Nitrogen pentoxide
| 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/CIRCUMSTANCES OF POISONING |
| 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 ENTRY |
| 5.1 Oral |
| 5.2 Inhalation |
| 5.3 Dermal |
| 5.4 Eye |
| 5.5 Parenteral |
| 5.6 Others |
| 6. KINETICS |
| 6.1 Absorption by route of exposure |
| 6.2 Distribution by route of exposure |
| 6.3 Biological half-life by route of exposure |
| 6.4 Metabolism |
| 6.5 Elimination by route of exposure |
| 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) and other guideline levels |
| 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 Others |
| 9.4.7 Endocrine and reproductive systems |
| 9.4.8 Dermatological |
| 9.4.9 Eye, ears, nose, throat: local effects |
| 9.4.10 Haematological |
| 9.4.11 Immunological |
| 9.4.12 Metabolic |
| 9.4.12.1 Acid-base disturbances |
| 9.4.12.2 Fluid and electrolyte disturbances |
| 9.4.12.3 Others |
| 9.4.13 Allergic reactions |
| 9.4.14 Other clinical effects |
| 9.4.15 Special risks |
| 9.5 Others |
| 9.6 Summary |
| 10. MANAGEMENT |
| 10.1 General principles |
| 10.2 Life supportive procedures and symptomatic treatment |
| 10.3 Decontamination |
| 10.4 Enhanced elimination |
| 10.5 Antidote treatment |
| 10.5.1 Adults |
| 10.5.2 Children |
| 10.6 Management discussion |
| 11. ILLUSTRATIVE CASES |
| 11.1 Case reports from literature |
| 12. ADDITIONAL INFORMATION |
| 12.1 Specific preventive measures |
| 12.2 Other |
| 13. REFERENCES |
| 14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE ADDRESSES |
NITROGEN OXIDES
International Programme on Chemical Safety
Poisons Information Monograph (Group Monograph) G017
Chemical
1. NAME
1.1 Substance
Nitrogen oxides
1.2 Group
Nitric oxide
Nitrous oxide
Nitrogen dioxide
Nitrogen pentoxide
1.3 Synonyms
Nitiric oxide: mononitrogen monoxide;
nitrogen monoxide
Nitrous oxide: dinitrogen monoxide:
laughing gas; factitious air;
hyponitrous acid anhydride;
mononitrogen monoxide; nitric oxide;
nitrogen oxide;
Nitrogen pentoxide: dinitrogen pentoxide;
nitric anhydride;
Nitrogen dioxide: nitrogen tetroxide
1.4 Identification numbers
1.4.1 CAS number
Nitric oxide 10102-43-9
Nitrous oxide 10024-97-2
Nitrogen dioxide 10102-44-0
1.4.2 Other numbers
1.5 Brand names, Trade names
1.6 Manufacturers, Importers
2. SUMMARY
2.1 Main risks and target organs
Inhalation of any oxides of nitrogen causes toxic
effects. The main target organ is the lung.
2.2 Summary of clinical effects
There may be three stages of toxicity. Initially there
may be mild irritation of the upper respiratory tract,
cough, sore throat, conjunctivitis, dyspnoea, headache,
vertigo, and tightness of the chest.
After a latent period of 3 to 30 hours, inflammation of the
lungs, pulmonary oedema, dyspnoea, wheezing and cyanosis
resulting in severe respiratory failure.
Approximately half the patients who survive pulmonary oedema
develop bronchiolitis obliterans within a few weeks.
2.3 Diagnosis
Diagnosis depends on a history of exposure and the
presence of symptoms and signs related to the respiratory
system.
Arterial blood gas studies may show hypoxia, hypercapnia and
acidosis.
Pulmonary function tests may show obstructive, restrictive
and diffusion defects.
2.4 First-aid measures and management principles
First-aid measures:
Remove the patient to from the source of exposure and admit
to hospital as soon as possible.
Management principles:
Establish an adequate airway and maintain respiration.
Give oxygen and assisted ventilation if necessary. Treat
bronchospasm with bronchodilators.
Remove secretions.
