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Phosphine

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/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 substance
   3.2 Chemical structure
   3.3 Physical properties
      3.3.1 Colour
      3.3.2 State/form
      3.3.3 Description
   3.4 Hazardous 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 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
   7.3 Carcinogenicity
   7.4 Teratogenicity
   7.5 Mutagenicity
   7.6 Interactions
8. TOXICOLOGICAL/TOXINOLOGICAL ANALYSES AND 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 and 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 and 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 and 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 (diagnostic) investigations and their interpretation
   8.5 Overall interpretation of all toxicological analyses and toxicological investigations
   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 Neurologic
         9.4.3.1 Central nervous system (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 Others
      9.4.7 Endocrine and reproductive systems
      9.4.8 Dermatologic
      9.4.9 Eye, ear, nose, throat
      9.4.10 Haematologic
      9.4.11 Immunologic
      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: Pregnancy, breastfeeding, enzyme deficiencies
   9.5. Others
   9.6 Summary
10. MANAGEMENT
   10.1 General principles
   10.2 Life supportive procedures and symptomatic treatment
   10.3 Decontamination
   10.4 Elimination
   10.5 Antidote
      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), DATE(S)
    PHOSPHINE

    International Programme on Chemical Safety
    Poisons Information Monograph 865
    Chemical

    1.  NAME

        1.1  Substance

             Phosphine

        1.2  Group

             Phosphorous hydride

        1.3  Synonyms

             Hydrogen phosphide; trihydrogen phosphide;
             phosphorus trihydrides; phosphoretted hydrogen; 2phospane;
             celphos; delicia; detia; gas-ex-B; celphos

        1.4  Identification numbers

             1.4.1  CAS number

                    7803-51-2

             1.4.2  Other numbers

                    DOT UN 2199 (DOT = Dept. of Transport)

        1.5  Main brand names/Trade names

             Al Pare Alutal; Celphide; Celphine; Celphos; Delicia Gas
             toxin; Detia Gas Ex-B/P/T; L-Fume; Phosphine; Phostex;
             Phostoxin; Quickfos; Zedesa

        1.6  Main manufacturers/main importers

             To be completed by each poison control centre.

    2.  SUMMARY

        2.1  Main risks and target organs

             Phosphine is a colourless gas which is odourless when
             pure, but the technical product has a foul odour, described
             as "fishy" or "garlicky", because of the presence of
             substituted phosphine and diphosphine (P2H4).
    

             Other impurities may be methane, arsine, hydrogen and
             nitrogen. For fumigation, it is produced at the site of
             hydrolysis of a metal phosphide (AlP, Zn3P2, Mg3P2)
             and supplied in cylinders either as pure phosphine or diluted
             with nitrogen.
    
             Phosphine is flammable and explosive in air and can
             autoignite at ambient temperatures.  It is slightly soluble
             in water and soluble in most organic solvents.  Metal
             phosphides are usually powders of various colours, which
             hydrolyse to yield phosphine and metal salts.
    
             Inhalation of phosphine may cause severe pulmonary irritation 
             leading to acute pulmonary oedema, cardiovascular
             dysfunction, CNS excitation, coma and death. 
             Gastrointestinal disorders, renal damage and leukopenia may
             also occur.
    
             Exposure to 1400 mg/m3 (1000 ppm) for 30 minutes may be
             fatal.
    
             Ingestion of phosphides, particularly aluminum and zinc
             phosphides, may induce severe gastrointestinal irritation
             leading to haemorrhage, cardiovascular collapse, acute
             neuropsychiatric disorders, respiratory and renal failure
             within a few hours.  Hepatic damage may develop later.

        2.2  Summary of clinical effects

             Initial clinical manifestations of mild phosphine
             inhalation mimic an upper respiratory tract infection.  Other
             symptoms may include nausea, vomiting, diarrhoea, headache,
             fatigue and dizziness.  In severe exposure, lung irritation
             with persistent coughing, ataxia, paraesthesia, tremor,
             diplopia and jaundice may also occur.  Very severe cases may
             progress to acute pulmonary oedema, cardiac dysrhythmias,
             convulsions, cyanosis and coma. Oliguria, proteinuria and
             finally anuria may be induced.
    
             Deliberate ingestion of phosphides, especially AID
             (Phostoxin), causes nausea, vomiting, and sometimes
             diarrhoea, retrosternal and abdominal pain, tightness in the
             chest and coughing, headache and dizziness. In severe cases,
             gastrointestinal haemorrhage, tachycardia, hypotension,
             shock, cardiac arrhythmias, hypothermia, metabolic acidosis,
             cyanosis, pulmonary oedema, convulsions, hyperthermia and
             coma may occur. Clinical features of renal insufficiency and
             hepatic damage including oliguria, and jaundice may develop
             later, if the patient does not die.
    

             Death, which may be sudden, usually occurs within four days
             but may be delayed for one to two weeks.  Postmortem
             examinations have revealed focal myocardial infiltration and
             necrosis, pulmonary oedema and widespread small vessel
             injury.
    
             Chronic poisoning from inhalation or ingestion of
             phosphine/phosphides may cause toothache, swelling of the
             jaw, necrosis of mandible, weakness, weight loss, anaemia,
             and spontaneous fractures.

        2.3  Diagnosis

             Major accidental release of stored phosphine presents
             serious toxic and explosion/fire hazards for man and even
             animals.  The diagnosis of phosphine poisoning is easy, but
             the clinical manifestations of phosphine and the phosphides
             may be similar to those of other toxic chemicals such as
             arsenic sulphide and calcium oxide.  A silver nitrate-
             impregnated paper test can be used for the breath and gastric
             fluid of the patients exposed to phosphine/phosphide: silver
             nitrate and phosphine/phosphides react to form silver
             phosphide which confirms the diagnosis.  Other laboratory
             investigations such as cell blood counts, haemoglobin,
             haematocrit, arterial blood gas analyses, renal and liver
             function tests and cardiopulmonary monitoring and
             investigations (ECG and chest X-ray) are essential for the
             assessment of organ effects and the management of
             phosphine/phosphide poisoning.

        2.4  First aid measures and management principles

             Remove the patient from exposure site, and keep at rest.
             If the patient is unconscious and breathing stops,
             immediately ventilate artificially and if the heart stops,
             begin cardiopulmonary resuscitation.  In case of ingestion,
             after consideration of tracheal intubation, perform gastric
             aspiration and lavage with cold water and preferably sodium
             bicarbonate solution (2%).  Do not give milk, fats or saline
             emetics.  Administration of repeated doses of activated
             charcoal through the gastric tube may be useful.  Monitor and
             support vital functions, particularly cardiopulmonary, G.I.,
             renal and hepatic functions.
    
             Treat shock conventionally and correct acidosis based on
             blood gas analyses.
    
             No antidote is available for phosphine/phosphide poisoning. 
             Early recognition and management of the poisoning is
             essential.

    3.  PHYSICO-CHEMICAL PROPERTIES

        3.1  Origin of substance

             Phosphine is extremely rare in nature.  It occurs
             transiently in marsh gas and other sites of anaerobic
             degradation of phosphorus-containing matter.
    
             Although phosphorus could be expected to occur naturally as a
             phosphide, the only phosphide in the earth's crust is found
             in iron meteorites as the mineral schreibersite (Fe,Ni)3P,
             in which cobalt and copper may also be found (WHO, 1988).
    
             Atmospheric phosphine results from emission and effluents
             from industrial processes and from the use of phosphides as
             rodenticides and fumigants.
    
             Unexpected focal release of phosphine may occur due to the
             action of water on phosphides present as impurities in some
             industrial materials. Although some phosphine is supplied in
             cylinders, it is often produced as and when required, by
             hydrolysis of a metal phosphide.  Phosphine is also produced
             as a by-product or evolved incidentally in various industrial
             processes (WHO, 1988; Casarett, 1991).

        3.2  Chemical structure

             Phosphine is trihydrogen phosphide
             Molecular formula: PH3
             Molecular weight: 34
    
             Metal phosphides that are commonly used as rodenticide and
             fumigants are:
    
             zinc phosphide (Zn3P2, CAS No. 1314-84-7, molecular
             weight = 258.1)
    
             aluminum phosphide (AlP, CAS No. 20859-73-8, molecular weight
             = 57.96)
    
             magnesium phosphide (Mg3P2, CAS No. 12057-74-8, molecular
             weight = 134.87)
    
             (Deichman & Gerarde, 1964; WHO, 1988).

        3.3  Physical properties

             3.3.1  Colour

                    Colourless

             3.3.2  State/form

                    Gas

             3.3.3  Description

                    Pure phosphine is a colourless gas at ambient
                    temperature and pressure.
                    Melting point: -133.5C
                    Boiling point -87.4C 
                    Phosphine is odourless when pure, at least up to a
                    concentration of 282 mg/m3 (200 ppm), which is
                    highly toxic level.  The odour of technical phosphine
                    depends on the presence of odoriferous impurities and
                    their concentrations and odour threshold is usually in
                    the range 0.14 to 7 mg/m3.
    
                    Pure phosphine has an autoignition temperature of
                    38C, but because of the presence of other phosphorus
                    hydrides, particularly diphosphine (P2H4), as
                    impurities, the technical product often ignites
                    spontaneously at room temperature.
    
                    Phosphine has intense ultraviolet absorption in the
                    185 to 250 nm (1850 to 2000 A) region.

        3.4  Hazardous characteristics

             Phosphine forms explosive mixtures with air at
             concentrations greater than 1.8%.  The relative molecular
             mass of phosphine is 34. It dissolves in water to form a
             neutral solution, but its water solubility is very low (0.25
             at room temperature).  Phosphine dissolves more easily in
             organic solvents, particularly in trifluoroacetic acid and
             carbon disulphide (Beliles, 1981).
    
             In air, the upper and lower explosion limits depend on the
             temperature, pressure, and proportion of phosphine, oxygen,
             inert gases and water vapour present, and also on the level
             of ultraviolet irradiation.  In aqueous solutions, oxidation
             of phosphine results in the production of hypophosphorous
             acid.
    
             The technical grade of phosphine contain impurities of higher
             phosphines (diphosphine) and substituted phosphines, which
             are responsible for the characteristic foul odour of
             phosphine which is often described as "fishy" or
             "garlicky".
    
             Depending on the method of manufacturer, other impurities may
             include methane, arsine, hydrogen and nitrogen (Polson et
             al., 1983).
    

             An important reaction of phosphine is with metal, especially
             with copper and copper-containing alloys, which causes severe
             corrosion. The reaction is enhanced in the presence of
             ammonia or moisture and salt.  Eighteen carat gold jewellery
             reacts at one-eighth of the rate of copper (WHO, 1988).
    
             Phosphine and the metal phosphides have only been detected in
             the general environment in relation to the recent use of
             metal phosphides in pest control and in relation to a number
             of industrial activities.
    
