Arsine
| 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 Brand names, Trade names |
| 1.6 Manufacturers, Importers |
| 2. SUMMARY |
| 2.1 Main risks and target organs |
| 2.2 Summary of clinical effects |
| 2.3 Diagnosis |
| 2.4 First aid measures and management principles |
| 3. PHYSICO-CHEMICAL PROPERTIES |
| 3.1 Origin of the substance |
| 3.2 Chemical structure |
| 3.3 Physical properties |
| 3.3.1 Colour |
| 3.3.2 State/Form |
| 3.3.3 Description |
| 3.4 Hazardous characteristics |
| 4. USES |
| 4.1 Uses |
| 4.1.1 Uses |
| 4.1.2 Description |
| 4.2 High risk circumstance 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 Other |
| 6. KINETICS |
| 6.1 Absorption by route of exposure |
| 6.2 Distribution by route of exposure |
| 6.3 Biological half-life by route of exposure |
| 6.4 Metabolism |
| 6.5 Elimination and excretion |
| 7. TOXICOLOGY |
| 7.1 Mode of action |
| 7.2 Toxicity |
| 7.2.1 Human data |
| 7.2.1.1 Adults |
| 7.2.1.2 Children |
| 7.2.2 Relevant animal data |
| 7.2.3 Relevant in vitro data |
| 7.2.4 Workplace standards |
| 7.2.5 Acceptable daily intake (ADI) |
| 7.3 Carcinogenicity |
| 7.4 Teratogenicity |
| 7.5 Mutagenicity |
| 7.6 Interactions |
| 8. TOXICOLOGICAL ANALYSES 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 exposure |
| 9.2.4 Eye contact |
| 9.2.5 Parenteral exposure |
| 9.2.6 Other |
| 9.3 Course, prognosis, cause of death |
| 9.4 Systematic description of clinical effects |
| 9.4.1 Cardiovascular |
| 9.4.2 Respiratory |
| 9.4.3 Neurological |
| 9.4.3.1 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 Other |
| 9.4.7 Endocrine and reproductive systems |
| 9.4.8 Dermatological |
| 9.4.9 Eye, ear, nose, throat: local effects |
| 9.4.10 Haematological |
| 9.4.11 Immunological |
| 9.4.12 Metabolic |
| 9.4.12.1 Acid-base disturbances |
| 9.4.12.2 Fluid and electrolyte disturbances |
| 9.4.12.3 Others |
| 9.4.13 Allergic reactions |
| 9.4.14 Other clinical effects |
| 9.4.15 Special risks |
| 9.5 Other |
| 9.6 Summary |
| 10. MANAGEMENT |
| 10.1 General principles |
| 10.2 Life supportive procedures and symptomatic/specific treatment |
| 10.3 Decontamination |
| 10.4 Elimination |
| 10.5 Antidote treatment |
| 10.5.1 Adults |
| 10.5.2 Children |
| 10.6 Management discussion |
| 11. ILLUSTRATIVE CASES |
| 11.1 Case reports from literature |
| 12. ADDITIONAL INFORMATION |
| 12.1 Specific preventive measures |
| 12.2 Other |
| 13. REFERENCES |
| 14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE ADDRESS(ES) |
ARSINE
International Programme on Chemical Safety
Poisons Information Monograph 044
Chemical
1. NAME
1.1 Substance
Arsine
1.2 Group
Arsenic hydride
1.3 Synonyms
Arsenic trihydride; arsenic hydride;
hydrogen arsenide; arseniuretted hydrogen;
arsenous hydride;arsenowodor (polish);
arsenwasserstoff (german);
monoarséniure trihydrique;
arséniure d'hydrogène gazeux;
acide arsénhydrique (french)
1.4 Identification numbers
1.4.1 CAS number
7784-42-1
1.4.2 Other numbers
NIOSH: CG 6475000
DOT: 2188
UN 2188
1.5 Brand names, Trade names
No data available
1.6 Manufacturers, Importers
Matheson Gas Products (USA); Phoenix Research Corp. (USA)
2. SUMMARY
2.1 Main risks and target organs
Arsine is a highly toxic gas. It has powerful haemolytic
properties which can result in acute intravascular hemolysis
and secondary renal failure. Mortality rate is high. A
peripheral neuropathy can develop within months following
acute poisoning.
