Bromine
| 1. NAME |
| 1.1 Substance |
| 1.2 Group |
| 1.3 Synonyms |
| 1.4 Identification numbers |
| 1.4.1 CAS number |
| 1.4.2 Other numbers |
| 1.5 Main brand names, main trade names |
| 1.6 Main manufacturers, main importers |
| 2. SUMMARY |
| 2.1 Main risks and target organs |
| 2.2 Summary of clinical effects |
| 2.3 Diagnosis |
| 2.4 First-aid measures and management principles |
| 3. PHYSICO-CHEMICAL PROPERTIES |
| 3.1 Origin of 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 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 |
| 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 ADDRESS(ES) |
BROMINE
International Programme on Chemical Safety
Poisons Information Monograph 080
Chemical
1. NAME
1.1 Substance
Bromine
1.2 Group
Halogen
1.3 Synonyms
Brom (German);
Brome (French);
Bromo (Italian);
Broom (Dutch).
1.4 Identification numbers
1.4.1 CAS number
7726-95-6
1.4.2 Other numbers
DOT: 1744 59 (designated corrosive material)
IMIS: 0390
NIOSH RTECS: EF 9100000
UN: 1744
1.5 Main brand names, main trade names
1.6 Main manufacturers, main importers
United States Manufacturers (Weiss, 1980):
Arkansas Chemicals Inc., El Dorado, Arkansas 71730
Bromet Company, Magnolia, Arkansas 71753
Dow Chemical Company, Midland, Michigan 48640
2. SUMMARY
2.1 Main risks and target organs
Inhalation of the irritant bromine vapours and/or direct
contact (liquid or vapour) with skin and mucous membranes
will produce direct tissue injury. Injury may occur at
various levels of the respiratory tract depending on the
concentration of bromine and duration of exposure. Target
organs include the upper and lower respiratory tract, skin,
and eyes.
In theory, although never demonstrated in the literature, the
potential exists for bromine to accumulate in body tissues as
bromide after an inhalation or direct skin contact. If
accumulated to sufficiently high concentrations, bromide
would subsequently produce neurotoxic and acne-like effects
as seen with the ingestion of bromide compounds or the
chronic inhalation of methyl bromide. However, due the
extreme irritant nature of bromine, the duration of exposure
is generally severely limited, reducing any likely body
burden of bromide.
2.2 Summary of clinical effects
Acute
Dermal: Pure bromine (liquid or vapour) is extremely
irritating to the skin. Unlike most other chemical agents,
there is no immediate visible skin reaction after contact.
The delay before initial signs of injury become apparent
often results in more extensive damage. The most common
local effects are blister formation, brownish discoloration
of the skin and slow-healing ulcers (Sagi et al., 1985).
Mucous Membranes: Exposure to low concentrations produces
lacrimation, rhinorrhoea, eye irritation with mucous
secretions from the oropharyngeal and upper airways,
coughing, dyspnoea, choking, wheezing, epistaxis, and
headache. A brownish discoloration of the tongue and buccal
mucosa may occur and be accompanied by a characteristic
breath odour. Inflammatory lesions of the upper airway,
photophobia and blepharospasm are seen with higher
concentrations (Parmeggiani, 1983). Upper and lower
respiratory tract: Initial irritant symptoms of bromine
vapour inhalation include: dyspnoea, coughing, choking, and
wheezing. In addition, immediate or delayed
bronchoconstriction and the development of laryngeal spasm,
glottal oedema, asthma and cheobronchitis. With increased
parenchymal penetration, there may be associated
peribronchiolar abscesses, pulmonary infiltrates consistent
with chemical pneumonitis, bronchiolitis obliterans and
pulmonary oedema (Edelman, 1991; Rom & Barkman, 1983). Acute
obstructive ventilatory impairment may lead to severe
hypoxaemia, metabolic acidosis, measles-like rash and
subsequent death. It should be noted that more severe
respiratory symptoms may be delayed for several hours after
the exposure (Lossos et al., 1990; Kraut & Lilis, 1988).
Central nervous system: The bromide ion is a central nervous
system depressant producing ataxia, slurred speech, tremor,
nausea, vomiting, lethargy, dizziness, visual disturbances,
unsteadiness, headaches, impaired memory and concentration,
disorientation and hallucinations. This has only been
documented in the literature with reference to overdoses of
bromide-containing medications and the inhalation of
bromide-containing fumigants. Although theoretically
possible, this has not been reported in the medical
literature from acute (or chronic) exposure to bromine.
Respiratory: There are few reports about the chronic
complications of an acute exposure to bromine. However, the
literature has described the chronic manifestations of
chlorine inhalation. Bromine is potentially capable of
extensive damage to the lower respiratory tract. Limited
studies have reported diffuse interstitial pulmonary
fibrosis, emphysema and/or airway hyperreactivity secondary
to acute exposure to bromine (Lossos et al., 1990; Kraut &
Lilis, 1988).
