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Mustard gas

1. Name
   1.1 Substance
   1.2 Group
   1.3 Synonyms
   1.4 Identification numbers
      1.4.1 CAS
      1.4.2 Other numbers
   1.5 Brand names/Trade names
   1.6 Manufacturers, importers
2. SUMMARY
   2.1 Main risks and target organs
   2.2 Summary of clinical effects
   2.3 Relevant laboratory analyses/sample collection
   2.4 First-aid measures and management principles
3. PHYSICO-CHEMICAL PROPERTIES
   3.1 Origin of the substance
   3.2 Chemical structure (formula, molecular weight)
   3.3 Physical properties
      3.3.1 Colour
      3.3.2 State/form
      3.3.3 Description
   3.4 Other characteristics
4. USES/HIGH RISK CIRCUMSTANCES OF POISONING
   4.1 Uses
      4.1.1 Uses
      4.1.2 Description
   4.2 High risk circumstances of poisoning
   4.3 Occupationally exposed populations
5. ROUTES OF ENTRY
   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 by route of exposure
7. TOXICOLOGY
   7.1 Mode of action
   7.2 Range of 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) and other guideline levels
   7.3 Carcinogenicity
   7.4 Teratogenicity
   7.5 Mutagenicity
   7.6 Interactions
8. Toxicological analyses
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 exposure
      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 CNS
         9.4.3.2 Peripheral nervous system
         9.4.3.3 Autonomic nervous system
         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 Eyes, ears, 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 Other
      9.4.13 Allergic reactions
      9.4.14 Other clinical effects
      9.4.15 Special risks
   9.5 Other
10. MANAGEMENT
   10.1 General principles
   10.2 Relevant laboratory analyses
      10.2.1 Sample collection
      10.2.2 Biomedical analysis
      10.2.3 Toxicological analysis
   10.3 Life support procedures and symptomatic/specific treatment
   10.4 Decontamination
   10.5 Elimination
   10.6 Antidote treatment
      10.6.1 Adults
      10.6.2 Children
   10.7 Management discussion
11. ILLUSTRATIVE CASES
   11.1 Case reports from the literature
   11.2 Internally-extracted data on cases
12. ADDITIONAL INFORMATION
   12.1 Availability of antidotes
   12.2 Specific preventative mesaures
   12.3 Other
13. REFERENCES
14. AUTHOR(S), REVIEWER(S), ADDRESS(ES), DATE(S)
        1.  Name
 
        1.1  Substance
 
             Mustard gas (sulphur mustard)
 
        1.2  Group
 
             Alkylating agents
 
        1.3  Synonyms
 
             1, 1' thiobis [2 chloroethane]
             bis-(2-chloroethyl) sulphide
             beta, beta' dichloroethyl sulphide
             2, 2' dichloroethyl sulphide
             bis (beta-chloroethyl) sulphide
             1-chloro-2 (beta-chlorodiethylthio) ethane
             sulphur mustard
             yellow cross liquid
             Kampfstoff "Lost"
             Yperite
             H
             HT
             HD
 
        1.4  Identification numbers
 
             1.4.1  CAS
 
                    505-60-2
 
             1.4.2  Other numbers
 
                    No other numbers found. 
 
        1.5  Brand names/Trade names
 
             To be filled in by centre using the monograph.
 
        1.6  Manufacturers, importers
 
             To be filled in by centre using the monograph.
 
 
    2.  SUMMARY
 
        2.1  Main risks and target organs
 
             Acute poisoning - Main risks
             
             Mustard gas is a powerful irritant and vesicant, used as a 
             chemical warfare agent. The main risk of acute poisoning 
             exists with the use of sulphur mustard vapour in war and 
             occasionally during laboratory work. However, due to its 
             persistence poisoning may occur at a later stage.
             
             Target organs: Skin, eyes, respiratory tract, bone 
             marrow.
             
             Chronic toxicity - Main risks
             
             Workers employed in the manufacture of mustard gas are at an 
             increased risk to develop cancer.  Risk of mortality from 
             influenza, pneumonia and chronic respiratory disease was also 
             reported to be higher in persons occupationally exposed to 
             mustard gas.
             
             Delayed toxic effects of sulphur mustard may occur months and 
             years after exposure, mainly with respiratory disorders.
             
             Target organs: Lung, larynx, pharynx, oral cavity, bone 
             marrow and sexual organs.
 
        2.2  Summary of clinical effects
 
             Acute poisoning
             
             Effects of exposure to mustard gas vapour or liquid are 
             typically delayed for several hours. The delay is shorter in 
             case of liquid contamination. In the first hour after 
             exposure to mustard gas vapour or liquid no signs or symptoms 
             are usually produced, but nausea, retching, vomiting and eye 
             smarting have been occasionally reported. 
             
             Exposure to superlethal concentrations may induce 
             convulsions, coma and death within one hour after 
             exposure.
             
             Nausea, fatigue, headache, eye inflammation with intense eye 
             pain, lachrymation, blepharospasm, photophobia and 
             rhinorrhoea, followed by reddening of face and neck, soreness 
             of throat and increased pulse and respiratory rate develop at 
             two to six hours post exposure.   
             Six to twenty four hours post exposure the above symptoms are 
             generally increased in severity and are accompanied by skin 
             inflammation followed by blister formation in the warmest 
             areas such as genito-perineal area, buttocks, axillae and on 
             the inner aspects of thighs.
             
             In the next twenty four hours the condition generally 
             worsens, blistering becomes more marked, coughing appears. 
             Mucus, pus and necrotic slough may be expectorated. Intense 
             itching of skin and increased skin pigmentation occur.
             
             The blood count may reveal anaemia and neutropenia four days 
             post exposure. In general, initial leukocytosis on the first 
             2 to 3 days after exposure is followed by leukopenia in 
             severe intoxicated patients.
             
             A few hours after the ingestion of mustard contaminated food 
             or water, the following signs and symptoms develop: nausea, 
             vomiting, abdominal pain, bloody vomiting and diarrhoea with 
             signs of shock and prostration in severe poisoning. The 
             patients who are severly intoxicated may die during the 
             second week after exposure due to respiratory complications 
             and septic shock.
             
             Chronic toxicity
             
             Increased risk of cancer of oral cavity and respiratory tract 
             has been observed in workers chronically exposed to mustard 
             gas. Development of cancer is likely after a single exposure. 
             Cases of leukaemia, lung and stomach cancers were observed in 
             Iranian combatants who were exposed once to sulphur 
             mustard.
 
        2.3  Relevant laboratory analyses/sample collection
 
             Blood, urine and blister fluids should be collected for 
             haematological, biochemical and toxicological analyses.
             
             Acute overdose
             
             Full blood count, serum electrolytes, urea, protein levels. 
             Arterial blood gasses determination is indicated in cases of 
             pulmonary oedema and Adult respiratory distress syndrome. 
             Culture of sputum and eye exudate.  Blood cultures where 
             indicated.
             