             The metal phosphides are solid with grey colour and melting
             points of more than 750C.  They hydrolyse very quickly and
             produce phosphine which is more toxic than the metal
             phosphide.
    
             The volumes released in industrial operations are much
             smaller and are therefore of less significance in relation to
             atmospheric pollution.
    
             Residues in fumigated foods are 0.01 mg/m3 (0.01 ppm) or
             less and are negligible. Higher residue levels may be found
             with storage at low temperature.  About 10% of the residues
             are water soluble and appear to be hypophosphite and
             pyrophosphate.  The remainder may have included insoluble
             aluminium salts (WHO 1988).
    
             Residue levels of phosphine in fumigated foods are generally
             regulated at 0.1 mg/kg (0.1 ppm) or sometimes 0.01 mg (0.01
             ppm). However, among populations whose diet in mainly derived
             from stored products, the daily intake would be unlikely to
             exceed 0.1 mg/day, even if the phosphine and phosphides
             survived cooking.

    4.  USES/HIGH RISK CIRCUMSTANCES OF POISONING

        4.1  Uses

             4.1.1  Uses

                    Fumigants
                    Pesticide for use on vertebrate animals

             4.1.2  Description

                    Phosphine is mainly used as a fumigant in pest
                    control.  Zinc phosphide is used as a rodenticide
                    because of its reaction with stomach acid in the
                    rodent to release phosphine.  For fumigation, the acid
                    has to be supplied.  Since they hydrolyse in neutral
                    moist conditions, aluminum and magnesium phosphides

                    are preferred as fumigants. Aluminum phosphide has
                    also been used as a rodenticide;  magnesium phosphide
                    may be used as a pesticide.
    
                    Zinc phosphide is available in bulk, typically to a
                    specification of at least 80% Zn3P2, and as paste
                    containing 5% or 2.5% for use as a rodenticide by
                    mixing in bait. Aluminum and magnesium phosphides are
                    available in a number of commercial formulations. 
                    Aluminum phosphide formulations usually contain
                    approximately 75% active ingredient and magnesium
                    phosphide products contain 43% active ingredient (WHO,
                    1988).

        4.2  High risk circumstances of poisoning.

             No subgroups of the general population have been
             identified to be at special risk from phosphine and the
             phosphides except children, who might find and eat bait
             containing phosphides.  Zinc phosphide pastes and tablets of
             zinc, aluminum and magnesium phosphides which are available
             without restriction in some countries may be used in suicide
             attempts.  Many reports of high mortality (> 50%) due to
             metal phosphide poisonings in India have recently been
             published.

        4.3  Occupationally exposed populations.

             Occupational exposure can be divided into 4 general
             categories: (a) workers producing phosphine and phosphides;
             (b) workers in operations that can release phosphine, e.g.,
             welding, metallurgy, semi-conductors (c) fumigators and
             pest-control operators; and (d) transport workers. e.g.
             drivers, seamen. Exposure patterns and the potential for
             control of exposure differ from case to case.
    
             Exposure to phosphine and phosphorus oxides, which occurs
             during the manufacture of metal phosphides, varies according
             to the method of manufacture.  High levels of exposure may
             occur in the direct methods involving the reaction of red
             phosphorus with powdered metal, in which the air phosphine
             concentrations of 0.4 to 1.6 mg/m3 (0.3 to 1.13 ppm) may
             occur.  Concentration of > 2 mg/m3 require the use of
             personal respiratory protection. 
    
             In recorded cases, atmospheric levels to which operatives
             were exposed while adding zinc/aluminum phosphides to wheat
             were undetectable. Levels encountered when stores were
             re-entered for loading or turning were much higher, ranging
             from 18 to 35 mg/m3 (13 to 25 ppm).
    

             Exposure to phosphine has also been described in the
             operation of acetylene generators and in the production of
             phosphorus. A badly ventilated cargo of ferrosilicon,
             particularly in barges, can release phosphine accidentally by
             the reaction of water with calcium phosphide, one of the
             impurities present.
    
             Many metals contain phosphorus in small amounts, and
             phosphine can be generated in a variety of metallurgical
             processes.
    
             Although phosphine is used extensively in semi-conductor
             manufacture, there are no published figures for occupational
             exposure in this industry.  There are also no published data
             relating to exposure to phosphine in the synthesis of
             organophosphine or phosphonium derivatives. The occupational
             exposure limit for phosphine in various countries differ from
             0.1 mg/m3 to 0.5 mg/m3 in long term and up to 1.5 mg/m3
             (1.1 ppm) in short term exposure (WHO, 1988; Deichmann &
             Gerarde, 1969).

    5.  ROUTES OF EXPOSURE

        5.1  Oral

             Deliberate oral ingestion of the metal phosphides,
             particularly AlP (Phostoxin), is not rare in some parts of
             the world.  Accidental oral ingestion of the metal
             phosphides, particularly zinc phosphide, have also been
             reported.

        5.2  Inhalation

             Inhalation is the commonest route of phosphine
             poisoning.

        5.3  Dermal

             The skin is not a common route of absorption of
             phosphine and phosphides. However, dermal absorption of zinc
             phosphide in rabbits was reported by US National Pest Control
             Association (WHO, 1988).

        5.4  Eye

             No data available.

        5.5  Parenteral

             Stephenson (1967) mentioned the possibility of zinc
             phosphide injection.

        5.6  Others

             No data available.

    6.  KINETICS

        6.1  Absorption by route of exposure

             Inhaled phosphine is generally considered to be rapidly
             absorbed through the lungs.  After inhalation, aluminum and
             magnesium phosphides deposited on the moist surfaces of the
             respiratory tract would release phosphine, but zinc
             phosphide, which hydrolyses significantly only under acid
             conditions, would be stable for some time.  However, the
             transfer of a proportion of inhaled zinc phosphide to the
             intestinal tract by particulate clearance mechanisms in the
             lung would permit hydrolysis to phosphine by gastric acid, as
             well as absorption of the zinc phosphide.  The lung also
             absorbs particles and it is known that zinc phosphide is
             absorbed intact from the gut. Inhaled zinc phosphide dust
             might be absorbed directly via the respiratory tract and then
             hydrolysed in the tissues.
    
             In the rat, ingestion of zinc phosphide results in detectable
             amounts of acid-hydrolysable phosphide in the liver. Human
             ingestion of tablets containing aluminum phosphide yielded
             evidence of acid-hydrolysable phosphide in blood and liver. 
             These results indicate that metal phosphides can be absorbed
             directly.  In the rat, recovery of phosphide from the
             following administration of zinc phosphide in corn oil was 4
             times higher than when administered in water, suggesting that
             absorption of unhydrolysed material is greater.
    
             In general, dermal absorption of phosphine and phosphides is
             insignificant.

        6.2  Distribution by route of exposure

             Inhaled phosphine produces neurological and hepatic
             symptoms suggesting that it reaches the nervous system and
             liver.  Ingested  phosphides have been shown to reach the
             blood and liver in rats and human beings. On the other hand,
             muscle tissue of animals poisoned with supralethal doses of
             zinc phosphide does not contain detectable levels of
             phosphine or phosphide and does not produce toxic effects
             when fed to test animals.  The presence of acid-hydrolyzable
             phosphide in the kidney and liver of a fatal case of zinc
             phosphide has been reported (WHO, 1988).

        6.3  Biological half-life by route of exposure

             The biological half-life of phosphine and phosphides in
             man has not been reported and may be difficult to estimate. 
             Experimentally, the amount of acid-hydrolyzable phosphide
             found in the liver of a rat fed phosphide for 15 days is
             nearly twice that of a rat fed for 7 days.  However, this
             limited study cannot be considered to provide evidence of a
             long biological half-life and/or the accumulation of metal
             phosphides (WHO, 1988).

        6.4  Metabolism

             Metal phosphides are hydrolysed to phosphine.  In the
             rat, phosphine that is not excreted in the expired air is
             oxidized and appears in the urine, chiefly as hypophosphite
             and phosphite.  The fact that (a) phosphine is incompletely
             oxidized; and (b) the proportion of an administered dose that
             is eliminated as expired phosphine increases with the dose,
             suggests that the oxidative pathway is slow (WHO, 1988). 
             Oxyhaemoglobin is denatured and a variety of enzymes are
             inhibited by reaction with phosphine (WHO, 1988).

        6.5  Elimination and excretion

             Zinc phosphide suspended in corn oil was given to rats
             by gavage and phosphine concentrations were measured in a
             metabolic chamber over the following 12 hours.  After doses
             of 0.5, 1, 2, 3 and 4 mg, the proportions of the administered
             doses as phosphine were 1.5%, 1.7%, 3.2%, 15.6% and 23.5%,
             respectively, but some or much of this could have been
             derived from faeces or intestinal gas rather than by
             desorption and exhalation.  Hypophosphite is the principal
             urinary excretion product (WHO, 1988).

    7.  TOXICOLOGY

        7.1  Mode of action

             Phosphine reduces the respiration of wheat partly by
             damaging the microflora present.  The activity of glutamate
             decarboxylase is reduced when the moisture content is 18% or
             more.  Alcohol dehydrogenase activity is reduced to zero
             within 7 days as a result of phosphine treatment of the grain
             at a moisture content of more than 24%.  Catalase activity in
             wheat is reduced by about 20% after 2 weeks exposure to
             phosphine fumigations.  Phosphine markedly inhibits
             respiration and the growth of microorganisms in wheat with a
             moisture content up to 29%.  The amount of adenosine
             triphosphate (ATP) is reduced by phosphine fumigation, but
             adenosine diphosphate (ADP) is not, indicating that the
             respiratory activity in treated grain is markedly reduced
             (WHO, 1988).
    

             Studies on isolated rat liver showed that mitochondrial
             oxygen uptake is inhibited by phosphine due to its reaction
             with cytochrome C and cytochrome C oxidase.  Phosphine
             inhibits insect catalase, though this appears to be an
             indirect effect and might be a consequence not a cause of
             toxicity.
    
             There have not been any systemic studies on the mechanism of
             phosphine toxicity in man.  Various effects on intermediary
             metabolism have been described.  Dose-related increases in
             blood and urinary porphyrin concentrations due to zinc
             phosphide have been reported.  In a study on rabbits, changes
             in serum glutamic-pyruvic and glutamic oxalacetic
             transaminase, leucine aminopeptidase, aldolase, alkaline
             phosphatase and albumin in the first 24 hours of zinc
             phosphide poisoning have been observed.  Dysfunction of
             hepatic fat metabolism was also reported.  Loss of cell
             viability and cell membrane integrity accounts for the raised
             hepatic enzymes and the bronchiolitic effect.  There is no
             adequate explanation for the fact that phosphine does not
             cause the haemolysis that is characteristic of arsine.
    