Give corticosteroids if moderate respiratory symptoms or
pulmonary oedema are present.
Keep under observation.
3. PHYSICO-CHEMICAL PROPERTIES
3.1 Origin of the substance
Oxides of nitrogen are synthesized or occur as
by-products of chemical processes or fires.
On a global scale, quantities of nitric oxide and nitrogen
dioxide produced naturally by bacterial and volcanic action
and by lightning by far outweigh those generated by man's
activities (WHO, 1977).The major source of man-made emission
of oxides of nitrogen is the combustion of fossil fuels in
stationary sources (heating, power generation) and in motor
vehicles (internal combustion engines).Other sources are
industrial processes such as manufacture of nitric acid and
explosives, smoking, gas-fired appliances and oil stoves.
Burning plastics, shoe polish, nitrocellulose, and welding
operations produce oxides of nitrogen (Horvath, 1980).
Nitric oxide is prepared industrially by passing air through
an electric arc or by oxidation of ammonia over platinum
gauze.
Laboratory preparation is by reacting sodium nitrite with
ferrous sulphate.
Nitrous oxide is prepared by thermal decomposition of
ammonium nitrate.
Nitrogen dioxide is prepared industrially from nitric oxide
and in the laboratory from lead nitrate.
Nitrogen pentoxide is produced by dehydration of nitric acid
by phosphorus pentoxide (Budavari, 1996).
3.2 Chemical structure
Nitric oxide
Molecular weight 30.01
Nitrogen dioxide
Molecular weight 44.02
Nitrogen pentoxide
Molecular weight 108.02
3.3 Physical properties
3.3.1 Colour
See section 3.3.3
3.3.2 State/form
See section 3.3.2
3.3.3 Description
Nitrogen dioxide
Molecular formula: NO2
Boiling point 21.15°C
Melting point -9.3°C
Molecular mass 44.02
Condensation point 21°C
Specific gravity at 20°C 1.448 (liquid)
A reddish brown gas. Liquid below 21.15°C.
Nitrogen pentoxide
Molecular formula: N2O5
Boiling point 47.0°C
Melting point 30°C
Molecular mass 108.02
Colourless hexagonal crystals.
Nitrous oxide
Molecular formula: N2O
Boiling point 88.46°C
Melting point -90.81°C
Vapour pressure (Pascals at 20°C) 4.93 (Mellor, 1967)
Solubility: Soluble in alcohol and ether.
A colourless gas with slightly sweetish odour and
taste.
Nitric oxide
Molecular formula NO
Boiling point: -151.8 °C
Molecular mass: 30.01
A colourless gas.
(Budavari, 1996)
3.4 Hazardous characteristics
Nitrogen dioxide
It has an irritating odour and is highly poisonous.Under
normal atmospheric conditions it exists in equilibrium with
nitrogen tetroxide (N204). Heavier than air. Nitrogen
dioxide produces nitrous acid (HN02) and nitric acid
(HN03) on contact with water.
Nitrogen pentoxide
Sublimes at -32.4°C but undergoes moderately rapid
decomposition into 02 and the NO2/N204 equilibrium
mixture at temperatures above -10°C. Freely soluble in
chloroform without appreciable decomposition.
Nitrous oxide
Supports combustion.Very stable and rather inert chemically
at room temperatures.Dissociation begins above 300°C when
the gas becomes a strong oxidizing agent.
Nitric oxide
Burns when heated with hydrogen. It combines with oxygen to
form nitrogen dioxide and with halogens to form nitrosyl
halides, e.g. NOCl.
(Budavari, 1996)
4. USES/CIRCUMSTANCES OF POISONING
4.1 Uses
4.1.1 Uses
4.1.2 Description
Nitric oxide
In the manufacture of nitric acid, bleaching of rayon;
as a stabilizer (to prevent free radical
decomposition) for propylene, methyl ether etc.
Nitrogen dioxide
Intermediate in nitric and sulphuric acid production.
It is also used in nitration of organic compounds and
explosives in the manufacturing of oxidized cellulose
compounds. Has been used to bleach flour. Proposed as
oxidizing agent in rocket propulsion.