             Skin blisters may be aspirated and the fluid obtained 
             analysed for thiodiglycol. The same estimation may be 
             performed in blood and urine in order to differentiate 
             blistering produced by mustard gas from that produced by 
             other agents such as Lewisite.  Contents of blisters are not 
             toxic to attendants (Sulzberger, 1943).  However, secondary 
             exposure of the nursing and technical staff occured in Iran 
             after caring for the patients and handling the blister 
             fluid.
             
             Chronic toxicity
             
             Mutagenicity can be evaluated by counting sister chromatid 
             exchanges in lymphocytes (Wulf et al., 1985).
 
        2.4  First-aid measures and management principles
 
             Life support
             
             Support respiratory and cardiovascular function.  Treat 
             pulmonary oedema and respiratory distress syndrome. The 
             patients with severe leukopenia (_1000 WBC/mm) should be 
             isolated to avoid secondary infection and septic shock.
             
             Eye decontamination
             
             Irrigate the eyes immediately with copious amounts of normal 
             saline or water for at least 15 minutes. Since sulphur 
             mustard is lipid soluble, it is advisable to use diluted 
             infant shampoo as well.
             
             Skin decontamination
             
             Remove any contaminated clothing.  Wash exposed area 
             thoroughly with water and neutral soap.  Areas of liquid 
             contamination should be decontaminated using Fullers' earth. 
             Washing with organic solvents such as paraffin followed by 
             the use of soap and water has also been recommended.
             
             Gut decontamination
             
             Emesis should not be induced.  Gastric lavage is indicated 
             after ingestion of food or water contaminated with mustard 
             gas. Airways should be protected by cuffed endotracheal 
             intubation. Prior to gastric lavage stomach contents should 
             be diluted by 100 to 200 mL of milk or water. 
             
             Activated charcoal is of unproven benefit, but may be 
             used.
             
             Symptomatic treatment
             
             Provide adequate analgesia. Routine use of morphine is not 
             indicated due to its depression of respiration.
             Correct fluid and electrolyte imbalance carefully, avoiding a 
             net positive fluid balance.  Systemic and inhaled 
             corticosteroids are effective in antagonizing pulmonary 
             toxicity.
             
             Treat eyes with antibiotics, preferably sulphacetamide 20% 
             solution, and mydriatics. In case of keratitis the use of 
             corticosteroid eye drops is contraindicated.
             
             Dark glasses are helpful, but contact lenses are 
             contraindicated. Reassure the patient that visual recovery is 
             usual. Seek ophthalmological opinion. 
             
             Treat skin lesions with standard therapy for severe chemical 
             burns, preferably with silver sulphadiazine cream.
             
             Treat infection with appropriate antibiotic.
             
             Observe patients who ingested contaminated food or water with 
             mustard gas for the development of complications caused by 
             gastrointestinal tract burns, such as haemorrhage and 
             perforation.
             
             Blood transfusion may be required in patients with bone 
             marrow depression.
 
    3.  PHYSICO-CHEMICAL PROPERTIES
 
        3.1  Origin of the substance
 
             Mustard gas is a synthetic substance prepared by 
             treating ethylene with sulfur chloride (Levinstein process) 
             or by treating 2, 2'- dihydroxyethyl sulfide with HCl gas 
             (German process) (Merck Index, 1989). The synthesis was first 
             reported by Victor Meyer in 1886. Mustard gas was first used 
             as a chemical warfare agent in 1917.
 
        3.2  Chemical structure (formula, molecular weight)
 
             (ClCH2CH2)2S
 
               CH2CH2Cl
              / 
             S 
              \ 
               CH2CH2Cl
 
             MW 159.08
 
 
        3.3  Physical properties
 
             3.3.1  Colour
 
                    Colourless or yellow liquid (1 atm. and 
                    15C).
 
             3.3.2  State/form
 
                    Oily liquid at 1 atm. and 15C.
 
             3.3.3  Description
 
                    Melting point:  13 to 14C
                    Boiling point: 215  to 217C
                    Vapour pressure at:   0C  0.025 mm
                                          30C  0.090 mm
                    Solubility: very sparingly in water; soluble in fats 
                    and organic solvents.
                    Heavier than water.
                    Weak mustard or garlic like odour.
 
        3.4  Other characteristics 
 
             Hydrolysed by water to thiodiglycol and hydrochloric 
             acid.  Half life for hydrolysis is 5 minutes at 37C. 
             Hydrolysis is catalysed by increased temperature and presence 
             of alkalies.  Oxidized by bleaching powder and chloramines 
             into sulfoxides (harmless) and sulfones (possess vesicant 
             activity) and sulfides.
             
             Vapour has marked penetrating power; penetrates cloth, 
             leather, wood and paint on metallic surfaces. Metal, glass 
             and glazed tiles are impermeable.  Persistent in the 
             environment. Hydrolyses with water only occurs after thorough 
             mixing. Since it is heavier than water it sinks and it is 
             believed that it can provide a continuing local source of 
             poison for some time. Dangerous oily film of sulphur mustard 
             remains on the water surface.
             
             Contact with sea water turns mustard gas from its normal 
             liquid state to viscous or even solid one. It is believed 
             that large quantities lie loose in lumps on the sea bed of 
             Baltic sea where gas bombs were dumped at the end of the 
             second world war (Perera & Thomas, 1987).
             
             It decomposes at high temperatures and produces toxic 
             compounds containing sulphur and chlorine oxides with strong 
             lachrymatory actions.

 
    4.  USES/HIGH RISK CIRCUMSTANCES OF POISONING
 
        4.1  Uses
 
             4.1.1  Uses
 
             4.1.2  Description
 
                    In chemical warfare with intention to:
                    
                    (a) to prevent or delay certain activities within 
                    restricted areas;
                    
                    (b) to disturb or exhaust personnel by compelling them 
                    to wear respirators or to remain on gas-proof premises 
                    for lengthy periods (under special weather conditions 
                    only) (Lundquist, 1983).
                    
                    It may be used as liquid or vapour and may be 
                    delivered by artillery shell, rocket, bomb or aircraft 
                    spray.
                    
                    The use is likely to be influenced by the following 
                    meteorological factors:
                    
                    (a) Temperature. High temperatures increase the 
                    toxicity of mustard gas. Low temperature may freeze it 
                    and so increase its persistence. The danger of 
                    carrying such an agent into a warm building on boots 
                    and equipment and so giving off toxic vapour, should 
                    be born in mind.
                    
                    (b) Rain. Heavy rain reduces its toxicity.
                    
                    (c) Atmospheric stability. Persistence of vapour is 
                    prolonged by inversion (the air temperature higher 
                    than that of the ground).
 
        4.2  High risk circumstances of poisoning
 
             Mustard gas is suitable for tactical attacks in limited 
             operations or restricted areas putting army personnel at the 
             highest risk of exposure. Civilian inhabitants in the 
             neighbourhood of military activities may be exposed to some 
             risk of being affected by both chemical contamination and 
             drifting chemical clouds (Lundquist, 1983).  Due to its 
             persistency mustard gas can remain in the ground and in water 
             for a long time especially so in cold conditions. Exposure 
             may therefore occur some time after the attack. 
             