             Although the exact mechanism of action of phosphine in man is
             not known, non-competitive inhibition of mitochondrial
             cytochrome oxidase in mouse liver, housefly and granary
             weevil is mentioned by some authors (Singh et al., 1985;
             Chopra et al., 1986; Khosta et al., 1988).

        7.2  Toxicity

             7.2.1  Human data

                    7.2.1.1  Adults

                             Phosphine and the metal phosphides
                             are highly toxic to human beings and
                             animals.
    
                             The odour of phosphine depends on the
                             impurities it contains.  When pure it has no
                             odour, even at a concentration of 28 mg/m3.
                             Phosphine prepared conventionally without
                             purification, has a fishy or garlic-like
                             odour due to its impurities.  These may be
                             absorbed by stored products during fumigation
                             with a resultant loss of odour, even though
                             phosphine remains at toxic concentrations. 
                             Phosphine is in class D of the safety
                             classification, because 20 to 50% of
                             attentive persons can detect the threshold

                             limit value (TLV) of 0.42mg/m3 by smell. 
                             However, the smell of phosphine cannot be
                             relied on as a warning of toxic
                             concentrations.
    
                             Zinc phosphide baits and formulated aluminium
                             phosphide pellets are widely used. 
                             Occasional accidental or more usually
                             suicidal exposure to the metal phosphides may
                             be encountered.  Ingestion, the only highly
                             toxic route, has almost always been with
                             suicidal intent and the symptoms are always
                             acute.
    
                             There is negligible exposure of the general
                             population to phosphine.  Many cases of acute
                             phosphine poisoning due to occupational
                             exposure have been reported in the literature
                             (WHO, 1988).
    
                             In one incident, 12 inhabitants of an
                             apartment house developed nausea and one died
                             when phosphine was emitted from an adjacent
                             warehouse containing bags of aluminum
                             phosphide which became damp. Some passengers
                             on ships and barges carrying cargoes of
                             ferrosilicon of grain under fumigation have
                             also been poisoned by phosphine, with
                             symptoms similar to those of acute
                             occupational poisoning.  In a further
                             incident, 2 adults and one child died when a
                             granary sharing a party wall with their house
                             was fumigated. It was estimated that
                             phosphine concentration in the bedroom
                             reached 1.2 mg/m3. Symptoms were initially
                             non-specific and insidious and illustrate the
                             risk of sustained exposures to relatively low
                             concentrations.   At autopsy, there was
                             congestion of all organs; pulmonary oedema
                             and focal emphysema were found in the lungs
                             and there was vacuolation in the liver (WHO,
                             1988).
    
                             Many cases of acute deliberate zinc phosphide
                             poisoning by ingestion have been reported in
                             the literature.  Stephenson (1967) reviewed
                             20 patients with zinc phosphide poisoning by
                             ingestion in which the approximate doses were
                             recorded.  Of these, 10 patients died after
                             ingestion of 4.5 to 180 g; 6 cases had
                             ingested 20 g or more.  In the 10 non-fatal
                             cases, the doses ranged from 0.5 to 50 g and
                             7 ingested less than 20 g.  The main clinical

                             manifestations were metabolic acidosis,
                             methaemoglobinaemia, hypocalcaemic tetani,
                             reduced blood coagulation, pulmonary oedema;
                             and gastrointestinal, neuropsychiatric and
                             cardiovascular disorders.  Postmortem
                             findings included blood in all the serous
                             cavities, pulmonary congestion and oedema,
                             haemorrhagic changes in the intestinal
                             epithelium, centrilobular congestion and
                             necrosis and yellow discolouration of the
                             liver, and patchy necrosis of the proximal
                             convoluted - tubules of the kidneys.
    
                             An unsuccessful suicidal attempt by a 25
                             year-old man who ingested 6 tablets of AID
                             (Phostoxin) in water was reported.  Immediate
                             symptoms were severe retrosternal pain, a
                             generalized burning sensation and vomiting. 
                             There was circulatory collapse necessitating
                             resuscitation and subsequently cerebral,
                             renal and hepatic dysfunction appeared.
    
                             Harger and Spobyar (1958) reviewed 54 cases
                             of acute phosphine poisoning with 26 deaths
                             since 1900.  In 6 of 11 reports, cargoes of
                             ferrosilicon were cited as the source of
                             phosphine and in these cases, the victims
                             were passengers or crew members of the ships
                             or barges concerned.  Other cases involved
                             the exposure of welders to calcium carbide
                             and raw acetylene and of submariners to
                             sodium phosphide.  The most common autopsy
                             finding was congestion of the lungs with
                             marked oedema.
    
                             Metal workers at a large shipyard in Norway,
                             drilling deep holes in spheroidal graphite
                             iron, became ill during work.  The symptoms
                             were mostly nausea, dizziness, chest
                             tightness, dyspepsia and disturbances of
                             smell and taste.  Measurement of phosphine
                             concentration in the worker's breathing zone
                             (with Drager tubes) showed a phosphine
                             concentration of about 1.4 mg/m3 (1 ppm). 
                             After installing local exhaust ventilation on
                             the drilling machines, there were no longer
                             any measurable amounts of phosphine, and
                             there were no complaints from the workers. 
                             When the local exhaust ventilation was
                             removed for technical reasons 5 years later
                             illness among the workers recurred. 
                             Measurement of phosphine levels just above
                             the machines, showed concentration up to 56

                             to 70 mg/m3 (40 to 50 ppm).  When the local
                             exhaust ventilation was re-installed, the
                             phosphine concentrations dropped to
                             unmeasurable amounts, and no further cases
                             were reported. (WHO 1988).

                    7.2.1.2  Children

                             Two children and 29 of 31 crew
                             members aboard a grain freighter became
                             acutely ill after inhaling the toxic fumigant
                             phosphine; one child died. Predominant
                             symptoms were headache, fatigue, nausea,
                             vomiting, cough and shortness of breath. 
                             Abnormal physical findings included jaundice,
                             paraesthesia, ataxia, intention tremor and
                             diplopia.  Focal myocardial infiltration with
                             necrosis, pulmonary oedema and widespread
                             small vessel injury were found postmortem.
                             The surviving child showed ECG and
                             echocardiographic evidence of myocardial
                             injury and transient elevation of MB fraction
                             of serum creatinine phosphokinase.  Phosphine
                             gas was found to have escaped from the holds
                             through a cable housing located near the
                             midship ventilation intake and around hatch
                             covers on the forward deck (Wilson et al.,
                             1980).
    
                             Occasional reports on accidental phosphine
                             poisoning in children have been
                             published.
    
                             Reports of deaths of children and adults in
                             chemical accidents involving phosphine have
                             been published (Wilson et al., 1980).
    
                             Acute phosphine poisoning following ingestion
                             of aluminum phosphide has been reported in
                             young children and adults. Eight patients
                             aged 14 to 25 years with acute aluminum
                             phosphide poisoning reported by Misra et al.
                             (1988).  The clinical picture consisted of
                             acute gastritis, altered sensorium and
                             peripheral vascular failure, cardiac
                             arrhythmias, jaundice and renal failure. Six
                             patients died, the mean hospital stay was 19
                             (range 4 to 72) hours.  These patients had
                             taken 2 or more AlP tablets, whereas the two
                             patients survived had taken one tablet or
                             less.
    

                             Postmortem examination revealed pulmonary
                             oedema, gastrointestinal mucosal congestion,
                             and petechial haemorrhages on the surface of
                             liver and brain.

             7.2.2  Relevant animal data

                    Animal experiments have revealed that rabbits
                    exposed to 70 mg phosphine/m3 (50 ppm) for 10
                    minutes do not develop any symptoms but exposure to
                    140 mg/m3 (500 ppm) is fatal in 2.5 to 3 hour, and
                    700 mg/m3 (500 ppm) is fatal 25 to 30 minutes.  Rats
                    survive exposure to 80 and 800 mg/m3 for 4 and 1
                    hour, respectively.  All animals exhibited signs of
                    respiratory irritation and died of pulmonary oedema. 
                    Pathological examination of the lungs revealed
                    bronchiolitis and atelectasis; there was no evidence
                    of haemolysis but all organs were hyperaemic.  The
                    liver showed fatty infiltration and there was cloudy
                    swelling of kidney tubular cells. Neurohistological
                    studies in rats revealed widening of the perivascular
                    spaces, vacuolization of the nuclei of ganglion cells,
                    a reduction in the Purkinje cells and a glial
                    reaction.  In one study a 4-hour LC50 for phosphine
                    inhalation in male rats was estimated as 15 mg/m3
                    (11 ppm), but in another study on female rats it was
                    reported as 55 mg/m3.  The LC95 was 420 (260 to
                    670) mg/h/m3.  The US National Pest Control
                    Association submitted a value of 19.6 mg/L for an
                    inhalation LC50 of 10% zinc phosphide powder in
                    rats.
    
                    In an oral study on 35 rats of both sexes administered
                    doses of 20, 40, 50 and 80 mg/kg LD50 for zinc
                    phosphide was 40.5 to 2.9 mg/kg body weight. The
                    LD50 for kit fox was reported as 93 mg zinc
                    phosphide/kg body weight. A dose of 100 mg/kg
                    bodyweight of zinc phosphide was fatal for dogs after
                    starving but not after feeding.
    
                    An acute dermal LD50 of 2000 to 5000 mg/kg body
                    weight for zinc phosphide (94% Zn3P2) in rabbits
                    is reported by the US National Pest Control
                    Association (WHO, 1988).
    
                    Inhalation exposure to phosphine at 28 mg/m3 (20
                    ppm) for 4 hours a day was fatal for rabbits and
                    guinea pigs.  Pretreatment with sub-lethal
                    concentrations of phosphine reduced resistance to
                    near-lethal concentrations.  At low concentrations (up
                    to 14 mg/m3), animals displayed no signs until about
                    0.5 hour before death when they exhibited diminished

                    reactivity, became stuporous with shallow respiration
                    and died in coma and occasionally with signs of
                    pulmonary oedema.
    
                    Zinc phosphide was mixed with the diet of rats at 0
                    (control), 50, 100, 200 and 500 mg/kg. Deaths occurred
                    at the  two higher dosage regimens in 1/12 and 10/12
                    animals, respectively. There was a dose-dependent
                    reduction in haemoglobin, red cells and haematocrit
                    (WHO, 1988).
    
                    No long-term studies on phosphine and metal phosphide
                    exposure have yet been reported.

             7.2.3  Relevant in vitro data

                    No data available.

             7.2.4  Workplace standards

                    Occupational exposure limits for phosphine in
                    various countries are shown in Table 1.  The
                    recommended exposure limits for phosphine in many
                    countries are higher than the registered regulatory
                    requirement.  However, the exposure limits for
                    phosphine varies from 0. mg/m3 to 1.5 mg/m3 in
                    short-term exposure.
    