Dermal: There is a rare cutaneous manifestation of bromide
accumulation known as bromoderma tuberosum, which progresses
from red papules to pustules that enlarge and develop into
indurated lesions with a central ulcer (Sticht & Kaferstein,
1988). This effect is related to the ingestion of bromides
formerly used in medications and, in theory, to chronic
inhalation of low-level concentrations of bromine (Sax,
1984).
Other: Most available data come from studies involving
chronic exposure to bromides in the form of oral medications.
This type of exposure has lead to depression, ataxia and
psychoses (bromism). Chronic exposure to methyl bromide has
caused peripheral neuropathy. Soviet literature has
described loss of corneal reflexes, joint pain, vegetative
disorders, thyroid dysfunction and depression of bone marrow
(Sticht & Kaferstein, 1988). However, there is no published
evidence that these chronic occur effects with the inhalation
and/or dermal absorption of bromine liquid or vapour.
2.3 Diagnosis
Signs characteristic of acute bromine poisoning include:
* after exposure of skin, delayed onset of burns
* brownish discolouration of tongue and buccal mucosa
* characteristic odour on the breath
Bromine gas blood concentrations are not clinically useful.
Bromine is generally unmeasurable since it changes directly
to hydrobromic and bromic acid. No specific laboratory
studies are needed unless otherwise indicated by the severity
of symptoms (see Section 2.4.)
2.4 First-aid measures and management principles
Acute contact with bromine liquid or vapour requires
removal from the source of the bromine contamination.
Eye: The eye(s) should be irrigated with copious amounts of
water for at least 15 minutes. If irritation, pain,
swelling, lacrimation or photophobia persist, further medical
evaluation is recommended.
Dermal: Remove contaminated clothing and wash affected area
thoroughly with copious volumes of water for 20 minutes.
Since effects may be delayed, close observation for
blistering and discoloration of the skin is required for the
next 24 hours (Sagi et al., 1985).
Inhalation: Respiratory support in accordance with
symptomatology, including: maintenance of an adequate airway,
oxygen, antibronchospasm therapy (beta adrenergic agonist,
aerosols, aminophylline and/or short course of
corticosteriods) and antibiotics if there is evidence of
infection. Initial testing should include: chest x-ray to
view inflammatory changes in the parenchyma, spirometry
(flow-volume loop with and without bronchodilator) to
determine air flow capacity and reversibility, diffusing
capacity (DLco) to assess changes in the alveolar-capillary
permeability, arterial blood gases to evaluate blood
oxygenation (Po2) and ventilation (Pco2), and complete white
blood count. Repeat chest radiograph and spirometry are
recommended to determine the progression or resolution of
residual effects. Ventilation-perfusion scanning does not
usually provide significant additional information, except to
rule out other processes, such as pulmonary emboli. Careful
examination is important to detect pathology (fine wheezes in
subtle or early asthma and fine crackles in early pulmonary
oedema) not revealed by the studies noted above.
Ingestion: Not relevant
3. PHYSICO-CHEMICAL PROPERTIES
3.1 Origin of the substance
Bromine occurs naturally in the earth's crust as a
non-metallic element. Like other halogens, it is very
reactive and principally found in the form of inorganic
bromides (Na, K, NH4, Ca and Mg) and as a component secondary
to chlorine in minerals and biological systems (humans and
animals). A pure bromine-containing mineral, bromite (AgBr)
is found in Mexico (Sticht & Kaferstein, 1988). Bromine is
derived from sea water and naturally occurring brines.
Most sources outside of the United States (United Kingdom,
France, Japan Israel and Soviet Union) recover bromine from
salt lakes and sea water (Stokinger, 1981). The bromine
concentration in sea water averages about 0.0065%, while the
Dead Sea contains an average concentration of 1.5% (Sticht &
Kaferstein, 1988).
Before the bromine can be steamed out of the sea water, the
bromine is concentrated by vaporization and the addition of
sulphur dioxide. Water is then added to the resultant
hydrogen bromide to produce a concentrated bromide solution.
The remainder of the process is similar to bromine recovery
from brines. The by-products of hydrochloric and sulfuric
acid are recycled to the incoming water to reduce the pH
sufficiently to promote efficient chlorination.
Most production in the United States is limited to naturally
occurring brines in Michigan and Arkansas and accounts for
about two-thirds of the world's annual production (Sticht &
Kaferstein, 1988). The oil-field brines in Arkansas are more
concentrated (5000 ppm) than in Michigan and represent the
principal area of bromine production in the United States
(Leddy, 1983). The brine (bromine-containing carnallite) is
oxidized with elemental chlorine to liberate the bromine
which is then condensed, distilled and dried. The bromine is
stored and shipped in glass bottles with lead caps and
lead-lined metal barrels, drums and tanks. Steam and
chlorine are emitted from steaming-out towers and the spent
brine is neutralized and pumped back into the subterranean
strata (Leddy, 1983). In some cases, the debrominated brine
is processed further to produce calcium and magnesium brine
chemicals (Meyer, 1977).
3.2 Chemical structure
Bromine (Br): Atomic Weight 79.904; Atomic Number 35;
Valences 1 to 7; Elemental State Br2, molecular weight
159.82; two stable isotopes 79Br and 81Br (Budivari,
1996).