It is a human carcinogen.
2.2 Summary of clinical effects
The onset of symptoms is related to the inhaled
concentration of arsine. Initial clinical manifestations
generally occur 30 to 60 minutes after exposure, but may be
delayed up to several hours. Symptoms include headache,
nausea, vomiting, thirst, abdominal pain, shivering,
hemoglobinuria. A garlicky odor of the breath may be noted.
Anuria, jaundice, hypotension, metabolic acidosis and
multiorgan failure may develop subsequently, as a consequence
of massive hemolysis.
Anemia is slowly reversible secondary to disturbances of
erythropoiesis.
Skin discoloration and lines on nails may occur.
A sensory peripheral neuropathy may develop over months
following acute poisoning.
2.3 Diagnosis
Acute: diagnosis is based on a history of exposure to
arsine gas and early onset of headache, nausea and abdominal
pain, dark red or brown discolouration of the urine and
garlic-like odour on the breath.
Chronic: arsine intoxication should be suspected when
fatigue, muscular weakness, cramps and haemolytic anemia
occur in workers potentially exposed to low
concentration.
2.4 First aid measures and management principles
Inhalation: remove from exposure, monitor for
respiratory distress, and administer supplemental oxygen.
Maintain adequate hydration by starting intravenous fluids.
Maintain urinary flow by correcting hypotension.
Exchange transfusion or repeated transfusions of whole blood
may be effective if significant haemolysis has occured.
Dermal and eye exposure: immediately flush exposed areas
with running water for at least 15 minutes.
Toxic effects may have a delayed onset and exposed victims
should be observed for a minimum of 24 hours.
3. PHYSICO-CHEMICAL PROPERTIES
3.1 Origin of the substance
Arsine is produced when metallic arsenides are
decomposed by water or reducing acids.
Main methods of manufacturing: hydrolysis of aluminium
arsenide or treatment of aluminium arsenide with hydrogen
chloride, reduction of arsenic trioxide with zinc in
hydrochloric acid, decomposition of arsenides of
electropositive metals. (HSDB, 1996)
Arsenic is a widespread contaminant of many ores such as
zinc, lead, and copper. Arsine can be formed, as a side
reaction, when an acid or water contacts these arsenic
bearing ores.
Numerous industrial processes can lead to the accidental
formation and liberation of arsine fumes, including the
smelting and refining of metals (zinc), plating, galvanizing,
soldering, electrolytic processing of hydrogen, preparation
of acetylene from calcium carbide (Clayton & Clayton,
1981).
3.2 Chemical structure
Molecular formula: AsH3
Molecular weight: 77.93
3.3 Physical properties
3.3.1 Colour
Colourless
3.3.2 State/Form
Gas
3.3.3 Description
Density: 2.695
Melting point: -117 °C
Boiling point: -62.5 °C
Vapor pressure: 11 mm Hg at 20 °C
Dissociation pressure at 0 °C = 0.806 atm
Solubility in water: 28 mg/100 at 20 °C
Soluble in benzene, chloroform
Slightly soluble in ethyl alcohol and in alkalis
(Budavari, 1989).
Disagreeable garlic odour. The odour threshold of 0.5
ppm should not be considered a reliable indicator of
the presence of toxic concentrations of arsine
gas.
3.4 Hazardous characteristics
Decomposes when heated at 300 °C, depositing arsenic
which volatilizes at 400°C.
On exposure to light, moist arsine decomposes quickly
depositing shiny black arsenic.
Aqueous solutions are neutral.
Traces are best removed by absorption in potassium
permanganate solution or in bromine water.
Extremely flammable when exposed to heat, sparks or
flames.
Moderately explosive when exposed to Cl2, HNO3, (K + NH3),
on contact with warm and dry air or powerful shock
(Budavari, 1989; Sax & Lewis, 1989; HSDB, 1996).
4. USES
4.1 Uses
4.1.1 Uses
Chemical used in synthesis;
not otherwise specified
Other industrial/commercial product
4.1.2 Description
Arsine has few industrial applications.
It is used as a doping gas in the processing of semi-
conductors in the microelectronics industry, and in
organic synthesis.
Arsine is stored under pressure in glass lined
cannisters.