Nitrogen pentoxide
Used in chloroform solution as a nitrating agent.
Nitrous oxide
To oxidize organic compounds at temperatures above
300°C to make nitrites from alkali metals at their
boiling points, in rocket fuel formulations (with
carbon disulphide) and in the preparation of whipped
cream. Also used as an anaesthetic gas (Budavari,
1996).
4.2 High risk circumstance of poisoning
Poisoning occurs following exposure to industrial,
manufacturing or agricultural sources which evolve nitrous
fumes (oxides of nitrogen).
Nitrogen dioxide and nitric oxide are the principal hazards.
Nitrous oxide is narcotic in high concentrations but it is
less irritant than other oxides of nitrogen.
4.3 Occupationally exposed populations
Occupational exposure usually occurs from manufacture of
dyes, fertilizers, celluloid and lacquers; and from welding
glass blowing and food bleaching.
Firemen may be exposed to nitrogen oxide during chemical
plant fires or from burning mattresses (Ellenhorn &
Barceloux, 1988).
Nitrogen oxides are also released from processes such as
electroplating, engraving, photogravure operations etc.
(Gosselin et al., 1984).
Severe symptoms and death has been reported in farmers
working in or near silos. This syndrome, known as silo
filler's disease, is due to acute exposure to oxides of
nitrogen produced by silage (Ellenhorn & Barceloux 1988).
Occupational exposure occurs in anaesthesia.
5. ROUTES OF ENTRY
5.1 Oral
Not known.
5.2 Inhalation
Inhalation of some oxides of nitrogen such as nitric
oxide and nitrogen dioxide causes poisoning. On contact with
air, nitric oxide is converted to highly poisonous nitrogen
dioxide.
The effects of nitrogen dioxide are insidious: inhalation may
cause only slight pain or go unnoticed, but may cause death
later.
5.3 Dermal
Nitric acid , formed when fumes of nitrogen oxides mix
with sweat, has caused skin burns (Haddad and Winchester,
1990).
5.4 Eye
Fumes of nitrogen oxides can cause eye irritation
(Haddad and Winchester, 1990).
5.5 Parenteral
Not known.
5.6 Others
Not known.
6. KINETICS
6.1 Absorption by route of exposure
Nitrogen oxides are largely absorbed by and react with
pulmonary alveolar structures and terminal respiratory
bronchioles.
They are less soluble than most irritant gases and have a
greater tendency to reach the bronchioles and alveoli (Haddad
and Winchester, 1990).
6.2 Distribution by route of exposure
Within the lungs, nitrogen oxides react with water to
form nitrous and nitric acids causing extensive local
damage.
6.3 Biological half-life by route of exposure
The biological half-life of endogenous nitrogen oxides
in vascular endothelium is very short.
6.4 Metabolism
No data available.
6.5 Elimination by route of exposure
No data available.
7. TOXICOLOGY
7.1 Mode of Action
Of the five principal oxides of nitrogen, nitrous oxide
is comparatively harmless. The principal target organ for
other oxides is the lung. Nitric oxide is less toxic tot he
lung than nitrogen dioxide. Little is known about toxicology
of nitrogen trioxide (N2O3) and nitrogen pentoxide
(N2O5) (Gosselin et al., 1984).
It is now generally accepted that nitrogen dioxide is the
principal causative factor of the pulmonary changes following
the inhalation of oxides of nitrogen ("nitrous fumes")
(Milne, 1969).
Nitrogen oxides are irritant and destructive to lung tissues
because they are slowly hydrolysed to acids. The upper
respiratory tract is largely spared perhaps because these
gases have a low solubility in aqueous media and because they
are only slowly hydrolysed.
The mild upper respiratory irritant effect is a result of
nitrogen dioxide being converted to nitric acid in the
presence of water.
Nitric acid destroys respiratory epithelium and alveolar
membranes and may produce metabolic acidosis. The mild
initial irritant effects allow widespread dissemination of
nitrogen oxides throughout the lungs and result in diffuse
delayed inflammation.
