    fluid into the affected  airways  (oedema).  There is some damage to
    erythrocytes in pulmonary capillaries, which aggregate, thus causing
    occlusion.  Gaseous exchange is interfered with, and death is the
    result of hypoxia/anoxia.  Other authors (Cameron & Courtice, 1946)
    have also shown that pulmonary oedema is the primary cause of death in
    several species after acute phosgene poisoning (440 mg/m3).  The area
    of lung affected appears to depend on the level of exposure.  Gross et
    al. (1965) postulated that at lower levels the alveolar bronchioles
    and alveoli are the primary target tissues.  At higher levels more
    proximal respiratory tissues are at risk of developing lesions.  The
    relationship between the primary target site in the lung and dose of
    phosgene was confirmed in rats (Diller et al., 1985).  Changes within
    the blood-air barrier (pulmonary oedema) were noted at phosgene levels
    of 20 mg/m3 (5 ppm) or more and at durations of exposure of 10 min or
    longer (50 ppm-min).  The lowest dose of phosgene producing an
    increase in protein levels in pulmonary lavage fluid was also
    200 mg/m3 min (50 ppm-min), and that for the production of widening
    within the pulmonary interstices was 100 mg/m3 min (25 ppm-min). 
    However, there was no apparent threshold of phosgene concentration for
    these two parameters.  Concentrations of phosgene studied were 0.4 to
    20 mg/m3 (0.1 to 5 ppm).  Changes noted at low concentrations (0.4 to
    10 mg/m3; 0.1 to 2.5 ppm) were primarily located at the transition
    from terminal bronchioles to the alveolar ducts, while at higher
    concentrations (20 mg/m3, 5 ppm) damage to the alveolar pneumocytes
    (type 1) was reported (Diller et al., 1985).

         The earliest ultrastructural change observed in the
    bronchoalveolar region of lungs of rats exposed to 400 mg/m3
    (100 ppm) for 10 min was characterized by vesiculation of bronchiolar
    epithelium immediately after exposure (Pawlowski & Frosolono, 1977). 
    This was followed, 30 min after the exposure, by extracellular
    accumulation of serous fluid in interstitial spaces and alveoli.  The
    final events were cellular disruption and necrosis.

         The extent of the long-term effects after acute exposure appears
    to depend on the severity of the initial pathology (Coman et al.,
    1947; Diller, 1985b).

         The relative sensitivity of female mice and male hamsters,
    rabbits, guinea-pigs and rats to 4-h phosgene exposures at
    concentrations of 0.4, 0.8, 2 and 4 mg/m3 (0.1, 0.2, 0.5 and 1 ppm)
    was studied by Hatch et al. (1986).  As an indicator of phosgene-
    induced pulmonary oedema, levels of lavage fluid  protein (LFP) were
    measured 18-20 h after exposure.  Groups of seven or eight animals
    were examined at each exposure level.  Phosgene-induced changes in LFP
    levels in mice, hamsters and rats occurred at phosgene levels of
    0.8 mg/m3 (about 190 mg/m3 min) and above, whereas the minimal
    effective dose in guinea-pigs and rabbits was 2 mg/m3 (about
    480 mg/m3-min).

         Rats were exposed 4 h/day, 5 days/week for 17 exposures at a
    level of 0.5 or 1 mg/m3 (0.125 or 0.25 ppm) and killed on days 3, 7,
    10, 13 or 17 or on days 2 or 20 after exposure.  After day 7 the lung
    wet weights were increased by 20-25% (p < 0.05 in the high-level
    group).  In the low-level group the lung wet weights increased with
    exposure time but were significantly increased only at day 17.  These
    changes were paralleled by an increased activity of the pulmonary
    glucose-6-phosphate dehydrogenase.  The non-protein sulfhydryl content
    in the lungs was elevated throughout exposure in both groups.  All
    deviations were reversible after exposure ceased.  At day 17 in the
    high-level group a moderate multifocal accumulation of mononuclear
    cells in the walls of the terminal bronchioli and their adjacent
    alveoli was observed.  A minimal amount of type II alveolar cell
    hyperplasia was also found in this region.  Macrophages with
    vacuolated cytoplasm were seen in the lumens of some alveolar ducts
    and alveoli.  The lesions in the lungs of the low-dose animals were
    described as being minimal (Franch & Hatch, 1986).  A no-observed-
    effect-level could not be demonstrated in this study.

         The effects of low-level acute exposure to phosgene in male rats
    was also studied by Currie et al. (1987a), who exposed groups of adult
    animals (250-300 g) for 4 h to 0.5 to 4 mg/m3 (0.125 to 1 ppm). 
    Dose-related changes in body weight, wet and dry lung weights, LFP,
    total cell counts, and cell differentials were measured at the
    conclusion of the exposure and 3 days after exposure, at least 10
    animals being sacrificed each time.  A dose-response relationship for
    the measured parameters was noted.  Both wet and dry lung weights
    increased after exposure to 120 and 240 ppm-min, and an increase in

    LFP was noted at > 60 ppm-min.  The most sensitive cellular
    indicator of phosgene pulmonary damage was the increase in the
    percentage of polymorphonuclear leukocytes (PMN); there was a
    significant increase at 60 ppm-min.  Both PMN and LFP can be used as
    sensitive indicators of pulmonary damage by phosgene after acute
    exposure.  All parameters returned to control levels 3 days after
    exposure, indicating that the pulmonary damage within the dose-range
    studied was reversible.

         In Table 3, effects of inhalation exposure to phosgene have been
    summarized according to the degree of exposure, expressed as
    mg/m3-min.  Pulmonary bacterial clearance appears to be the most
    sensitive end-point for acute phosgene toxicity in rats (about
    100 mg/m3-min).  The lowest dose of phosgene that produced an
    increase in protein levels in pulmonary lavage fluid and changes in
    the blood-air barrier (pulmonary oedema) was 100 to 200 mg/m3-min. 
    This effect can be considered as the early critical effect of acute
    exposure to phosgene.  Data presented in Table 4 suggest that
    evaluation of exposure according to Haber's law can be applied as the
    basis for constructing dose-effect relationships only in the case of
    acute relatively high exposures.

         Studies of pulmonary physiology in animals mirror the
    pathological observations (Gibbon et al., 1948; Boyd & Perry, 1960; 
    Long & Hatch, 1961; Rhinehart & Hatch, 1964).  Progressive loss of
    capacity for gas exchange is the initial and critical event.  The
    respiration rate is increased but there is increased resistance and
    poor ventilation.

    7.2  Skin and eye irritation; sensitization

         Very little information on this subject is available.  Skin
    irritation is possible if concentrations are high enough, but the
    hazard is minimal compared to the severe lung damage that can be
    produced by much longer levels (Diller, 1985a; Borak, 1991).  No
    studies on sensitization have been reported.  Eye irritation and
    corneal oedema have been reported in dogs exposed to lethal
    concentrations of phosgene (Winternitz et al., 1920).

        Table 4.  Toxicity of phosgene after repeated exposure by inhalation


    Speciesa      Exposure                               Effects                                    Reference

    Rat           0.4 mg/m3; 6 h/day, 5 days/week,       Pulmonary bacterial clearance inhibited    Selegrade et al.
                  4-12 weeks                                                                        (1989)

    Rat           0.5-1 mg/m3 4 h/day 5 days/week, 17    Lung wet weight increase (20-25%); GPDb    Franch & Hatch (1986)
                  exposures                              activity increase; alveolar cell
                                                         hyperplasic; macrophages with vacuolated

    Guinea-pig    0.8 mg/m3 for 300 min daily, 5 days    Pulmonary oedema in 70% of animals         Cameron et al. (1942)

    Cat           0.8 mg/m3 for 300 min daily, 5 days    Pulmonary oedema in 70% of animals         Cameron et al. (1942)

    Mouse         4 mg/m3 for 300 min daily, 5 days      L(CT)90                                    Cameron & Foss

    Rat           4 mg/m3 for 300 min daily, 5 days      Pulmonary oedema in 80% of animals         Cameron & Foss

    Rabbit        4 mg/m3 for 300 min daily, 5 days      L(CT)20                                    Cameron & Foss

    Dog           96-160 mg/m3 for 30 min                Up to 20-fold increase in airway           Rossing (1964)
                  1-3 times per week,                    resistance
                  12 weeks

    a    Sex not specified                             b    GPD= glucose-6-phosphate dehydrogene