3.3 Physical properties
3.3.1 Colour
Dark reddish brown.
3.3.2 State/form
3.3.3 Description
Boiling Point: -59.47°C
Melting Point: -7.25°C
Flash Point: -7.3°C
Autoignition
Temperature: Not found
Specific Gravity: Liquid = 3.12 at 20°C
Vapour = 5.5 at 20°C
Vapour Pressure: 175 mmHg at 20°C, 3.385 psia
(0.2303 atm)
Solubility
(g/100 mL at 20°C): Water 3.55g; Freely soluble in
alcohol, ether, CHCl3, CCl4
and CS2.
Explosive Limits: Not combustible, but may cause
fire on contact with
combustibles
pH: Not found
Viscosity: Not found
(Sax, 1984; Sticht & Kaferstein, 1988; OSHA, 1989;
Budivari, 1996; Meyer, 1977; Weiss, 1980)
3.4 Hazardous characteristics
Bromine is a dark reddish-brown, volatile, diatomic
liquid with a suffocating odour at room temperature. It is
the only liquid non-metallic element. Because the vapour
pressure is so high, the dark red vapours are immediately
detectable when a container is opened.
The corrosive property of bromine is considered a major
hazard by the United States Department of Transportation.
Bromine is capable of dissolving metals and non-metals and
spontaneously combines with aluminum, titanium copper,
phosphorus, arsenic, gold and antimony. It will not corrode
platinum, lead or nickel. The corrosive reaction results in
a non-hazardous bromide. (Sittig, 1985; Budivari, 1996;
Meyer, 1977)
As an oxidizer, bromine will react with inorganic matter,
such as wood or sawdust; tremendous heat is produced
increasing the risk of combustion following bromine spills.
Bromine spills should be neutralized with a 5 to 10% solution
of sodium thiosulphate. Sawdust should never be used to
absorb bromine. Explosions are also possible if ammonium
hydroxide is used in an attempt to neutralize a spill (Meyer,
1977).
Bromine is slightly soluble in water, producing hydrogen
bromide. Hydrogen bromide is a corrosive colourless gas with
a pungent odor that is extremely soluble in water. In the
presence of sunlight and humid air or hot water, it forms
hydrobromic acid with concentrations up to about 60% (Sticht
& Kaferstein, 1988). Although less toxic than bromine, it
has all the irritant qualities of bromine.
Bromine should be stored in its original container, separated
from combustible, organic or other readily oxidizable
materials and protected against physical damage and sunlight.
Bromine should be kept above 20°F (- 6.6°C) to prevent
freezing but heating above atmospheric temperatures should be
avoided as raised vapour pressure could rupture the container
(OSHA, 1989).
When handling bromine in significant quantities, full body
protection (constructed of resistant material) should be
worn.
Bromine will readily dissolve in alcohol, ether and other
organic solvents.
When elemental chlorine is used in the treatment of waste
water, it releases free bromine and bromine chloride from the
bromide solution. Acute toxicity of bromine and chlorine have
been studied in fish; however, no US drinking water limits
have been set for bromine (Calabrese & Kenyon, 1991).
Although bromine has been used as a water disinfectant for
swimming pools, it is not recommend for this purpose in
drinking water due to its cumulative neurotoxicity and the
lack of sufficient research (NAS, 1977).
4. USES
4.1 Uses
4.1.1 Uses
4.1.2 Description
Pure bromine is used in the synthesis of a
variety of bromine-containing substances. In the
early 1970s, about 75% of the production of bromine
went into the making of ethylene dibromide (EDB) as an
antiknock agent in leaded gasoline. With the United
States' mandate to reduce vehicle exhaust emissions,
EDB use significantly declined in the 1980s. Export
of EDB has maintained production in the US at about
40% (Leddy, 1983).
Fumigant production in the form of methyl bromide and
ethylene dibromide account for about 10% of the total
bromine marketed, while high density bromine fluids
account for about 25%. The high density bromine
fluids (calcium bromide and zinc bromide) are used
around the world as completion fluids in oil wells
(Leddy, 1983). The remaining market for bromine is in
the manufacture of various organic compounds including
tetrabromobisphenol A, decarbromodiphenyl oxide,
hexabromocyclododecane and
pentabromocholorocyclohexane which are blended with
various polymeric materials to modify the finished
products.
Other uses for bromine include flame retardants,
cleaning agents, dyestuffs, photography, water
sanitation, pharmaceuticals, bleaching fibers and
silk, and chemical warfare gas (Sticht & Kaferstein,
1988; Sittig, 1985).
4.2 High risk circumstance of poisoning
Because of bromine's high reactivity with other
elements, the forms of inorganic bromides found in the
environment pose no danger of poisoning. Primary risk of
poisoning is through industrial sources during bromine
recovery and/or when bromine is applied to the synthesis of
bromine-containing substances noted above. It is estimated
that 20,000 workers in the US have the potential for
occupational exposure to bromine (Broderick & Schwartz,
1992)
4.3 Occupationally exposed populations
Professions that would be potentially at risk of
exposure include:
Drug Makers
Dye Makers
Gold Extractors
Gasoline Additive Makers
Organic Chemical Synthesizers
Petroleum Refinery Workers
Photographic Chemical Makers
Silk and Fibre Bleachers
(NIOSH, 1977)
5. ROUTES OF ENTRY
5.1 Oral
Unknown
5.2 Inhalation
During an accidental spill or leak during transportation
or manufacturing.