Fibrotic destruction of terminal bronchioles (bronchiolitis
obliterans) occurs as a late complication (Ellenhorn &
Barceloux, 1988).
Nitrogen dioxide decomposition may also produce nitrates
which are capable of causing vasodilatation and mild
methaemoglobinaemia.
7.2 Toxicity
7.2.1 Human data
7.2.1.1 Adults
The presence of nitrogen dioxide may
be difficult to perceive and it is
frequently undetectable at concentrations
causing mucosal irritation. Early symptoms
are often mild, even in cases where there is
serious late toxicity. At levels of 100 to
150 ppm toxicity occurs within 30 to 60
minutes and at levels of 200 to 700 ppm
fatalities result after short exposure
(Ellenhorn & Barceloux, 1988).
Chest discomfort occurs after exposure to 15
ppm for 1 hour and the sensation becomes
unpleasant at 25 ppm. After 1 minute at 50
ppm subjects feel substernal pain. Longer
exposure at this concentration causes
reversible inflammatory changes in the lungs.
Higher concentrations may be fatal
(Dreisbach, 1987).
7.2.1.2 Children
No data available.
7.2.2 Relevant animal data
In the rat, exposure to 0.5 ppm for 4 hours
causes reversible degranulation of lung cells. Mice
exposed continuously for 3 months to 0.5 ppm become
more susceptible to infection when challenged with
pneumococci. Weight loss occurs in monkeys exposed to
this concentration but other animals are not
affected.
In the rat, continuous exposure to 2 ppm of NO2 for 3
days caused epithelial hyperplasia in the terminal
bronchioles. Exposure for more than one year caused
thinning of the membrane lining the lungs.
Intermittent exposure of rats to 4 ppm for a year
caused no discernible permanent damage to the lungs
(Dreisbach, 1987).
Animals exposed to 70 ppm for 8 hours developed
periorbital oedema and corneal opacities (Ellenhorn
and Barceloux, 1988).
7.2.3 Relevant in vitro data
No data available.
7.2.4 Workplace standards
Nitrogen dioxide:
Threshold limit value (time weighted average):
3 ppm (6 mg/m3)
Threshold limit value - STEL: 5 ppm (10 mg/m3)
NIOSH recommends 1 ppm of nitrogen dioxide as a
workplace environmental standard (NIOSH, 1976).
Nitric oxide:
Threshold limit value: 25 ppm
7.2.5 Acceptable daily intake (ADI) and other guideline
levels
Not relevant.
7.3 Carcinogenicity
Unknown
7.4 Teratogenicity
Unknown
7.5 Mutagenicity
Unknown
7.6 Interactions
Unknown
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
Sample collection
Collect blood samples to assess arterial blood gases and
methaemoglobin levels.
Biomedical analysis
Arterial blood gas studies show hypoxia, hypercapnia and
acidosis with early changes in the alveolar - arterial oxygen
gradient.
Pulmonary function tests show obstructive, restrictive and
diffusion defects as a result of destruction of alveoli,
interstitium and bronchioles (Ellenhorn & Barceloux,
1988).
8.6 References
9. CLINICAL EFFECTS
9.1 Acute poisoning
9.1.1 Ingestion
Unknown
9.1.2 Inhalation
The irritant effects of oxides of nitrogen
cause inflammation of the lungs, leading to profuse
exudation into the alveolar spaces. Pulmonary oedema,
rapid breathing and cyanosis are early features.
Relapse may occur after 2 to 3 weeks with the onset of
bronchiolitis obliterans.
Chest X-ray shows fluffy confluent bilateral
infiltrates in patients with pulmonary oedema, and a
nodular pattern in cases of bronchiolitis
obliterans.
9.1.3 Skin exposure
Skin burns can occur when nitrous fumes mix
with sweat to form nitric acid.
9.1.4 Eye contact
Exposure to nitrogen oxides can cause conjunctivitis.
9.1.5 Parenteral exposure
Not relevant.
9.1.6 Other
Not relevant.
9.2 Chronic poisoning
9.2.1 Ingestion
Unknown.