4.2 High risk circumstance of poisoning
Most cases of arsine poisoning do not result from use of
the gas itself; rather they occur when arsine is accidentally
generated as by-product of a chemical reaction involving a
metal containing an arsenic impurity and an acid or a strong
alkali.
Numerous industrial production processes can lead to the
accidental formation and liberation of arsine fumes: smelting
and refining of metals (zinc), plating, galvanizing,
soldering, electrolytic processing of hydrogen. (Clayton &
Clayton, 1981).
Acute episodes of arsine poisoning may occur in environments
unrelated to metal processing and be difficult to identify.
Williams et al. (1981) described an arsine exposure involving
artists working on the restoration of a famous painting,
where nascent hydrogen came in contact with small amounts of
arsenic in the paint.
Another circumstance of poisoning is during the cleaning of
tanks or drains that had been used to store arsenical
compounds.
Combustion products, which include arsine, may be present in
runoff from fire control or dilution may cause
pollution.
4.3 Occupationally exposed populations
Workers in the metallurgical industry involved in the
production process and the maintenance of furnaces.
Workers in the microelectronics industry (Sheehy & Jones,
1993).
Workers involved in the cleaning of storage tanks.
5. ROUTES OF EXPOSURE
5.1 Oral
Not relevant
5.2 Inhalation
Well absorbed. Important route in occupational exposure.
5.3 Dermal
Contact with arsine gas causes chemical burns. Contact
with liquid arsine may cause tissue to freeze.
It has been suggested that arsine can enter the body through
cuts and breaks in the skin (Compton JAF, 1987 Military Chem
Biol Agents, p 102, cited in HSDB, 1996).
5.4 Eye
Contact with arsine gas causes chemical burns. Contact
with liquid arsine may cause tissue to freeze.
5.5 Parenteral
Not relevant
5.6 Other
No data available
6. KINETICS
6.1 Absorption by route of exposure
Arsine is rapidly and well absorbed by inhalation
(Clayton & Clayton, 1981).
6.2 Distribution by route of exposure
Arsine is highly lipid soluble. After inhalation it can
easily cross the alveolo-capillary membrane and the red blood
cell membrane.
It accumulates in its oxidized form, arsenite, in the red
blood cells, liver, kidneys, spleen and lungs. Arsenite binds
to haemoglobin, thus reducing its availability to bind oxygen
(Clayton & Clayton, 1994).
6.3 Biological half-life by route of exposure
Half-life of the oxidised form (As3+) after ingestion is
7 hours (Baselt, 1988).
It may be prolonged in the presence of impaired renal
function (Risk & Fuortes, 1991).
6.4 Metabolism
Arsine is gradually converted to arsenite (As3+) and
further monomethylarsonic and dimethylarsinic acids.
Methylation is the most significant route of detoxification
in mammals, including humans (Clayton & Clayton, 1994).
6.5 Elimination and excretion
Inorganic arsenic and the monomethylarsonic and
dimethylarsinic acids are primarily excreted in the urine,
over a long period of time.
Following inhalation of inorganic arsenic compounds, the
fractions in the urine are approximately 20% inorganic
arsenic, 20% methylarsonic acid, and 60% dimethylarsinic acid
(Clayton & Clayton, 1994).
7. TOXICOLOGY
7.1 Mode of action
Arsine is highly lipid soluble. It can easily cross the
alveolo-capillary membrane and into the red blood cell.
Blair et al., (1990) performed in vitro experiments on red
blood cells exposed to arsine gas. They provided evidence
that arsine depletes the reduced glutathione content of the
red blood cells, resulting in an oxidation of sulfhydryl
groups in hemoglobin and, possibly, red cell membranes. These
effects produce membrane instability with rapid and massive
intravascular hemolysis.
Arsine also binds to haemoglobin to form an arsine-
haemoglobin complex (Gosselin et al., 1982).
Hatlelid et al., (1996) demonstrated that arsine-induced
haemolysis of dog red blood cells was completely blocked by
carbon monoxide preincubation and was reduced by pure oxygen
compared to incubations in air. They suggested that a
reaction occurs between arsine and hemoglobin in the heme-
ligand binding pocket or with the heme iron.
In a case report of death occurring within 24 hours after
exposure, the kidneys had severe injury. The renal tubules
were dilated and the epithelium displayed vacuolization to
complete necrosis, even though it had been too short a time
for haematuria to develop (Browning, 1969). Hirata et al.