5.3 Dermal
During an accidental spill or leak during transportation
or manufacturing and/or improper handling or use of
protective equipment.
5.4 Eye
During an accidental spill or leak during transportation
or manufacturing and/or improper handling or use of
protective equipment.
5.5 Parenteral
Unknown.
5.6 Others
No data available.
6. KINETICS
6.1 Absorption by route of exposure
The reactivity of bromine in biological systems makes it
difficult to study the pharmacokinetics and to separate the
effects of the bromine from those of the bromine compounds
and metabolites.
Inhalation
Absorption of bromine vapours by other routes is usually
minimal compared with the dose delivered by inhalation. The
physical characteristics of the bromine are extremely
important in determining the site and depth of lung
penetration and systemic absorption, as well as the local
effects of the exposure. The appearance or odour of bromine
are usually adequate to alert the person to the presence of
the material and afford time for escape.
The toxic effects of the bromine vapour on the respiratory
tract are primarily due to its water solubility. Bromine is
slightly more water soluble than chlorine and will produce
immediate irritation of the upper airways (Broderick &
Schwartz, 1992). However, when the person is caught in a
confined space or in an overwhelming vapour cloud, inhalation
may cause irritation to the lower airways.
6.2 Distribution by route of exposure
No data available.
6.3 Biological half-life by route of exposure
The biological half-life for bromide through ingestion
is 12 to 30 days; however, there are no data available on the
inhalation of bromine (Sticht & Kaferstein, 1988).
6.4 Metabolism
Due to its reactivity, bromine does not persist as an
element in living tissue but quickly forms bromide. In this
form, it may be deposited in the tissues, displacing other
halogens (Sticht & Kaferstein, 1988). However, there are no
data available regarding the metabolism of inhaled
bromine.
6.5 Elimination by route of exposure
No data available.
7. TOXICOLOGY
7.1 Mode of Action
The injurious effects of bromine are generally felt to
be similar to those of chlorine (Rom & Barkman, 1983;
Broderick & Schwartz, 1992; Schwartz, 1987). Due to its
potent oxidatising action, bromine liberates nascent oxygen
or oxygen free radicals from the water present in mucous
membranes. Nascent oxygen is a potent oxidizer, capable of
producing tissue damage. The extent of the damage is
dependent on the dose of bromine and the availability of
water to react with it. In addition, the formation of
hydrobromic and bromic acids will result in secondary
irritation during the reaction. Contact with the respiratory
epithelium produces initial alveolar capillary congestion
followed by focal and confluent patches of high-fibrinogen
oedematous fluid. The fluid is interstitial at first but can
fill the alveoli. Once this occurs, copious frothy,
blood-tinged sputum is seen. A granulocyte response may occur
several hours after inhalation. Hyaline membrane formation
can occur later resulting in clinical deterioration at a time
when signs of improvement have occurred. Poor oxygen
diffusion, hypoxia and hypercapnia result from development of
atelectasis, emphysema and membrane formation. Acute
obstructive ventilatory impairment leads to severe
hypoxaemia, metabolic acidosis and death usually due to
cardiac arrest secondary to the hypoxaemia.
7.2 Toxicity
7.2.1 Human data
7.2.1.1 Adults
Exposure Effects Levels (ppm)
0.05 to 3.5 Odour Threshold
0.1 TLV-TWA Limit
>1.0 Irritation Level
40 to 60 Toxic pneumonitis &
pulmonary oedema
1000 Fatal within a few
minutes
(Calabrese & Kenyon, 1991; Fazzalari,1978)
7.2.1.2 Children
No data available.
7.2.2 Relevant animal data
Post mortem on guinea pigs and rabbits exposed
to bromine at 300 ppm for three hours revealed the
presence of pulmonary oedema; pseudomembranous deposit
on the trachea; and bronchi and haemorrhage of the
gastric mucosa (Stokinger, 1981).
The mortality of mice exposed to 240 or 750 ppm
bromine was dependent on the duration of exposure
(Bitron & Aharonson, 1978).
7.2.3 Relevant in vitro data
Not relevant.
7.2.4 Workplace standards
TLV-TWA: 0.1 ppm (approximately 0.66 mg/m3)
adopted in 1986 (ACGIH, 1991).
TLV-STEL: 0.3 ppm (approximately 2.0 mg/m3) adopted
in 1986 (ACGIH, 1991).