             Furthermore 'accidental' release following an attack on 
             stocks of mustard gas can cause several casualties as well as 
             severe environmental damage (Marshall, 1987).
             
             Accidental exposure may occur during dumping of unused 
             mustard gas or during coincidental encounters with improperly 
             disposed of containers.
             
             Food and water are easily contaminated when exposed to liquid 
             or vapour forms of mustard gas. Intoxication is likely 
             following ingestion of contaminated food and water. Mustard 
             gas is freely soluble in oils and fats and large quantities 
             can be absorbed by food with a high fat content. Only food 
             sealed in impermeable containers such as tins, glass or 
             glazed earthenware jars and foil wrappings is completely 
             protected (See Section 12.2 for Decontamination of food and 
             water). 
             
             Laboratory workers involved in organic synthesis of sulphur 
             mustard and also health professionals, who are involved in 
             the caring of the patients and handling of blister fluids, 
             are at risk.
 
        4.3  Occupationally exposed populations
 
             Military staff in the battle field are at risk of acute 
             exposure in case of chemical warfare. Chemical accidents with 
             sulphur mustard may occur during manufacturing, 
             transportation, storage and use.
             
             Workers employed in the manufacture of mustard gas are 
             believed to be at risk of developing cancers of the oral 
             cavity and the respiratory tract (Wada et al. 1968,  Easton 
             et al. 1988).
 
    5.  ROUTES OF ENTRY
 
        5.1  Oral
 
             Oral exposure is likely if food or water are 
             contaminated with mustard gas.  Air that is polluted with 
             sulphur mustard may cause oesophagogastric damage if 
             swallowed.
 
        5.2  Inhalation
 
             Usual route of entry.

 
        5.3  Dermal
 
             Mustard gas has a marked penetrating power making skin a 
             common route of entry.
 
        5.4  Eye
 
             Usual route of entry.
 
        5.5  Parenteral
 
             Unknown.
 
        5.6  Others
 
             Unknown.
 
    6.  KINETICS
 
        6.1  Absorption by route of exposure
 
             Mustard gas is absorbed in the respiratory tract when 
             inhaled.
             
             It has been demonstrated that 80%  of sulphur mustard applied 
             to the skin evaporates, 10% remains in the skin and 10% gets 
             absorbed systemically (Renshaw, 1946). It can penetrate the 
             skin by contact with either the liquid or vapour. The rate of 
             penetration is proportional to dose, temperature and 
             humidity.
 
        6.2  Distribution by route of exposure
 
             Equilibrium between blood and tissues was achieved 
             within 5 minutes after perfusion of the lung in dog (IARC, 
             1975).
             
             Mustard gas is highly fat soluble and expected to accumulate 
             in those tissues with a high fat content.
             
             Levels of mustard in the tissues of an Iranian patient who 
             died 7 days after exposure to mustard gas were qualitatively 
             analysed (Drasch et al., 1987). The concentrations of sulphur 
             mustard determined by GC/MS and atomic absorption 
             spectrophotometer in the tissues were as follows:
             
             fat (from thigh)             15.1 mg/kg
             brain                        10.7 mg/kg
             abdominal skin               8.4 mg/kg
             kidney                       5.6 mg/kg
             muscle                       3.9 mg/kg
             liver                        2.4 mg/kg
             cerebrospinal fluid          1.9 mg/L
             spleen                       1.5 mg/kg
             blood                        1.1 mg/L.
 
        6.3  Biological half-life by route of exposure
 
             The precise half life is not known.
             
             The parent compound could be detected in human urine up to a 
             week after acute exposure but not several days later 
             (Vycudilik, 1985).
 
        6.4  Metabolism 
 
             Metabolic studies with radioactively labelled mustard 
             gas were performed in rodents (Somani & Babu, 1989). The 
             following metabolic pathways were proposed: hydrolyses to 
             thiodiglycol and S-oxidation to sulfoxide and sulfone, 
             followed by conjugation. Urinary metabolites in rats 
             consisted of thiodiglycol and conjugates (15%), 
             glutathione-bis-beta-chloroethylsulfide conjugates (45%), 
             glutathione-bis-beta chloroethylsulfone (7%), 
             bis-beta-chloroethylsulfone and conjugates (8%), and small 
             amounts of cysteine conjugates.
             
             Urinary metabolites formed from intraperitoneal injection in 
             rats were bis-cysteinylethylsulfone and thiodiglycol.
 
        6.5  Elimination and excretion by route of exposure
 
             The urinary excretion of unmetabolized  sulphur mustard 
             is low (Drasch et al., 1987). This is probably caused by its 
             strong fixation to the lipid compartments of the body (See 
             6.2).
             
             The major portion of mustard gas excreted in the urine 
             represents compounds formed by alkylation, followed by 
             metabolites formed by enzymatic action.
             
             The majority of an intravenously-injected dose of 1.5 mg/kg 
             35S-mustard gas was excreted in the urine within 72 hours in 
             mice and rats; approximately 6% was eliminated in the faeces 
             (IARC, 1975).
 
    7.  TOXICOLOGY
 
        7.1  Mode of action
 
             Sulphur mustard is an alkylating agent. Alkylating 
             agents bind covalently to various nucleophilic molecules such 
             as DNA, RNA, proteins and components of cell membranes 
             (Somani & Babu, 1989).
             
             DNA: Mustard gas causes cross linking of DNA strands. 
             Alkylation of DNA can result in the disruption of its 
             function, i.e. coding errors, breakage of the strand, low 
             fidelity repair, inhibition of replication and cell 
             death.
             
             It has been proposed that DNA damage can be followed  by 
             release of plasminogen activator which may play a role in 
             skin blistering by disrupting the dermal-epidermal 
             junction.
             
             RNA: Alkylation of RNA molecules can result in altered 
             translation and altered protein synthesis resulting in cell 
             death.
             
             Proteins: Binding to proteins mainly with the thiol group of 
             cysteine produces structural changes which may alter the 
             normal physiology of the cell i.e. altered enzyme 
             activity.
             
             Membranes: Mustard gas can either alkylate structural 
             proteins located in the cell membrane or induce lipid 
             peroxidation which may result in irreversible changes and 
             cell death.
             
             NAD+ depletion: The cell has a capacity to repair damaged DNA 
             but the repair process can further disrupt functioning of the 
             cell. Enzymes involved in the DNA repair mechanism utilise 
             NAD+ and cause NAD+ depletion. Consequently glycolysis 
             becomes inhibited which could lead to  cell death 
             (Papirmeister, 1983).
 
        7.2  Range of toxicity
 
             7.2.1  Human data

 
                    7.2.1.1  Adults
 
                             Death has been recorded by dermal 
                             exposure after 1 hour at 64 mg/kg, and by 
                             inhalation at 1500 mg min/m3 (Marshall, 
                             1987).
                             
                             The toxicity of mustard gas vapour is 
                             expressed in terms of the profile of exposure 
                             (Ct) in mg min/m3, and that of liquid in 
                             g/cm2. 
                             
