Methyl bromide
1. NAME
1.1 Substance
Methyl bromide
1.2 Group
Halogenated hydrocarbon
1.3 Synonyms
CH3 Br
Bromomethane
Monobromomethane
MBX
1.4 Identification numbers
1.4.1 CAS Number
74-83-9
1.4.2 Other numbers
RTECS PA 4900000
IN - UN/NA 1062
EEC N° 602-002-00-2
EINECS N° 200-813-2
1.5 Main brand names/main trade names
Dowfume MC-2
Dowfume MC-33
Embafume
Meth-O-Gas
1.6 Main manufacturers/main importers
2. SUMMARY
2.1 Main risks and target organs
Methyl bromide is a very toxic fumigant gas with poor
olfactory warning properties. Severe poisoning and death
have occured during application due to inadvertent spread,
clean-up operations, and premature entry into fumigated
places.
The target organs are:
The central nervous system, the respiratory system, kidneys,
eyes and skin.
The local exposure to the eyes can cause severe irritation,
blurred vision, temporary blindness and severe corneal
burns.
Methyl bromide can cause severe irritation and corrosive
injury of the skin in particular when the gas or liquid is
trapped in gloves, boots or other clothing.
2.2 Summary of clinical effects
Symptoms may only appear after a delay of several
hours.
A delayed onset of symptoms is typical and serious symptoms
can develop from a few minutes to as long as 48 hours
postexposure.
Methyl bromide has local and systemic effects. It is a severe
eyes, skin and mucous membrane irritant. Exposure to high
concentrations causes pulmonary oedema.
Prolonged skin contact may cause blisters and vesicles
resembling a second-degree burn.
The most important systemic effects are: neurological:
headaches, dizziness, coma, tremors, prolonged and
generalized seizures and permanent brain damage.
Several neuropsychiatric signs and symptoms may be observed
during acute and chronic methyl bromide poisonings. Low level
subacute exposure to the vapour have produced
polyneuropathy.
Late sequelae include: bronchopneumonia, renal failure with
anuria, severe weakness with or without evidence of
paralysis, disturbances of gait, blurred vision and
neuropsychiatric disorders.
2.3 Diagnosis
Diagnosis is made primarily on a history of exposure to
the compound and typical symptoms. Serum bromide levels may
be useful to make the diagnosis but do not necessarily
correlate with the severity of poisoning.
2.4 First-aid measures and management principles
Exposed people should be monitored for a minimum of 24
to 48 hours to detect delayed symptoms especially pulmonary
edema.
In case of poisoning, management is primarily
supportive.
Measures for decontamination include: In case of inhalation
remove source of contamination or remove the victim from the
site of exposure to the fresh air. Take proper precautions to
ensure that the rescuers guard their own safety before
attempting rescue. e.g. wear appropriate protective equipment
and use breathing apparatus.
Remove all contaminated clothing and wash affected skin with
soap and water.
Copiously irrigate exposed eyes with water.
In case of respiratory and cardiac arrest initiate
cardiopulmonary resuscitation inmediately.
Administer supplemental oxygen and treat bronchospasm,
pulmonary edema, seizures and coma.
High dose thiopental anaesthesia seems effective in the
treatment of CH3Br induced generalised seizures that have
proved to be unresponsive to regular treatment with
antiepileptic drugs.
The usage of Dimercaprol (BAL) and acetylcysteine have not
been critically tested in controlled studies and their
reported effectiveness concerned only less severely poisoned
patients
3. PHYSICO-CHEMICAL PROPERTIES
3.1 Origin of the substance
Synthetic
3.2 Chemical structure
CH3 Br
H
|
H-C-Br
|
H
3.3 Physical properties
3.3.1 Colour
3.3.2 State/Form
3.3.3 Description
It is a colorless gas at room temperature and
standard pressure with a boiling point of about 4°C.
It is heavier than air. It is odourless except at high
concentrations when it has a burning taste and a sweet
chloroform-like smell.