OSHA PEL: TWA 0.1ppm (approximately 0.7 mg/m3); STEL
0.3 ppm (approximately 2.0 mg/m3) (ACGIH, 1991)
NIOSH REL: TWA 0.1 ppm (approximately 0.7 mg/m3);
STEL 0.3 ppm (approximately 2.0mg/m3) (ACGIH,
1991)
Country/ TWA STEL
Organization
ppm mg/m3 ppm mg/m3
Australia 0.1 0.7 0.3 2
Belgium 0.1 0.66 0.3 2
Denmark 0.1 0.7 - -
Finland - - 0.1 0.7
France - - 0.1 0.7
Germany 0.1 0.7 "I" "I"
Hungary - - - 0.7
Japan 0.1 0.65 - -
Poland - 0.7 - -
Sweden 0.1 0.7 0.3 2
Switzerland 0.1 0.7 0.2 1.4
United Kingdom 0.1 0.7 0.3 2
US: ACGIH 0.1 0.66 0.3 2
US: NIOSH/OSHA - 0.7 - 2
USSR 0.1 - - 0.5
(ILO, 1991)
"I" = Local Irritant
7.2.5 Acceptable daily intake (ADI) and other guideline levels
Acceptable Daily Intake (ADI)
Oral: 1 mg bromide/kg body weight (Sticht &
Kaferstein, 1988).
7.3 Carcinogenicity
No data have been found implicating bromine as a
carcinogen (Calabrese & Kenyon, 1991; Alderson, 1986).
7.4 Teratogenicity
No data have been found implicating bromine as a
teratogen (Calabrese & Kenyon, 1991).
7.5 Mutagenicity
No data have been found implicating bromine as a mutagen
(Calabrese & Kenyon, 1991).
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
Biomedical Analysis
Initial testing should include: chest x-ray to view
inflammatory changes in the parenchyma, spirometry
(flow-volume loop with and without bronchodilator) to
determine air flow capacity and reversibility, diffusing
capacity (DLco) to assess changes in the alveolar-capillary
permeability, arterial blood gases to evaluate blood
oxygenation (Po2) and ventilation (Pco2) and complete white
blood cell count. Repeat chest radiographs and spirometry
are recommended to determine the progression and resolution
of residual effects. Careful examination is important to
detect pathology (fine wheezes in subtle or early asthma and
fine crackles in early pulmonary oedema) not evident from the
studies noted above.
9. CLINICAL EFFECTS
9.1 Acute poisoning
9.1.1 Ingestion
Not relevant.
9.1.2 Inhalation
Upper and Lower Respiratory Tract: Initial
symptoms due to irritation by bromine vapour
inhalation include: dyspnoea, coughing, choking, and
wheezing; immediate or delayed bronchoconstriction;
and the development of laryngeal spasm, glottal
oedema, asthma and tracheobronchitis. With increased
parenchymal penetration, there may be associated
peribronchiolar abscesses, pulmonary infiltrates
consistent with chemical pneumonitis, bronchiolitis
obliterans and pulmonary oedema (Edelman, 1991; Rom &
Barkman, 1983). Acute obstructive ventilatory
impairment may lead to severe hypoxaemia, metabolic
acidosis, measles-like rash and subsequent death. It
should be noted that more severe respiratory symptoms
may be delayed for several hours after the exposure
(Lossos et al., 1990; Kraut & Lilis, 1988).
9.1.3 Skin exposure
Pure bromine (liquid or vapour) is extremely
irritating to the skin. Unlike most other chemical
agents, there is no immediate visible skin reaction
with contact. Lack of action due to the delay in
initial signs of injury often re4sults in more
extensive damage. The most common local effects are
blister formation, brownish discoloration of the skin
and slowly healing ulcers (Sagi et al., 1985).
9.1.4 Eye contact
Exposure to low concentrations produce
irritation of the eye with lacrimation. Photophobia
and blepharospasm are seen with higher concentrations
(Parmeggiani, 1983).
9.1.5 Parenteral exposure
Not relevant.
9.1.6 Other
Not relevant.
9.2 Chronic poisoning
9.2.1 Ingestion
Not relevant.
9.2.2 Inhalation
There are few reports on the chronic
complications of acute exposure to bromine. However,
the literature has described the chronic
manifestations of chlorine inhalation. Bromine is
potentially capable of extensive damage to the lower
respiratory tract. Limited studies have reported
diffuse interstitial pulmonary fibrosis, emphysema
and/or airway hyperreactivity secondary to acute
exposure to bromine (Lossos et al., 1990; Kraut &
Lilis, 1988).
9.2.3 Skin exposure
There is a rare cutaneous manifestation of
bromide accumulation known as bromoderma tuberosum,
which progresses from red papules to pustules that
enlarge and develop into indurated lesions with a
central ulcer (Sticht & Kaferstein, 1988). This
effect is related to the ingestion of bromides
formerly used in medications and may, in theory, occur
after chronic inhalation of low concentrations of
bromine (Sax, 1984).
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 course and prognosis of a bromine exposure is
depends on the concentration and duration of the exposure.
Effects may vary from mild irritation of mucous membranes
to severe damage of the skin and lung parenchyma. Death
is secondary to severe hypoxaemia/metabolic acidosis due to
acute obstructive ventilatory impairment.
9.4 Systematic description of clinical effects
9.4.1 Cardiovascular
In an acute bromine exposure, significant
hypoxaemia and hypercapnia secondary to marked
respiratory obstruction and/or restriction are
responsible for the cardiovascular changes. Initial
sinus tachycardia and cardiac arrhythmias may progress
to cardiac arrest with progressive pulmonary
obstruction.