                             Effects on eyes:
                             
                             50 mg min/m3  maximum safe dosage
                             70 mg min/m3  mild reddening of the eyes
                             100 mg min/m3  partial incapacitation due to 
                             eye effects
                             200 mg min/m3  total incapacitation due to 
                             temporary blindness
                             
                             Effects on skin:
                             
                             100 to  400 mg min/m3  erythema
                             200 to 1000 mg min/m3  skin burns
                             750 to10000 mg min/m3  severe incapacitating 
                             skin burn
                             50 g/cm2 erythema in 5 min.
                             250-500 g/cm2 blistering in 5 min.
                             
                             Increased temperature enhances the effects.
 
                    7.2.1.2  Children
 
                             Not known.
 
             7.2.2  Relevant animal data
 
                    LD50 (percutaneous):rat 9 mg/kg
                                          dog 20 mg/kg
                                          rabbit 100 mg/kg
                    
                    LC50 (inhalation):    rat 100 mg/m3 for 10 minutes
                                          rabbit 280 mg/m3 for 10 minutes
                                          monkey  80 mg/m3 for 10 minutes

 
             7.2.3  Relevant in vitro data 
 
                    Mutagenicity and genotoxicity of mustard gas 
                    were observed in several in vitro tests such as 
                    bacterialscreening tests, human Hela cells and mouse 
                    lymphocytes (Dabney, 1989).
                    
                    Increased sister chromatid exchanges were seen in 
                    lymphocytes of exposed fishermen (Wulf, et al. 
                    1985).
 
             7.2.4  Workplace standards
 
                    McNamara et al., (1975) proposed the following 
                    workplace standards with personal protective 
                    devices:
                    
                    Ceiling               0.4   mg/m3
                    CL - 6 minutes        0.3   mg/m3
                    CL - 3 hours          0.01  mg/m3
                    CL - five 8 hour days 0.003 mg/m3.
                    
                    A ceiling is the concentration that must not be 
                    exceeded for any period of time and places a limit on 
                    the maximum upper excursion of concentration during 
                    the averaging hours.
                    
                    A control limit (CL) is the maximum average airborne 
                    concentration of a substance to which it is believed 
                    that essentially all members of a specified population 
                    can be exposed for a specified period without adverse 
                    effects.
 
             7.2.5  Acceptable daily intake (ADI) and other guideline levels
 
                    ADI is not determined.
                    
                    Mc Namara et al. (1975) have also proposed the levels 
                    of exposure for the general population:
                    
                    Ceiling               0.01 mg/m3
                    CL -  3 hours         0.00033 mg/m3
                    CL -  8 hours         0.00017 mg/m3
                    CL - 72 hours         0.00001 mg/m3
                    
                    The definitions for a ceiling and a control limit (CL) 
                    are given in Section 7.2.4.

 
        7.3  Carcinogenicity
 
             Mustard gas is a well documented animal carcinogen and 
             is listed as an accepted human carcinogen (IARC, 1975). 
             Increased mortality from oral cavity and respiratory tract 
             cancer has been shown in several studies in humans exposed to 
             mustard gas, with risk of mortality being greater from 
             chronic occupational exposure than from sporadic exposure 
             (Case & Lea, 1955; Wada et al. 1968; Easton et al., 
             1988)
 
        7.4  Teratogenicity
 
             Teratogenic potential of orally administered sulphur 
             mustard was evaluated in rats and rabbits. Maternal toxicity 
             was observed at all concentrations of mustard gas but 
             significant fetal effects such as decreased weights, reduced 
             ossification and skeletal anomalies were observed only at the 
             highest dose (2 mg/kg). It was concluded that sulphur mustard 
             is not teratogenic in rats and rabbits (Somani & Babu, 
             1989).
             
             However, nitrogen mustards, compounds related to sulphur 
             mustard and used in cancer chemotherapy were shown to be 
             teratogenic in all laboratory species tested (Schardein, 
             1985). Multiple defects including cleft palate, central 
             nervous system, jaw, limb and digit abnormalities were 
             observed. In humans, digital defects and kidney malformations 
             were described.
 
        7.5  Mutagenicity
 
             Simple mutations, structural chromosomal aberrations, 
             sex chromosome loss and nondisjunction and heritable 
             translocations have all been observed in numerous in vitro 
             tests (Dabney, 1989).
             
             Sister chromatid exchanges were measured in fishermen exposed 
             to leaking mustard gas shells (Wulf et al., 1985) and were 
             found to be significantly higher than in a control group 
             matched for sex, age and tobacco consumption.
 
        7.6  Interactions
 
             No information found.
 
    8.  Toxicological analyses
 
        To be completed. 

 
    9.  CLINICAL EFFECTS
 
        9.1  Acute poisoning
 
             A characteristic feature of exposure to sulphur mustard 
             is an asymptomatic period which may last for up to two hours. 
             The duration of this latent period depends on the mode of 
             exposure, environmental temperature and individual 
             sensitivity.
 
             9.1.1  Ingestion
 
                    A few hours after ingestion nausea, vomiting, 
                    abdominal pain, bloody vomiting and diarrhoea, and in 
                    cases of severe poisoning shock and prostration, may 
                    be expected. Systemic toxic effects in the respiratory 
                    tract, skin, eye, and bone marrow may occur 
                    thereafter.
 
             9.1.2  Inhalation
 
                    20 to 60 minutes post exposure: Usually none, 
                    but nausea, retching, vomiting and eye smarting can 
                    occur. Respiratory irritation with coughing and 
                    dyspnoea may also occur.
                    
                    2 to 6 hours post exposure: Nausea, fatigue, headache, 
                    rhinorrhea, sore throat. Voice becomes hoarse and may 
                    be completely lost. Pulse and respiratory rate are 
                    increased. Eye symptoms and signs are described in 
                    Section 9.1.4.
                    
                    6 to 24 hours post exposure: Increase in severity of 
                    above effects.
                    
                    48 hours post exposure: Severe coughing, mucus, pus 
                    and slough may be expectorated.
                    
                    4 days or more post exposure: Initial leukocytosis 
                    followed by leucopenia.
 
             9.1.3  Skin exposure
 
                    20 to 60 minutes post exposure: Usually none, 
                    but a mild erythema with pruritus may occur.
                    
                    2 to 6 hours post exposure: Nausea, fatigue, headache, 
                    reddening of the face and neck, increased pulse and 
                    respiratory rate. 
                    
                    6 to 24 hours: Increase in severity of above effects. 
                    Inflammation of inner thighs, genitalia, perineum, 
                    buttocks, axillae followed by blister formation. 
                    Blisters vary in size are pendulous and filled with 
                    clear yellow fluid.
                    
                    48 hours post exposure: condition worsened. Marked 
                    blistering, intense itching of the skin and increased 
                    skin pigmentation occur.
                    
                    4 days or more post exposure: leucopenia.
 
             9.1.4  Eye contact
 
                    20 to 60 minutes post exposure: usually none, 
                    but eye smarting is possible.
                    
                    2 to 6 hours post exposure: inflammation, intense 
                    pain, lachrymation, blepharospasm, photophobia.
                    
