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Phosgene

1. NAME
   1.1 Substance
   1.2 Group
   1.3 Synonyms
   1.4 Identification numbers
      1.4.1 CAS number
      1.4.2 Other numbers
   1.5 Main brand names, main trade names
   1.6 Main manufacturers, main importers
2. SUMMARY
   2.1 Main risks and target organs
   2.2 Summary of clinical effects
   2.3 Diagnosis
   2.4 First aid measures and management principles
3. PHYSICO-CHEMICAL PROPERTIES
   3.1 Origin of the substance
   3.2 Chemical structure
   3.3 Physico-chemical properties
      3.3.1 Colour
      3.3.2 State/Form
      3.3.3 Description
   3.4 Hazardous characteristics
4. USES
   4.1 Uses
      4.1.1 Uses
      4.1.2 Description
   4.2 High risk circumstances of poisoning
   4.3 Occupationally exposed population
5. ROUTES OF EXPOSURE
   5.1 Oral
   5.2 Inhalation
   5.3 Dermal
   5.4 Eye
   5.5 Parenteral
   5.6 Others
6. KINETICS
   6.1 Absorption by route of exposure
   6.2 Distribution by route of exposure
   6.3 Biological half-life by route of exposure
   6.4 Metabolism
   6.5 Elimination and excretion
7. TOXICOLOGY
   7.1 Mode of action
   7.2 Toxicity
      7.2.1 Human data
         7.2.1.1 Adults
         7.2.1.2 Children
      7.2.2 Relevant animal data
      7.2.3 Relevant in vitro data
      7.2.4 Workplace standards
      7.2.5 Acceptable daily intake (ADI)
   7.3 Carcinogenicity
   7.4 Teratogenicity
   7.5 Mutagenicity
   7.6 Interactions
8. TOXICOLOGICAL ANALYSES & BIOMEDICAL INVESTIGATIONS
   8.1 Material sampling plan
      8.1.1 Sampling and specimen collection
         8.1.1.1 Toxicological analyses
         8.1.1.2 Biomedical analyses
         8.1.1.3 Arterial blood gas analysis
         8.1.1.4 Haematological analyses
         8.1.1.5 Other (unspecified) analyses
      8.1.2 Storage of laboratory samples & specimens
         8.1.2.1 Toxicological analyses
         8.1.2.2 Biomedical analyses
         8.1.2.3 Arterial blood gas analysis
         8.1.2.4 Haematological analyses
         8.1.2.5 Other (unspecified) analyses
      8.1.3 Transport of laboratory samples &specimens
         8.1.3.1 Toxicological analyses
         8.1.3.2 Biomedical analyses
         8.1.3.3 Arterial blood gas analysis
         8.1.3.4 Haematological analyses
         8.1.3.5 Other (unspecified) analyses
   8.2 Toxicological Analyses and Their Interpretation
      8.2.1 Tests on toxic ingredient(s) of material
         8.2.1.1 Simple Qualitative Test(s)
         8.2.1.2 Advanced Qualitative Confirmation Test(s)
         8.2.1.3 Simple Quantitative Method(s)
         8.2.1.4 Advanced Quantitative Method(s)
      8.2.2 Tests for biological specimens
         8.2.2.1 Simple Qualitative Test(s)
         8.2.2.2 Advanced Qualitative Confirmation Test(s)
         8.2.2.3 Simple Quantitative Method(s)
         8.2.2.4 Advanced Quantitative Method(s)
         8.2.2.5 Other Dedicated Method(s)
      8.2.3 Interpretation of toxicological analyses
   8.3 Biomedical investigations & their interpretation
      8.3.1 Biochemical analysis
         8.3.1.1 Blood, plasma or serum
         8.3.1.2 Urine
         8.3.1.3 Other fluids
      8.3.2 Arterial blood gas analyses
      8.3.3 Haematological analyses
      8.3.4 Interpretation of biomedical investigations
   8.4 Other biomedical investigations
   8.5 Overall Interpretation
   8.6 References
9. CLINICAL EFFECTS
   9.1 Acute poisoning
      9.1.1 Ingestion
      9.1.2 Inhalation
      9.1.3 Skin exposure
      9.1.4 Eye contact
      9.1.5 Parenteral exposure
      9.1.6 Other
   9.2 Chronic poisoning
      9.2.1 Ingestion
      9.2.2 Inhalation
      9.2.3 Skin contact
      9.2.4 Eye contact
      9.2.5 Parenteral exposure
      9.2.6 Other
   9.3 Course, prognosis, cause of death
   9.4 Systematic description of clinical effects
      9.4.1 Cardiovascular
      9.4.2 Respiratory
      9.4.3 Neurological
         9.4.3.1 Central Nervous System
         9.4.3.2 Peripheral Nervous System
         9.4.3.3 Autonomic
         9.4.3.4 Skeletal and smooth muscle
      9.4.4 Gastrointestinal
      9.4.5 Hepatic
      9.4.6 Urinary
         9.4.6.1 Renal
         9.4.6.2 Other
      9.4.7 Endocrine and reproductive systems
      9.4.8 Dermatological
      9.4.9 Eye, ear, nose, throat: local effects
      9.4.10 Haematological
      9.4.11 Immunological
      9.4.12 Metabolic
         9.4.12.1 Acid-base disturbances
         9.4.12.2 Fluid and electrolyte disturbances
         9.4.12.3 Others
      9.4.13 Allergic reactions
      9.4.14 Other clinical effects
      9.4.15 Special risks
   9.5 Other
   9.6 Summary
10. MANAGEMENT
   10.1 General principles
   10.2 Life supportive procedures and symptomatic / specific treatment
   10.3 Decontamination
   10.4 Enhanced Elimination
   10.5 Antidote treatment
      10.5.1 Adults
      10.5.2 Children
   10.6 Management discussion
11. ILLUSTRATIVE CASES
   11.1 Case reports from literature
12. ADDITIONAL INFORMATION
   12.1 Specific preventive measures
   12.2 Other
13. REFERENCES
14. AUTHOR(S), REVIEWER(S), DATES (INCLUDING UPDATES), COMPLETE ADDRESS(ES)
    PHOSGENE