9.4.2 Respiratory
Initial irritant symptoms of bromine vapour
inhalation include: dyspnoea, coughing, choking, and
wheezing, in addition, immediate or delayed
bronchoconstriction and the development of laryngeal
spasm, glottal oedema, asthma and tracheobronchitis.
With increased parenchyma penetration, there may be
associated peribronchiolar abscesses, pulmonary
infiltrates consistent with chemical pneumonitis,
bronchiolitis obliterans and pulmonary oedema
(Edelman, 1991; Rom & Barkman, 1983). Acute
obstructive ventilatory impairment may lead to severe
hypoxaemia, metabolic acidosis, measles-like rash and
subsequent death. It should be noted that the onset
of severe respiratory symptoms may be delayed for
several hours after the exposure (Lossos et al., 1990;
Kraut & Lilis, 1988).
There are few reports on the chronic complication of
acute exposure to bromine. However, the literature
has extensively described the chronic manifestations
of chlorine inhalation. Bromine is potentially
capable of extensive damage to the lower respiratory
tract. Limited studies have reported diffuse
interstitial pulmonary fibrosis, emphysema and/or
airway hyperreactivity secondary to acute exposure to
bromine (Lossos et al., 1990; Kraut & Lilis,
1988).
9.4.3 Neurological
9.4.3.1 Central Nervous System (CNS)
The bromide ion is a central nervous
system depressant producing ataxia, slurred
speech, tremor, nausea, vomiting, lethargy,
dizziness, visual disturbances, unsteadiness,
headaches, impaired memory and concentration,
disorientation and hallucinations. This has
only been documented in the literature with
reference to overdoses of bromide-containing
medications and the inhalation of
bromide-containing fumigants.
9.4.3.2 Peripheral nervous system
Chronic exposure to methyl bromide
has caused peripheral neuropathy; however,
there are no data on pure bromine
exposure.
9.4.3.3 Autonomic nervous system
No data available.
9.4.3.4 Skeletal and smooth muscle
No data available.
9.4.4 Gastrointestinal
Not relevant.
9.4.5 Hepatic
No data available.
9.4.6 Urinary
9.4.6.1 Renal
No data available.
9.4.6.2 Others
No data available
9.4.7 Endocrine and reproductive systems
No data available.
9.4.8 Dermatological
Pure bromine (liquid or vapour) is extremely
irritating to the skin. Unlike most other chemical
agents, there are no immediate visible skin reaction
with contact. Lack of action due to the delay in
initial signs of injury often results in more
extensive damage. The most common local effects are
blister formation, brownish discoloration of the skin
and slowly healing ulcers (Sagi et al., 1985).
There is a rare cutaneous manifestation of bromide
accumulation known as bromoderma tuberosum, which
progresses from red papules to pustules that enlarge
and develop into indurated lesions with a central
ulcer (Sticht & Kaferstein, 1988). This effect is
related to the ingestion of bromides formerly used in
medications and, in theory, to chronic inhalation of
low level concentrations of bromine (Sax,
1984).
9.4.9 Eye, ears, nose, throat: local effects
Exposure to low concentrations produce
irritation of the eye with lacrimation, rhinorrhoea,
choking and burning sensation of the throat. With
higher concentrations, there may be photophobia and
blepharospasm, epistaxis, hoarseness, stridor and
laryngeal oedema.
9.4.10 Haematological
No data available.
9.4.11 Immunological
No data available.
9.4.12 Metabolic
9.4.12.1 Acid-base disturbances
With severe exposure to bromine,
metabolic acidosis may follow acute
respiratory acidosis secondary to acute
pulmonary obstruction and pulmonary oedema.
With poor pulmonary function, inadequate
ventilation leads to excess carbonic
acid.
9.4.12.2 Fluid and electrolyte disturbances
No data available.
9.4.12.3 Others
No data available
9.4.13 Allergic reactions
No data available.
9.4.14 Other clinical effects
No data available.
9.4.15 Special risks
There is one report of neonatal bromism
(neurological depression and hypotonia) secondary to
maternal exposure to bromides at a photographic
laboratory. However, no data are available on pure
bromine exposure.
9.5 Others
No data available.
9.6 Summary
10. MANAGEMENT
10.1 General principles
Acute contact with bromine liquid or vapour requires
removal from the source of the bromine contamination.
Eye: The eye(s) should be irrigated with copious amounts
of tepid water for at least 15 minutes. If irritation, pain,
swelling, lacrimation or photophobia persist, further medical
evaluation is recommended.
Dermal: Remove of contaminated clothing and thoroughly
wash the affected area with copious volumes of water for 20
minutes. Since the effects may be delayed, close observation
for blistering and discoloration of the skin is required for
the next 24 hours (Sagi et al., 1985).
Inhalation: Respiratory support in accordance with
symptomatology, including: maintenance of an adequate airway,
oxygen, antibronchospasm therapy (inhaled beta adrenergic
agonist, aminophylline and/or short course of
corticosteriods) and antibiotics if there is evidence of
infection. Assisted or supported ventilation with tracheal
intubation and positive pressure ventilation may be
needed.