Molecular weight: 94.95
Relative density( specific gravity): 1.73 at 0°C
Flash point: none
194°C burns with difficulty
Critical temperature: 194°C
Autoignition temperature: 536.7°C
Vapor pressure at 20°C : 1420 mm Hg
Solubility in water at 20°C ; 1.75 g/100 g of
solution
Methyl bromide is freely soluble in alcohol,
chloroform, ether, carbon disulfide, carbon
tetrachloride, and benzene. It is stable and non
corrosive (EHC,1994).
Melting point : -93.6 °C
Boiling point: 3.56 °C
(Windholz, 1983).
3.4 Other characteristics
Methyl bromide hydrolyses to methanol and hydrobromic
acid in aqueous solution.
4. USES/CIRCUMSTANCES OF POISONING
4.1 Uses
4.1.1 Uses
4.1.2 Description
Methyl bromide is commercially available as a
liquefied gas and used as a fumigant for the control
of nematodes, fungi and weeds. The formulations also
may contain chloropicrin or amyl acetate as warning
agents.
It is used widely as a fumigant for all types of dry
foodstuffs, in grain elevators, mills, ships,
warehouses, greenhouses and food-processing
facilities.
It is also used as a soil fumigant applied prior to
planting either being injected into the soil as a
liquid or applied to the soil under sheeting in the
liquid form using evaporating jars and allowed to
vaporize in situ (cold method) or by heating (hot
method). The methods permitted in various countries
differ. The type of plastic sheeting is also important
(EHC, 1994)
The industrial uses of methyl bromide include:
methylating agent in chemical manufacture and as a
low-boiling solvent e.g. for extracting oils from
nuts, seeds and flowers.
It has also been used as a refrigerant and fire
extinguishers (Baselt 1982; Hayes and Laws,
1992).
4.2 High risk circumstance of poisoning
Earlier poisoning incidents involving the general public
were mainly from the methyl bromide in fire extinguishers.
More poisoning incidents have involved unauthorized entry
into fumigated buildings or persons living near fumigated
buildings, greenhouses or fields being fumigated with methyl
bromide.
Most of occupational poisonings have arisen from its
manufacture or from its use as a fumigant (Hustinx et al,
1993).
4.3 Occupational exposed populations
Up to 1955. the majority of methyl bromide poisoning
incidents resulted from chemical manufacture and filling
operations. Since 1955, fumigation has become the major
source of fatalities. The highest risk group are fumigators
and greenhouse workers. In many countries the use of methyl
bromide is restricted to trained and licensed personnel
(EHC,1994).
5. ROUTES OF ENTRY
5.1 Oral
No data available.
5.2 Inhalation
Inhalation is the primary route of exposure. Acute,
subchronic and chronic poisonings have ocurred following
inhalation of methyl bromide. It is readily absorbed through
the lungs (Hayes and Laws, 1991). An inhalation study in
humans was carried out to determine systemic uptake of low
concentrations of methyl bromide from air during nasal or
oral breathing. Two male and two female volunteer subjects
inhaled about 0.1 mg/m3 (25 ppb) 14C-labelled methyl
bromide once through the nose and once through the mouth. The
uptake (% of methyl bromide inhaled) was 55.4% nasal and 52.1
% oral (Raabe, 1988)
5.3 Dermal
Dermal exposure can result from direct contact with
liquid methyl bromide e.g. from accidental splashing or
through contact with contaminated boots,clothing, bandages or
gloves. These articles are often made of rubber which can
absorb methyl bromide (Alexeef and Kilgore, 1983). Dermal
exposure to gaseous methyl bromide can also cause poisoning.
Methyl bromide may be absorbed through the skin provoking
the same symptoms as described for inhalation (Baselt 1982,
Gosselin et al, 1984).
When liquid methyl bromide is spilled on the skin, it
evaporates rapidly producing a cool or burning
sensation.
5.4 Eye
Methyl bromide may cause irritation and tearing. It may
also cause severe burns of the cornea.