    International Programme on Chemical Safety
    Poisons Information Monograph 419
    Chemical

    1.  NAME

        1.1  Substance

             Phosgene

        1.2  Group

             Halogenated aliphatic hydrocarbon

        1.3  Synonyms

             Carbonic Dichloride;
             Carbon Dichloride Oxide;
             Carbon Oxychloride;
             Carbonyl Chloride;
             Carbonyl Dichloride;
             CG;
             Chloroformyl Chloride;
             Diphosgene;
             Phosgen

        1.4  Identification numbers

             1.4.1  CAS number

                    75-44-5

             1.4.2  Other numbers

                    UN No. 1076
                    NIOSH: SY 5600000

        1.5  Main brand names, main trade names

             To be added by centre using monograph.

        1.6  Main manufacturers, main importers

             To be added by centre using monograph.

    2. SUMMARY

        2.1  Main risks and target organs

             Main risk is inhalation of the gas leading to pulmonary
             oedema. The main target organ is the lung.

        2.2  Summary of clinical effects

             The predominant effect is on the lung causing initial
             respiratory distress, and ocular burning. Pulmonary (non-
             cardiogenic) oedema can develop 8 to 24 hours post exposure
             and death is secondary to anoxia. Ocular and dermal exposure
             may lead to irritation or burns.

        2.3  Diagnosis

             The diagnosis is based on history of exposure to
             phosgene and/or the occurrence of clinical manifestations of
             mucous membrane irritation including cough, ocular
             irritation, chest pain, a feeling of suffocation, and
             dyspnea. Clinical diagnosis by chest x-ray shows diffuse
             interstitial infiltrates and chest sounds reveal bilateral
             crackles.

        2.4  First aid measures and management principles

             Remove subject from exposure, establish and maintain
             airway as necessary and administer supplemental oxygen. The
             treatment of phosgene poisoning is primarily supportive.
             Copious fluids should be used for suspected dermal or eye
             exposure. Remove clothing.