    7.3  Long-term exposure

         Long-term exposure studies of phosgene have not been conducted. 
    However, there have been a limited number of studies on the effects of
    phosgene following repeated exposures over periods of time  (dosing 1
    to 3 times per week for up to 12 weeks) (Clay & Rossing, 1964;
    Rossing, 1964).  Adult mongrel dogs (sex not identified) were exposed
    to phosgene at concentrations between 96 and 160 mg/m3 for 30 min, 1
    to 3 times per week.  Rossing (1964) exposed 14 animals 3 times weekly
    until increased airway resistance was noted, and then the frequency of
    exposure was decreased to 1 or 2 times weekly for 12 weeks.  Seven
    animals died during the first 3 weeks of exposure and only three
    animals survived the full 12 weeks; two of which were maintained for
    12 weeks with further exposure.  The lungs of all animals were
    examined within 48 h after-exposure.  After the initial inflammatory
    reaction, the ensuing lesion consisted of chronic bronchiolitis and
    emphysema that persisted for the duration of the exposure period. 
    After cessation of exposure, elastance dropped rapidly to normal, but
    airway resistance was still elevated 11 weeks after exposure.In a
    similar experiment, Clay & Rossing (1964) studied the development of
    pulmonary emphysema in adult mongrel dogs after exposure to phosgene
    at concentrations between 96 and 160 mg/m3 for 30 min at a rate of 1
    to 3 exposures per week.  Group size varied between four and seven
    animals.  The number of exposures varied between 1 and 25, and the
    dogs were killed either immediately or up to 2 weeks after exposure. 
    However, in view of the low number of animals used, the experimental
    design and the lack of reported dose-response information, these data
    are difficult to use in assessing quantitatively the long-term risk to
    humans from phosgene exposure.

    7.4  Reproductive and developmental toxicity

         No data were found on reproductive or developmental effects of
    phosgene in experimental animals.

    7.5  Mutagenicity and related end-points

         No studies on the mutagenicity of phosgene have been reported.

    7.6  Carcinogenicity

         No adequate studies are available for the assessment of the
    carcinogenicity of phosgene.  In a review of the potential
    carcinogenicity of 266 substances found in various workplaces, data
    from one study involved 20 guinea-pigs and 20 rats that were exposed
    by inhalation to phosgene for 24 and 18 months, respectively.  No
    pulmonary neoplasms were observed (Schepers, 1971), but information on
    dosing regimen, sex or strain of animals was lacking.

    7.7  Immunotoxicity

         In one study, the immunotoxic effects in Fischer-344 male rats of
    a single 4-h exposure to 0, 0.4, 2.0 or 4 mg phosgene/m3 were
    reported (Burleson & Keys, 1989).  As a measure of pulmonary
    immunocompetence the authors measured the natural killer (NK) 
    activity of pulmonary cells on the day after phosgene exposures.  At
    exposures of 2 and 4 mg/m3 there was a significant decrease in
    pulmonary NK activity, which was considered by the authors to be an
    indication of decreased immunocompetence.  At 4 mg/m3 this decrease
    was still significant 4 days after exposure.  A significant decrease
    was also noted at 2 mg/m3 one day after exposure, but no effect was
    seen at 0.4 mg/m3.  Phosgene did not affect NK activity in blood
    lymphocytes, but NK activity in the splenic cells was decreased 1 day
    after exposure to 4 mg/m3.  Effects on NK activity in lymphocytes and
    splenic cells at other phosgene doses and days post-treatment were not
    reported. Decreased immunocompetence in rats resulting from a 4-h
    exposure to phosgene was reported by Ehrlich & Burleson (1991).  After
    male Fischer-344 rats (8-10 weeks old) were exposed to phosgene at
    4 mg/m3 for 4 h, the animals were infected with a rat-adapted
    influenza virus and the virus titre measured at 2 h and 1, 2, 3, 4, 5
    and 7 days post-infection.  The virus titre was measured in three
    replicate experiments using three rats per group.  Following an
    initial decrease in the viral titre at 2 h after infection, the virus
    titre increased by a factor of 10 on the day after infection and
    remained significantly higher than in controls up to 4 days after
    infection.  The virus was cleared below detectable levels after 5 days

         Bacterial clearance was assessed in male Fisher-344 rats exposed
    to 0, 0.4 or 0.8 mg/m3 (0.1 or 0.2 ppm) phosgene for 6 h (Yang et
    al., 1995).  Immediately after exposure to phosgene the animals were
    infected with  Streptococcus zooepidemicus, and the number of
    bacteria in the pulmonary lavage fluid was assessed up to 72 h later. 
    Pulmonary bacterial clearance was significantly reduced  (p <0.05)
    following exposure to 0.4 mg/m3 (0.1 ppm) phosgene (LOEL = 0.1 ppm). 
    Based on an analysis of other immunological parameters (e.g.,
    pulmonary NK activity and pulmonary macrophage function), the authors
    indicated that bacterial clearance appeared to be the most sensitive
    end-point for acute phosgene toxicity in rats.

         CD-1 mice were exposed to phosgene concentrations of 0.04 to
    0.4 mg/m3 (0.01 to 0.1 ppm) for 4 h and infected with  S. zoo-
     epidimicus or inoculated with B16/BL6-melanoma tumour cells.  At and
    above 0.1 mg/m3 (0.025 ppm), mortality due to the infection with
     S. zooepidimicus and the number of B16/BL6 melanoma tumours in the
    lungs were both elevated.  An 8-h exposure to 0.04 mg/m3 increased
    the mortality due to  S. zooepidimicus but not the number of B16/BL6
    melanoma tumours (Selgrade et al., 1989).

         F-344 rats were exposed to phosgene concentrations of 0.2 to
    4 mg/m3 (0.05 to 1 ppm) and their lungs lavaged 0, 4, 20 or 44 h
    later.  At and above 0.4 mg/m3 the concentrations of prostaglandin E2
    as well as of leukotrienes B4, C4, D4 and E4 were decreased by 29 to
    69%.  The eicosanoid concentrations after exposure to 0.4 and 1 mg/m3
    returned to normal 44 h later.  After exposure to 0.4 or 4 mg/m3, but
    not to 0.2 mg/m3, the number of alveolar macrophages was decreased,
    whereas the number of neutrophils was increased at 44 h after exposure
    to 0.4 mg/m3, but not to 4 mg/m3 (Madden et al., 1991).

         Pulmonary effects have also been observed in male Fisher-344 rats
    exposed for a longer term to phosgene (Selgrade et al., 1995). Groups
    of animals were exposed to 0, 0.4 or 0.8 mg/m3 (0, 0.1 or 0.2 ppm)
    for 6 h/day, 5 days/week for 4 or 12 weeks, or to 2 mg/m3 (0.5 ppm)
    for 6 h/day, 2 days/week for 4 or 12 weeks. When assessed immediately
    after 4 or 12 weeks of exposure, pulmonary bacterial clearance was
    inhibited following exposure to 0.4 mg/m3 (0.1 ppm) phosgene (LOEL =
    0.1 ppm).  This effect appeared reversible, since pulmonary bacterial
    clearance was unchanged when assessed 4 weeks after a 12-week exposure
    period. These subchronic effects on pulmonary bacterial clearance were
    similar to those observed previously, following acute exposure to
    phosgene (Yang et al., 1995). In animals administered the same dose of
    phosgene, pulmonary bacterial clearance was more severely affected in
    animals exposed to the higher concentration of this substance (i.e.,
    2 mg/m3 (0.5 ppm), 6 h/day, 2 days/week, compared to 0.8 mg/m3
    (0.2 ppm) 6 h/day,  5 days/week). A significant reduction in pulmonary
    NK activity was observed following exposure to 2 mg/m3 (0.5 ppm).

    7.8  Mechanism of toxicity 

         Although the exact mechanism of phosgene toxicity remains
    unknown, it seems likely that the original hypothesis of Winternitz et
    al. (1920), suggesting that hydrochloric acid was the causal agent for
    the pulmonary effects noted, is incorrect. Current data indicate that
    the effects from phosgene exposure result from the acylation of tissue
    components, although the production of HCl may play a minor role,
    particularly at high levels of exposure (Diller, 1985a).  Nash &
    Pattle (1971) studied the chemical reactivity of phosgene when bubbled
    through aqueous solutions at various pH values, some containing
    amines, phenoxide ions or sulfite.  From these data it was concluded
    that molecular phosgene could penetrate all layers of the blood-air
    barrier, causing the observed pathology by reacting with chemical
    groups in the cells.  It was shown mathematically that insufficient
    HCl to produce the observed effects could be generated under
    physiological conditions and phosgene exposures as high as 100 mg/m3
    (25 ppm).