5.5 Parenteral
No data available
5.6 Others
No data available
6. KINETICS
6.1 Absorption by route of exposure
Methyl bromide may be absorbed by inhalation or dermal
contact. Inhalation experiments in rats, beagles and humans
have shown that methylbromide is rapidly absorbed through the
lungs. It is also rapidly absorbed in rats following oral
administration (EHC, 1994)
6.2 Distribution by route of exposure
After absorption, methyl bromide or metabolites are
rapidly distributed to many tissues including the lungs,
adrenals, kidneys, liver, brain, testis and adipose
tissue.
The disposition of 14C-methyl bromide has been evaluated in
rats by several authors after oral,intraperitoneal and
inhalation exposure. Following oral or inhalation exposure,
75 to 85% of the body burden was eliminated by rats 65 to 72
hours post exposure.
The major organs of distribution of radioactivity observed
immediatly after exposure included fat, lungs, liver,
adrenals and kidneys concentrations of one-third to one-tenth
less were found in the brain. More than 90% of the tissue
radioactivity was attributed to metabolized methyl bromide
(Hayes and Laws, 1991).
Methylation of proteins and lipids has been observed in
tissues from several species, including humans, exposed by
inhalation.
Methylated DNA adducts have also been detected following in
vivo and in vitro exposure of rodents or rodents cells
(EHC, 1994).
6.3 Biological half-life by route of exposure
The biological half-life of the bromide ion is 10 to12
days (Hustinex et al, 1993). No data are available about
methyl bromide half-life.
6.4 Metabolism
The metabolism of methyl bromide has not been
elucidated. It is known to be partially converted to
inorganic bromide in man. The contribution of this
metabolite to the toxicity of the parent is not clear but it
is felt that methyl bromide itself is the primary toxic agent
(Baselt, 1982).
Bromide concentrations in blood and target organs were
reported to be increased in humans and in laboratory animals
after exposure to methyl bromide (Hine, 1969)
6.5 Elimination by route of exposure
Depending on the route of exposure, 30 to 50% of the
absorbed methyl bromide was recovered as 14CO2, 16 to 40%
was recovered as metabolized methyl bromide in the urine and
only 4 to 20% was recovered in the expired air as parent
compound.
Medinsky et al observed extensive biliary excretion of 14C
activity as indicated by the fact that 46% of the dose was
recovered in bilis within 24 hours following oral
administration of 14C-methyl bromide (Hayes and Laws,
1991).
7. TOXICOLOGY
7.1 Mode of action
The mode of action of methyl bromide is still not
understood. Proposed mechanisms of toxicity include the
direct cytotoxic effect of the intact methyl bromide molecule
or toxicity due to one of its metabolites. The bromide ion
concentration are insufficient to explain methyl bromide
toxicity. Methyl bromide reacts in vitro with a number of
SH enzymes and causes progressive and irreversible inhibition
interfering with microsomal metabolism. Its ability to
methylate sulfhydryl groups and thus inactivate enzymes has
been postulated to play an important role in its toxicity
(Baselt, 1982; Gosselin et al, 1984).
Honma et al (1985) concluded that CNS toxicity seems to be
due to the methyl bromide molecule itself or the methyl
moiety incorporated into the tissue and does not appear to be
attributable to inorganic bromide or methyl alcohol.
7.2 Toxicity
7.2.1 Human data
7.2.1.1 Adults
Fatal poisoning have resulted from
exposures to relatively high concentrations (
from 33000 mg/m3 or 8600 ppm onwards) of
methyl bromide vapours. Nonfatal poisoning
has resulted from exposure to concentrations
as low as 390 to 1950 mg/m3 (100 to 500
ppm) (EHC, 1994).
7.2.1.2 Children
No data available
7.2.2 Relevant animal data
Methyl bromide is very toxic to all animals
species by all routes of administration studied.