    3.  PHYSICO-CHEMICAL PROPERTIES

        3.1  Origin of the substance

             Synthetic production, generally at the site where it is
             to be used.

        3.2  Chemical structure

             Molecular Formula: CCl2O
             Molecular Weight: 98.92
             Structural Name: Carbonic dichloride

        3.3  Physico-chemical properties

             3.3.1  Colour

                    Clear

             3.3.2  State/Form

                    Gas

             3.3.3  Description

                    Suffocating odour similar to newly mown hay
                    when mixed with air. Slightly soluble in water, in
                    which it decomposes minimally. Very soluble in
                    benzene, toluene, acetic acid and most liquid
                    hydrocarbons (Allen, 1991; American Conference of
                    Governmental Industrial Hygienists Inc., 1991;
                    Budavari, 1996).
    
                    Condenses at 0C to a clear fuming liquid.
                    Boiling Point: 8.3C
                    Melting Point: -118C
                    Density: 1.37 at 20C
                    Vapour density: 3.4
                    Vapour Pressure: 1215 mm Hg at 20C

        3.4  Hazardous characteristics

             May react violently with hexa-fluoro-isopropylidene-
             amino-lithium. Forms a shock-sensitive explosive when mixed
             with potassium. Reacts with sodium azide to form the
             dangerously explosive carbonyl. Dangerous reactions may occur
             with aluminium, sodium, lithium, isopropyl alcohol or 2,4-
             hexadyn-1,6-diol. Phosgene decomposes to hydrochloric acid
             and carbon monoxide in the presence of moisture (water or
             steam). It produces toxic fumes when heated to decomposition
             (Allen, 1991). Phosgene may be released by photodecomposition
             of chlorinated hydrocarbons and also from the reaction of
             methylene chloride with heat (Gerritsen & Buschmann, 1960;
             English, 1964).

    4.  USES

        4.1  Uses

             4.1.1  Uses

             4.1.2  Description

                    Intermediate in the production of isocyanates,
                    carbamates, organic carbonates, chloroformates and
                    related pesticides, dyes, and herbicides. Used as a
                    chemical weapon (WWI). Prepared from carbon monoxide
                    and chlorine or nitrosyl chloride; or from oleum and
                    carbon tetrachloride for use in the polyurethane and
                    polycarbonate industries (Allen, 1991; American
                    Conference of Governmental Industrial Hygienists Inc.,
                    1991; Budavari, 1996).

        4.2  High risk circumstances of poisoning

             As a result of occupational exposure due to photo-
             decomposition of many of the chlorinated organic compounds
             such as methylene chloride or carbon tetrachloride. Also when
             produced by heat decomposition of many chemicals, as in fires
             (Allen, 1991; American Conference of Governmental Industrial
             Hygienists Inc., 1991).

        4.3  Occupationally exposed population

             Workers in the polyurethane or polycarbonate industries
             (Allen, 1991). Also chemists, glass workers, welders and
             firemen potentially exposed through decomposition of
             chlorinated hydrocarbons (Currie et al, 1987). Some risk to
             public when using non-inflammable chemical paint removers in
             the presence of an open flame (Gerritsen & Buschmann, 1960;
             English, 1964).

    5.  ROUTES OF EXPOSURE

        5.1  Oral

             Not relevant.

        5.2  Inhalation

             Phosgene is readily inhaled. Odour is detected at 0.5 to
             1 ppm and anosmia (odour fatigue) is seen following chronic
             exposure (Allen, 1991). No systemic absorption (Currie et
             al., 1987).

        5.3  Dermal

             Severe skin irritant (Sax & Lewis, 1989).

        5.4  Eye

             Extremely irritating to the eye, no absorption
             occurs.

        5.5  Parenteral

             Not relevant.

        5.6  Others

             Not relevant.

    6.  KINETICS

        6.1  Absorption by route of exposure

             There is no data available which suggests systemic
             absorption other than through the lungs (Richardson &
             Gangolli, 1994). Only moderately water soluble therefore
             causes lower airway irritation. Intrapulmonary hydrolysis to
             HCl and CO2 or Cl2.

        6.2  Distribution by route of exposure

             No systemic absorption.