         Early evidence that acylation of amino, hydroxyl and sulfhydryl
    groups was the major mechanism was reported by Potts et al. (1949). 
    Rats and mice exposed to 0.5 mg ketene/litre for 1.5 min showed
    clinical signs and pathological lesions identical to those cause by 

    phosgene.  Ketene is a known acrylating agent that does not break down
    to a strong acid.

         The effects on pulmonary ultrastructure and enzyme activities in
    adult rats from exposure to phosgene for 10 min at 400 mg/m3
    (100 ppm) were studied by Pawlowski & Frosolono (1977) and Frosolono &
    Pawlowski (1977).  Homogenates of the combined lungs from six to eight
    rats were assayed for several enzyme activities in duplicate
    immediately after exposure and at 30 and 60 min post-exposure.  A
    decrease in the enzymatic activity of 10-80% was noted at all time
    periods for  p-nitrophenyl phosphatase, cytochrome C oxidase, ATPase
    and lactic dehydrogenase (Frosolono & Pawlowski 1977).  Using the same
    protocol Pawlowski & Frosolono (1977) examined the cascade of
    ultrastructural changes in the terminal bronchiolar epithelium after
    exposure.  An immediate vesiculation of cells was followed by septal
    extracellular oedema and, finally intracellular oedema, cell
    disruption and necrosis.  The authors suggested that the biochemical
    changes preceded major ultrastructural changes in the alveolar region.

         Currie et al. (1985) studied the effects on energy metabolism of
    exposure to 4 mg/m3 (1 ppm) for 4 h (CœT = 960 mg/m3-min) in rats. 
    An attempt was made to correlate the onset of pulmonary oedema with
    alterations in energy metabolism.  At the exposures studied, there was
    a significant reduction in the respiratory control index, which
    coincided with the highest level of percentage water in the lung.  In
    addition, a decrease in ATP concentration was noted.  It was concluded
    that reductions in ATP levels and Na-K-ATPase activity play a major
    role in damage to the lung after phosgene exposure and prior to the
    onset of oedema.

         Studies by Currie et al. (1987b) have confirmed these findings at
    lower doses.  Rats were exposed for 4 h to 48, 120, 240, 480 or
    960 mg/m3-min (12, 30, 60, 120 or 240 ppm-min).  Decreased ATP
    levels were noted prior to the onset of oedema at doses as low as
    48 mg/m3-min (12 ppm-min) after exposure for 4 h.  Further studies by
    Frosolono & Currie (1985), using the same exposure regimen as Currie
    et al. (1985) (i.e., 960 mg/m3-min), indicated that phosgene may
    alter the level of pulmonary surfactant thus altering the homeostatic
    mechanism for fluid balance in the lung.

         Jaskot et al. (1991) studied the effect of inhaled phosgene on
    lung anti-oxidant systems in Fischer-344 male rats.  Levels of 0, 0.4,
    1, 2 and 4 mg/m3 were administered for 4 h and a satellite group
    received 1 mg/m3 for 8 h.  Changes in glutathione (GSH) and
    anti-oxidant associated enzymes (GSH peroxidase, GSH reductase,
    glucose-6-phosphate dehydrogenase and superoxide dismutase) were
    measured 0, 1, 2, 3 and 7 days post-exposure in groups of 12 animals
    per dose.  At all dose levels significant increases were noted for one
    or more components of the anti-oxidant system studied.  Peaking at 2
    to 3 days post-exposure, the changes noted were similar to those
    observed after exposure to the pulmonary irritants ozone and nitrogen

         The role of arachidonic acid metabolites in the pathogenesis of
    phosgene-induced lung injury (oedema and vascular permeability) was
    studied in rabbits (Guo et al., 1990).  Animals (four to six per
    group) were exposed to 6000 mg/m3-min (1500 ppm-min) of phosgene and
    killed 30 min after-exposure.  The effects were compared to those of a
    control group of eight animals.  Lungs were perfused for 90 min and
    cyclooxygenase- and lipoxygenase-generated metabolites of arachidonic
    acid were measured.  Phosgene exposure did not enhance the
    cyclooxygenase metabolism of arachidonic acid but did result in a
    10-fold increase in lipoxygenase metabolites (leukotriene).  A marked
    decrease in the gain in lung weight after phosgene exposure was
    reported when the perfused lung was pretreated with leukotriene
    receptor blockers.  The results suggest that lipoxygenase metabolites
    of arachidonic acid contribute to the phosgene-induced pulmonary
    damage, but the mechanism by which phosgene stimulates the metabolism
    of arachidonic acid is still unknown.

         Evidence that the non-cardiogenic pulmonary oedema and mortality
    resulting from phosgene inhalation was the result of an influx of
    neutrophils into the lung was provided by Ghio et al. (1991).  After
    exposure of rats to 2 mg phosgene/m3 (0.5 ppm) for 60 min, 
    significant increases in the percentage of neutrophils and
    concentrations of protein and thiobarbitunic acid reactive products in
    bronchoalveolar lavage fluid were noted.  These increases were
    significantly less after treatment prior to exposure with:
    cyclophosphamide to deplete the leukocytes; inhibition of the
    production of the chemotaxis leukotriene B4, which directs the influx
    of neutrophils into the lung; or treatment with colchicine, which
    decreases leukocyte migration.  These treatments in mice exposed to
    8 mg phosgene/m3 (2.0 ppm) for 90 min resulted in decreased
    mortality.  Colchicine reduced neutrophil influx, lung injury and
    mortality in mice even when administered 30 min after exposure.

         Preliminary evidence that F-actin in lung cells may be a target
    of phosgene was reported by Werrlein et al. (1994).  In cultured ovine
    pulmonary artery endothelial cells and rat airway epithelial cells
    exposed to phosgene there was a dose-dependent decrease in the F-actin
    content and organization.  Exposure of sheep to 0.15 L(CT)50 
    (96 mg/m3 for 20 min) led to a decrease in the F-actin concentration
    of endothelial cells.  Exposure of sheep to 0.83 L(CT)50 (548 mg/m3
    for 20 min) disrupted basal lamina and produced paracellular leakage
    paths in the cultured cells.  If they occur  in vivo, these effects
    of phosgene on F-actin may contribute to the decreased barrier
    function and increased permeability of vascular tissues.


    8.1  General population and occupational exposure

         The information on the effects of high-level, short-term phosgene
    exposure in humans is derived from wartime experiences as well as from
    industrial accidents.  General population and occupational exposures
    to high levels of phosgene will be discussed together, since the
    immediate effects and outcome of such exposures are identical in both
    populations.  As with animal experiments (see section 7.1), the acute
    effects in humans are reported as a result of a combination of
    exposure level and time of exposure (mg/m3-min).  The exposure levels
    at which perception of the odour is possible compared to those that
    cause varying degrees of toxicity and death in humans are presented in
    Table 5.  In "trained subject" the lowest level at which the odour
    (like mouldy hay) is perceived is 1.6-2 mg/m3 (NIOSH, 1976), but at
    such levels workers may not detect the odour due to olfactory fatigue
    (Proctor & Hughes, 1991). Under normal conditions the odour is
    recognized only at levels greater than 6 mg/m3 (1.5 ppm).  Signs of
    irritation of mucous membranes are observed at > 12 mg/m3 (3 ppm),
    early lung damage at > 120 mg/m3-min (>30 ppm-min), and death
    (L(CT)50) at approximately 2000 mg/m3-min (approximately
    500 ppm-min) (Diller & Zante, 1982; Diller, 1985a).

         As shown in Table 5, concentrations of phosgene vapour 
    > 2 mg/m3 (3 ppm) will result in irritation of the eyes and nose. 
    Such concentrations in contact with moist skin will also lead to
    irritation and erythema (Borak, 1991), but there is no evidence that
    they would result in serious skin injury.  At 12 mg/m3 (3 ppm) the
    only effect reported on the human eye was inflammation (conjunctival
    hyperaemia) (Grant & Schumann, 1993).  Liquid phosgene splashed in the
    eye, however, caused complete corneal opacification, conjunctival
    adhesions and perforation in one victim (Grant & Schumann, 1993). 
    Although skin contact can result in severe burns, no reports of such
    cases are available.