10.2 Life supportive procedures and symptomatic treatment
Acute contact with bromine liquid or vapour requires
removal from the source of the bromine contamination.
Eye: The eye(s) should be irrigated with copious amounts
of water for at least 15 minutes. If irritation, pain,
swelling, lacrimation or photophobia persist, further medical
evaluation is recommended.
Dermal: Remove contaminated clothing and wash affected
area thoroughly with copious volumes of water for 20 minutes.
Since effects may be delayed, close observation for
blistering and discoloration of the skin is required for the
next 24 hours (Sagi et al., 1985).
Inhalation: Respiratory support in accordance with
symptomatology, including: maintenance of an adequate airway,
oxygen, antibronchospasm therapy (beta adrenergic agonist,
aerosols, aminophylline and/or short course of
corticosteriods) and antibiotics if there is evidence of
infection. Initial testing should include: chest x-ray to
view inflammatory changes in the parenchyma, spirometry
(flow-volume loop with and without bronchodilator) to
determine air flow capacity and reversibility, diffusing
capacity (DLco) to assess changes in the alveolar-capillary
permeability, arterial blood gases to evaluate blood
oxygenation (Po2) and ventilation (Pco2), and complete white
blood count. Repeat chest radiograph and spirometry are
recommended to determine the progression or resolution of
residual effects. Ventilation-perfusion scanning does not
usually provide significant additional information, except to
rule out other processes, such as pulmonary emboli. Careful
examination is important to detect pathology (fine wheezes in
subtle or early asthma and fine crackles in early pulmonary
oedema) not revealed by the studies noted above.
Ingestion: Not relevant
10.3 Decontamination
Acute contact with bromine liquid or vapour requires
removal from the source of the bromine contamination.
Eye: The eye(s) should be irrigated with copious amounts
of tepid water for at least 15 minutes.
Dermal: Removal of contaminated clothing and thorough
washing of affected area with copious volumes of water for 20
minutes.
Inhalation: Maintain adequate fresh air source.
10.4 Enhanced elimination
Contaminated clothing should be discarded. When
bromide-containing medications are ingested; the compounds
are degraded to bromide and excreted in the urine over a
period of weeks (biological half-life of 12-20 days).
Bromide also occurs naturally in the urine (Schaller, 1985).
However, there are no data on excretion of bromide after a
bromine exposure (inhalation or dermal).
10.5 Antidote treatment
10.5.1 Adults
No data available.
10.5.2 Children
No data available.
10.6 Management discussion
No data available.
11. ILLUSTRATIVE CASES
11.1 Case reports from literature
Burns caused by bromine and some of its compounds:
Three cases of exposure to bromine-containing compounds were
reviewed which emphasise the significance of the delay in the
appearance of clinical signs and symptoms. Prompt first aid,
including copious irrigation with water, reduced the extent
and depth of the injury (Sagi et al., 1985).
Accidental Bromine Exposure in an Urban Population: An
Acute Epidemiological Assessment:
In 1984, a large number of people in Geneva, Switzerland, was
exposed to bromine gas for several hours at concentrations
above the short-term exposure limit (0.3 ppm); 91 exposed
individuals were evaluated. The main symptoms were: acute
conjunctivitis (90%); upper respiratory tract irritation
(68%); cough (47%); and headache (46%). Follow-up one month
later revealed that, in all cases, the moderate eye and upper
airway irritation was self-limiting (Morabia et al.,
1988).
Pneumomediastinum: Complication of exposure to bromine
A maintenance technician in a chemical company developed a
cough with severe bronchospasm and spontaneous
pneumomediastinum following an accidental exposure to
bromine. The chest radiograph on admission was normal and
only a surveillance chest x-ray taken a few hours later
demonstrated the presence of eumomediastinum. This indicates
the need for vigilance and serial chest radiographs after an
exposure (Lossos et al., 1990).
Chemical Pneumonitis Due to Exposure to Bromine Compounds
A laboratory technician developed chemical pneumonitis
following an accidental exposure to bromide compounds
(hydrogen bromide and phosphorus tribromide). The patient's
course was protracted with recurrent pulmonary infiltrates
despite having no subsequent exposures. The case illustrated
the importance of close medical follow-up after an irritant
respiratory exposure (Kraut & Lilis, 1988).
12. ADDITIONAL INFORMATION
12.1 Specific preventive measures
Although bromine is not combustible, it may react with
other chemicals causing fire and explosion. Good
ventilation, local exhaust or breathing protection are
recommended; also protective gloves and clothing, face-shield
or eye protection in combination with breathing protection
(Chemical Safety Sheets, 1991).
12.2 Other
An International Chemical Safety Card (ICSC), produced
by the IPCS, exists - No. 0107.
13. REFERENCES
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Hygienists) (1991) Guide to Occupational Exposure Values 1991.
Cincinnati, ACGIH.
Alderson M (1986) Occupational Cancer. London, Butterworth &
Company Ltd, 48.
Bitron MD & Aharonson EF (1978) Delayed mortality of mice
following inhalation of acute doses of CH2O, SO2, Cl2, and Br2.