        6.3  Biological half-life by route of exposure

             No data available.

        6.4  Metabolism

             Literature is conflicting as to the production of either
             CO2 (Leikin & Paloucek, 1996) or Cl2, the more frequently
             stated metabolite is Cl2 and will be referred to from here
             on (Gosselin et al., 1984). Conversion to HCl and Cl2 in
             the lower airways which are thought to be the triggers for
             resulting pulmonary inflammation and oedema.

        6.5  Elimination and excretion

             No data available.

    7.  TOXICOLOGY

        7.1  Mode of action

             Intrapulmonary conversion to HCl and Cl2 which reacts
             readily with the hydroxyl, sulfhydryl and ammonia groups
             found in proteins, intermediate metabolites and vitamins
             leading to degeneration of the blood-air barrier and
             subsequent oedema (Diller, 1980; Leikin & Paloucek,
             1996).

        7.2  Toxicity

             7.2.1  Human data

                    7.2.1.1  Adults

                             The LC50 in humans is estimated at
                             500 to 800 ppm for one minute. Levels of 2 to
                             5 ppm will induce mild respiratory symptoms,
                             with prolonged exposure to such levels
                             considered dangerous. Exposure to levels
                             greater than 50 ppm are considered massive

                             and will likely be rapidly fatal
                             (Parmeggiani, 1983; Ellenhorn & Barceloux,
                             1988; Olsen, 1994). At doses of 200 ppm
                             phosgene has been shown to pass through the
                             blood-air barrier and react with the blood
                             constituents to cause clotting (Richardson &
                             Gangolli, 1994).

                    7.2.1.2  Children

                             No data available

             7.2.2  Relevant animal data

                    Acute: LC50 in the rat 25 ppm over 20
                    minutes. Phosgene levels as low as 0.5  ppm for two
                    hours can cause definite pathological changes in the
                    rat lung. Pulmonary vasoconstriction and oedema has
                    been witnessed in rabbits acutely inhaling phosgene.
                    When dogs inhaled 72 ppm for 30 minutes obvious
                    emphysema and pulmonary consolidation developed at 4
                    to 9 days post exposure (American Conference of
                    Governmental Industrial Hygienists Inc., 1991).
                    Exposures as low as 0.5 ppm for 120 minutes can cause
                    detectable changes in alveolar epithelium in the rat
                    although evidence of lasting damage is limited (Gross
                    et al, 1965).
    
                    Subchronic: In a study of goats, cats, rabbits,
                    guinea pigs, rats and mice exposure at 0.8 mg/m3 of
                    phosgene (5 hours per day for 5 consecutive days)
                    resulted in pulmonary oedema in 41% of exposed
                    animals, 4% of the animals developed extensive
                    pulmonary lesions. Identical exposure times at
                    4mg/m3 for the same species depressed respiratory
                    tract ciliary function and caused lung lesions. Guinea
                    pigs inhaling 10 mg/m3 for 10 minutes/day for 7 days
                    exhibited tolerance development, however such
                    tolerance has been shown to trigger chronic effects
                    such as bronchitis (American Conference of
                    Governmental Industrial Hygienists Inc., 1991).

             7.2.3  Relevant in vitro data

                    No data available

             7.2.4  Workplace standards

                    TLV-TWA: 0.1 ppm (0.40 mg/m3)
                    PEL 0.1 ppm
                    IDLH 2 ppm
                    (American Conference of Governmental Industrial
                    Hygienists Inc., 1991)

             7.2.5  Acceptable daily intake (ADI)

                    Not relevant.

        7.3  Carcinogenicity

             No data available.

        7.4  Teratogenicity

             No data available.

        7.5  Mutagenicity

             No data available.

        7.6  Interactions

             No data available.