        Table 5.  Correlation of phosgene dose and effects in humansa


    Effects                                                      Dose levelb

    Perception of odour                          1.6 mg/m3                     0.4 ppm

    Recognition of odour                         6 mg/m3                       1.5 ppm

    Irritation of eyes, nose, and throat         12 mg/m3                      3 ppm

    Beginning lung damage                        >120 mg/m3-minc               > 30 ppm-min

    Pulmonary oedema                             >600 mg/m3-minc               > 150 ppm-min

    L(CT)1                                       approx 1200 mg/m3-minc        approx 300 ppm-min

    L(CT)50                                      approx 2000 mg/m3-minc        approx 500 ppm-min

    L(CT)100                                     approx 5200 mg/m3-minc        approx 1300 ppm-min

    a    From: Diller (1985a)
    b    A conversion factor of 4 was used to calculate mg/m3 from the ppm value used by author.
    c    These values should be considered in relation to Haber's Law (see section 7.1).

         With respect to pulmonary damage, three distinct
    clinicopathological phases (initial reflex syndrome, clinical latent
    phase and clinical oedema phase) have been reported in humans acutely
    exposed to phosgene levels of 120 mg/m3-min to 1200 mg/m3-min
    (30-300 ppm-min) (Diller & Zante, 1982; Diller, 1985a).  During and
    immediately after exposure the individual experiences pain in the eyes
    and throat (an irritating or burning sensation) and tightness in the
    chest, which may be accompanied by shortness of breath and coughing. 
    This is followed by a latent phase, which is often asymptomatic. 
    Depending on total dose this period may last from 1 to 24 h.  The
    oedema phase is manifested when enough lung is affected to become
    clinically apparent, i.e. shortness of breath, productive cough,
    and/or expectoration of large amounts of frothy and possibly bloody
    sputum.  If enough of the lung is involved the person may become
    cyanotic and enter into shock.  If the exposure is in the lethal
    range, the early phases may be truncated, and the latent phase may be
    very short or non-existent.  It has been reported that radiographs
    taken immediately after exposure can be used to predict the severity
    of ensuing pulmonary oedema (Ardran, 1964).  The author stated that an
    increase in lung volume following expiration is highly predictive for
    the future development of oedema.

    8.2  Case reports - individual accidents

         The most definitive data on both the short- and long-term effects
    of acute phosgene exposure in humans is found in case reports of
    industrial accidents.  Such accidents may also pose a potential hazard
    to adjacent communities.  In Hamburg, Germany, an industrial storage
    tank released 11 tonnes of phosgene into the atmosphere in 1928
    (Hegler, 1928).  The atmospheric conditions were conducive to the slow
    spread of the gas outside the plant.  No exposure levels were
    reported.  During a period of 5 days, over 300 people became ill, of
    whom 10 died.  The initial symptoms were severe irritation of the eyes
    and throat, coughing, tightness of the chest, nausea and vomiting. 
    Autopsies of some of the victims revealed typical pulmonary lesions
    and nonspecific lesions in other organs that were attributable to 
    local hypoxia (Wohwill, 1928).  The author also felt that some
    degenerative lesions in the brain and spinal cord were due directly to
    phosgene, but this has not been confirmed in subsequent studies. The
    only reference to the long-term effects in this population was that
    there was no apparent damage to health 2 months after the accident.

         In November 1966, phosgene was accidentally released from  a
    factory in Japan; 382 people were poisoned and 12 were hospitalized
    (Sakakibara et al., 1967).  Signs and symptoms observed in the 12
    patients on admission were headache (9), nausea (9), cough (8),
    dyspnoea (7), fatigue (7), pharyngeal pain (5), chest tightness (5),
    chest pain (5), and fever (3).  Lacrimation and redness of the eyes
    were only observed in one patient.  Seven patients showed evidence of
    pulmonary oedema as revealed by chest X-rays 48 h after the exposure. 
    These findings indicate that pulmonary oedema may develop even 48 h
    after exposure without initial symptoms of eye or nose irritation.

         Other industrial accidents that have been reported usually 
    involved only a few people and no details of exposure levels were
    given.  The clinicopathological syndrome was similar in all of these
    reports (Everett & Overholt, 1968; Stavrakis, 1971; Regan, 1985).  The
    predominant finding during and immediately following exposure  was
    irritation of mucous membranes.  Victims described intense pain in the
    eyes with profuse lacrimation.  At the same time there was a burning
    sensation in the throat and tightness of the chest.  Coughing ensued,
    often of a very severe nature.  Victims sometimes did not show any
    other symptoms.  However, more common was the subsequent development
    of pulmonary oedema, which, if sufficiently severe, resulted in death
    due to interference with gas exchange.  In none of the case reports of
    direct phosgene exposure was any data on the actual levels of phosgene

         Several case studies of phosgene poisoning have been reported
    where the patient was not working directly with phosgene.  Such
    reports include those of Seidelin (1961) on carbon tetrachloride used
    to extinguish a fire, those of Glass et al. (1971) and Sjogren et al.
    (1991) on the decomposition of trichlorethylene during welding and
    those of Gerritsen & Buschmann (1960) and Snyder et al. (1992)
    reporting possible phosgene poisoning due to the thermal degradation
    of methylene chloride used to remove paint.  All of these chemicals
    are known to be degraded thermally to phosgene.  Furthermore, the
    progression of effects (clinical latent phase) after exposure, the
    development of dyspnoea, chest discomfort and pulmonary oedema in all
    subjects was typical of phosgene poisoning reported in case studies of
    direct phosgene exposure.

         There are relatively few reports on the long-term sequelae of an
    acute exposure.  In a review of this subject, Diller (1985a,b) found
    that the vast majority of survivors of acute exposure have a good
    prognosis.  However, some of those exposed to high levels of phosgene
    showed chronic symptoms such as shortness of breath and reduced
    physical capacity, which persisted, in some cases, for the rest of
    their lives. However, the severity and duration of such effects was
    also related to subsequent smoking habits.  Pre-existing pulmonary
    disease such as emphysema was exacerbated by phosgene exposure. While
    most published reports indicate that the respiratory tract is the
    primary target organ for phosgene poisoning, a few reports have
    indicated effects on other organs, especially the heart and brain
    (Diller, 1985a,b).  Neurasthenia is the most common of these
    conditions associated with acute phosgene exposure.  Others are an
    epilepsy-like syndrome, loss of speech, peripheral Raynaud-like
    syndrome and a type of paralysis characterized by disfunction of the
    peroneal nerve.  A causal relationship between phosgene exposure and
    such effects has yet to be confirmed.  It has been suggested by Diller
    (1985b) that such changes are more likely a result of anoxia from the
    pulmonary oedema rather than the direct action of phosgene.

    8.3  Epidemiological studies

         Phosgene, isopropyl alcohol, aniline and caustic soda are raw
    materials used in a Russian plant for the manufacture of the
    herbicide,  isopropylphenyl carbamate.  Levina & Kurando (1967) found
    phosgene at levels of about 0.5 mg/m3 in 30% of all air samples.  In
    89 workers studied no mention was made of pulmonary problems. 
    However, methaemoglobinaemia and anaemia were detected and attributed
    to exposures to aniline and the herbicide itself.

         At a phosgene factory in the USA the medical records of all
    workers exposed (326) and 6228 non-exposed workers were compared
    (NIOSH, 1976).  Limited air sampling conducted during a 2-month period
    using the NBP method of analysis with 20-min sampling time (passive
    dosimetry Table 2), indicated an average exposure to phosgene of
    0.01 mg/m3 (ND to 0.08 mg/m3).  Out of 56 fixed-position samplers
    (2-h or 20-min collection) 51 showed phosgene levels of up to
    0.52 mg/m3 and five samples showed levels greater than 0.55 mg/m3
    (off the scale).  Deaths attributable to respiratory disease and
    pulmonary function (defined as "lung problems") were compared.  No
    chronic lung problems associated with working at these phosgene levels
    were reported, nor was there any increased mortality from respiratory
    disease in the exposed workers.