                    1 to 10 days post exposure: corneal epithelial loss 
                    and stromal opacification.  Secondary infection and 
                    uveitis may occur, but are uncommon.  Late: 
                    abnormalities of limbal and vascular bed, ischemia and 
                    ulceration.
 
             9.1.5  Parenteral exposure
 
                    Not known.
 
             9.1.6  Other
 
                    Not known.
 
        9.2  Chronic poisoning
 
             9.2.1  Ingestion
 
                    Not known.
 
             9.2.2  Inhalation
 
                    Increased incidence of cancer of oral cavity 
                    and respiratory tract was reported among workers 
                    employed in the manufacture of mustard gas (Wada et 
                    al. 1968, Easton et al. 1988).
                    
                    Nishimoto et al. (1970) found high prevalence of 
                    chronic obstructive lung disease in workers exposed 
                    repeatedly to mustard gas or lewisite.
                    
                    Delayed toxic effects, mainly on the respiratory tract 
                    (obstructive and restrictive lung disease), and 
                    malignancy may occur years after a single 
                    exposure.
 
             9.2.3  Skin exposure
 
                    Exposure may result in diffuse changes of skin 
                    pigmentation with areas of hyperpigmentation and 
                    hypopigmentation and scarring of the skin.
 
             9.2.4  Eye contact
 
                    Direct exposure of sulphur mustard droplets to 
                    the eyes have occured amongst Iranian combatants in 
                    the field. As a result erosive keratoconjunctivitis 
                    and blepharospasms occured.
 
             9.2.5  Parenteral exposure
 
                    Not known.
 
 
             9.2.6  Other
 
                    Not known.
 
        9.3  Course, prognosis, cause of death
 
             Most of the victims with minimal exposure to mustard gas 
             recover without any consequences.
             
             The majority of eye lesions are resolved in 28 days post 
             exposure. 
             
             Superficial skin lesions heal in 14 to 21 days, while deep 
             skin lesions may be expected to heal in up to 60 days. 
             However, residual scaring with itching may last up to 10 
             years and longer.
             
             The time course for the resolution of respiratory tract 
             lesions is difficult to predict but lung function tests may 
             provide a useful guide. Initial obstructive lung disease 
             followed by restrictive lung disease. 
             
             Initial leukocytosis followed by leucopenia is a usual 
             finding in mustard gas poisoning and recovers within 14 days. 
             Marked leucopenia is a sign of sinister prognosis, leading to 
             overwhelming infection and multiple organ failure and 
             death.
             
             Death may also result due to pulmonary oedema, Adult 
             respiratory distress syndrome, airway obstruction, arrythmias 
             and cardiac arrest.
 
        9.4  Systematic description of clinical effects
 
             9.4.1  Cardiovascular
 
                    Acute: Arrhythmias - AV block and possibly 
                    cardiac arrest (NATO, 1973).
                    
                    Chronic: None described.
                    
                    Acute-on-chronic: None described.
 
             9.4.2  Respiratory
 
                    Acute: Coughing and tachypnoea.  Inflammation 
                    of bronchial mucosa with bleeding, purulent 
                    secretions, and sloughing of the necrotic mucosa. 
                    Haemorrhagic oedema in peribronchial alveoli.  In 
                    severe cases a syndrome similar to adult respiratory 
                    distress syndrome can develop.
                    
                    Chronic: Chronic bronchitis.  Bronchial stenosis. 
                    Significantly increased incidence (p < 0.001) of lung 
                    cancer  was reported in workers employed in the 
                    manufacture of mustard gas (Easton et al., 1988). Wada 
                    et al. (1968) observed an increased incidence of 
                    cancer, while Nishimoto et al. (1970) reported an 
                    increased incidence of chronic obstructive lung 
                    disease in Japanese factory workers involved in 
                    production of mustard gas.  
                    
                    Acute respiratory tract infections were shown to be a 
                    more common cause of death in the elderly exposed to 
                    mustard gas compared to the un-exposed (Easton et al., 
                    1988).
 
             9.4.3  Neurological
 
                    9.4.3.1  CNS
 
                             Acute: Apathy, mental disturbance 
                             and anxiety states were reported among 
                             soldiers exposed to mustard gas during the 
                             First World War. Neuropsychiatric disorders 
                             including insomnia, anxiety, agitation, 
                             depression and acute psychosis were observed 
                             in Iranian combatants.
                             
                             Chronic: The above features may persist for 
                             some time.
                             
                             Occasionally chronic psychosis with a poor 
                             response to treatment has occured.
 
                    9.4.3.2  Peripheral nervous system
 
                             Cases of peripheral polyneuropathy 
                             have been observed.
 
                    9.4.3.3  Autonomic nervous system
 
                             None described.
 
                    9.4.3.4  Skeletal and smooth muscle
 
                             None described.
 
             9.4.4  Gastrointestinal
 
                    Acute: Nausea, vomiting, abdominal pain, bloody 
                    diarrhoea. 
                    
                    Chronic: Perforation, bleeding and late stricture 
                    formation can result from burns in the 
                    gastrointestinal tract.
 
             9.4.5  Hepatic
 
                    None described. 
                    
                    Transient elevation of transaminases were observed in 
                    Iranian patients with sulphur mustard 
                    poisoning.
 
             9.4.6  Urinary
 
                    9.4.6.1  Renal
 
                             None described.
                             
                             Transient elevation of proteinuria and 
                             haematuria were observed in Iranian 
                             patients.
 
                    9.4.6.2  Other
 
                             None described.

 
             9.4.7  Endocrine and reproductive systems
 
                    None described.
                    
                    Cases of abnormal sperm shape, oligospermia and 
                    occasionally azospermia were observed in Iranian 
                    patients.
 
             9.4.8  Dermatological
 
                    Acute: (a) Striking erythema of the skin, 
                    accompanied by intense itching particularly in 
                    axillary and genito perineal areas. As erythema fades, 
                    areas of increased pigmentation appear; (b) Blistering 
                    of the skin. Blisters vary in size, are delicate and 
                    can be easily rubbed off. Rubbing can lead to the 
                    development of new crops of blisters (Nikolsky's 
                    sign), which can appear as late as two weeks post 
                    exposure.  Blisters are uncomfortable and may feel 
                    tense, but are not painful. However, when they appear 
                    over joints, they are reputedly painful and may hinder 
                    movement of these joints. Blisters are filled with 
                    fluid which may cause blistering if applied to skin. 
                    Healing is characterised by hyper and 
                    hypo-pigmentation changes; (c) Deep burning, which can 
                    lead to full thickness skin loss, accompanied with 
                    severe pain. Skin burns characteristically take longer 
                    to heal than typical thermal burns. 
                    
                    Chronic: Diffuse changes of skin pigmentation with 
                    areas of hyperpigmentation.  Scarring of the 
                    skin.
 
             9.4.9  Eyes, ears, nose, throat: local effects
 
                    Acute:
                    
                    Eyes: marked conjunctivitis, local oedema, 
                    blepharospasm, lachrymation, miosis, photophobia, 
                    severe eye pain. 
                    