9.2.2 Inhalation
No adverse effects were found in workers
exposed for several years at 30 to 35 ppm oxides of
nitrogen (ACGIH, 1986).
9.2.3 Skin exposure
No data available.
9.2.4 Eye contact
No data available.
9.2.5 Parenteral exposure
Unknown.
9.2.6 Other
Unknown.
9.3 Course, prognosis, cause of death
Clinical features depend on the duration and intensity
of exposure and follow a triphasic pattern.
Initially, there is mild irritation of the upper respiratory
tract.
Mild cases become asymptomatic within several hours. The
severity of initial symptoms does not correlate well with
subsequent pulmonary pathology, although patients with mild
nitrogen dioxide exposure often recover without any late
complications.
After a latent period of 32 hours (in some instances lasting
up to 72 hours) patients may develop inflammation of the
lungs and pulmonary oedema.
About 50% patients surviving pulmonary oedema develop
bronchiolitis obliterans in 2 to 6 weeks.
In a few instances, bronchiolitis obliterans may be the
initial presentation with symptoms including progressive
dyspnoea, cyanosis, cough and wheezing.
The patient may be even more intensely ill during this
relapse than during the initial reaction.
Recovery can take up to 6 months. Emphysematous change
persists, depending on the severity of the original
damage.
Death can occur due to asphyxia within a few hours of the
onset of pulmonary oedema.
Exposure to high concentrations in the region of 100 to 500
ppm may leads to sudden death from bronchospasm and
respiratory failure. Delayed pulmonary oedema can cause
death. Several weeks after exposure, bronchiolitis obliterans
can cause death.
9.4 Systematic description of clinical effects
9.4.1 Cardiovascular
Rapid and weak pulse, cyanosis, venous
congestion and hypotension occur secondary to anoxia
and haemoconcentration (Gosselin et al. 1984).
Hypotension may occur due to a direct effect of
nitrates on blood vessels (Haddad and Winchester,
1990).
9.4.2 Respiratory
Usually no symptoms occur at the time of
exposure with the exception of a slight cough and
perhaps fatigue and nausea. Exposure to low
concentrations may result in impaired pulmonary
defence mechanisms (macrophages, cilia) with
complications.
Only relatively high concentrations of nitrogen oxides
produce prompt coughing, choking, production of mucoid
and frothy sputum, headache, nausea, abdominal pain
and dyspnoea and tightness and burning pain in the
chest. There may be haemoptysis.
Inhalation of nitrogen dioxide for a short period
causes increased airways resistance (Horvath, 1980).
This seems to be due to histamine release (Guidotti,
1978).
A symptom-free period may follow exposure and lasts
for 5 to 72 hours. Fatigue, uneasiness, restlessness,
cough, tachypnoea and dyspnoea, appear insidiously as
adult respiratory distress syndrome gradually
develops.
Increasingly rapid and shallow respiration, cyanosis,
coughing with frothy expectoration, and physical signs
of bronchospasm and pulmonary oedema such as crackles
and wheezes can be observed. Vital capacity is rapidly
reduced. A serous exudate may develop in the pleural
cavity, but its volume is usually small. Anxiety,
mental confusion, lethargy, and finally loss of
consciousness occur as a result of hypoxia.
Chest X-ray may show widespread, coarse mottling
throughout the lung fields. Lungs may be
radiologically clear within a few days, in parallel
with clinical improvement (Milne, 1969). Circulatory
collapse is secondary to anoxia and
haemoconcentration.
Death may occur within a few hours of the first
evidence of pulmonary oedema.
Sometimes a second acute phase follows the initial
pulmonary reaction after a quiescent period of 2 to 6
weeks. Cough, tachypnoea, dyspnoea, fever, tachycardia
and cyanosis at this stage are usually due to
bronchiolar inflammation which may lead to
bronchiolitis obliterans (Milne, 1969).The relapse
may be abrupt and fulminating, leading either to
death or a slow convalescence.
Chest X-ray reveals widespread bilateral mottling.
Blood gas analysis indicates hypoxia.
In non-fatal cases, convalescence may be complicated
by infection, bronchitis, bronchiolitis obliterans,
pneumonia and general weakness. Rarely, diffuse
pulmonary fibrosis may develop.