         Polednak (1980) described a study of a cross-section of workers
    exposed to phosgene at a uranium processing plant between 1943 and
    1947.  The study contained one group of 699 white male workers exposed
    routinely to low (but undetermined) levels of phosgene with daily
    episodes (4 or 5 daily) of exposures to levels above 4 mg/m3.  A
    second group of 106 white males involved in accidents resulting in
    acute exposures to phosgene at levels estimated by the authors to be
    greater than 200 mg/m3-min.  This estimate was based on initial
    symptoms reported and clinical data obtained immediately after
    exposure.  All workers reported detecting the odour of phosgene, 82
    reported chest pain and dyspnoea, 25 showed x-ray and clinical
    evidence of pneumonitis and 1 worker died 24 h after the exposure from
    pulmonary oedema (based on clinical symptoms).  The control group
    contained 9352 non-exposed workers at the same facility.  Those
    workers employed for 2 days or more in departments where phosgene
    exposure was possible were considered to be in the exposed group. 
    Mortality data was determined by examination of the Social Security
    Administration records and coding the cause of death using the Eighth
    Revision of the International Classification of Diseases.  As of 1974
    there was no evidence of excess mortality from diseases of the
    respiratory system in the group of 699 male workers (about 30 years
    after exposure).  In fact standardized mortality ratios (SMR) for
    death from all causes were essentially the same in both the exposed
    and control groups.  The Task Group noted that possible simultaneous
    exposure to ionizing radiation was not taken into account.

         In 1974, 30 deaths had occurred in the 106 workers exposed to
    high levels of phosgene (SMR = 113).  No deaths from lung cancer were

    noted but three deaths (1.37 expected) were due to respiratory
    diseases.  One worker in this group died from pulmonary oedema 24 h
    after exposure.

         A follow-up of the workers from the cohort studied by Polednak
    (1980) was made by Polednak & Hollis (1985).  Similar trends to those
    reported earlier were noted 35 years after exposure.  Of the 694
    workers chronically exposed, there were 14 deaths from diseases of the
    respiratory tract (13.1 expected) (SMR = 107; 59-180 95% CI). In 1974,
    the SMR for lung cancer within the 699 chronically exposed workers was
    127 (95%, CI 66-220) and in 1979 it was 122 (72-193, 95% CI).  The
    slightly elevated SMR values were not significantly higher than
    controls.  The SMR for death from all causes was 97 (85-111 95% CI) in
    the exposed workers and 101 (98-104 95% CI) in controls.  In the high-
    exposure group there were 41 deaths from all causes compared to 33.9
    expected (SMR = 121; 86-165 95% CI).  Five deaths were coded to
    diseases of the respiratory tract (SMR = 266; 86-622 95% CI).  In two
    of these cases, bronchitis due to phosgene poisoning had been reported
    in 1945 during clinical examination after exposure.

         There have been no epidemiological or case reports linking the
    development of reproductive or teratogenic effects in humans to acute
    and/or chronic phosgene exposures.


         No information concerning the effects of phosgene in the
    laboratory and field has been reported.


    10.1  Evaluation of human health risks

    10.1.1  Exposure

         Exposure to phosgene is primarily by inhalation.  There are three
    exposure situations:  chronic exposure of the general population to
    extremely low levels; chronic exposure in the workplace to very low
    levels; and accidental acute exposure to high levels.  It is likely
    that the principle source of exposure to phosgene for the majority of
    the general population is through the photo-degradation and thermal
    degradation of chlorinated hydrocarbons, especially solvents and
    polymers (e.g., tri- and tetrachloroethylene and PVC).  On the basis
    of limited data, average levels of phosgene in ambient air can be
    expected to vary between 80 and 130 ng/m3.

         Available data are inadequate to determine quantitatively the
    exposure to phosgene in the workplace.  Those working simultaneously
    with flames (or thermal energy sources) and organochlorine solvents or
    PVC can be exposed to phosgene levels well above present threshold
    limit values (time-weighted average) of 0.4 mg/m3.

         Accidental release of phosgene during its manufacture, use or
    transport can lead to high levels of exposure for workers and for the
    general population in the vicinity of the accident.

    10.1.2  Health effects

         Phosgene is a highly reactive chemical, hydrolysing to
    hydrochloric acid, and is capable of acrylating nucleophilic groups,
    such as amino, hydroxyl and sulfhydryl groups, in tissues.

         In all species studied, including humans, the major target organ
    is the lung.  High concentrations can also cause skin and eye
    irritation. For health effects after acute exposure, Haber's Law,
    which states that the toxicological effect is due to the product of
    exposure (C) and time (T), holds between levels of 4 and 800 mg/m3
    (1 and 200 ppm) using lung disease and death as toxicological end-
    points.  This law does not, however, prevail for chronic exposure. 
    The cascade of events after acute inhalation exposure in humans and
    experimental animals are similar.  It  occurs in a dose-related manner
    and results in pulmonary oedema and death in humans, which is
    dose-dependent at levels exceeding 120 mg/m3-min.  Three distinct
    clinicopathological phases can be recognized: pain in the eyes and
    throat and tightness of the chest, often with shortness of breath,
    wheezing and coughing; a latent phase that is often asymptomatic and
    can last up to 24 h depending upon the concentration and duration of
    exposure; and the final phase of pulmonary oedema.  Evaluation of animal data

         The L(CT)50 and L(CT)100 values for single exposure vary widely
    among animal species (Table 3).  In all species the characteristic
    pathological feature is the delayed clinical manifestation of
    pulmonary oedema, which is dose-dependent.  The extent of the
    long-term chronic effects of acute exposure appears to depend on the
    severity of the initial pathology.Single exposure of rats for 4 h to
    between 0.5 and 4 mg/m3 resulted in a dose-related increase in lavage
    fluid protein (LFP)  concentration and an increased percentage of
    polymorphonuclear leukocytes (PMN) in the alveoli.  Changes in the LFP
    and PMN were the most sensitive parameters occurring at 240 mg/m3-
    min.  These changes were reversible within 3 days after exposure. 
    There have been no long-term exposure studies in animals, and studies
    in dogs exposed 1-3 times/week for 12 weeks are of limited value for
    risk assessment in view of inadequate study design and lack of dose-
    response.  Available data in experimental animals are inadequate for
    the assessment of the potential reproductive, developmental,
    neurotoxic and carcinogenic effects resulting from phosgene exposures.

         Single 4-h exposures to 0.1 mg phosgene/m3 in mice have resulted
    in a demonstrable decrease in pulmonary host resistance to bacteria. 
    Rats exposed to 2 or 4 mg/m3 for 4 h had decreased pulmonary cell
    natural killer (NK) activity, whereas no effect was seen at a level of
    0.4 mg phosgene/m3 for 4 h.  Increased infectivity by influenza virus
    was reported in rats exposed for 4 h to 4 mg/m3.  Virus titres were
    not detectable 4 days after infection.  Mortality was increased after
    exposure to  S. zooepidemicus and inoculation of B16/BL6 pulmonary
    melanoma tumours in mice exposed to phosgene levels at or above
    0.1 mg/m3.  No effect was reported at a level of 0.04 mg/m3. 
    Pulmonary bacterial clearance was reduced in rats exposed to
    0.4 mg/m3 (0.1 ppm) phosgene for 6 h and to 0.4 mg/m3 (0.1 ppm) for
    6 h/day, 5 days/week for 4 to 12 weeks.  This effect was reversible
    following termination of exposure.  Evaluation of human data 

         As a result of industrial accidents and occupational monitoring
    (levels and health status), it has been reported that some humans can
    only recognize the odour of phosgene at levels of about 6 mg/m3,
    making this an unacceptable parameter for early warning.  After
    short-term exposure, throat and eye irritation occurs at a level of
    12 mg/m3 and eye irritation is noted at 16 mg/m3.  The risk of
    morbidity and mortality after acute exposure, is determined by the
    dose (CœT), not solely by concentration.  It has been calculated that
    doses below 100 mg/m3-min result in no effect, whereas pulmonary
    oedema results from doses above 600 mg/m3-min.  It should be
    recognized, however, that death has been recorded at doses above
    400 mg/m3-min, although with proper medical intervention death may be
    prevented.  Exposures for several hours at or below the odour
    threshold (6 mg/m3) may result in severe tissue damage and death.

         A review of the health status of workers who have recovered from
    acute phosgene exposures has shown no adverse effects.  However, full
    recovery may take several months.