    Table 1 - Occupational exposure limits for phosphine in various
              countries
    
                                                                       
    
    Country             Legal        mg/m3        Comment
    
    Australia            Rec          0.4           TLV TWA
    Belgium              Rec          0.4           TLV
    Bulgaria             Rec          0.1           MPC
    Czechoslovakia       Rec          0.1           MAC TWA
                                      0.2           MAC Ceiling value
    Finland              Reg          0.1           MPC TWA
    Germany              Rec          0.15          8.h TWA
                                      0.3           5 min STEL
    I.R.Iran             Rec          0.3           TLV
    Italy                Rec          0.4           8.h TWA
    Hungary                           0.1
    Netherlands          Rec          0.4           TWA
                                      1.5           STEL
    Poland               Reg          0.1           Ceiling value
    Romania              Reg          0.2           TWA
                                      0.5           Ceiling value
    Sweden               Reg          0.4           1-day TWA
    Switzerland          Reg          0.15          TWA
    United Kingdom       Rec          0.4           8-h TWA
                                      1.0           10 min TWA
    USA                  Rec          0.4           TWA
                                      1.0           STEL
    USSR                 Reg          0.1           Ceiling value
    Yugoslavia           Reg          0.1           MAC TWA
                                                                       
    
    Rec.=Recommendation
    Reg.=Registered regulatory requirement
    TLV=Threshold limit value
    TWA=Time - weighted average
    MPC=Maximum permitted concentration
    MAC=Maximum allowable concentration
    STEL=Short - term exposure limit

             7.2.5  Acceptable daily intake

                    Residues of phosphine or metal phosphides in
                    fumigated foods are considered negligible at 0.01
                    mg/kg or less.  Reported various national and
                    international standards for phosphine residues in food
                    are 0.01 mg/kg (1 ppm) except for whole food grains in
                    India, for which the standard is 0.05 mg/kg.  However,
                    the acceptable limit of phosphine residue in milled
                    food grain in this country was reported as 0.01 mg/kg. 
                    Therefore the acceptable daily intake of
                    phosphine/phosphide residues could be extrapolated as
                    0.01 mg or less (WHO, 1988).

        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/TOXINOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS

        8.1  Material sampling plan

             8.1.1  Sampling and specimen collection

                    8.1.1.1  Toxicological analyses

                             Different sampling methods for
                             phosphine and the metal phosphides are
                             available.
    
                             I.Gaseous phosphine: Workplace air monitoring
                             and  fumigation control demand a measurement
                             range from approximately 0.04 mg/m3 to
                             greater than the lower explosion limit of
                             25000 mg/m3.  Thus, methods covering
                             concentrations differing by six orders of
                             magnitude are required.  Techniques are
                             available that (a) directly indicate the
                             concentration in a grab sample or a
                             time-weighted average sample, (b) absorb or
                             adsorb phosphine from a known volume of air
                             for subsequent analysis directly or by
                             desorption and gas analysis and (c) give a
                             continuous record of time-dependent
                             concentrations. Some methods are given in
                             table 2.
    

    
    Table 2 - Methods of sampling and analysis
    
                                                                                             
    
    Method                           Range               Efficiency       Interference
                               ppm           mg/m3
                                                                                             
    
    Sampling
    
    Silver nitrate          0.05-8.0       9.07-11.3       90%
    (0.1 N)
    impregnated paper
    
    Ethanolic mercuric      0.05-3.0       0.07-4.2                           NH3
    chloride
    
    Acidic potassium        0.01-0.05                      100%               H3S
    permanganate (0.1N)
    impinger
    
    Silver diethyl-         0.6-18         0.85-25         54-86.2%           H2S, AsH3,
    dithiocarbomate                                                           SbH3
    (0.5%) bubbler
    
    Mercuric chloride       10-28          14-28                              AsH3
    (0.5%) aqueous
    bubbler
    Toluene impinger                                       41.5%
    
    Mercuric chloride       0.05-2.5       0.07-3.5        88.0%              SO2, H2S,
    (0.1%) conductance                                                        AsH3, SbH3
    cell
    
    Silver nitrate          0.05-4.1       0.07-5.8        95%                H2A, AsH3
    impregnated
    silica gel
    
    Auric chloride          0.01-1000      0.014-1 400     100%               AsH3, SbH3
    impregnated
    silica gel
    
    Ethanolic mercuric      0.0006                         88-100%            AsH3, SO2,
    chloride (0.1%)                                                           HCN, H2S
    
    Mercuric cyanide        0.014-1.18     0.02-1.7        80%
    impregnated
    silica gel
                                                                                             
    

                             Phosphine can be detected by filter paper
                             impregnated with a mixture of silver nitrate
                             and mercuric chloride. Direct-indicating
                             detector tubes are commercially available for
                             spot sampling.
    
                             There are directly-indicating continuous
                             samplers in which phosphine-containing gas is
                             passed through a paper tape impregnated with
                             a mixture containing silver nitrate which 
                             develops a colour corresponding to the
                             phosphine concentrations.
    
                             II. Residues: Fumigated foodstuffs may
                             contain gaseous phosphine (adsorbed or in
                             trapped air) and residual aluminium or
                             magnesium phosphide. Interstitial and
                             adsorbed phosphine can be purged by nitrogen
                             and trapped in reagents for classical
                             analyses.
    
                             Total phosphine and phosphide is measured by
                             extraction of the fumigated stored product
                             with silver nitrate or with sulphuric acid. 
                             The sulphuric acid method is preferred
                             because it also measures the capacity of the
                             product to release phosphine and this is of
                             more biological significance than the
                             measurement of free phosphine only.
    
                             III. Metal phosphide: Hydrolysis of metal
                             phosphides with acid yields phosphine, which
                             can be measured by any of the methods already
                             described.
    
                             IV. Inhaled expiration: Silver nitrate
                             impregnated paper test can be used for the
                             breath of patients exposed to phosphine. 
                             Silver nitrate and phosphine react to form
                             silver phosphide which confirms the
                             diagnosis.
    
                             V. Gastric fluid: Gastric fluid (vomited or
                             through gastric tube) must be collected in a
                             clean glass tube or beaker for toxicological
                             analysis.
    
                             VI. Blood: Phosphine that is not excreted in
                             the expired air is oxidized and has no
                             significant effect on diagnosis.  Thus blood
                             sampling for toxicological analysis may not
                             be required except for research purposes.
    

                             V. Urine:  Oxidative metabolites mainly as
                             phosphite and hypophosphate may be present in
                             the urine . Urine sampling for the estimation
                             of the metabolites may be required.

                    8.1.1.2  Biomedical analyses

                             Blood samples
    
                             In case of cardiac dysfunction, estimation of
                             cardiac enzymes including LDH and CPK may be
                             indicated.  Biochemical analyses particularly
                             require liver and kidney function tests. 
                             Urine samples including a 24-hour collection
                             are necessary to perform routine urine
                             analysis and to estimate creatinine clearance
                             and other investigations such as
                             beta-macroglobulin and N-acetyl beta-glucose
                             aminidase (NAG) as required.

                    8.1.1.3  Arterial blood gas analysis

                             Arterial blood samples must be taken
                             for urgent estimation of PH, PaO2, PaCO2,
                             bicarbonate and the other parameters as usual
                             in severely poisoned patients in  order to
                             assess and correct acidosis and pulmonary
                             dysfunction.  Repeated sampling for arterial
                             blood gases may be required for the
                             management of patients with severe
                             phosphine/phosphide poisoning.

                    8.1.1.4  Haematological analyses

                             Blood samples must be taken in the
                             usual haematology tubes for cell blood count,
                             haemoglobin, haematocrit.  Estimation of
                             prothrombin time rate may be indicated
                             clinically.

                    8.1.1.5  Other (unspecified) analyses

             8.1.2  Storage of laboratory samples and specimens

                    8.1.2.1  Toxicological analyses

                             Blood and urine samples should be
                             stored at -20C for further analyses. 
                             However, no data are available on the
                             stability of phosphine/phosphides in
                             biological fluids.

                    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 and specimens

                    8.1.3.1  Toxicological analyses

                             Transportation of samples must
                             follow the required safety regulations.

                    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)

                             Phosphine can be detected by filter
                             papers impregnated with a mixture of silver
                             nitrate and mercury (II) chloride.  Aluminum
                             and magnesium phosphide can be hydrolysed
                             conventionally but zinc phosphide requires
                             acid hydrolysis to produce phosphine for
                             detection.

                    8.2.1.2  Advanced Qualitative Confirmation Test(s)

                             Direct-indicating detector tubes are
                             commercially available for qualitative
                             confirmation of phosphine.  Other
                             direct-indicating tubes of lower sensitivity
                             are available for the estimation of the
                             higher phosphine concentrations used in
                             fumigation.

                    8.2.1.3  Simple Quantitative Method(s)

                             Colorimetric method is a simple
                             quantitative technique for phosphine. Filter
                             papers impregnated with a mixture of silver
                             nitrate and mercury (II) chloride which
                             detect phosphine can be made

                             semi-quantitatively by appropriate
                             configuration and measurement for stain
                             length of colour comparison.  Calzodari
                             (1986) also reported a colorimetric method
                             involving oxidation of PH3 with bromine water
                             and reduction of phosphomolibate.
    
                             The quantity of phosphine bubbled through a
                             solution of mercury (II) chloride and
                             undergoing the reaction:
    
                                  PH3.3HgCl2----->P(HgCl)3 + 3 HCl
    
                             can be measured by the change in electrical
                             conductivity  using a conductance cell or by
                             potentiometric titration of HCl against
                             NaOH.

                    8.2.1.4  Advanced Quantitative Method(s)

                             Chan et al. (1983) reported a
                             headspace gas chromatographic technique using
                             a nitrogen phosphorus detector to estimate
                             phosphine applied to postmortem specimens
                             following ingestion of aluminum
                             phosphide.
    
                             Gas chromatography is the most sensitive
                             method for the determination of the phosphine
                             content of air samples.
    
                             Usually, samples are adsorbed from a solid
                             absorbent coated with mercury (II) cyanide,
                             although samples taken in syringes, gasbags
                             or tonometers can be used. Microcolorimetric
                             and thermionic detectors have detection
                             limits of 5000 and 20 pg, respectively.  The
                             limit for flame photometric and argon and
                             helium beta-ionization detectors is 5 pg and
                             that for mass spectrometry is 1 ng. 
                             Photoionisation detection is also commonly
                             used.  Flame photometry combines both
                             sensitivity and stability.

             8.2.2  Tests for biological specimens

                    8.2.2.1  Simple Qualitative Test(s)

                             Silver nitrate impregnated paper
                             test can be used for the breath and gastric
                             fluid of the patients exposed to
                             phosphine/phosphides.  Silver nitrate and

                             phosphide/phosphides react to form silver
                             phosphide which is dark grey (Chugh et al.,
                             1989).  Blood and urine samples cannot be
                             used for phosphine detection, because
                             absorbed phosphine is rapidly oxidized and
                             excreted mainly as phosphite and
                             hypophosphite in the urine.