    8.  TOXICOLOGICAL ANALYSES & BIOMEDICAL INVESTIGATIONS

        8.1  Material sampling plan

             8.1.1  Sampling and specimen collection

                    8.1.1.1  Toxicological analyses

                    8.1.1.2  Biomedical analyses

                    8.1.1.3  Arterial blood gas analysis

                    8.1.1.4  Haematological analyses

                    8.1.1.5  Other (unspecified) analyses

             8.1.2  Storage of laboratory samples & specimens

                    8.1.2.1  Toxicological analyses

                    8.1.2.2  Biomedical analyses

                    8.1.2.3  Arterial blood gas analysis

                    8.1.2.4  Haematological analyses

                    8.1.2.5  Other (unspecified) analyses

             8.1.3  Transport of laboratory samples &specimens

                    8.1.3.1  Toxicological analyses

                    8.1.3.2  Biomedical analyses

                    8.1.3.3  Arterial blood gas analysis

                    8.1.3.4  Haematological analyses

                    8.1.3.5  Other (unspecified) analyses

        8.2  Toxicological Analyses and Their Interpretation

             8.2.1  Tests on toxic ingredient(s) of material

                    8.2.1.1  Simple Qualitative Test(s)

                    8.2.1.2  Advanced Qualitative Confirmation Test(s)

                    8.2.1.3  Simple Quantitative Method(s)

                    8.2.1.4  Advanced Quantitative Method(s)

             8.2.2  Tests for biological specimens

                    8.2.2.1  Simple Qualitative Test(s)

                    8.2.2.2  Advanced Qualitative Confirmation Test(s)

                    8.2.2.3  Simple Quantitative Method(s)

                    8.2.2.4  Advanced Quantitative Method(s)

                    8.2.2.5  Other Dedicated Method(s)

             8.2.3  Interpretation of toxicological analyses

        8.3  Biomedical investigations & their interpretation

             8.3.1  Biochemical analysis

                    8.3.1.1  Blood, plasma or serum

                    8.3.1.2  Urine

                    8.3.1.3  Other fluids

             8.3.2  Arterial blood gas analyses

             8.3.3  Haematological analyses

             8.3.4  Interpretation of biomedical investigations

        8.4  Other biomedical investigations

        8.5  Overall Interpretation

        8.6  References

    9.  CLINICAL EFFECTS

        9.1  Acute poisoning

             9.1.1  Ingestion

                    Not relevant

             9.1.2  Inhalation

                    Moderate exposure results in mild cough, mucous
                    membrane irritation and ocular irritation. The patient
                    is generally asymptomatic for 30 minutes to 24 hours
                    after exposure. Delayed symptoms then occur including:
                    chest pain, discomfort, thirst, headache, nausea,
                    increased cough with haemoptysis, cyanosis, a feeling
                    of suffocation and dyspnoea (Parmeggiani, 1983;
                    Gosselin et al, 1984; Ellenhorn & Barceloux, 1988;
                    Olsen 1994; Leikin & Paloucek, 1996).
    
                    Clinical diagnosis by chest x-ray shows diffuse
                    interstitial infiltrates and chest sounds reveal
                    bilateral crackles (Lim et al, 1996). The patient
                    develops signs and symptoms secondary to hypoxia and
                    pulmonary oedema. Death would result from anoxia
                    (Parmeggiani, 1983).
    
                    Massive exposures can result in pulmonary
                    intravascular haemolysis, thrombus formation and
                    immediate death due to pulmonary circulation occlusion
                    (Richardson & Gangolli, 1994).

             9.1.3  Skin exposure

                    Possibility of dermal burning with massive
                    exposures, some dermal irritation with lower
                    exposures.

             9.1.4  Eye contact

                    Ocular irritation and severe burning. A case of
                    severe exposure to liquid phosgene resulted in corneal
                    opacification.

             9.1.5  Parenteral exposure

                    Not relevant.

             9.1.6  Other

                    No data.

        9.2  Chronic poisoning

             9.2.1  Ingestion

                    Not relevant.

             9.2.2  Inhalation

                    Symptoms of cough and shortness of breath are
                    occasionally persistent (Currie et al., 1987).
                    Documented cases show return to normal limits of lung
                    function within a period of weeks, however complete
                    recovery may take a period of years (English, 1964;
                    Lim et al., 1996). The inhalation of phosgene may
                    increase the severity of subsequent viral influenza
                    (Erlich & Burleson, 1991).

             9.2.3  Skin contact

                    No data available

             9.2.4  Eye contact

                    No data available.