         Available data on human health effects associated with chronic
    exposure to phosgene are extremely limited.  Epidemiological studies
    of phosgene production workers and uranium workers reported no adverse
    effects on human health.  However, these investigations are of limited
    value owing to the small numbers of exposed workers, lack of reliable
    quantitative information on exposure to phosgene, concomitant exposure
    to other substances, limited number of end-points examined and limited
    reporting of relevant information.  Available data are therefore
    considered inadequate to assess the risk associated with long-term
    exposure to low levels of phosgene.

    10.1.3  Guidance value

         Available data is considered inadequate to derive a meaningful
    health-based guidance value for exposure of the general population to
    phosgene. Information from epidemiological studies of occupationally
    exposed workers is insufficient to characterize quantitatively
    exposure-response relationships associated with potentially adverse
    health effects resulting from exposure to this substance. Appropriate
    studies in laboratory animals are lacking, and the available
    toxicological investigations do not provide relevant data upon which
    development of a credible guidance value for the long-term exposure of
    humans to phosgene can be based.

         Recent toxicological studies of rats subchronically exposed by
    inhalation to low levels of phosgene indicate that early pulmonary
    effects may occur at present TLV values.  Thus, consideration by
    appropriate authorities should be given to re-evaluating current
    occupational exposure guidelines for this substance.

    10.2  Evaluation of effects on the environment

         The levels of phosgene now found in the environment would not be
    expected to result in significant effects to aquatic or terrestrial
    biota.  However, no data were found to substantiate or refute this

         Damage to plants and aquatic organisms, owing to the rapid
    release of hydrochloric acid, could occur in areas where accidental
    release of phosgene has occurred.


    11.1  Conclusions

    a)   Phosgene is an extremely reactive chemical with the potential  to
         cause adverse effects in humans, the primary target organ being
         the respiratory system.

    b)   Acute severe phosgene exposure primarily causes respiratory
         disease (pulmonary oedema) and may result in death.  Survivors
         may recover completely provided they receive proper medical

    c)   Present levels of exposure to phosgene in the general  population
         are extremely low and do not pose a health risk  in the short
         term.  However, humans working with chlorinated solvents such as
         trichloroethane, tetrachloroethylene and methylene chloride or
         who are exposed to chlorinated hydrocarbon polymers (e.g., PVC)
         in contact with flames or other thermal energy sources can be
         exposed to levels of phosgene known to cause adverse effects in
         humans.  This could apply to firemen, welders, painter or  people
         working at home with the above-mentioned materials.

    d)   Accidental industrial releases can cause health problems in 
         workers and in the nearby community.

    e)   Workers have been shown not be at risk in closed-system
         industrial facilities that manufacture or use phosgene and employ
         good industrial practice.

    f)   No human or animal data are available on the effects of chronic
         low-level exposures to phosgene.

    g)   No data are available concerning adverse effects on organisms in
         the environment.  However, accidental release would be expected
         to give rise to adverse effects.

    11.2  Recommendations for protection of human health

    a)   Present occupational exposure limits for phosgene should be

    b)   Data should be obtained on the release of phosgene by the
         incineration of chlorine-containing organic materials.

    c)   International and national regulations regarding transport of
         phosgene should be followed in order to avoid accidental

    d)   Analytical methods capable of monitoring whole shift individual
         exposure (e.g., paper tape monitors) should be used routinely in
         the workplace.


    a)   The mechanism(s) of phosgene toxicity need to be clarified in
         order to improve risk assessment and therapy.

    b)   Data gaps in the areas of reproduction/development toxicity,
         mutagenicity and carcinogenicity following chronic low level
         exposure should be addressed.  More data should be gained about
         the long-term effects of acute exposure.


         No international body has evaluated the human health or
    environmental risks from exposure to phosgene.  Similarly, no health-
    based guidance values have been developed by such groups.

         Regulatory standards for phosgene established by national  bodies
    in some countries have been summarized by the ILO (ILO, 1991).


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    1.1  Identité, propriétés physiques et chimiques et méthodes d'analyse

         Le phosgène est un gaz incolore, extrêmement réactif à la
    température et à la pression ambiantes, dont l'odeur suffocante
    rappelle celle du foin moisi. Cette odeur est décelable à des
    concentrations comprises entre 1,6 et 6 mg/m3.

         Il existe des méthodes d'analyse pour la mise en évidence du
    phosgène dans l'air ou qui peuvent être utilisées dans le cadre des
    programmes d'hygiène et de sécurité du travail pour la mesure de la
    dose totale (par ex. ruban de papier indicateur).

    1.2  Usages et sources d'exposition humaine et environnementale

         Le phosgène est utilisé à plus de 99% sur le lieu de production
    dans des systèmes clos.  On le prépare en faisant réagir, en présence
    d'un catalyseur carboné, du chlore anhydre sur du monoxyde de carbone
    en proportions équimoléculaires.  La production mondiale est estimée à
    plus de 3 millions de tonnes.

         La présence de phosgène dans l'environnement est due aux
    émissions d'origine industrielle et à la décomposition thermique des
    solvants et des polymères chlorés. Cependant, il peut également
    provenir en proportion importante de l'oxydation photochimique des
    chloréthylènes, comme le trichloréthylène et le tétrachloréthylène.

    1.3  Transport, distribution et transformation dans l'environnement

         Le phosgène étant très réactif, il n'est vraisemblablement que
    peu transporté d'un compartiment à l'autre.

         Le phosgène s'élimine de l'air ambiant par une décomposition en
    phase hétérogène (catalyse de surface) et une lente hydrolyse en phase
    gazeuse. Il peut être transporté sur de longues distances et sa
    diffusion de la troposphère vers la stratosphère accélère probablement
    le processus de décomposition par photolyse.
    1.4  Concentrations dans l'environnment et exposition humaine

         L'exposition humaine, qu'il s'agisse de la population générale ou
    de certaines catégories professionnelles, se produit par inhalation.

         La concentration moyenne du phosgène dans l'air ambiant peut
    varier d'environ 80 à 130 ng/m3, encore que les données soient peu
    nombreuses à ce sujet. En raison de la diversité des pratiques en
    matière d'hygiène du travail dans le monde, il est impossible de
    donner un chiffre pour caractériser l'exposition des travailleurs qui
    produisent ou utilisent du phosgène ou, plus particulièrement,
    l'exposition des pompiers. A l'heure actuelle, les valeurs-seuils (en
    moyenne pondérée par rapport au temps) relevées dans 15 pays s'étagent
    de 0,4 à 0,5 mg/m3.

         La littérature ne donne pas d'indications sur la teneur de l'eau,
    du sol et des aliments en phosgène.

    1.5  Cinétique et métabolisme

         On ne possède que très peu de données sur l'absorption, le
    métabolisme, la distribution et la destinée du phosgène. La principale
    voie d'exposition est la voie respiratoire, le gaz pénétrant dans les
    tissus de l'arbre pulmonaire et ne se retrouvant par conséquent qu'en
    quantités minimes dans le reste de l'organisme. Sa demi-vie très brève
    (0,026 secondes) en solution aqueuse exclut toute rétention importante
    dans l'organisme. On ne dispose d'aucune donnée sur le métabolisme du
    phosgène. Ses produits d'hydrolyse, à savoir l'acide chlorhydrique et
    le dioxyde de carbone, sont éliminés de l'organisme par les processus
    physiologiques normaux.

         La toxicité du phosgène est due au fait qu'il provoque
    l'acylation des protéines et qu'il donne naissance à de l'acide
    chlorhydrique. Cette acylation se produit au niveau des groupements
    amino, hydroxyles et sulfhydriles des protéines et entraîne une
    inhibition marquée des enzymes qui interviennent dans le métabolisme
    énergétique ainsi qu'une rupture de la barrière air/sang.

    1.6  Effets sur les animaux d'expérience et les systèmes d'épreuve
         in vitro

    1.6.1  Exposition à court et à long terme

         Chez toutes les espèces étudiées, c'est le poumon qui est
    l'organe cible principal. La valeur du L(CT)50 varie de
    900 mg/m3-min (225 ppm-min ) chez la souris à 1920 mg/m3-min
    (480 ppm-min) chez le cobaye.  Une valeur de 1000 mg/ m3
    (250 ppm-min) a été obtenue chez le singe.  Chez toutes les espèces,
    on constate la même pathologie caractéristique, à savoir un oedème
    pulmonaire dont les manifestations cliniques sont retardées et qui est
    lié à la dose.  Les anomalies anato-mopathologiques observées à faible
    concentration au niveau des bron-chioles terminales et des alvéoles,
    sont caractéristiques d'un irritant pulmonaire.  En revanche, à forte
    concentration, l'oedème pulmonaire qui se développe perturbe les
    échanges gazeux et finit par entraîner la mort.