9.4.3 Neurological
9.4.3.1 Central Nervous System (CNS)
The effects are secondary to
hypoxia. There may be confusion.
9.4.3.2 Peripheral nervous system
Not known
9.4.3.3 Autonomic nervous system
Not known
9.4.3.4 Skeletal and smooth muscle
Not known
9.4.4 Gastrointestinal
There may be nausea.
9.4.5 Hepatic
Not known
9.4.6 Urinary
9.4.6.1 Renal
Unknown
9.4.6.2 Others
Unknown
9.4.7 Endocrine and reproductive systems
Unknown
9.4.8 Dermatological
Skin burns from nitric acid may occur due to
the mixture of fumes with sweat (Haddad and
Winchester, 1990).
9.4.9 Eye, ears, nose, throat: local effects
There may be conjunctivitis and sore throat.
9.4.10 Haematological
Severe haemoconcentration occurs due to the
fluid loss in pulmonary oedema. Leucocytosis can
occur even in the acute initial phase (Haddad and
Winchester, 1990).
Changes in blood chemistry (such as decreased red cell
membrane acetylcholinesterase activity, red cell
glucose-6-phosphate dehydrogenase, total haemoglobin
and haematocrit and an increase in red cell
peroxidized lipids) have been seen in young adults
exposed to nitrogen dioxide 1 or 2 ppm for 3 hours
daily for 3 days (Gosselin et al., 1984).
Methaemoglobinaemia has been reported (Haddad and
Winchester, 1990).
9.4.11 Immunological
Unknown.
9.4.12 Metabolic
9.4.12.1 Acid-base disturbances
Metabolic acidosis can occur due to
the formation of nitrous acid and the
development of lactic acidosis (Haddad and
Winchester, 1990).
9.4.12.2 Fluid and electrolyte disturbances
Pulmonary inflammation and oedema
result in fluid loss from blood.
9.4.12.3 Others
Unknown
9.4.13 Allergic reactions
Unknown
9.4.14 Other clinical effects
Unknown
9.4.15 Special risks
Pregnancy: Unknown.
Breast feeding: Unknown.
Enzyme deficiencies: Unknown.
9.5 Others
American astronauts on the Apollo - Soyuz mission were
briefly exposed by accident to nitrogen dioxide. Elevated
urinary levels of hydroxylysine glycosides suggested collagen
breakdown in the pulmonary parenchyma (Ellenhorn & Barceloux,
1988).
9.6 Summary
10. MANAGEMENT
10.1 General principles
Remove the patient from the source of exposure.
Establish an adequate airway and maintain respiration.
Give oxygen and assisted ventilation if necessary.
Remove secretions.
Advise strict bed rest.
Asymptomatic patients should be kept under observation for up
to 72 hours.
10.2 Life supportive procedures and symptomatic treatment
Establish an adequate airway and respiration. Remove
frothy exudate from respiratory tract. Give oxygen for
dyspnoea and cyanosis. If severe pulmonary oedema is
present, assisted ventilation may be needed.
Give normal saline or plasma expanders intravenously or blood
transfusion to maintain adequate perfusion pressure.
Do frequent sputum cultures. Treat infection with appropriate
antibiotics.
Correct acid-base abnormalities.
If pulmonary oedema is not present, ensure a urine output of
at least 1500 ml daily by giving adequate fluids.
If symptoms of irritation or bronchospasm occur give a
bronchodilator such as salbutamol by nebulizer.
Give methylprednisolone 20 to 80 mg orally or intravenously.
Repeat daily for 8 weeks before gradually decreasing the dose
(Haddad and Winchester, 1990).
10.3 Decontamination
Eye contact:
Irrigate exposed eyes with copious amounts of water.
10.4 Enhanced elimination
Not relevant
10.5 Antidote treatment
10.5.1 Adults
No specific antidote.
10.5.2 Children
No specific antidote.
10.6 Management discussion
For bronchospasm, atropine, epinephrine, expectorants,
and sedative drugs are ineffective and harmful (Gosselin et
al., 1984).