                    Nose: profuse rhinorrhea and  rarely epistaxis.
                    
                    Oral cavity, pharynx, larynx: inflammation and 
                    ulceration of the palate, nasopharynx, oropharynx and 
                    larynx, with hoarseness of voice and temporary 
                    aphonia.
                    
                    Chronic: 
                    
                    Eyes: corneal ulceration, adhesions of the iris to the 
                    lens capsule, visual impairment and permanent 
                    blindness.
                    
                    Oral cavity, pharynx, larynx: Increased incidence of 
                    cancer was reported in British workers employed in the 
                    production of mustard gas (Easton et al., 
                    1988).
 
             9.4.10 Haematological
 
                    Acute: Early leucocytosis, followed by mild 
                    leucopenia.   Severe leukopenia, trombocytopenia and 
                    erythropenia indicate bone marrow depression.
                    
                    Chronic: Bone marrow depression leading to leukaemia.
 
             9.4.11 Immunological
 
                    Immunosuppression, by sulphur mustard, 
                    observed  either as cellular (mainly T-cells) or 
                    humoral (IgA suppression) was observed in Iranian 
                    patients.
                    
                    Acute: See 9.4.13. 
                    
                    Chronic: See 9.4.13.
 
             9.4.12 Metabolic
 
                    9.4.12.1 Acid-base disturbances
 
                             Acute: Tachypnoea may cause 
                             respiratory alkalosis which may be followed 
                             by acidosis due to pulmonary oedema and 
                             chemical burns.
                             
                             Chronic: None described.
 
                    9.4.12.2 Fluid and electrolyte disturbances
 
                             Acute: Dehydration.
                             
                             Chronic: None described. 
 
                    9.4.12.3 Other
 
                             None described.
 
             9.4.13 Allergic reactions
 
                    Acute: Cutaneous sensitization may occur from 
                    repeated exposure of 1 to 3 weeks.
                    
                    Chronic: Sensitivity to mustard gas. A morbilliform 
                    rash and eczematoid dermatitis around old skin lesions 
                    are characteristic of sensitization reactions (NATO, 
                    1973).
                    
                    Acute-on-chronic: Sensitized individuals may have a 
                    shorter latent period than nonsensitized persons for 
                    development of dermal symptoms (NATO, 1973).
 
             9.4.14 Other clinical effects
 
                    None described.
 
             9.4.15 Special risks
 
                    Pregnancy: The risk for the development of 
                    fetal malformations following the exposure to nitrogen 
                    mustards was estimated to 1:3 (Schardein, 1985), but 
                    no information was found on sulphur mustard. Fetal 
                    abnormalities such as cleft lip was observed in a few 
                    cases of the Iranian victims.
                    
                    Breast feeding: No information found, but due to high 
                    solubility of mustard gas in fats it could be expected 
                    that it would appear in the milk of the exposed 
                    lactating mothers.
                    
                    Enzyme deficiency: No data available.
 
        9.5  Other
 
             None described.
 
 
    10. MANAGEMENT
 
        10.1 General principles
 
             Management of mustard gas poisoning consists of 
             decontamination and symptomatic treatment. The importance of 
             rapid and efficient decontamination can not be 
             overemphasized.
 
        10.2 Relevant laboratory analyses

 
             10.2.1 Sample collection
 
                    To be completed.
 
             10.2.2 Biomedical analysis
 
                    Full blood count, serum electrolytes, urea, 
                    protein levels. Arterial blood gasses determination is 
                    indicated in case of pulmonary toxicity.
                    
                    Culture of sputum and eye exudate.
                    
                    Blood cultures where indicated.
                    
                    Skin blisters may be aspirated and the fluid obtained 
                    analysed for thiodiglycol. The same estimation may be 
                    performed in blood and urine in order to differentiate 
                    blistering produced by mustard gas from that produced 
                    by other agents such as Lewisite. Contents of blisters 
                    are not toxic to attendants. (Sulzberger, 
                    1943).
 
                    10.2.3 Toxicological analysis 
 
                             To be completed.
 
        10.3 Life support procedures and symptomatic/specific treatment
 
             Life support:
             
             Mantain respiratory and circulatory function.
             
             Replace extracellular fluid loss, electrolytes and proteins.
             
             Blood transfusion is indicated in case of bone marrow depression.
             
             Symptomatic treatment:
             
             GENERAL:
             
             Analgesics. The choice of analgesic depends on the severity 
             of pain in each individual. Mild analgesics can be given 
             together with diazepam to dissociate pain from panic. Routine 
             use of morphine is contraindicated due to its depression of 
             respiration.  Carbamazepine 200 mg thrice daily has been 
             reported to control intense burning pain during skin healing 
             (Newman-Taylor & Morris, 1991).  Give appropriate antibiotics 
             as indicated.   Antiemetics, i.e. phenothiazines if vomiting 
             persits.

             SKIN: 
             
             Bland lotions (Prapoderm) for erythema and mild blistering. 
             Silver sulphadiazine. Corticosteroid preparations (i.e. 
             Hydrocortisone lotion, Beclomethasone dipropionate) reduce 
             irritation and itching.   Antihistamines (i.e. promethazine, 
             dimethidine) can be of value in reducing itching.  Skin 
             grafting may occasionaly be necessary in full thickness 
             burns.
             
             EYES:
             
             Start immediate irrigation with normal saline or water. Use 
             Vaseline on follicular margins to prevent sticking.  Avoid 
             cocaine because it may produce sloughing of the corneal 
             epithelium.  Topical corticosteroids (i.e. 1% prednisolone 
             four times a day) should be continued until all signs of 
             inflammation have gone in order to prevent late corneal 
             dissolution. In case of corneal erosion and keratitis topical 
             corticosteroid must not be used. Use Chloramphenicol eye 
             drops, as appropriate.  Mydriatics i.e. hyoscine (0.5%) is 
             administered to prevent sticking of the iris to the lens. 
             Dark glasses may alleviate photophobia.  Give reassurance 
             that ocular and visual recovery is usual.  Contact lenses are 
             contraindicated.  Topical ascorbate and citrate drops are 
             indicated when severe burns with limbal ischaemia and 
             epithelial defects persist for more than 5 days and are 
             accompanied by structural changes. Apply 10% potassium 
             ascorbate and 10% sodium citrate alternatively each once an 
             hour (half hourly drops) for 14 hours. These drops can be 
             safely discontinued when a stable epithelial covering 
             develops.  Seek ophthalmological opinion.
 
        10.4 Decontamination
 
             Remove victims from the source of decontamination.
             
             Eye decontamination:  Irrigate the eyes immediately with 
             copious amounts of normal saline or water for at least 15 
             minutes.
             
             A solution of diluted infant shampoo may be useful for eye 
             decontamination. 
             
             Skin decontamination: Remove any contaminated clothing.  Wash 
             exposed area thoroughly with water and neutral soap.  Areas 
             of liquid contamination should be decontaminated using 
             Fullers' earth.  Washing with organic solvents such as 
             paraffin oil followed by the use of soap and water has also 
             been recommended.