Acute inhalation studies have shown:
LC50 rat, 30 minutes exposure = 2800 ppm ( NIOSH,
1984)
LC50 rat, 30 minutes exposure = 11000 mg/ m3
(NIOSH,1984)
LC50 rat, 8 hours exposure = 302 ppm
(NIOSH,1984)
LC50, rat , 24 hours exposure = 50 mg/m3 , about 13
ppm
(NIOSH, 1984)
LC50, mouse, 1 hour exposure = 4.68 mg/L, about 1200
ppm
(ACGIH, 1986; USEPA, 1985)
LC50 mouse, 2 hour exposure = 1540 mg/L, about 393 pp.
(USEPA, 1985)
Oral experimental studies have shown:
LD50, rat: 214 mg/kg (IARC, 1986, USEPA, 1985)
Long-term inhalation studies:
Rats, rabbits and guinea pigs were exposed for 7.5 to
8 hours/day, 5 days/week for up to 6 months to methyl
bromide at 65, 130, 250, 420 and 850 mg/m3.
Increased mortality occured early in the study at
concentrations of 130 mg/m3 (34 ppm) in rabbits and
420 mg/m3 (108 ppm) in rats and guinea pigs.
Surviving animals exhibited signs of severe injury to
the nervous system such as paralysis of the legs,
hyperexcitability and convulsions. These signs were
also seen in monkeys exposed at 250 mg/m3. Lung,
liver and kidney damage were observed in high-dose
animals (IARC, 1986).
Cysteine has been shown to reduce the toxicity of
methyl bromide when administered to rats, mice and
rabbits orally or s.c. 30 minutes before or s.c.
within 5 minutes after acure poisoning. Cysteine
prevented the death, paralysis, paresis and spasms
which developed on the 3rd to 4th days after methyl
bromide inhalation in other animals (EHC,
1994)
7.2.3 Relevant in vitro data
No data available
7.2.4 Workplace standards
Time-weighted average (TLV-TWA) 5 ppm (20
mg/m3)
Threshold limit values TLV /ACGIH 1987-88
7.2.5 Acceptable daily intake (ADI)
In 1988, the JMPR evaluated the toxicology of
the bromide ion (FAO/WHO, 1988a; 1988b) and concluded
that the level causing no toxicological effect
was:
Rat-240 ppm, equivalent to 12 mg bromide/kg bw/day
Human-9 mg bromide/kg bw/day
The acceptable daily intake (ADI) of 1 mg/kg bw was
confirmed
7.3 Carcinogenicity
Groups of males and female rats were given oral doses of
methyl bromide (0, 0.4, 2, 10 or 50 mg/kg body weight) in oil
5 times/week for 13 weeks. There was incresed incidence of
cancers of the forestomach in high-dose animal groups (ACGIH,
1986 , IARC, 1986). In a second study, daily oral
administration of methyl bromide at 25 or 50 mg/kg bw did not
cause tumours (IARC 1986).
Human data is limited and inconclusive. According to the IARC
(1986) the evidence for the carcinogenicity of methyl bromide
to humans is inadequate and the evidence in experimental
animals is limited. NIOSH, (1984) has recommended that methyl
bromide be considered as a potential occupational
carcinogen.
7.4 Teratogenicity
Methyl bromide did not cause birth defects or
fetotoxicity in rats or rabbits which were exposed daily by
inhalation at 20 or 70 ppm during gestation or prior to
breeding (rats only) (IARC, 1986).
No human data is available.
7.5 Mutagenicity
Methyl bromide was mutagenic in several short-term tests
using bacteria, cultured mammalian cells, insects and whole
animals. Micronuclei (chromosome fragments) were observed in
bone marrow and blood cells of rats and mice repeatedly
exposed to methyl bromide by inhalation. Alkylation of DNA in
liver and spleen was detected in mice exposed to methyl
bromide by inhalation or injection (IARC 1986)
7.6 Interactions
No data available.
8. TOXICOLOGICAL AND BIOMEDICAL INVESTIGATIONS
9. CLINICAL EFFECTS
9.1 Acute poisoning
9.1.1 Ingestion
No cases of ingestion have been reported.
