Phosphine

 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: -133.5�[C
 Boiling point -87.4�[C 
 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
 38�[C, 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 750�[C. 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 -20�[C 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 ƒ‰ 106/mm3. On recovery, both the platelet and
 red cell counts increased to 210,000/mm3 and
 4.8 ƒ‰ 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 92�[F (33�[C). 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
 (>1000�[C) 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,
 Treatment. 5th edition. Illinois, Springfield, pp. 361-393.
 
 Beliles, R.P.(1981) in: Patty's Industrial Hygiene and Toxicology
 (eds: Clayton, G.D. and Clayton, F.E.) New York, John Wiley &
 Sons. pp. 1228-1229.
 
 Calzodari S G (1986) Colorimetric determination of residues of
 phostoxin. Tecnica Molitoria:37(8):609-622 (In Italian with
 English abstract).
 
 Calzodari S G (1990) Residue problem after disinfestation of
 cereals. Tecnica Molitoria 41(4):272-275 (In Italian with English
 abstract).
 
 Casarett L J (1991) Inorganic Rodenticide.In: Casarett and Doull's
 Toxicology: The Basis Science of Poisons. New York Macmillan Press
 Ltd, pp 566-569.
 
 Chan L T F (1983) Phosphine analysis in post-mortem specimens
 following ingestion of aluminum phosphide. J. Analyt. Toxicol.
 7(4):165-167.
 Chopra J S, Karla O P, Malik V S, Sharma R, & Chandna A (1988)
 Aluminum Phosphide poisoning: a prospective study of 16 cases in
 one year. Postgrad. Md. J. 62, 1113-1115.
 
 Chugh S N, Ram S, Chug K, & Malhotra K C (1989a) Spot diagnosis of
 aluminum phosphide ingestion: an application of a simple test.
 J Assoc Physicians India 37(3): 219-220.
 
 Chugh S N, Ram S, Mehta L K, Arora B B, & Malhotra K C (1989b)
 Adult respiratory distress syndrome following aluminum phosphide
 poisoning. J Assoc Physicians India, 37(4): 271-272.
 
 Chugh S N, Ram S, Sharma A, Arora B B, Saini A S, & Malhotra K C
 (1989c) Adrenocortical involvement in aluminum phosphide
 poisoning. Indian J Med Res 90: 289-294.
 
 Chugh S N, Ram S, Singhal H R, & Malhotra K C (1989d) Significance
 of heart rate response in shock due to aluminum phosphide
 poisoning. J Assoc Physician India 37(11): 708-709.
 
 Chugh S N, Singhal H R, Mehta L, Chugh K, Sankar V, & Malhotra KC
 (1990) Plasma renin activity in shock due to aluminum phosphide
 poisoning. J Assoc Physicians India 36(8): 398-399.
 
 Deichmann W B, & Gerard H W (1964) Toxicology of drugs and
 chemicals. New York and London, Academic Press, p. 472.
 
 Ellenhorn M J, & Barceloux D G (1990), Medical Toxicology. New
 York and London, Elsevier, pp 1053-1054.
 
 Gossel R E, Hodge H C, Smith R P, & Gleason M N (1977) Clinical
 Toxicology of commercial products, Baltimore, The Williams and
 Wilkins Co. Section III pp 275-279.
 
 Grant W M (1974) Toxicology of the eye. 2nd ed. Illinois,
 Springfield p.826.
 
 Haddad L M, & Winchester J F. (1983) Clinical management of
 poisoning and drug overdosage. Philadelphia and London W.B.
 Saunders Co. pp. 805-806.
 
 Harger R N & Spolyar L W (1985) Toxicity of phosphine with a
 possible fatality from this poison. Am Med Assoc Arch Ind Health
 18: 497-504.
 
 Khosla S N, N an N & Kumar P (1988a) Cardiovascular complications
 of Aluminum phosphide poisoning. Angiology 39(4):355-359.
 
 Khosla S N, Nand N & Kohsla P (1988b) Aluminum Phosphide
 poisoning.J Trop Med Hyg 91(4):196-198.
 
 Misra U K, Tripathi A K, Pandey R & Bhargwa B (1988) Acute
 phosphine poisoning following ingestion of aluminium phosphide.
 Human toxicol 7:343-345.
 
 Polson C J, Green M A, & Lee M R (1983) Clinical toxicology. 3rd
 ed. London Pitman Books Ltd. pp 241-2.
 
 Roman R, & Dubey M (1983) The electrocardiographic changes in
 quick phosphine poisoning. Indian Heart J 37(3):193-195.
 
 Singh S, Dilawari J B, Vashist R, Malhotra H S, & Sharma B K
 (1983) Aluminum Phosphide ingestion. Br Med J 290 (6475):
 1110-1111.
 
 Singh R B, Rastogi S S, & Singh D S (1989) Cardiovascular
 manifestations of aluminum phosphide intoxication. J Assoc
 Physicians India 37(9):590-592.
 
 Sowunmi O (1985) Phosphine residues on cowpeas fumigated with
 phostoxin tablets. Bull Acad Nat Med (Paris) 169(6): 897-904 (In
 French with English abstract).
 
 Stephenson J B P (1967) Zinc phosphide poisoning. Arch Environ
 Health 15:83-88.
 
 Thienes W C, & Haley T J (1972) Clinical toxicology. 5th ed.
 Philadelphia, Febiger. p. 193.
 
 Vale J A, & Meredith T J, (1983) in: Clinical management of
 poisoning and drug overdosage (eds: Haddad and Winchester).
 Philadelphia,W.B.Saunders. pp. 805-806.
 
 Wilson R, Lovejoy F H, Jaeger R J, & Londrigan P L (1980) Acute
 phosphine poisoning aboard a grain freighter. JAMA 244 (2):
 148-150.
 
 World Health Organization (1988) Phosphine and selected metal
 phosphides, IPCS, Environmental Health Criteria 73, WHO,
 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)