             9.2.5  Parenteral exposure

                    Not relevant.

             9.2.6  Other

                    No data.

        9.3  Course, prognosis, cause of death

             Following massive exposures there is the possibility of
             immediate death due to pulmonary vasculature occlusion.
             Moderate exposures present as initial lung irritation,
             bronchitis and ocular burning. From 30 minutes to 24 hours
             later, the patient can develop chest pain, coughing,
             haemoptysis, dyspnea and death due to pulmonary oedema. If
             the patient survives 2 to 3 days then the prognosis is good,
             with a small chance of permanent lung damage.

        9.4  Systematic description of clinical effects

             9.4.1  Cardiovascular

                    Hypovolemia, due to pulmonary oedema, leading
                    to hypotension and tachycardia (Leikin & Paloucek,
                    1996).

             9.4.2  Respiratory

                    Respiratory distress including chest pain,
                    increasing cough, haemoptysis, a feeling of
                    suffocation, dyspnoea and pulmonary oedema. Chest
                    sounds reveal inspiratory and expiratory crackles.
                    Chest x-rays show diffuse interstitial infiltrates
                    (Parmeggiani, 1983; Ellenhorn & Barceloux, 1988;
                    Richardson & Gangolli, 1994; Lim et al., 1996).

             9.4.3  Neurological

                    9.4.3.1  Central Nervous System

                             Headache, confusion due to hypoxia.
                             (Leikin & Paloucek, 1996)

                    9.4.3.2  Peripheral Nervous System

                             No data

                    9.4.3.3  Autonomic

                             No data

                    9.4.3.4  Skeletal and smooth muscle

                             No data

             9.4.4  Gastrointestinal

                    Nausea, vomiting.

             9.4.5  Hepatic

                    No data

             9.4.6  Urinary

                    9.4.6.1  Renal

                             No data

                    9.4.6.2  Other

                             No data

             9.4.7  Endocrine and reproductive systems

                    No data

             9.4.8  Dermatological

                    Possibility of dermal irritation and burns with
                    large exposures (Leikin & Paloucek, 1996).

             9.4.9  Eye, ear, nose, throat: local effects

                    Ocular irritation, corneal burns, sensation of
                    mucous membrane irritation (Leikin & Paloucek,
                    1996).

             9.4.10 Haematological

                    Possibility of haemolysis and thrombus
                    formation with massive exposures leading to occlusion
                    in the pulmonary vasculature (Richardson & Gangolli,
                    1994).

             9.4.11 Immunological

                    No data

             9.4.12 Metabolic

                    9.4.12.1 Acid-base disturbances

                             Metabolic acidosis would be
                             expected as a consequence of severe
                             hypoxemia.

                    9.4.12.2 Fluid and electrolyte disturbances

                             Hypovolemia due to pulmonary oedema
                             (Leikin & Paloucek, 1996).

                    9.4.12.3 Others

                             No data

             9.4.13 Allergic reactions

                    No data

             9.4.14 Other clinical effects

                    No data.

             9.4.15 Special risks

                    Pregnancy: one case of exposure with normal
                    infant (Gerritsen & Buschmann, 1960).
                    Breast feeding: no data.
                    Enzyme Deficiencies: no data.

        9.5  Other

             No data

        9.6  Summary

    10. MANAGEMENT

        10.1 General principles

             Maintain airway and use positive pressure ventilation
             if necessary. Assessment of condition is mainly via clinical
             presentation and radiographs which show diffuse increased
             haziness. Treatment of hypoxia with supplemental with oxygen.
             Some sources recommend the use of steroids and antibiotics
             (if there are signs of infection), however this remains
             controversial (Finkel, 1983). Administer fluids as necessary,
             with caution not to worsen the pulmonary oedema (Lim et al.,
             1996). Patients displaying immediate symptoms should be
             observed for the possibility of delayed pulmonary oedema
             (Ellenhorn & Barceloux, 1988).

        10.2 Life supportive procedures and symptomatic / specific
             treatment

             Maintain a clear airway.
             Administer oxygen.
             Endotracheal intubation and support ventilation using
             appropriate mechanical devices may be necessary.
             Monitor for 12 to 24 hours for possible delayed-onset
             pulmonary oedema.