                    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)

                             Khan et al. (1983) estimated
                             phosphine levels in post mortem specimens
                             liberated after acidification and found a
                             small amount in blood (0.5 ng/mL) and liver
                             (3 ng/g) but a large quantity (3000 ng/g) in
                             the stomach and contents. See also 8.2.1.4.
                             

                    8.2.2.5  Other Dedicated Method(s)

             8.2.3  Interpretation of toxicological analyses

                    Diagnosis of phosphine/phosphide poisoning is
                    normally based on the history of exposure and clinical
                    manifestation.  However, qualitative toxicological
                    analyses confirm the diagnosis and the quantitative
                    tests may be used for the evaluation of the severity
                    and prognosis.

        8.3  Biomedical investigations and their interpretation

             8.3.1  Biochemical analysis

                    8.3.1.1  Blood, plasma or serum

                             Kidney and liver function tests and
                             cardiac enzymes, particularly blood urea,
                             electrolyte, creatinine, bilirubin, alkaline
                             phosphatase, transaminases, lactic
                             dehydrogenases and creatine phosphokinase,
                             should be estimated in all patients
                             hospitalized after phosphine/phosphide
                             poisoning.  Further investigation, such as
                             plasma cortisol level (Chugh et al, 1989) and
                             plasma renin activity (Chugh et al, 1990)
                             should only be done as clinically
                             indicated.
    

                             In case of zinc phosphide poisoning, serum
                             zinc concentration may be elevated
                             (Stephenson, 1967) - in this case, by 590 to
                             605 g/100 mL (Normal 120 to 200 g/mL).  Serum
                             magnesium and aluminium concentrations may
                             also increase in Mg3P2 and AlP poisoning,
                             respectively.

                    8.3.1.2  Urine

                             Routine urinalysis and further
                             investigations such as estimation of
                             beta-microglobulin, N-acetyl-glucose
                             aminidase (NAG) and 24 hour urine creatinine
                             are required to evaluate renal function.

                    8.3.1.3  Other fluids

             8.3.2  Arterial blood gas analyses

                    Serial arterial blood gas analyses may be
                    required in order to assess respiratory and acid-base
                    abnormalities and to correct them.

             8.3.3  Haematological analyses

                    Routine haematological tests such as cell blood
                    count, haemoglobin, haematocrit are required for all
                    patients with phosphide/phosphine poisoning.  Further
                    investigations such as prothrombin time ratio should
                    be done as clinically indicated.

             8.3.4  Interpretation of biomedical investigations

                    Biochemical and haematological tests are
                    required to assess the effects of phosphine/phosphide
                    poisoning.The results should be considered in
                    conjunction with the clinical picture and other
                    paramedical investigation such as electrocardiogram
                    and chest X-ray.  Re-evaluation of the patient's
                    condition and repetition of biomedical and
                    haematological tests may be necessary.

        8.4  Other biomedical (diagnostic) investigations and their
             interpretation

             Electrocardiographic changes in phosphine poisoning were
             reported by Roman and Dubey (1985), who found cardiac
             arrhythmias, usually heart block and myocardial ischaemia. 
             Wilson et al. (1980) also found similar ECG and
             echocardiographic changes in child after phosphine poisoning;
             they reported a transient elevation of the MB fraction of

             serum creatinine phosphokinase and focal myocardial
             infiltration with necrosis and widespread small vessel injury
             at postmortem.
    
             Misra et al. (1988), in a study of 8 cases of attempted
             suicide by ingestion of aluminum phosphide tablets, found
             circulatory failure in all cases and cardiac arrhythmias in
             three patients.  ECG changes included sinus arrhythmia with
             ST segment depression in leads II and III; AVF and T- wave
             inversion in V5-V6; and premature complexes which were
             followed by ventricular tachycardia.

        8.5  Overall interpretation of all toxicological analyses and
             toxicological investigations

             Cardiac monitoring with serial ECG recording, as well as
             the other investigations are required for poisoning by
             phosphine/phosphide.
    
             Sample collection
    
             Blood samples (10mL) for biochemical investigations are
             usually collected in dry glass tubes without any
             preservative.  Blood samples for haematology should be
             collected in anticoagulant tubes as instructed by the
             laboratory.  A 24-hour urine collection may be needed for the
             estimation of creatinine and phosphine metabolite
             concentrations.
    
             Biochemistry
    
             Routine urinalysis, blood urea, electrolytes, creatinine,
             bilirubin, alkaline phosphates, transaminases (ALT, AST),
             lactic dehydrogenase (LDH), creatinine phosphokinase (CPK)
             should be measured in all patients with phosphine/phosphide
             poisoning.  If the results are abnormal (high LDH and CPK or
             renal dysfunction), further biochemical investigations (e.g.
             LDH and CPK, urine creatine, beta-microglobulin,
             N-acetyl-glucose aminidase) should be determined.
    
             Haematology
    
             Cell blood counts (CBC), haemoglobin (Hb) and haematocrit
             (HCT) should be investigated in all patients with
             phosphine/phosphide poisoning.  If there are any
             abnormalities or signs of gastrointestinal haemorrhage, or
             hepatic failure, CBC, Hb and HCT must be repeated and further
             tests including platelet counts, and prothrombin time ratio
             should also be performed.
    
             Arterial blood gas analyses
    
             Arterial pH and blood gases should be investigated in all
             patients with respiratory dysfunction.  Repeated arterial
             blood gas analyses may be required in order to correct pH and
             blood gas abnormalities.
    
             Toxicological analysis
    
             Exhaled air can be tested for phosphine by an impregnated
             silver nitrate paper.  The paper test can also be used to
             identify phosphine in the gastric contents.  Blood samples
             are of no practical use for the estimation of
             phosphine/phosphide, since absorbed phosphine is rapidly
             oxidised in the blood.  However, Chan et al. (1983) reported
             postmortem blood concentrations of phosphine of 5 ng/mL.
             Urine can be tested for the oxidative metabolites of
             phosphine (phosphite and hypophosphite).
    
             Other investigations
    
             Since phosphine initially affects the respiratory and
             cardiovascular system, respiratory function tests
             (spirometry), chest X-ray and ECG are required. 
             Cardiorespiratory monitoring in an ICU with serial ECG
             recording is necessary in severe cases.  Further
             investigation such as electroencephalography (EEG) and
             electromyography (EMG) should be performed as clinically
             indicated.

        8.6  References

    9.  CLINICAL EFFECTS

        9.1  Acute Poisoning

             9.1.1  Ingestion

                    Deliberate ingestion of the metal phosphides
                    particularly AlP (Phostoxin) and Mg3P2 tablets or
                    pellets for suicidal purpose is common in the
                    countries in which these fumigants are sold without
                    restriction.  Oral use of zinc phosphide paste (Zelio)
                    for suicidal attempts is also common in some
                    countries, including Islamic Republic of Iran, and the
                    author has seen and treated many of these patients
                    (see 9.3).
    
                    Acute poisoning by phosphine and the metal phosphides
                    is common in some countries, particularly in India and
                    Iran. Phosphine poisoning is either occupational or
                    accidental, but the acute metal phosphides poisonings
                    are mainly suicidal (Vale & Meredith, 1983).

             9.1.2  Inhalation

                    Phosphine inhalation is the commonest route of
                    intoxication and may occur accidentally or
                    occupationally.  The metal phosphides, particularly
                    AlP and Mg3P2 may be easily hydrolysed in moisture
                    and produce phosphine.  Following oral ingestion of
                    the metal phosphides, phosphine produced in the
                    stomach may also be inhaled (see 9.3).

             9.1.3  Skin Exposure

                    Skin exposure is not a common route of
                    intoxication by phosphine and the metal phosphide,
                    because skin absorption is not significant.

             9.1.4  Eye contact

                    It seems that phosphine does not affect the
                    eyes significantly.  There are no data available on
                    the effects of phosphine/phosphides on the eyes either
                    in animals or man.

             9.1.5  Parenteral Exposure

                    No data available.

             9.1.6  Other

                    No data available.

        9.2  Chronic poisoning

             9.2.1  Ingestion

                    No data available.

             9.2.2  Inhalation

                    No long-term studies of chronic exposure to
                    phosphine and the metal phosphides have been reported. 
                    Chronic poisoning is generally occupational, but no
                    reports with evidence of chronic poisoning by
                    phosphine and the metal phosphine have been published. 
                    Chronic effects include anaemia, bronchitis,
                    gastrointestinal disorders, speech and motor
                    disturbances, toothache, swelling of the jaw,
                    mandibular necrosis, weakness, weight loss and
                    spontaneous fracture have been reported but these are
                    by no means general (WHO, 1988).  Complications of
                    acute poisoning may occur but are distinct from the
                    effects of chronic poisoning.

             9.2.3  Skin contact

                    No data available.

             9.2.4  Eye contact

                    No data available.

             9.2.5  Parenteral Exposure

                    No data available.

             9.2.6  Other

                    No data available.

        9.3  Course, prognosis, cause of death

             The initial clinical manifestations of mild phosphide
             inhalation may mimic upper respiratory tract infection
             including cough, feelings of cold, sore throat, tachypnea,
             respiratory irritation and tightness of breath.  Other
             symptoms may include nausea, vomiting, diarrhoea, headache,
             fatigue and dizziness.  In severe exposure, lung irritation
             with persistent coughing, ataxia, paraesthesia, tremor,
             diplopia, hypotension, weak pulse and jaundice may also
             occur.  Very severe cases may progress to acute pulmonary
             oedema, cardiac dysrhythmia, convulsion, cyanosis,
             hypothermia followed by hyperthermia and coma.  Severe
             metabolic acidosis, cardiovascular collapse, oliguria,
             proteinuria and finally anuria may occur which may require
             haemodialysis.
    
             Most severely poisoned patients may die within a few hours
             due to cardiovascular collapse, myocardial injury or
             pulmonary oedema.
    
             In a study of acute phosphine poisoning aboard a grain
             freighter, the predominant symptoms in 29 crew members and
             two children were headache, fatigue, nausea, vomiting, cough
             and shortness of breath (Wilson et al., 1980).  Abnormal
             physical findings included jaundice, paraesthesia, ataxia,
             intention tremor and diplopia.  Focal myocardial infiltration
             with necrosis, pulmonary oedema and widespread small vessel
             injury were found at postmortem examination of a dead child. 
             The surviving child showed ECG and echocardiographic evidence
             of myocardial injury and transient elevation of the MB
             fraction of creatinine phosphokinase.
    
             Deliberate ingestion of the metal phosphides especially AlP
             (Phostoxin) causes nausea, vomiting, retrosternal and
             abdominal pain, tightness in the chest and coughing,
             headache, dizziness and sometimes diarrhoea.  In severe

             cases, gastrointestinal haemorrhage, tachycardia,
             hypotension, shock, cardiac arrhythmias, cyanosis, pulmonary 
             oedema, metabolic acidosis, convulsions and coma may
             occur.
    