(1990, cited in Clayton & Clayton, 1994) has demonstrated in
hamsters that glutathione depletion increases arsine-induced
nephrotoxicity. These observations suggest a direct toxic
effect on the kidney.
7.2 Toxicity
7.2.1 Human data
7.2.1.1 Adults
The odour threshold, of 0.5 ppm, can
produce clinical toxicity and may not provide
an adequate warning (Budavari, 1983).
Exposure to 3 to 10 ppm can cause symptoms
within a few hours (US EPA, 1982).
Symptoms of arsine toxicity have been
observed with brief exposure to 30 ppm (100
mg/m3) (Risk & Fuortes, 1991).
A half-hour exposure at 25 to 50 ppm (80-160
mg/m3) is considered lethal (Blackwell &
Robbins, 1979).
Inhalation of 250 ppm (800 mg/m3) of arsine
gas is instantly lethal (NIOSH, 1979).
The IDLH (Immediately Dangerous to Life and
Health) concentration is 6 ppm (NIOSH,
1990).
7.2.1.2 Children
No data available.
7.2.2 Relevant animal data
Animals exposed 3 hours a day to concentrations
between 0.5 and 2 ppm experienced red blood cell
toxicity within a few weeks (ACGIH, 1986).
No effects on the hematopoeitic system were observed
following a single exposure to 0.5 ppm arsine, which
is 10 times the TLV set by the ACGIH, but a 90-day
arsine exposure to 0.025 ppm (one-half the TLV) caused
a significant anemia in rats (Clayton & Clayton,
1994).
7.2.3 Relevant in vitro data
No data available.
7.2.4 Workplace standards
TLV-TWA : 0.05 ppm or 0.016 mg/m3 (ACGIH,
1995)
NIOSH recommends a ceiling of 0.002 mg/m3
The ACGIH has proposed a Biological Exposure Indice
(BEI) of 50 œg of arsenic in the urine per gram of
creatinine for monitoring exposure to arsine.
7.2.5 Acceptable daily intake (ADI)
No data available
7.3 Carcinogenicity
Arsine and airborne arsenic compounds have been
associated with carcinogenicity (Hubert et al., 1988). An
increased risk of lung cancers has been reported in several
epidemiological studies (Kuratsune et al., 1974; Lee-
Feldstein, 1983 cited in Clayton & Clayton, 1994).
Arsine is a human carcinogen (RTECS, 1991).
In 1994, NIOSH has recommended that arsine be regulated as a
potential human carcinogen.
The free radicals produced in the reduction of arsenite to
dimethylarsinic acid damage DNA and are responsible for the
carcinogenicity and potential genotoxicity of arsenic
(Yamanaka et al., 1991 cited in Clayton & Clayton,
1994).
7.4 Teratogenicity
Morrissey et al. (1990) reported an animal experiment
where pregnant mice and rats were exposed to arsine at
concentrations of 0.025, 0.5, or 2.5 ppm. Although arsine
caused increases in maternal spleen size and measurable
levels of arsenic in maternal blood and fetal livers, it did
not adversely impact fetal development based on the end
points used.
Several studies have reported an increased rate of
miscarriage among women who work in the semiconductor
industry, where arsine is used in the manufacture of
microchips (LaDou, 1983; Calabrese et al., 1987).
7.5 Mutagenicity
Arsenic compounds have mutagenic activity in the sister
chromatid exchange test (Andersen, 1983).
Cytogenetic effects including endoreduplication, chromosomal
aberrations and sister chromatid exchanges, have been
reported in Syrian hamster embryo cells in a dose-dependent
manner with sodium arsenite (Clayton & Clayton, 1994).
7.6 Interactions
No data available
8. TOXICOLOGICAL 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
Not relevant
9.1.2 Inhalation
Initial clinical manifestations often occur 30
to 60 minutes after exposure, but can be delayed up to
several hours, depending on the concentration and
duration of the exposure. Symptoms include headache,
nausea, vomiting, thirst, abdominal pain, bile-
containing diarrhea, and shivering, accompanied by a
sensation of cold and paresis in the limbs.
Haemoglobinuria develops a few hours after exposure. A
garlic-like odour on the breath may be noted. Anuria,
jaundice, hypotension, metabolic acidosis and
multiorgan failure may develop subsequently, as a
consequence of massive haemolysis.