        10.3 Decontamination

             Remove victim from exposure and give supplemental
             oxygen. Rescuers should wear self-contained breathing
             apparatus, and eye and skin protection. The patient should be
             transported to a hospital immediately (Olsen, 1994). If
             dermal exposure is suspected wash copiously with soap and
             water, remove contaminated clothing immediately. Eyes should
             be washed with flowing water for at least 15 minutes
             (American Conference of Governmental Industrial Hygienists
             Inc., 1991; Leikin & Paloucek, 1996).

        10.4 Enhanced Elimination

             No data.

        10.5 Antidote treatment

             10.5.1 Adults

                    No antidote available.

             10.5.2 Children

                    No antidote available.

        10.6 Management discussion

             Early reports of the effectiveness of methenamine in
             treatment of phosgene poisoning have been disproven (Diller,
             1980). While this compound has been shown to have protective
             effects when administered prior to exposure the
             administration post-exposure has no therapeutic benefit.
    
             Drugs disrupting the neutrophil influx associated with the
             oxidant pathway in phosgene such as aminophylline and
             terbutaline, ibuprofen and colchicine have been shown to
             reduce oedema in animal studies (Lazar et al., 1989; Kennedy
             et al., 1990; Ghio et al., 1991; Wyatt & Allister,
             1995).

    11. ILLUSTRATIVE CASES

        11.1 Case reports from literature

             Gas Tank Leakage: A gas tank leak resulted in the
             poisoning of 56 persons. Six cases are documented by Lim et
             al. (1996). Symptoms were cough, increased sputum production,
             dyspnea, chest tightness and chest pain followed by pulmonary
             oedema. Diagnosis was through clinical presentation (for
             example, case one demonstrated bilateral inspiratory and
             expiratory crackles and increased diffuse haziness in both
             lungs on the chest x-ray. WBC were 12.7103/L, LDH 409
             units. Initial arterial blood gases PaO2 68.9 mmHg, PaCO2
             34.7 mmHg, pH 7.392). Treatment involved intubation and
             ventilation (started at 8 L/min oxygen, later reduced), drug
             treatment was with methylprednisolone, aminophylline and
             antibiotics with ventilation controlled by diazepam and
             vecuronium (Lim et al., 1996).
    
             Pregnant Woman Exposed Through Use Of Paint Stripper: The
             phosgene exposure of a pregnant woman through the reaction of
             fumes from non-inflammable chemical paint remover, containing
             methylene chloride, to phosgene by a kerosene stove was
             reported by Gerritsen & Buschmann (1960). She reported chest
             tightness, blood-stained sputum and later dyspnea and
             cyanosis. A chest x-ray revealed diffuse opacities and she
             was treated with oxygen, antibiotics and cortisone. She
             recovered and later gave birth to a healthy child.
    
             Welding: A welder using an argon shielded electric arc in
             an atmosphere containing tricholoroethylene developed
             symptoms of breathlessness followed by pulmonary oedema 12
             hours post-exposure. He was dyspneic 10 days later (Sjogren
             et al, 1991).

    12. ADDITIONAL INFORMATION

        12.1 Specific preventive measures

             Phosgene should be used only in a well ventilated, non-
             combustible area.  It should never be stored with water.
             Ensure that storage cylinders remain cool. All environs
             should have absorption facilities. Sodium hydroxide or
             anhydrous ammonia can be used to neutralise phosgene.
             Phosgene at concentrations similar to the TLV can be detected
             by an indicator paper colour change from yellow to deep
             orange (indicator paper: paper soaked in alcoholic or carbon
             tetrachloride solution containing equal parts of p-dimethyl-
             amino-benzaldehyde and colourless diphenylamine and dried).
             Transporters should avoid throwing or dropping cylinders and
             precautions should be taken to prevent them falling. Most
             industries (such as the dye industry) have interior
             regulations for working with this highly toxic gas.
             (Parmeggiani, 1983; American Conference of Governmental
             Industrial Hygienists Inc. 1991; Richardson and Gangolli,
             1994).