             Clinical features of renal failure and hepatic damage
             including oliguria, proteinuria, anuria and jaundice may
             develop later if the patient survives.  In 8 cases of
             attempted suicides by ingestion of aluminum phosphide
             tablets, the clinical picture consisted of acute gastritis,
             peripheral vascular failure, cardiac arrhythmia, jaundice and
             renal failure (Misra et al, 1988).  Six patients died and
             postmortem examination in two of them revealed pulmonary
             oedema, gastrointestinal mucosal congestion, and petechial
             haemorrhages on the surface of the liver and brain.
    
             In 15 cases of aluminum phosphide poisoning reported by
             Khosla et al. (1988), all had severe symptoms such as shock,
             cardiac arrhythmias, pulmonary oedema, and renal failure, of
             which, only 7 patients survived.
    
             In a prospective study of 16 cases of aluminum phosphide
             poisoning by Chopra et al. (1986), profuse vomiting, pain in
             the upper abdomen and shock were the most common presenting
             features.  Only 6 patients succumbed to their illness. 
             Analysis of various prognostic factors revealed that
             ingestion of aluminum phosphide tablets taken from a freshly
             opened bottle was associated with a greater risk of fatal
             outcome.
    
             The mortality of attempted suicide by acute
             phosphine/phosphide poisoning is 37 to 80% (Singh et al.,
             1985; Chopra et al.,1988; Khosla et al., 1988.) in suicidal
             patients.  However, in occupational or accidental exposure to
             phosphine, the mortality is much lower and depends on the
             severity of exposure, age and other predisposing factors of
             the patients.
    
             Death, which may be sudden, usually occurs within four days
             but may be delayed for one to two weeks.  Acute metal
             phosphide poisoning, particularly deliberate aluminum
             phosphide (Phostoxin) poisoning, may cause death within a few
             hours (Singh et al., 1985; Chopra et al., 1986; Khosla et
             al., 1988; Misra et al., 1988).
    
             Severity of phosphine/phosphide poisoning:
    
             Deliberate ingestion of the metal phosphides, particularly
             aluminum phosphide (Phostoxin), is usually more severe than
             occupational phosphine intoxication.  However, the clinical
             severity of phosphine/phosphide poisoning could be classified
             as follows.
    

             (a) Mild exposure may present as slight respiratory,
             gastrointestinal and neuropsychiatric disorders such as
             cough, shortness of breath, nausea, vomiting, headache,
             fatigue and dizziness.
    
             (b) Moderate exposure may cause cardiovascular, renal and
             hepatic dysfunction, as well as more severe respiratory,
             gastrointestinal and neuropsychiatric involvement, e.g.
             tachycardia, hypotension, persistent coughing, paraesthesia,
             tremor, diplopia, ataxia, intention tremor, retrosternal and
             abdominal pain, shortness of breath, oliguria, jaundice and
             diarrhoea.
    
             (c) Severe exposure may progress to shock, gastrointestinal
             haemorrhage, pulmonary oedema, cardiac arrhythmias, metabolic
             acidosis, cyanosis, convulsions and coma. Renal failure and
             liver damage may also occur.

             Common causes of death following phosphine/phosphide
             poisoning are pulmonary oedema, cardiac arrhythmias and
             myocardial injury. A secondary cause of death may be renal
             failure.
    
             Stephenson (1967) classified patients seriously poisoned by
             phosphine into 3 groups: (a) those who die within a few hours
             with pulmonary oedema (b) the majority of fatal cases who die
             after about 30 hours, and (c) those who survive the first 3
             days who may not be in danger, despite extensive liver damage
             and renal dysfunction.

        9.4  Systematic description of clinical effects

             9.4.1  Cardiovascular

                    Cardiovascular effects of aluminum phosphide
                    poisoning were studied by Khosla, Nand and Kumar
                    (1988).  Twenty-five cases of aluminum phosphide
                    poisoning were observed by the authors over a period
                    of 2 years; 16 cases (64%) had evidence of cardiac
                    dysfunction.  Despite adequate treatment, 40% of the
                    patients died.  Shock and cardiac dysrhythmia were the
                    main effects. In another study by Singh & Rastogi
                    (1989), out of 32 cases of aluminum phosphide
                    poisoning, cardiac arrhythmia (28), dyspnoea (25),
                    palpitation (25), cyanosis (12), hypotension (12) and
                    shock (15) were the main clinical manifestations. 
                    Hypermagnesaemia due to myocardial and liver damage
                    occurred in 13 patients.
    

                    Roman & Dubey (1985) and Khosla et al. (1988) have
                    reported circulatory failure, cardiac dysrhythmias,
                    myocarditis and cardiac failure; the dysrhythmias
                    included complete heart block, atrial fibrillation,
                    chaotic atrial and ventricular tachycardia.

             9.4.2  Respiratory

                    The respiratory tract is a major target for
                    phosphine poisoning.  The initial symptoms include
                    cough, sore throat, tightness in the chest,
                    retrosternal pain, dyspnoea, followed by persistent
                    coughing, pulmonary oedema and respiratory distress
                    syndrome which may induce mortality.  In a study of 59
                    cases of phosphine poisoning by Harger & Spolyar
                    (1958), 26 patients died mainly due to respiratory
                    disorders.  The commonest finding at autopsy was
                    congestion of the lungs with marked oedema.

                    Wilson et al. (1980), in a study of 2 children and 29
                    crew members aboard a grain freighter with phosphine
                    poisoning, reported cough, shortness of breath and
                    pulmonary oedema. On postmortem examination they found
                    pulmonary oedema and pleural effusion.  Misra et al.
                    (1988) on postmortem examination in two patients,
                    found pulmonary oedema and desquamation of the lining
                    epithelium of the bronchioles.  In a study by Khosla
                    et al. (1988) on 15 cases of aluminum phosphide
                    poisoning, pulmonary oedema was the main cause of
                    mortality in 7 patients.

                    Chugh et al. (1989) reported 4 cases of adult
                    respiratory distress syndrome (ARDS) following
                    aluminum phosphide poisoning.  All their patients had
                    shock on admission and developed ARDS within 6 hours. 
                    Exhalation of phosphine was detected by positive
                    silver nitrate test.  In a study by Khosla and Nand
                    (1988) on 15 cases of aluminum phosphide poisoning,
                    pulmonary oedema was one of the main findings which
                    contributed to the cause of death in 8 patients.
                    Chemical pneumonia may also be associated with
                    pulmonary toxic effects.

             9.4.3  Neurologic

                    9.4.3.1  Central nervous system (CNS)

                             The CNS is a major target in
                             phosphine poisoning.  Neurologic symptoms
                             included headache, vertigo, tremors, and
                             unsteady gait, progressing to convulsion,
                             coma and death.  Wilson et al. (1980)
                             described CNS symptoms of acute phosphine

                             poisoning in 2 children and 29 crew members
                             aboard a grain freighter as headache,
                             fatigue, drowsiness, dizziness and
                             paraesthesia weakness, followed by tremor on
                             physical examination, intention tremor in 9
                             patients ataxia in 2 patients, convulsion and
                             coma in a child who died.  Disturbances of
                             smell and taste, dizziness and other clinical
                             manifestations of phosphine poisoning were
                             observed in the workers at a large shipyard
                             in Norway (WHO, 1988).
    
                             Miara et al. (1988) described CNS effects in
                             8 cases of acute phosphine poisoning as
                             drowsiness (3), stupor (2) and delirium (1). 
                             On postmortem examination, the brain was
                             markedly congested with areas of exudation,
                             and small haemorrhages were observed.

                    9.4.3.2  Peripheral nervous system

                             Some patients with
                             phosphine/phosphide poisoning develop
                             paraesthesia, fatigue and weakness (Wilson et
                             al., 1980; Misra et al., 1988).  Peripheral
                             neuropathy (neuritis) may occur, but no
                             studies of the effects of phosphine/phosphide
                             on the peripheral nervous system have been
                             reported.

                    9.4.3.3  Autonomic nervous system

                             There is no evidence of direct toxic
                             effects of phosphine/phosphide on the
                             autonomic nervous system, but indirect
                             effects through the adrenal gland and the
                             central nervous system may induce
                             tachycardia, hypotension, shock, and
                             gastrointestinal disorders.

                    9.4.3.4  Skeletal and smooth muscle

                             Transient elevation of MB fraction
                             of creatinine phosphokinase in a surviving
                             child with phosphine poisoning reported by
                             Wilson et al. (1980) revealed cardiac and
                             skeletal muscle involvement. Gastrointestinal
                             and vascular disorders, such as abdominal
                             pain and vascular collapse, may be associated
                             with smooth muscle constriction.

             9.4.4  Gastrointestinal

                    Initial symptoms following ingestion of the
                    metal phosphides, particularly aluminum phosphide are
                    nausea, vomiting and abdominal pain (Chopra et al.,
                    1986).  As Misra et al. (1988) reported, within 5
                    minutes of ingestion of aluminium phosphide tablets,
                    patients develop epigastric pain and vomiting; dryness
                    of the mouth, abdominal cramp and diarrhoea may also
                    occur.  In severe cases, haematemesis and melaena may
                    develop but gastrointestinal haemorrhage has not been
                    recorded as a cause of death (in phosphine/phosphide
                    poisoning).  At autopsy, gastrointestinal mucosal
                    congestion and haemorrhage have been found.

             9.4.5  Hepatic

                    The liver may be affected by phosphine/
                    phosphide poisoning, but the effects are delayed and
                    rarely cause death.  Jaundice may occur 24 hours or
                    more after exposure.  In 31 cases of phosphine
                    poisoning studied by Wilson et al. (1980), jaundice
                    occurred in 52% of the patients. Liver function tests
                    were abnormal in a further 10 patients.  Abnormalities
                    included elevations of transaminases (mainly SGPT) and
                    lactic dehydrogenase (5 patients).
    
                    Misra et al. (1988) found one patient with jaundice
                    among 8 patients with phosphine poisoning they
                    studied.  The patient died because of renal and
                    hepatic failure and ventricular tachycardia.  On
                    autopsy, petechial haemorrhages were seen on the
                    surface of the liver and histopathological examination
                    showed vascular degeneration of hepatocytes.

             9.4.6  Urinary

                    9.4.6.1  Renal

                             Toxic effects of phosphine and the
                             metal phosphides on the kidneys are rare and
                             may be delayed.  In 31 cases of phosphine
                             poisoning studied by Wilson et al. (1980),
                             renal symptoms were not prominent. 
                             Urinalyses of 30 patients revealed
                             abnormalities in 8, usually as microscopic
                             haematuria and bile in urine.  None of these
                             abnormalities persisted and all patients
                             improved within a week except one child who
                             died due to cardiovascular and pulmonary
                             toxic effects.
    