A sensory peripheral neuropathy may develop over the
first months after acute poisoning.
A transient pulmonary edema ascribed to a local
irritant action of the gas may occur (Gosselin et al.,
1984).
9.1.3 Skin exposure
Redness of the skin. Frostbite may result from
freezing of tissues on exposure to liquid
arsine.
9.1.4 Eye contact
Watering eyes, photophobia, blurred vision and
red staining of conjunctiva appear early after
exposure; these may be due to local irritant activity
of arsine.
9.1.5 Parenteral exposure
Not relevant
9.1.6 Other
No data available
9.2 Chronic poisoning
9.2.1 Ingestion
Not relevant.
9.2.2 Inhalation
Animal: subacute or chronic exposure to low
arsine concentrations causes major persistent
splenomegaly and slight suppression of bone marrow
erythroid precursors in mice (Hong et al., 1989).
Human: clinical signs include asthenia, anorexia,
headache, myalgias. Low grade hemolytic anemia and
basophilic stippling may develop after chronic
exposure (Goldfrank & Bresnitz, 1986).
A progressive peripheral neuropathy may develop.
Characteristic fingernail changes (Mees' lines) may be
observed (Risk & Fuortes, 1991).
Blood arsenic concentrations and urinary arsenic
excretion are increased.
Lung cancers have been reported. (Kuratsune et al.,
1974).
9.2.3 Skin exposure
No data available.
9.2.4 Eye contact
No data available.
9.2.5 Parenteral exposure
Not relevant
9.2.6 Other
No data available.
9.3 Course, prognosis, cause of death
The prognosis and outcome depend on the severity of
exposure.
In the acute mild clinical form with headache, asthenia,
myalgia, nausea and transient moderate hemoglobinuria,
complete recovery generally occurs within one to two
weeks.
In severe cases the clinical course may be prolonged due to
haemolysis and secondary renal failure. Anaemia reverses
slowly. The peripheral neuropathy improves over several
months.
Death may occur within hours after acute exposure in the case
of massive inhalation, as a result of acute cardiac failure
(Benowitz, 1992).
9.4 Systematic description of clinical effects
9.4.1 Cardiovascular
Moderate and transient sinus tachycardia
secondary to haemolysis or anemia, hypovolemia or
acute pulmonary edema.
Hypotension and cardiovascular shock due to direct
effects on the myocardium and hyperkalemia (Benowitz,
1992).
ECG: elevation of the T-wave, various degrees of heart
block.
General vasoconstriction due to peripheral
hypoxia.
9.4.2 Respiratory
Dyspnea secondary to haemolysis and hypoxia.
Transient pulmonary edema.
(Hotz & Boillat, 1991).
9.4.3 Neurological
9.4.3.1 Central nervous system (CNS)
Headache, dizziness, pyrexia.
Impairment of consciousness, agitation,
anxiety, disorientation, delirium,
hallucination. Coma.
9.4.3.2 Peripheral nervous system
Paresthesia, numbness, burning
sensations.
A delayed peripheral sensory-motor neuropathy
may develop over the first few months after
the acute phase of poisoning, peaking at the
3rd month and resolving within 6 to 9 months
(Gosselin et al., 1982). The neuropathy is
usually both less common and milder than that
induced by arsenic, though its occurence may
be underestimated.
9.4.3.3 Autonomic nervous system
Hyperpyrexia
9.4.3.4 Skeletal and smooth muscle
Shivering, muscular cramps. Tissue
necrosis of skeletal muscle (Hesdorffer et
al., 1986).
9.4.4 Gastrointestinal
Nausea, vomiting, abdominal cramps and diarrhea
appear early and are usually transient, but they can
be severe, and result in dehydration (Gosselin et al.,
1984).
9.4.5 Hepatic
Early onset of acute jaundice due to hemolysis.
Hepatomegaly. Moderate elevation of liver enzymes
(Hotz & Boillat, 1991).
9.4.6 Urinary
9.4.6.1 Renal
Dark red or green discoloration of
the urine due to haemoglobinuria. Oliguria
proceeding to prolonged anuria.
Necrosis of the tubular epithelium (Browning,
1969).