         On n'a pas connaissance d'études consacrées à une exposition de
    longue durée au phosgène.

         En ce qui concerne les durées d'exposition relativement courtes,
    on dispose d'une étude au cours de laquelle des rats on été exposés en
    une seule fois à du phosgène pendant 4 h à la concentration de
    2 mg/m3. On a observé une réduction de l'immunocompétence pulmonaire
    mesurée par l'activité des cellules NK.  Aucun effet n'a été constaté
    lors d'une exposition de 4 h à 0,4 mg/m3.

         Deux autres études ont été publiées au sujet des effets d'une
    exposition unique à du phosgène sur l'immunocompétence pulmo-naire. 
    Au cours de ces études, effectuées sur des rats et des souris, on a
    constaté que des rats infectés par le virus grippal présentaient,
    après 4 h d'exposition à 4 mg de phosgène par m3, un titre viral 10
    fois plus élevé 1 jour après l'infection, ce titre conservant une
    valeur élevée au cours des 4 jours suivants. En outre, chez les rats
    qui avaient été soumis pendant 4 h à une concentration de gaz comprise
    entre 0,2 et 4 mg/m3, on pouvait constater une diminution marquée du
    taux de prostaglandine E2 et de leucotriènes dès que la dose
    atteignait 0,4 mg/m3, avec réduction du nombre de macrophages
    alvéolaires et augmentation du nombre de neutrophiles à la
    concentration de 0,4 mg/m3.  Pour étudier la résistance de l'hôte, on
    a soumis des souris à des concentrations de phosgène comprises entre
    0,04 et 0,4 mg/m3 sur une durée de 4 h.  On a constaté, selon les
    cas, une augmentation de la mortalité consécutive à une infection par
     Streptococcus zooepidemicus ou un accroissement des mélanomes
    pulmonaires B16/BL6 à partir de 0,1 mg/m3.  Chez les rats exposés à
    du phosgène à raison de 0,4 mg/m3 (0,1 ppm) pendant 6 h ou à la même
    dose 6 h par jour, 5 j par semaine pendant 4 à 12 semaines , on a
    observé une réduction de la clairance bactérienne pulmonaire. L'effet
    était réversible après cessation de l'exposition.

    1.6.2  Effets non pulmonaires

         Le phosgène peut provoquer une irritation oculaire et cutanée. On
    n'a pas trouvé trace, dans la littérature, d'études portant sur le
    pouvoir sensibilisateur du phosgène.

         On ne dispose d'aucune donnée relative aux effets du phosgène sur
    la reproduction et le développement.

         Il n'existe pas de données suffisantes pour permettre une
    évaluation du pouvoir mutagène ou cancérogène du phosgène.

    1.7  Effets sur l'homme

         Chez l'homme, comme chez les animaux de laboratoire, l'organe
    cible est le poumon. Après exposition à des concentrations de phosgène
    comprises entre 120 et 1200 mg/m3-min , on a observé trois phases
    clinico-pathologiques distinctes. La phase initiale consiste en
    douleurs au niveau des yeux et de la gorge accompagnées d'une
    sensation de constriction thoracique, souvent avec dyspnée
    concomitante, respiration sifflante et toux; il peut également y avoir
    une hypo-tension, de la bradycardie et plus rarement, une arrythmie
    sinusale.  La seconde phase ou phase de latence, souvent
    asymptomatique, peut se prolonger pendant 24 h , selon l'intensité et
    la durée de l'exposition. Au cours de la troisième phase, un oedème
    pulmonaire parfois mortel peut se développer. Dans des populations
    exposées au phosgène à la suite d'accidents industriels, on a fait
    état de symptômes très divers comme des céphalées, des nausées, de la
    toux, de la dyspnée, une fatigue générale, des maux de gorge, une 

    sensation douloureuse de constriction thora-cique, des douleurs
    oculaires intenses et une forte lacrimation.  Lors d'une étude, on a
    observé la survenue d'un oedème pulmonaire après une phase de latence
    de 48 h.

         Les effets d'une exposition au phosgène ont été étudiés chez des
    groupes de travailleurs de deux usines, à savoir une unité de
    production de phosgène et une unité de traitement de l'uranium. Dans
    les deux cas, on n'a effectué que des prélèvements d'air et une
    surveillance individuelle limités et l'exposition n'est donc connue
    que de manière estimative.

         L'examen du dossier médical de la totalité des 326 travailleurs
    de l'unité de production de phosgène qui pouvaient avoir été exposés à
    ce gaz (jusqu'à 0,5 mg/m3 avec quelques dépassements de cette valeur;
    moyenne 0,01 mg/m3) n'a pas révélé de problèmes pulmo-naires
    chroniques ni de surmortalité par comparaison avec un groupe témoin de
    6226 personnes. Toutefois, l'absence de détails, dans le compte rendu,
    au sujet de l'exposition et des effets observés ne permet guère de
    tirer des conclusions définitives de cette étude.

         Dans le cas des travailleurs de l'usine de traitement de
    l'uranium, on a constitué deux groupes: l'un, de 699 personnes prises
    parmi les 1800 employés de cette période, a fait l'objet d'une étude
    transversale. Ces travailleurs avaient été vraisemblablement  soumis à
    une concen-tration de phosgène inférieure à 0,4 mg/m3 (avec 4 ou 5
    dépassements brefs par jour jusqu'à plus de 4 mg/m3).  L'autre groupe
    était constitué de 106 personnes qui avaient été impliquées dans des
    accidents et soumises à une exposition de plus de 200 mg/m3-min. 
    Dans le groupe exposé de manière chronique à de faibles concentrations
    de phosgène, l'examen des certificats de décès n'a pas fait ressortir
    de surmortalité due à une cause quelconque, à une affection
    respiratoire ou à un cancer du poumon.  Il n'y a d'ailleurs eu aucune
    mortalité par cancer du poumon, mais par contre une légère
    surmortalité d'origine respiratoire. On ne peut tirer de ces études
    que des conclusions limitées sur les effets chroniques du phosgène et
    cela, tant du fait de l'absence de données sur l'exposition que pour
    des raisons d'ordre méthodologique.

    1.8  Effets sur les autres êtres vivants au laboratoire et dans leur
         milieu naturel

         On ne possède aucun renseignement concernant les effets du
    phosgène sur les diverses formes vivantes présentes dans


    1.1  Identidad, propiedades físicas y químicas y métodos analíticos

         El fosgeno es un gas incoloro y altamente reactivo a temperatura
    y presión ambientes. Posee un olor sofocante parecido al del heno
    enmohecido, que puede percibirse a concentraciones comprendidas entre
    1,6 y 6 mg/m3.

         Existen métodos analíticos que permiten detectar el fosgeno en el
    aire y se utilizan en programas de higiene industrial que miden la
    dosis total (p.ej., sensores de cinta de papel).

    1.2  Usos y fuentes de exposición humana y ambiental

         Más del 99% del fosgeno producido se emplea  in situ en sistemas
    cerrados. Se produce haciendo reaccionar cantidades equimolares de
    cloro anhidro y monóxido de carbono en presencia de un catalizador de
    carbono. Se ha estimado que la producción mundial supera los 3
    millones de toneladas.

         El fosgeno ambiental procede de emisiones industriales y de la
    degradación térmica de algunos disolventes clorados y polímeros
    clorados. No obstante, una fuente importante de fosgeno ambiental es
    la oxidación fotoquímica de cloroetilenos tales como el tri- y el

    1.3  Transporte, distribución y transformación en el medio ambiente

         Debido a su alta reactividad, el transporte intercompartimental
    del fosgeno es en principio limitado.

         La eliminación del fosgeno del aire ambiente se produce por
    descomposición heterogénea (catálisis superficial) y por hidrólisis
    lenta en fase gaseosa. El fosgeno es transportado a larga distancia, y
    se cree que su difusión de la troposfera a la estratosfera acelera su
    degradación fotolítica.

    1.4  Niveles medioambientales y exposición humana

         La exposición humana tanto en la población general como en el
    entorno ocupacional se produce fundamentalmente por inhalación.