Patients must be followed-up for at least 6 weeks since
relapses can occur.
Asymptomatic patients could be discharged after 24 to 36
hours of observation but they should be followed up within
several weeks to assess pulmonary status.
11. ILLUSTRATIVE CASES
11.1 Case reports from literature
Cough, dyspnoea at rest and on exertion, chest pain,
headache, haemoptysis and weakness were the symptoms reported
by 116 people exposed to fumes from a malfunctioning engine
(Hedberg et al., 1989).
A chemist exposed to nitrogen dioxide (nitrous fumes) had
cough and slight headache only. Twelve hours later he was
awakened with dyspnoea and cough. On admission to hospital
soon after, he had severe acute pulmonary oedema. He was
discharged on the 7th day. On the 20th day after exposure he
was readmitted with dyspnoea, coughing and sweating. He
required intermittent positive pressure ventilation. He was
treated with corticosteroids and discharged 28 days later
(Milne, 1969).
12. ADDITIONAL INFORMATION
12.1 Specific preventive measures
Exposure to oxides of nitrogen at workplace should be
avoided by appropriate storage of chemicals and by following
proper safety standards.
12.2 Other
No data available.
13. REFERENCES
American Conference of Governmental Industrial Hygienists
Inc. (1986).Documentation of the threshold limit values and
biological exposure indices.5th Edition.Cincinnati, Ohio. 435 -
436.
Budavari S ed. (1996) The Merck Index: an encyclopedia of
chemicals, drugs, and biologicals, Rahway, New Jersey, Merck and
Co. Inc.
Cotlon FA, Wilkinson G ed. (1980) Advanced Inorganic Chemistry,
U.S.A., John Wiley and Sons Inc.
Dreishbach RH, Robertson WO ed (1987) Handbook of Poisoning:
Prevention, Diagnosis and TreatmentLos Altos, Appleton & Lange. p
202.
Ellenhorn MJ & Barceloux DG ed (1988). Medical Toxicology. New
York, Elsevier Science Publishing Company, Inc. p 876.
Gosselin RE, Smith RP, Hodge HC ed.(1984) Clinical Toxicology of
Commercial Products. Baltimore, Williams and Wilkins. p III 319-
326.
Guidotti TL (1978). The higher oxides of nitrogen: inhalation
toxicology. Environmental Research 15:43-72
Haddad LM and Winchester JF ed. (1990)Clinical management of
poisoning and drug overdose 2nd Edition.W.B. Saunders Company,
Philadelphia 1272 - 1280.
Horvath SM (1980) Nitrogen dioxide, pulmonary function and
respiratory disease. Bull. N.Y. Acid. Med. 56 (9): 835 - 846.
NIOSH: Criteria for a Recommended Standard - Oxides of nitrogen
(1976).DHEW Pub. No (NIOSH) 76 - 149.
Hedberg K, Hedberg CW, Iber C, et al (1989) An outbreak of
nitrogen dioxide induced respiratory illness among ice hockey
players. JAMA, 262 (21): 3014 - 3017
Lee JD ed. (1964) Concise Inorganic chemistry, 2nd Edition, Great
Britain, William Clowes & Sons Ltd. pp. 115 - 119.
Mellor JW ed. (1967) Mellor's Comprehensive Treatise on Inorganic
and theoretical chemistry.Volume VIII Supplement II Nitrogen Part
II. London, Longmans Green Co. Ltd. pp 189 - 195.
Milne JEH (1969) Nitrogen dioxide inhalation and bronchiolitis
obliterans. J. Occupational Medicine 11: 538 - 547.
WHO (1977). Environmental Health Criteria 4. Oxides of nitrogen.
World Health Organisation. Geneva, Switzerland.
14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE
ADDRESSES
Author(s): Dr. Ravindra Fernando & Miss. Deepthi Widyaratne
National Poisons Information Centre
Faculty of Medicine
Kynsey Road
Colombo 8
Sri Lanka.
Date: January 1992
Peer Review: London, United Kingdom, September 1992
Editor: M.Ruse (IPCS, May, 1999)