9.4.6.2 Other
No data
9.4.7 Endocrine and reproductive systems
Several studies have reported an increased
number of miscarriages among women occupationally
exposed to low arsine concentrations (LaDou, 1983;
Calabrese et al., 1987).
9.4.8 Dermatological
Bronzing of the skin.
The skin lesions usually encountered with arsenic
poisoning include hyperpigmentation and
hyperkeratosis. They are rarely observed.
Streaks across fingernails (Mees' lines) may appear
after acute exposure.
9.4.9 Eye, ear, nose, throat: local effects
Watering eyes, photophobia, blurred vision and
red staining of conjunctiva appear early after
exposure; they may be due to the local irritant
activity of arsine (Clayton & Clayton, 1981).
Tinnitus is a rare occurence.
9.4.10 Haematological
Haemolysis may be severe in the first two or
three days after exposure, leading to errors in the
interpretation of blood cell count (red blood cell
count, leucocyte count, hematocrit), because of the
formation of "ghost cells", which are red blood cells
which have lost their hemoglobin content.
The amount of free haemoglobin in the plasma can
increase by as much as one third of the total
haemoglobin level (Gosselin et al., 1982).
Anemia ensues subsequent to haemolysis. It may develop
very quickly and may be severe. It is of the
normochromic, normocytic and megaloblastic type and is
poorly reversible (Ringenberg et al., 1988). The slow
reversal of anemia can necessitate repeated
transfusions.
A leukocytosis and signs of disseminated intravascular
coagulation can be observed during the haemolytic
phase (Gosselin et al., 1982).
9.4.11 Immunological
No data available.
9.4.12 Metabolic
9.4.12.1 Acid-base disturbances
A metabolic acidosis can be
observed in severe cases, due to haemolysis
and/or renal failure.
9.4.12.2 Fluid and electrolyte disturbances
Fluid disturbances are due to
haemolysis, gastro-intestinal disturbances
and renal failure.
Plasma potassium level is usually within
normal range in the first hours after
poisoning; hyperkalemia is always associated
with severe renal function impairment and
acidosis.
9.4.12.3 Others
The serum level of free bilirubin
fraction is increased.
9.4.13 Allergic reactions
No data available
9.4.14 Other clinical effects
No data available
9.4.15 Special risks
No data available
9.5 Other
No data available
9.6 Summary
10. MANAGEMENT
10.1 General principles
Inhalation:
Make a proper assessment of circulation and neurological
status. Monitor for respiratory distress, administer
supplemental oxygen.
Maintain adequate hydration by starting intravenous fluids.
Maintain urinary flow by correcting hypotension and
dehydration. Some advocate the use of diuretics if these
measures do not maintain urine output.
Exchange transfusion or repeated transfusions may be
necessary if major haemolysis has occured.
Dermal and eye exposure: immediately flush exposed areas
with running water for at least 15 minutes.
Effects may be delayed, keep victim under observation.
10.2 Life supportive procedures and symptomatic/specific treatment
Respiratory and cardiovascular support as
necessary.
Maintain adequate hydration with intravenous fluids and keep
a brisk urinary flow with the use of diuretics if
required.
Correct acidosis and disturbances of fluid and electrolytes
as necessary.
Haemodialysis should be performed in case of severe renal
failure, and may be considered to enhance clearance of
arsenic from the body.
Repeated transfusions of whole blood for correction of
haemolysis and prolonged anemia.
10.3 Decontamination
Dermal and eye exposure: immediately flush exposed
areas with running water for at least 15 minutes.
10.4 Elimination
The most important treatment of haemolysis is exchange
transfusion which can remove the plasma haemoglobin and the
arsine-hemoglobin complexes.
Haemodialysis is indicated in severe renal failure.
10.5 Antidote treatment
10.5.1 Adults
The administration of DMSA (dimercaptosuccinic
acid) should be considered in case of elevated arsenic
blood level.
Fournier et al. (1988) administered successfully 30
mg/kg in 3 divided doses for 5 days to two patients
poisoned by arsenic salts.
DMSA was successfully used at 30 mg/kg/d in four 5
day-courses, in a patient with acute organo-arsenate
poisoning (Shum & Whitehead, 1994).
For heavy metal poisoning (mercury, lead and arsenic),
Reynolds (1996) recommends a dosage regimen of 10
mg/kg orally every 8 hours for 5 days, then every 12
hours for an additional 14 days.