                             Misra et al. (1988) found one patient with
                             acute renal failure of 8 cases of phosphine
                             poisoning reported.  This patient developed
                             anuria with blood urea of 80 mg/dL and serum
                             creatinine of 3.5 mg/dL on the second day of
                             admission.  Because of persistent anuria and
                             uraemia, the patient underwent peritoneal
                             dialysis but died 72 hours after admission
                             because of hepato-renal failure and
                             ventricular tachycardia. On postmortem
                             examination, the kidneys were congested with
                             focal areas of exudation and small
                             haemorrhages.
    
                             Chopra et al. (1986) reported one patient
                             with significant proteinuria (4.8 g/day)
                             which gradually disappeared over 10 days, and
                             another patient who developed renal
                             failure.
    
                             Plasma renin activity (PRA) is increased in
                             shock due to aluminum phosphide poisoning
                             (Chugh et al., 1990).  An initially high PRA
                             continued to rise, probably due to slow
                             release of toxic phosphine gas, which was
                             detected by a positive silver nitrate paper
                             test.  The rise in PRA was directly
                             proportional to the dose of aluminum
                             phosphide consumed and there was a direct
                             relationship between mortality and an
                             increased PRA.  The authors concluded that
                             angiotensin converting enzyme inhibitors may
                             have a role in combating shock in AlP
                             poisoning.

                    9.4.6.2  Others

                             No data available.

             9.4.7  Endocrine and reproductive systems

                    There is little information on the effects of
                    phosphine/phosphide on the endocrine and reproductive
                    systems.  Adrenocortical involvement in aluminum
                    phosphide poisoning was studied by Chugh et al. (1986)
                    in 50 cases.  A significant rise in plasma cortisol
                    (> 1048 nmol/L) was observed in 20 patients. 
                    Postmortem examination in 10 patients revealed mild to
                    moderate adrenal cortex changes including congestion,
                    oedema, and cellular infiltration.  There was no
                    evidence that adrenal insufficiency or haemorrhage was
                    the cause of shock in these patients.

             9.4.8  Dermatologic

                    There have been no reports of dermal symptoms
                    in phosphine/phosphide poisoning.

             9.4.9  Eye, ear, nose, throat

                    Local effects
    
                    There has been no reports on the local effects of
                    phosphine/phosphide on the eyes and ears.  The
                    irritant effects of phosphine on the nose and throat
                    are probably trivial in comparison with those on the
                    lung.  Initial clinical manifestations of mild
                    phosphine inhalation may mimic upper respiratory tract
                    infection, but these are overshadowed by the other
                    effects of phosphine poisoning including pulmonary,
                    gastrointestinal and cardiovascular disorders.

             9.4.10 Haematologic

                    The haematologic system is not a major target
                    in phosphine/phosphide poisoning.  However, marked
                    congestion of the spleen with focal areas of exudation
                    and small haemorrhages were found during the post
                    mortem examination of a patient who died due to
                    phosphine poisoning, though this was not the cause of
                    death (Misra et al., 1988).  A reduction in red blood
                    cells, haemoglobin and haematocrit due to phosphide
                    poisoning has been reported in animal experiments
                    (WHO, 1988) but the only report in humans was of a
                    patient who developed purpura, with transient
                    reduction of red blood cells, platelets and
                    haemoglobin which was ascribed to phosphine/phosphide
                    poisoning.

             9.4.11 Immunologic

                    No data available.

             9.4.12 Metabolic

                    9.4.12.1 Acid-base disturbances

                             Metabolic acidosis is a common
                             problem in severe phosphine poisoning,
                             although it has not been reported in
                             detail.

                    9.4.12.2 Fluid and electrolyte disturbances

                             Fluid and electrolyte disturbances
                             may occur in severe phosphine/phosphide
                             poisoning, particularly hypokalaemia
                             associated with metabolic acidosis, renal
                             dysfunction, and hypermagnesaemia.

                    9.4.12.3 Others

                             No data available.

             9.4.13 Allergic reactions

                    There has been a single case report of purpura
                    ascribed to phosphine poisoning.  The platelet count
                    was reduced to 60,000/mm3 and red blood cell to
                    3.1  106/mm3.  On recovery, both the platelet and
                    red cell counts increased to 210,000/mm3 and
                    4.8  106 /mm3, respectively.

             9.4.14 Other clinical effects

                    No data available.

             9.4.15 Special risks: Pregnancy, breastfeeding, enzyme
                    deficiencies

                    No data available.

        9.5. Others

             No data available.

        9.6  Summary

    10. MANAGEMENT

        10.1 General principles

             Management depends on the route of exposure and proper
             first aid treatment must be performed.
    
             (a) First aid
    
             In case of phosphine inhalation, the patient must be removed
             from the exposure site and rested.  Rescuers should follow
             fully safety procedures.  If a patient is unconscious, place
             in the semi-prone recovery position or otherwise maintain the
             airway and give oxygen if required.  If breathing stops,
             immediately ventilate the patient artificially (mouth-to-
             mouth/nose or mechanically with oxygen if available).  If the

             heart stops, begin cardiopulmonary resuscitation (CPR).  The
             patient must then be referred to the nearest medical centre
             for further treatment (Vale and Meredith, 1983).
    
             In case of ingestion of a metal phosphide, do not give milk,
             fats or saline emetics by mouth. If the patient is conscious,
             induce vomiting.  After vomiting, administer activated
             charcoal (50 g in water by mouth) if available.  Early
             clearance of zinc phosphide from the gut was recommended by
             Stephenson (1967) although he found Zn3P2 in gastric
             contents at autopsy when gastric lavage had been
             performed.
    
             (b) Medical treatment
    
             1. Gastric lavage, with tracheal intubation if appropriate,
             using 2% sodium bicarbonate solution (to limit hydrolysis of
             zinc phosphide).  Stephenson (1967) used copper sulphate as
             the precipitation solution for gastric lavage for Zn3P2. 
             Indian authors (Chopra et al, 1986; Khosla et al., 1988;
             Misra et al, 1988) applied potassium permanganate for gastric
             lavage.
    
             2. Activated charcoal or medicinal liquid paraffin may limit
             absorption of phosphine and zinc phosphide respectively and
             may be administered by mouth or stomach tube (although it did
             not work in the patient reported by Stephenson,1967). 
             Repeated doses of activated charcoal together with sorbitol
             (to avoid constipation) may be useful and has been used by
             the author but has not been yet reported for phosphine/
             phosphide poisoning.
    
             3. Monitor and support vital functions, particularly
             cardiovascular, respiratory, hepatic and renal functions. 
             Treat shock conventionally  (Chopra et al, 1986; Khosla et
             al, 1988). Dopamine and hydrocortisone succinate have been
             used to overcome the shock.
    
             4. Perform arterial blood gas analysis and correct
             respiratory dysfunction by clearing the airways, giving
             oxygen and perform artificial (mechanical) respiration if
             required.  Metabolic acidosis must also be treated by giving
             sodium bicarbonate according to the results of arterial pH
             and blood gas analyses.
    
             5. Hepatic and renal failure should be treated as required,
             with consultation with an experienced hepatologist and
             nephrologist.

        10.2 Life supportive procedures and symptomatic treatment

             Dehydration and shock was treated by infusion of
             dextrose-saline, dopamine hydrochloride and hydrocortisone
             hemisuccinate by Khosla et al (1988).  Severe metabolic
             acidosis must also be promptly treated by giving intravenous
             sodium bicarbonate.  Calcium gluconate has been used as a
             membrane stabilizing agent.  It was effective in controlling
             excitement and convulsions in some patients.  However, if
             convulsions do not respond to calcium, an anticonvulsant drug
             such as diazepam should be administered intravenously.
    
             Severe cases of phosphine/phosphide poisoning must be treated
             in an intensice care unit (ICU) in which vital facilities,
             particularly cardiopulmonary monitoring and resuscitation,
             would be available.  Mechanical respiration may be required
             in severely poisoned patients.  Unfortunately there is no
             specific treatment for phosphine/phosphide poisoning. 
             Therefore, life supportive procedures and symptomatic
             treatment should be applied whenever clinically indicated.

        10.3 Decontamination

             Depending on the route of entry different procedures
             for decontamination must be performed.  In case of
             inhalation, the patient must be removed from the contaminated
             area.  With the patient at rest, clear the airway and give
             oxygen and artificial respiration as required.  In the case
             of metal phosphide ingestion, vomiting should be induced
             while preparation is made for gastric aspiration and lavage. 
             Syrup of ipecac can be used as an emetic.  Alternatively,
             copper sulphate 0.5 g as 1% aqueous solution can be given and
             has the additional theoretical benefit of forming insoluble
             copper phosphide (Stephenson 1967).  Indian physicians
             (Chopra et al., 1986; Khosla et al., 1988, Misra et al.,
             1988) have used potassium permanganate solution (1:1000) as
             an oxidative agent for gastric lavage, although experimental
             and clinical evidence is lacking.
    
             It is obviously important to clear the metal phosphide (AlP.
             Zn3P2, Mg3P2) from the entire gastrointestinal tract. 
             A large dose (100 g) of mineral oil is recommended, but it is
             not always effective.  In such circumstances the dose should
             be repeated and, if necessary, followed by a magnesium
             sulphate purge, bearing in mind that this may lead to further
             water and electrolyte losses. Activated charcoal with
             sorbitol (Medicoal) may be effective and 5 to 10 g should be
             given every 2 to 3 hour by mouth or through a nasogastric
             tube.  Milk, fats and saline emetics must not be given as
             they may induce more toxicity with phosphine/phosphide.

        10.4 Elimination

             Since observed phosphine/phosphide is rapidly oxidised
             in the blood it seems that elimination techniques such as
             forced diuresis, alkinisation, haemoperfusion and dialysis
             will be ineffective.  Stephenson (1967) reported that forced
             diuresis was not effective in one patient. However,
             correction of dehydration and metabolic acidosis by
             intravenous administration of isotonic solution and sodium
             bicarbonate is required.  Repeated doses of activated
             charcoal with sorbitol by mouth or through a nasogastric tube
             (gastrointestinal dialysis) may be effective.  Haemodialysis
             is required for the treatment of acute renal failure which
             may complicate phosphine poisoning.

        10.5 Antidote

             10.5.1 Adults

                    No antidote is available for phosphine/
                    phosphide poisoning.

             10.5.2 Children

                    No antidote is available for phosphine/
                    phosphide poisoning.

        10.6 Management discussion

             Since the exact mechanism of toxicity of
             phosphine/phosphide poisoning is not clear in human beings,
             no specific treatment is available.  A review of the European
             cases by Stephenson (1967) suggests that early vomiting
             improves the prognosis.  Two young women swallowed similar
             quantities of zinc phosphide in a suicide pact.  One woman
             was induced to vomit by mechanical means shortly after
             poisoning; she had only transient symptoms and recovered
             completely.  Her friend would not vomit and despite gastric
             lavage one hour after poisoning, she died within 24
             hours.
    