American Industrial Hygiene Association Journal 39:129-138.
Broderick A & Schwartz DA (1992) Halogen Gases, Ammonia, and
Phosgene. In: Sullivan JB and Krieger GR, Eds. Hazardous
Materials Toxicology. Baltimore, Williams & Wilkins, 791-796.
Budvari S (ed) (1996) The Merck Index: An Encyclopedia of
Chemicals, Drugs, and Biologicals. Merck & Co. Inc., Whitehouse
Station, NJ, USA, pp 228-229.
Calabrese EJ & Kenyon EM (1991) Air Toxics and Risk Assessment.
Chelsea, Lewis Publishers Inc., 173-175.
Chemical Safety Sheets (1991), Samson Chem. Publishers,
Dordrecht, The Netherlands
Edelman PA (1991) Irritant Gas Inhalation. In: Hardwood-Nuss A
et al, Eds. The Clinical Practice of Emergency Medicine.
Philadelphia, J.B. Lippincott Company, 516-519.
Fazzalari FA (1978) Compilation of Odor and Taste Threshold Values
Data. Philadelphia, American Society for Testing and Materials.
Kraut A & Lilis R (1988) Chemical Pneumonitis due to Exposure to
Bromine Compounds. Chest 94(1): 208-210.
ILO (International Labour Office) (1991) Occupational Exposure
Limits for Airborne Toxic Substances. Geneva, ILO Publications,
54-55.
Leddy JL (1983) Salt, Chlor-Alkali and Related Heavy Chemicals.
In: Kent JA, ed. Riegel's Handbook of Industrial Chemistry. New
York, Van Nostrand Reinhold Company, 232-233.
Lossos IS et al (1990) Pneumomediastinum: a complication of
exposure to bromine. British Journal of Industrial Medicine
47:784.
Meyer E (1977) Chemistry of Hazardous Materials. Englewood
Cliffs, Prentice-Hall Inc., 109-117.
Morabia A et al (1988) Accidental Bromine Exposure in an Urban
Population: An Acute Epidemiological Assessment. International
Journal of Epidemiology 17(1): 148-152.
NAS (National Academy of Sciences) (1977) Advisory Center on
Toxicology. Drinking Water and Health. Washington, National
Academy of Sciences.
NIOSH (National Institute for Occupational Safety and Health)
(1977) In: Key MM et al. (eds) Occupational Diseases. Washington
D.C.
OSHA (Occupational Safety and Health Administration) (1988)
Chemical Information Manual. Rockville, Government Institutes
Inc., II-40 - II-43.
OSHA (1989) Industrial Exposure Control Technologies for OSHA
Regulated Hazardous Substances. Rockville, US Department of
Labor.
Parmeggiani L (1983) Encyclopedia of Occupational Health and
Safety. Geneva, Publication of the International Labour Office
326-327.
Rom WN & Barkman HW (1983) Respiratory Irritants. In: Rom WN,
ed. Environmental and Occupational Medicine. Boston, Little,
Brown and Company, 273-283.
Sagi et al. (1985) Burns caused by bromine and some of its
compounds. Burns 11:343-350.
Sax NI, ed. (1984) Dangerous Properties of Industrial Materials.
New York, Van Nostrand Reinhold Company, 518.
Schaller KH, ed. (1985) Analyses of Hazardous Substances in
Biological Materials, Volume 1. Weinheim (Federal Republic of
Germany), VCH, 67-68.
Schwartz DA (1987) Acute Inhalation Injury. Occupational
Medicine: State of the Art Reviews 297-318.
Sittig M (1985) Handbook of Toxic and Hazardous Chemicals and
Carcinogens. Park Ridge, Noyes Publications, 144-145.
Sticht G & Kaferstein H (1988) Bromine. In: Seiler H, Sigel H,
Sigel A, eds. Handbook on Toxicity of Inorganic Compounds. New
York, Marcel Dekker Inc., 143-154.
Stokinger HE (1981) The Halogens and the Nonmetals, Boron and
Silicon. In: Clayton GD, Clayton FE, eds. Patty's Industrial
Hygiene and Toxicology. New York: John Wiley & Sons Inc.,
2965-2971.
Weiss G, ed. (1980) Hazardous Chemicals Data Book. Park Ridge,
Noyes Data Corporation.
14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE
ADDRESS(ES)
Author: Dr O.M.J. Kasilo
Drug and Toxicology Information Service
University of Zimbabwe Medical School
P.O.Box A178, Avondale
Harare
Zimbabwe
Tel: 263-4-290233 direct/89163172
Fax: 263-4-732828/795019
Date: April 1990
Co-Author: P.A. Edelman, M.D.
Regional Poison Center
University of California, Irvine
1310 W. Stewart Dr. 306
Orange, CA 92668
USA
Tel: 1-714-6395006
Fax: 1-714-9974377/5325097
Date: January 1992
Peer
Review: Strasbourg, France, April 1990
Newcastle-upon-Tyne, United Kingdom, February 1992
Editor: Mrs J. Duménil
International Programme on Chemical Safety
Date: July 1999