             Gut decontamination: Emesis should not be induced.  Gastric 
             lavage is indicated after ingestion of mustard gas. Airways 
             should be protected by cuffed endotracheal intubation. Prior 
             to gastric lavage stomach contents should be diluted by 100 
             to 200 ml of milk or water.   Activated charcoal is of 
             unproven benefit but may be used.
 
        10.5 Elimination
 
             No reliable method established.
 
        10.6 Antidote treatment
 
             10.6.1 Adults
 
                    No specific antidote is available. See 10.7.
 
             10.6.2 Children
 
                    No specific antidote is available. See 10.7.
 
        10.7 Management discussion 
 
             Bone marrow depression in severe intoxicated patients 
             may be seen as an irreversible consequence of mustard gas 
             poisoning. Granulocyte, platelet and red cell transfusions as 
             well as bone marrow transplantation have been recommended for 
             treatment of aplastic anaemia. The value of Granulocyte 
             Colony Stimulating Factor has not been assessed but may be of 
             use.
             
             Several independent scientists (Callaway & Pearce, 1958; 
             Fasth & Sorbo, 1973; Vojvodic et al., 1985) have shown that 
             cysteine, thiosulfate and other thiols reduce the toxicity of 
             sulphur and nitrogen mustards (Nitrogen mustards are used in 
             chemotherapy of malignant diseases). The use of thiols has 
             been proposed in the treatment of mustard gas poisoning, but 
             has not been established.
             
             Numerous other supportive measures were used in treating 
             causalties from the Iran-Iraq war: H2 antagonists to prevent 
             stress ulceration. Heparin has been used to prevent deep 
             venous thrombosis. A single large dose of methyl prednisolone 
             (2 g) may prevent general tissue damage.  Administration of 
             Vitamins C, B12 and folate may be of use.
             
             Haemodialysis and haemoperfusion have been suggested, 
             although there is no firm theoretical basis for such 
             therapy.

 
    11. ILLUSTRATIVE CASES
 
        11.1 Case reports from the literature
 
             Mustard gas was used  for the first time by Germans in 
             1917 at Ypres. More than 14,000 British casualties were 
             produced in the first three months and by the end of the 
             first world war more than 120,000 British mustard casualties 
             had occurred. The most commonly injured areas of the body 
             were: eyes (86.1%), respiratory tract (75.3%), scrotum 
             (42.1%), face (26.6%), anus (23.9%), back (12.9%), armpits 
             (12.5%), neck (12%). 
             
             Adolph Hitler was exposed to mustard gas during the first 
             world war. He described his personal experience in "Mein 
             Kampf" (Vol. 1, 1924): "During the night of October 13 to 
             14th (1918) the British opened an attack with gas on the 
             front south of Ypres. They used the yellow gas whose effect 
             was unknown to us, at least from personal experience. I was 
             destined to experience it that very night. On a hill south of 
             Werwick, in the evening of 13 October, we were subjected to 
             several hours of heavy bombardment with gas bombs, which 
             continued through the night with more or less intensity. 
             About midnight a number of us were put out of action, some 
             for ever. Towards morning I also began to feel pain. It 
             increased with every quarter of an hour, and about seven 
             o'clock my eyes were scorching as I staggered back and 
             delivered the last dispatch I was destined to carry in this 
             war. A few hours later my eyes were like glowing coals, and 
             all was darkness around me."
             
             During the second world war mustard gas was not used but 
             Lundquist (1983) reports of a large number of Allied soldiers 
             and sailors who were exposed to mustard gas towards the ends 
             of second world war as a result of German bombing of the 
             harbour at Bari in Italy. Of the two dozen ships destroyed, 
             one was carrying a cargo of about  100 thousand kilograms of 
             mustard-gas bombs. Much of the mustard gas was released into 
             the water and some of it dissolved in the floating oil. More 
             than 1000 people were killed and of these deaths more than 
             100 were determined to have been specifically caused by 
             mustard-gas poisoning and many more to have been due to 
             various indirectly associated reasons, such as disablement 
             followed by drowning.
             
             Eleven fishermen have become exposed to mustard gas from 
             leaking shells that were dumped into the Baltic sea after the 
             Second World War (Wulf et al., 1985). They presented with 
             very inflamed skin, especially in the axilla and in the 
             genitofemoral regions, yellow blisters on the hands and legs, 
             painful irritation of the eyes and transient blindness. In 
             two pulmonary oedema developed. Haemoglobin values, 
             leucocyte, differential and platelet counts, lactate 
             dehydrogenase and aspartate aminotransferase activities and 
             serum creatinine were normal. Sister chromatid exchange count 
             was significantly higher than in a control group. All the 
             fishermen  recovered, but might have an increased cancer 
             risk.
             
             It is believed that mustard gas was used by Iraq in the 
             recent war against Iran. Dunn (1986) reports of an attack in 
             1984 using aerial bombs which, upon exploding at ground 
             level, released a grey cloud with a garlic like smell. 
             Victims of the attack suffered severe eye, bronchial and lung 
             damage accompanied by a skin rash. Several deaths followed 
             acute pulmonary dysfunction. It has been suggested that 
             during this attack mustard gas had been released from a bomb 
             in a form of micronized aerosol particles which were 
             sufficiently small to create only a skin rash, rather than 
             the typical skin lesions.
             
             Bockmeyer (1985) reports of three Iranian patients who were 
             treated in Germany following exposure to mustard gas during 
             the Iran-Iraq war. They all suffered from first or second 
             degree skin burns, corrosive changes in the mouth and pharynx 
             and damage to the respiratory tract. In the second week 
             changes in the blood picture appeared with the impairment of 
             clotting. All three patients had to be ventilated and two of 
             them required tracheotomy. Daily lavage with Prednisolon-21 
             hemisuccinate sodium and Dexapanthenol solution was also 
             used. N-acetylcystein  was applied intravenously and as an 
             aerosol. All three patients recovered in three months.
             
             Leipner et al. (1987) describe a late sequel of poisoning 
             with mustard gas, not described in the literature to date, in 
             a 22 years old patient. The patient was admitted to the 
             hospital two years post exposure for dermatomyositis. Chest 
             X-ray revealed lung fibrosis, mediastinal emphysema and 
             pulmonary hypertension. CAT scan of the thorax confirmed the 
             X-ray findings. Fibrosis was located in the dorsobasal 
             periphery of the right lung. Perivascular collections of air 
             were observed in the left lung communicating via the left 
             hilus with the mediastinal emphysema. This finding suggested 
             the presence of bronchial or lung parenchyma fistulas. 
             Bronchoscopy did not reveal any large defects in the trachea 
             and large bronchi. Lung function tests showed a restrictive 
             ventilatory disorder without a considerable obstructive 
             component.
             