             Early recognition and treatment of phosphine/phosphide
             poisoning is therefore of great importance.  Treatment of
             shock and metabolic acidosis together with the intensive care
             therapy of the cardiopulmonary effects are essential.

    11. ILLUSTRATIVE CASES

        11.1 Case reports from literature

             Cases of acute phosphine poisoning reported in the
             literature were reviewed by Harger & Spolyar (1958).  Since
             1900, a total of 59 cases with 26 deaths have been recorded.

             In 6 of 11 reports, cargoes of ferrosilicon were cited as the
             source of phosphine and in these cases the victims were
             passengers or crew members on the ships or barges concerned. 
             Other cases involved the exposure of welders to calcium
             carbide and/or raw acetylene and of submariners to sodium
             phosphide.
    
             Stephenson (1967) reported a fatal case of zinc phosphide
             poisoning and reviewed the European literature.  A 37-year
             old woman drank a mixture of 180 g zinc phosphide and water
             with suicidal intent.  The zinc phosphide was 85% technical
             grade powder used by a game-keeper to prepare rodent baits.
             Vomiting began one hour after ingestion and was frequent and
             violent.  She was discovered in a state of shock after about
             5 hours.  Her skin was cold and blue; blood pressure was
             unrecordable and heart sounds were inaudible.  Occasional
             ronchi were heard over the right lung.  The breath smelt of
             phosphine; one pint of pungent black fluid, smelling of
             phosphine was aspirated from her stomach.  After this, her
             rectal temperature was 92F (33C).  Arterial blood gas
             analysis is revealed severe metabolic acidosis corrected by
             1200 mEq sodium bicarbonate over 8 hours.  White blood cells
             were 15000/mm3 with 94% neutrophils.  Serum zinc
             concentration was 590 to 605 ng/100 mL (normal 120 to 200
             ng/100 mL). The ECG showed sinus tachycardia and slight S-T
             depression in the left ventricular leads.  Severe abdominal
             pain, hepatic factor and refractory tetany persisted for
             several hours.  Urine output diminished; fever and tachypnea
             preceded a rapidly developing confusional state and
             unexpected cardiac arrest occurred 41 hours after ingestion.
             Postmortem examination revealed congestion in all organs. 
             The lungs were oedematous, the gastric mucosa were deeply
             haemorrhagic and some centrilobular necrosis of the liver and
             patchy necrosis of the convoluted tubules of the kidneys were
             observed.
    
             Wilson et al. (1980) reported 31 cases of acute phosphine
             poisoning aboard a grain freighter.  These included 2
             children, one of whom died.  The predominant symptoms were
             headache, fatigue, nausea, vomiting, cough and shortness of
             breath.  The abnormal physical findings included jaundice,
             paraesthesia, ataxia, intention tremor, and diplopia.  Focal
             myocardial infiltration with necrosis, pulmonary oedema and
             widespread small vessel injury were found at postmortem
             examination.
    
             Singh et al (1985) reported 15 patients who had ingested 1.5
             to 9 g (mean 4.7 g) of phostoxin pellets or tablets
             (containing 58% aluminum phosphide); 13 cases were attempted
             suicides. Repeated vomiting and hypotension occurred in all
             patients, and 13 were in shock on admission.  Other common
             features included impaired sensorium, restlessness,
             tachycardia, tachypnea, pulmonary crepitations, oliguria,

             anuria and jaundice.  Half of the patients had raised blood
             urea, creatinine, bilirubin and transaminases. 
             Electrocardiographic abnormalities were observed in 6
             patients.  Metabolic acidosis with blood pH values of 6.97 to
             7.31 and bicarbonate of 4.6 to 14.5 m mol/L were present in
             all 6 patients tested.  Eleven patients died and postmortem
             examination revealed upper gastrointestinal congestion and in
             2 cases haemorrhagic fluid was present in the stomach.  Lungs
             were congested and heavy and showed fibrinous pulmonary
             oedema.  Examination of the liver revealed mild fatty
             infiltration and areas of centrizonal in two cases with
             haemorrhages in another.
    
             Chopra et al. (1980) described 16 patients suffering from
             aluminum phosphide poisoning which accounted for half the
             total number of cases of acute poisoning in their medical
             centre.  Profuse vomiting, upper abdominal pain and shock
             were the commonest presenting features.  Six patients who had
             taken unexposed tablets of AlP died because of cardiovascular
             collapse, pulmonary oedema and acute renal failure.
    
             Khosla et al. (1988) presented 25 cases of aluminum phosphide
             poisoning in which 16 (64%) cases had evidence of cardiac
             dysfunction; the mortality was 40%.  Peripheral circulatory
             failure, cardiac dysrhythmias, myocarditis and cardiac
             failure were the main cardiovascular findings.
    
             Misra et al. (1988) reported 8 cases of phosphine poisoning
             following ingestion of aluminum phosphide tablets for
             suicidal attempt. The clinical picture consisted of
             gastritis, altered sensorium and peripheral vascular failure
             in all cases, cardiac arrhythmia (3), jaundice and renal
             failure (1 each).  Six patients died with a mean hospital
             stay of 19 hours.  Post mortem examinations revealed
             pulmonary oedema, vascular degeneration of hepatocytes,
             dilatation of hepatic central veins and areas of nuclear
             fragmentation.

    12. ADDITIONAL INFORMATION

        12.1 Specific preventive measures

             The most important factor in the safe handling of
             phosphine and metal phosphides and in their formulation, is
             proper work practices.  Management should identify these,
             provide training for the operatives, and ensure that these
             practices are carried out.  Personal protective measures
             recommended to reduce the likelihood of absorption of
             phosphide preparations include the wearing of:
    

             (a) Synthetic rubber gloves
             (b) Rubber boots
             (c) Lightweight impervious overalls, and
             (d) Suitable eye protection
    
             Adequate washing facilities should be available at all times
             during handling.  Eating, drinking and smoking should be
             prohibited during handling.  The means to measure the
             concentration of phosphine in the air should be available and
             used as required.  When necessary, respiratory protective
             equipment should be worn.  In fumigation, each operator or
             other person liable to be exposed to the gas must be provided
             with an efficient means of respiratory protection.  Persons
             exposed to magnesium or aluminium phosphide (or any other
             readily hydrolysed phosphide), which may give rise to an
             airborne dust, should be protected by respiratory protective
             equipment.  This should be protective against gaseous
             phosphine, since hydrolysis of dust in the filter of a dust
             mask or respirator may give rise to high phosphine exposure
             (WHO, 88).
    
             No occupational accidents have been reported since 1957.  It
             seems that the established safety precautions are
             satisfactory. Stephenson (1967) recommended the prohibition
             of sale and distribution of zinc phosphide to all but
             experts.  This should also apply to aluminum and magnesium
             phosphides.
    
             Wilson et al. (1980) pointed out that ship crew members who
             work with toxic substances must be adequately educated in
             preventive measures.  Multilingual signs should be placed
             aboard ships as a reminder of toxic hazards. Most important,
             ship owners and masters ought, whenever possible, to consider
             substitution of less toxic fumigation for such highly
             poisonous agents as phosphine.
    
             Singh et al (1985), suggested that since the mortality of
             aluminum phosphide poisoning is so high and there is no
             specific antidote, a less toxic but equally effective agent
             should be sought to replace this lethal substance.
    
             Chopra et al (1988) indicated that the United Nations
             Organisation and its agencies WHO and FAO and others in
             consultation with state governments should quickly take
             appropriate steps to prevent further loss of lives as a
             result of self-poisoning with aluminum phosphide.
    
             Misra et al (1988) pointed out that the high mortality and
             lack of specific antidotes should caution the authorities
             dealing with the distribution and use of this pesticide.

        12.2 Other

             Leaks, spillages, and residues

             Small leaks and residues of compressed gas can be discharged
             slowly to the atmosphere in the open air.  Larger quantities
             should be burned using an appropriate burner.
    
             Spillages and residues of metal phosphides in containers will
             evolve phosphine for several days by reaction with
             atmospheric moisture.  Respiratory protective equipment will
             be required by those dealing with them.
    
             Residues at the site of spillage should be washed away using
             a large quantity of water and the area kept secure and well
             ventilated until the gas is no longer measurable.
    
             Combustible packages can be incinerated at high temperature
             (>1000C) using proper facilities.  Containers should not
             cleaned for re-use, but should be disposed of by deep burial,
             at an approved site, well away from habitation and where
             there is no danger of contamination of water sources (WHO,
             1988).  Sowunmi (1985) measured the phosphine residues on
             cowpeas fumigated with phostoxin tablets and showed them to
             be well below the 0.1 ppm tolerance limits for grain at all
             treatment levels.
    
             Calzolari (1990) compared the residue formation of phostoxin
             (AlP) with magnesium phosphide (Mg3P2) and reported that
             the latter left a much lower residue concentration, with no
             detectable PH3 after 120 hours.

    13. REFERENCES

        Arena, J.M., & Drew, R.H. (1986) Poisoning Toxicology, Symptoms,
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        Beliles, R.P.(1981) in: Patty's Industrial Hygiene and Toxicology
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        Sons. pp. 1228-1229.
    
        Calzodari S G (1986) Colorimetric determination of residues of
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        Calzodari S G (1990) Residue problem after disinfestation of
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        Casarett L J (1991) Inorganic Rodenticide.In: Casarett and Doull's
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        Chan L T F (1983) Phosphine analysis in post-mortem specimens
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        Chugh S N, Singhal H R, Mehta L, Chugh K, Sankar V, & Malhotra KC
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        Ellenhorn M J, & Barceloux D G (1990), Medical Toxicology. New
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        Haddad L M, & Winchester J F. (1983) Clinical management of
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        Thienes W C, & Haley T J (1972) Clinical toxicology. 5th ed.
        Philadelphia, Febiger. p. 193.
    
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        poisoning and drug overdosage (eds: Haddad and Winchester).
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        Wilson R, Lovejoy F H, Jaeger R J, & Londrigan P L (1980) Acute
        phosphine poisoning aboard a grain freighter. JAMA 244 (2):
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        Geneva.

    14. AUTHOR(S), REVIEWER(S), DATE(S)

        Author: Professor Mahdi Balali-Mood
        Director, Poisons Centre
        Imam Reza Hospital
        91735 Mashha
        P.O. Box 348
        Islamic Republic of Iran
    

        Tel: 98-51-93034
        Tlx: 512015 IR
        Fax: 98-51-92083
    
        Date: November 1991
    
        Peer review: Cardiff, UK (September, 1996)
    
        Editor: Dr M. Ruse (October, 1997)
    



    See Also:
       Toxicological Abbreviations
       Phosphine (HSG 28, 1989)
       Phosphine (ICSC)
       Phosphine (PDS)