         Se estima que la concentración promedio de fosgeno en el aire
    ambiente está comprendida aproximadamente entre 80 y 130 ng/m3,
    aunque hay pocos datos disponibles. Dada la diversidad de las
    prácticas de higiene industrial seguidas en todo el mundo, es
    imposible facilitar una cifra para los trabajadores que fabrican o
    usan fosgeno o para los bomberos. Actualmente los valores umbral de
    exposición (promedio ponderado en función del tiempo) en 15 países
    están comprendidos entre 0,4 y 0,5 mg/m3.

         No se ha informado sobre las concentraciones de fosgeno en el
    agua, el suelo y los alimentos.

    1.5  Cinética y metabolismo

         Hay muy pocos datos sobre la absorción, el metabolismo, la
    distribución  y el destino del fosgeno. La principal vía de exposición
    es la inhalación; el gas penetra en los tejidos del tracto
    respiratorio, y sólo una mínima parte llega a distribuirse en el
    organismo. Su muy breve vida media (0,026 segundos) en soluciones
    acuosas evita que sea retenido significativamente por el organismo. No
    se ha publicado información alguna sobre el metabolismo del fosgeno.
    Sus productos hidrolíticos, p.ej. el ácido clorhídrico y el dióxido de
    carbono, son eliminados por el organismo mediante los procesos
    fisiológicos normales.

         El fosgeno debe su toxicidad a la acilación de las proteínas, así
    como a la generación de ácido clorhídrico. La acilación afecta a los
    grupos amino, hidroxilo y sulfhidrilo de las proteínas, lo que da
    lugar a una notable inhibición de varias enzimas relacionadas con el
    metabolismo energético y a la descomposición de la barrera

    1.6  Efectos en animales de laboratorio y en sistemas de
         prueba in vitro

    1.6.1  Exposiciones únicas y de corta duración

         En todas las especies estudiadas el pulmón es el principal órgano
    blanco. La (CT)L50 varía entre 900 mg/m3-min (225 ppm-min) en el
    ratón y 1920 mg/m3-min (480 ppm-min) en el cobayo. Se ha informado de
    una (CT)L50 de 1000 mg/m3-min (250 ppm-min) en el mono. En todas las
    especies la manifestación patológica característica es la aparición
    retardada sintomática de edema pulmonar, que depende de la dosis. Los
    cambios anatomopatológicos observados en los bronquiolos terminales y
    en los alveolos a bajas concentraciones son típicos de los irritantes
    pulmonares, mientras que a exposiciones altas se produce edema, lo que
    interfiere en el intercambio gaseoso y conduce a la muerte.

         No se ha publicado ningún estudio sobre la exposición a largo
    plazo al fosgeno.

         Un estudio efectuado en ratas reveló que una sola exposición a
    una concentración de 2 mg/m3 de fosgeno durante 4 horas puede
    provocar una disminución de la inmunocompetencia pulmonar, a juzgar
    por la actividad citotóxica natural de las células pulmonares. No se
    observó ningún efecto a niveles de exposición de 0,4 mg/m3 mantenidos
    durante 4 horas.

         Se han publicado otros dos estudios sobre los efectos de
    exposiciones únicas de fosgeno en la inmunocompetencia pulmonar de la
    rata y del ratón. En ratas infectadas por el virus de la gripe tras 4
    horas de exposición a 4 mg/m3 se observó que la concentración del
    virus se había multiplicado por diez un día después de la infección,
    manteniéndose significativamente elevados los niveles durante 4 días.
    Además, en ratas expuestas a concentraciones de fosgeno comprendidas
    entre 0,2 y 4 mg/m3 durante 4 horas se detectó una disminución
    considerable de la prostaglandina E2 y de los leucotrienos a partir de
    0,4 mg/m3, y una disminución del número de macrófagos alveolares y un
    aumento del número de neutrófilos con 0,4 mg/m3. En un ensayo de
    resistencia en que se expuso a ratones a niveles de fosgeno
    comprendidos entre 0,04 y 0,4 mg/m3 durante 4 horas se observó un
    aumento de la mortalidad por  Streptococcus zooepidemicus o un
    aumento del número de tumores pulmonares melanomatosos B16/BL6 a
    niveles de 0,1 mg/m3 o superiores. La eliminación bacteriana pulmonar
    se redujo en ratas expuestas a 0,4 mg/m3 (0,1 ppm) de fosgeno durante
    6 horas o a 0,4 mg/m3 (0,1 ppm) durante 6 horas/día y 5 días/semana
    por espacio de 4 a 12 semanas. Este efecto se reveló reversible tras
    la terminación de la exposición.

    1.6.2  Efectos no pulmonares

         La exposición al fosgeno puede causar irritación de los ojos y de
    la piel. No se ha hallado en las publicaciones ningún estudio
    referente al potencial de sensibilización del fosgeno.

         No se dispone de datos sobre los efectos del fosgeno en la
    reproducción y el desarrollo.

         No se dispone tampoco de datos adecuados para evaluar la
    mutagenicidad o carcinogenicidad del fosgeno.

    1.7  Efectos en el hombre

         El órgano blanco en el hombre, como en los animales de
    laboratorio, es el pulmón. Se han descrito tres fases
    clinicopatológicas características tras la exposición a niveles de
    fosgeno comprendidos entre 120 y 1200 mg/m3-min. La fase inicial
    consiste en la aparición de dolor en los ojos y la garganta y de una
    sensación de opresión torácica, a menudo con disnea, sibilancias y
    tos; puede haber asimismo hipotensión, bradicardia y, rara vez,
    arritmias sinusales. La que sigue a continuación es la fase latente,
    porque es a menudo asintomática; puede durar hasta 24 horas según el
    nivel y duración de la exposición. En la tercera fase puede aparecer
    edema pulmonar, de consecuencias eventualmente mortales.

         Las poblaciones expuestas al fosgeno tras accidentes industriales
    han sufrido una amplia variedad de síntomas, incluidos cefaleas,
    náuseas, tos, disnea, fatiga, dolor faríngeo, opresión y dolor
    torácicos, dolor ocular intenso y lagrimeo grave. En un estudio se
    observó edema pulmonar tras una fase latente de 48 horas.

         Se han estudiado los efectos de la exposición al fosgeno a largo
    plazo en tres grupos de trabajadores de dos instalaciones: una planta
    de producción de fosgeno y un centro de procesamiento de uranio. En
    los dos casos el muestreo del aire y la vigilancia del personal se
    hicieron sólo de forma limitada, y únicamente se efectuaron
    estimaciones de la exposición de los trabajadores.

         El estudio de los registros médicos de los 326 trabajadores de la
    planta de producción de fosgeno potencialmente expuestos a este
    producto (concentraciones entre indetectables y de 0,5 mg/m3, valor
    éste superado sólo esporádicamente; promedio: 0,01 mg/m3) no reveló
    ni problemas pulmonares crónicos ni una mayor mortalidad por
    enfermedades respiratorias en comparación con un grupo de 6228
    controles. No obstante, la falta de datos de que adolece el informe en
    lo que respecta a la exposición y a los efectos hace difícil extraer
    conclusiones firmes del estudio.

         Se estudió a dos grupos de trabajadores de la planta de
    procesamiento de uranio: una muestra transversal de 699 trabajadores
    de los más de 18 000 empleados durante el periodo estudiado,
    potencialmente expuestos a niveles de fosgeno inferiores a 0,4 mg/m3
    (con 4 ó 5 exposiciones fugaces a niveles > 4 mg/m3 cada día), y un
    grupo de 106 trabajadores que se habían visto implicados en accidentes
    y expuestos a niveles > 200 mg/m3-min. En el grupo expuesto
    crónicamente a bajas concentraciones de fosgeno el análisis de los
    certificados de defunción no mostró una mayor mortalidad por todo tipo
    de causas o por enfermedad respiratoria o cáncer pulmonar. En el grupo
    afectado por accidentes químicos no se registró tampoco ningún aumento
    de las defunciones por todo tipo de causas; no hubo muertes por cáncer
    pulmonar, pero sí un ligero incremento del número de defunciones por
    enfermedades respiratorias. Habida cuenta tanto de la escasez de datos
    sobre la exposición como de la metodología del estudio, sus
    conclusiones tienen un valor limitado.

    1.8  Efectos en otros organismos en el laboratorio y sobre el terreno

         No se han publicado datos sobre los efectos del fosgeno en
    organismos en el medio ambiente.

    See Also:
       Toxicological Abbreviations
       Phosgene (HSG 106, 1998)
       Phosgene (ICSC)
       Phosgene (PIM 419)