             Thirty nine Iranian soldiers and doctors exposed to sulphur 
             mustard in the Iran-Iraq war were treated in the UK during 
             1985 and 1986 (Rees et al., 1991). They all suffered from 
             skin burns and most had mucosal damage and eye inflammation. 
             Severe cough which responded poorly to symptomatic treatment 
             was the most common respiratory effect.  Airflow obstruction 
             was a prominent feature. Low arterial PO2 was a common 
             finding. Chest x rays showed various abnormalities such as 
             lobar consolidation and widespread ill-defined opacities. 
             Three patients required artificial ventilation and two of 
             these died with respiratory, renal and bone marrow failure 7 
             and 14 days after exposure. In these patients remarkable 
             sloughing was shown in the tracheal and bronchial mucosa. 
             Bone marrow depression was common in patients with evidence 
             of moderate exposure. One patient died due to adrenal 
             haemorrhage associated with thrombocytopenia.
             
             Newman-Taylor and Morris (1991) reported about another five 
             Iranian soldiers treated in the UK in 1988, 11 days after 
             exposure to mustard gas. They had injuries of the skin, eyes, 
             mouth, upper respiratory tract and lungs. Skin burns involved 
             the exposed areas, axillae, buttocks and genitalia. The 
             treatment of skin burns included twice daily saline baths, 
             silver sulphadiazine cream dressings and paraffin gauze. Pain 
             was a prominent feature and was treated with opiates and 
             antihistamines. Carbamazepine 600 mg daily was successfully 
             used to control the pain unresponsive to opiates and 
             antihistamines. The eyes of the patients were severely 
             inflamed with a non-ulcerated keratitis and haemorrhagic 
             conjunctivitis which were treated with dexamethasone and 
             ascorbate drops 3-hourly. Three patients suffered severe 
             inflammation and ulceration of oral and laryngeal mucosae and 
             were treated with simple mouth washes. All patients had 
             productive cough, four of them had inspiratory crackles, 
             airway obstruction and hypoxemia. One patient had a lung 
             abscess caused by Methicillin resistant Staphylococcus 
             aureus. This patient also showed suppressed leucocyte 
             response to infection. Respiratory infections were treated 
             with antibiotics. The skin and the eyes recovered in 2 to 6 
             weeks without damage. The respiratory function improved 
             slowly but steadily during the six weeks of hospitalisation. 
             Nebulized bronchodilators were used but did not provide much 
             symptomatic or objective benefit.
             
             A follow up study of Japanese workers who were engaged in the 
             manufacture of mustard gas between 1929 and 1945 showed that 
             they had experienced 33 deaths from cancer of the respiratory 
             tract, compared with 0.9 expected. The tumours occurred 
             centrally and were of squamous or undifferentiated cell type 
             (Wada et al., 1968). 
             
             Easton et al. (1988) also provided evidence that chronic 
             exposure to mustard gas can cause cancers of respiratory 
             tract. Significant excesses of malignant tumours of oral 
             cavity, pharynx, larynx and lungs were observed among British 
             workers employed in manufacture of mustard gas during the 
             second world war. Incidence of deaths from nonmalignant acute 
             and chronic respiratory diseases was also increased.
             
             The reports on the possible long term respiratory effects of 
             acute exposure to mustard gas are controversial. One follow 
             up study on soldiers who were exposed to mustard gas during 
             the first world war suggests that mustard gas had no effect 
             on the development of lung cancer later in life (Case & Lea, 
             1955), while the other provided evidence that the incidence 
             was slightly increased among those war veterans exposed to 
             mustard gas (Beebe, 1960). It is probably unlikely that a 
             single exposure to mustard gas can cause cancer.
 
        11.2 Internally-extracted data on cases
 
             None available.
 
    12. ADDITIONAL INFORMATION
 
        12.1 Availability of antidotes 
 
             None established. See also 10.7.
 
        12.2 Specific preventative mesaures
 
             When food is suspected to be contaminated it should be 
             destroyed. However, where food is scarce the following 
             measures have been proposed (Ministry of Defence, 1987):
             
             All food that was exposed to liquid forms of mustard gas 
             should be destroyed.
             
             All high fat content food such as butter, fat, milk, cheese, 
             meat, bacon should be destroyed. 
             
             Low fat content food that has been contaminated with the 
             vapour form of mustard gas should be washed with 2% sodium 
             bicarbonate solution, peeled where applicable and cooked by 
             boiling. Low fat content dry foods should be exposed to the 
             air for 48 hours.
             
             Sugar, salt and  foods of high water content such as fruit 
             and vegetables, sugar, salt may be made unpalatable by the 
             formation of acid products of hydrolyses.
             
             Open water sources may become contaminated, but there is no 
             practicable means of decontaminating water in the field. 
             Water from deep sources such as springs and wells is likely 
             to be contaminated.

        12.3 Other
 
             Special equipment is available to test for the presence 
             of sulphur mustard in the environment.
 
    13. REFERENCES
 
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        Possible relation to mustard-gas injury and 1918 influenza 
        epidemic. J. Nat. Can. Inst., 25(6): 1231-1252.
        
        BOCKMEYER, M. (1985) [Documentation of mucosa alterations after 
        contact with poison gas (Lost)]. Laryng. Rhinol. Otol., 
        64: 532-534 (in German).
        
        CALLAWAY, S. & PEARCE, K. (1958) Protection against systemic 
        poisoning by mustard gas. Di (2-chloroethyl) sulphide, by sodium 
        thiosulphate and thiocit in the albino rat. Brit. J. Pharmacol. 
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        CASE, R.A.M. & LEA, A.J. (1955) Mustard gas poisoning, chronic 
        bronchitis and lung cancer. Brit. J. Prev. Soc. Med. 9: 62-72.
        
        DABNEY, B.J. (1989) Mustard gas. Poisindex Monographs. Micromedex 
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        DRASCH, G., KRETSCHMER, E., KAUERT, G. & von MEYER, L. (1987) 
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        DUNN, P. (1986) The chemical war: Journey to Iran. NBC Defense & 
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        EASTON, D.F., PETO, J. & DOLL, R. (1988) Cancers of respiratory 
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        FASTH, A. & SORBO, B. (1973) Protective effect of thiosulphate and 
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    14. AUTHOR(S), REVIEWER(S), ADDRESS(ES), DATE(S)
 
        Authors:    Dr L. Perharic Walton
                    National Poisons Unit
                    Guy's Hospital, London
                    Avonely Rd
                    London SE14 6TE
                    
                    Dr R.L. Maynard
                    Department of Health
                    Hannibal House
                    Elephant & Castle
                    London SE 1 5ER
 
                    Dr V.S.G. Murray
                    National Poisons Unit
                    Guy's Hospital, London
                    Avonely Rd
                    London SE14 6TE
                    
        Date:                May 1991
        Reviewer:            Dr J. Szajewski
                             Warsaw Poison Centre
        
        Peer Review:         17/10/95, INTOX-8, Berlin.
        Group:               Fountain J, Besbelli N, Borges A, Goto K, 
                             Hanafy M, and Burgess J.
        
        Finalised:           IPCS, September 1996
 
    



    See Also:
       Toxicological Abbreviations
       Mustard Gas (IARC Summary & Evaluation, Volume 9, 1975)