10.5.2 Children
No data available
10.6 Management discussion
The indications for treatment with a chelating agent
should be discussed to limit the development of a delayed
peripheral neuropathy even though its effectiveness has not
been clearly evidenced in arsine poisoning (Pairon et al.,
1992). DMSA is preferred over BAL which is contraindicated in
patients with renal impairment.
According to Gosselin et al. (1982), haemodialysis appears to
be more effective than blood exchange in removing arsenic
from the body. In the setting of arsine poisoning
haemodialysis combined with DMSA may enhance clearance
although data is lacking.
Blood exchange should be performed only in cases with massive
haemolysis. The total exchanged volume should not represent
more than two times the body blood volume.
Follow-up: monitor signs of peripheral sensory-motor
neuropathy.
11. ILLUSTRATIVE CASES
11.1 Case reports from literature
Gosselin et al. (1982) reported four cases of acute
arsine poisoning.
While engaged in the repair of a zinc furnace, four workers
were accidentally exposed to arsenious hydride (ASH3)
fumes. Acute intravascular haemolysis developed within a few
hours. On admission, the patients immediately underwent
exsanguinotransfusion; 8.2 to 10.2 L of blood were exchanged
through a continuous perfusion pump at the rate of 1 L/hour.
Two patients resumed diuresis during transfusion, but the
other two required repeated haemodialysis. Between the 10th
and 30th day, while renal function was gradually returning to
normal, mild megaloblastic anemia developed. This was
followed during the 3rd month by clinical and electric
evidence of polyneuritis of the lower and upper limbs, which
subsequently resolved. Regular measurements of arsenic levels
in the blood and urine were performed between and during
exsanguinotransfusion and haemodialysis. On admission the
arsenic blood level was extremely high in one patient: 6850
µg/L.
Risk & Fuortes (1991) described a case of chronic
occupational exposure to arsine in a 35-year-old male. The
illness progressed for half a year until the diagnosis was
made. Signs and symptoms included episodes of nausea,
headache, dizziness and progressive lower extremity weakness
and paresthesiae. Visits to several physicians and hospitals
led to treatment for ulcers, hepatitis and other diseases.
Severe liver dysfunction and marked leucocytopenia of unknown
etiology were found. The patient developed recuring intense
focal headaches, nausea, low grade fever, paresthesia and
hepatic and renal impairment, and was transferred to a
referral hospital. Suspicions of arsenic toxicity were
entertained because of progressive neuropathy and the
characteristic Mees' lines in the fingernails. Serum arsenic
level was normal (10 pg/mL). However, a 24-hour urine
collection two months later revealed arsenic excretion of
11.3 mg/24 hour (450 times higher than normal). Penicillamine
chelation was undertaken and led to high arsenic excretion.
After an initial brief bout of worsening symptoms, there was
significant amelioration.
12. ADDITIONAL INFORMATION
12.1 Specific preventive measures
Standard industrial hygiene procedures should be
employed to reduce workplace exposure to the lowest possible
level.
NIOSH (1994) recommends that occupational exposures to
carcinogens be limited to the lowest feasible
concentration.
Respiratory protection should be available and used.
In preemployment medical examination, special attention
should be given to past or present kidney disease and anemia.
Periodic examination should include tests to determine
arsenic levels in the blood and urine. The general status of
the blood and renal and liver functions should also be
evaluated (HSDB, 1996).
Following occupational exposure to arsine notification tothe
appropriate health authorities and a site inspection should
be made.
12.2 Other
No data
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14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE
ADDRESS(ES)
Author: MO Rambourg Schepens
Centre Anti-Poisons de Champagne Ardenne
Centre Hospitalier Universitaire.
F-51092 REIMS cedex. FRANCE
e-mail: marie-odile.rambourg@wanadoo.fr
Reviewer: WA Watson
Emergency Medicine
Truman Medical Center.
2301 Holmes Street. Kansas City, MO, USA
e-mail: wawatson@CCTR.UMKC.EDU
Date: June 1997
Peer review: Oslo (2 July, 1997) Members of group: Marie-Odile
Rambourg, Bill Watson, Rob Dowsett, Barbara Groszek, Michael
Ruse
Editor: Dr M. Ruse (August, 1997)
Editor: Dr. M. Ruse (July, 1997)