        12.2 Other

             No data

    13. REFERENCES

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        American Conference of Governmental Industrial Hygienists Inc.
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        Exposure Indices, Volume II, 6th edition, Cincinnati
    
        Budavari S ed. (1996) The Merck Index. An encyclopaedia of
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        and Co.
    
        Currie W, Hatch G & Frosolong M (1987) Pulmonary Alterations in
        Rats Due to Acute Phosgene Inhalation, Fundamental and Applied
        Toxicology, 8:107-114
    
        Diller W (1980) The Methenamine Misunderstanding in the Therapy of
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        Ellenhorn M & Barceloux D ed. (1988) Medical Toxicology -
        Diagnosis and Treatment of Human Poisonings, New York, Elsevier
        Publishing
    
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        Journal of Medicine, 1:38
    

        Erlich J & Burleson G (1991) Enhanced and prolonged Pulmonary
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        Finkel A ed. (1983) Hamilton and Hodges Industrial Toxicology, 4th
        edition, Massachusetts, John Wright Publishing
    
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        Ill-Ventilated Rooms Heated by Kerosene Stoves, British Journal of
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        Ghio A, Kennedy T, Hatch G & Tepper J (1991) Reduction of
        Neutrophil Influx Diminishes Lung Injury and Mortality Following
        Phosgene Inhalation, Journal of Applied Physiology, 71(2):657-665
    
        Gosselin R, Smith R, Hodge H & Braddock J ed. (1984) Clinical
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        Williams and Wilkins
    
        Gross P, Rinehart W & Hatch T (1965) Chronic Pneumonitis Caused by
        Phosgene, Archives of Environmental Health, 10:768-775
    
        Kennedy T, Rao N, Noah W, Michael J, Jafri Jr M, Gurtner G &
        Hoidal J (1990) Ibuprofen Prevents Oxidant Lung Injury and In
        Vitro Lipid Perioxidation by Chelating Iron, Journal of Clinical
        Investigation, 86(5):1565-1573
    
        Kennedy T, Michael J, Hoidal J, Hasty D, Sciuto A, Hopkins C,
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        Aminophylline, and Beta-adrenergic Agonists Protect Against
        Pulmonary Oedema Caused by Phosgene, Journal of Applied
        Physiology, 67(6):2542-2552
    
        Leikin J & Paloucek F ed. (1996) Poisoning and Toxicology
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        Chemistry
    

        Sax NI & Lewis RJ (1989) Dangerous properties of industrial
        materials, 7th Ed, Van Nostrand Reinhols, New York
    
        Sjogren B, Plato N, Alexandersson R, Eklund A & Falkenburg C
        (1991) Pulmonary Reactions Caused by Welding Induced Decomposed
        Trichloroethylene, Chest, 99(1):237-238
    
        Wyatt J & Allister C (1995) Occupational Phosgene Poisoning: A
        Case Report, Journal of Accident and Emergency Medicine, Abstract,
        12(3):212-213

    14. AUTHOR(S), REVIEWER(S), DATES (INCLUDING UPDATES), COMPLETE
        ADDRESS(ES)

        Author: Belinda Bray
        National Toxicology Group
        Adams Building
        Otago Medical School
        Dunedin. NEW ZEALAND
        Phone: (03) 479 1200
        E-mail: belinda.bray@stonebow.otago.ac.nz
        Date: 1996
    
        Reviewer: MO Rambourg Schepens
        Centre Anti-Poisons de Champagne Ardenne
        Centre Hospitalier Universitaire
        F-51092 REIMS Cedex FRANCE
        E-mail: marie-odile.rambourg@wanadoo.fr
        Date: July 1997
    
        Peer review: INTOX-10 Meeting, Rio, Brazil September 3rd 1997
        (Drs M Kowalczyk, L Lubomirov, R Mc Keown, J Szajewski, W Watson)
    
        Finalization/Edition: Drs MO Rambourg Schepens & M Ruse
        October 1997
    



    See Also:
       Toxicological Abbreviations
       Phosgene (EHC 193, 1997)
       Phosgene (HSG 106, 1998)
       Phosgene (ICSC)