9.1.2 Inhalation
Mild and moderate exposure may cause headache,
dizziness, abdominal pain, nausea, vomiting, chest
pain and difficulty breathing. Visual disturbances
such as blurred or double vision may also appear. A
characteristic delay of more than 1 hour up to 48
hours in the onset of symptoms has been described in
several human exposures. Severe poisoning may cause
tremors, convulsions, unconsciousness,and permanent
brain damage.
A great variety of central nervous system
manifestations have been described: numbness, ataxia,
tremor, myoclonus, positive Romberg' sign, great
agitation, change of personality. Whereas convulsions
generally occur in fatal cases, death usually is the
result of pulmonary edema leading to respiratory
failure or cardiovascular collapse.
Liver and kidney damage have also been described
(Ellenhorn and Barceloux, 1988, Baselt 1982, Hayes and
Laws,1992).
Inhalation of more than 10000 ppm for more than a few
minutes may cause death (Hayes and Laws, 1992)
9.1.3 Skin exposure
Methyl bromide can cause severe irritation and
corrosive skin injury, blisters and vesicles
resembling second-degree burns. In particular, severe
injury may occur if gas or liquid is trapped in
gloves, boots or other clothing.
Methyl bromide can be absorbed through the skin and
produce the same symptoms described for inhalation
(CCHOS, 1992)
9.1.4 Eye contact
Irritation and tearing. Blurred vision.
Temporary blindness and retinal bleeding have been
reported. Severe burns of the cornea have also been
described (Chavez et al, 1985).
9.1.5 Parenteral exposure
No data available
9.1.6 Other
No data available
9.2 Chronic poisoning
9.2.1 Ingestion
No data available
9.2.2 Inhalation
Chronic exposure is characterized by lethargy,
muscular pains; visual, speech and sensory
disturbances and mental confusion. More severe effects
include tremors, hallucinations, fainting spells and
seizures due to permanent brain damage.
Kidney and liver damage have also been reported
(Ellenhorn and Barceloux,1988). A fumigator
chronically exposed to methyl bromide developed
paresthesia of the extremities, dysesthesias and
visual impairment secondary to optic atrophy (Chavez
et al, 1985)
9.2.3 Skin exposure
Prolonged or repeated contact with liquid may
cause skin burns and lesions.
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
A delayed onset of symptoms is typical and serious
symptoms can develop within a few minutes to as long as 48
hours postexposure.
Death usually is the result of pulmonary edema,
cardiovascular collapse or intratable status epilepticus
(Hayes and Laws, 1991, Hustinx et al, 1993).
In severely poisoned patients recovery is frequently
prolonged and convalescence may take months. Permanent
sequelae are frequent, they are: psychiatric, motor and
sensory impairment ataxia, muscular weakness, irritability,
blurred vision, myoclonus and EEG disturbances.
9.4 Systematic description of clinical effects
9.4.1 Cardiovascular
Tachycardia is very common in mild and moderate
cases. Cardiovascular collapse has been described in
fatal cases (Gosselin et al, 1984).
9.4.2 Respiratory
Methyl bromide produces irritation of the
respiratory tract. Cough, chest pain, difficulty in
breathing and bronchospasm have been described.
Development of non-cardiogenic pulmonary oedema may be
immediately or delayed leading to respiratory failure.
Chest X-ray may show uni or bilateral infiltrative
changes with or without pleural effusion.
Pathological findings at autopsy include: pulmonary
oedema, bronchopneumonia, congestion and haemorrhage
(Hine, 1969)
9.4.3 Neurological
9.4.3.1 Central Nervous System
A great variety of manifestations
may appear, nearly every type of nervous
disturbance has been reported: numbness,
twitching of all limbs, ataxia, tremor,
myoclonus, great agitation, coma and tonic-
clonic generalized convulsions (status
epilepticus). Exageration of the patellar
reflexes and a positive Babinski's sign may
develop ( Hustinx et al, 1993).
Other manifestations are: headache,
dizziness, visual, speech and sensory
disturbances,sensation described as
"floating".
Remarkable abnormalities of the EEG have been
reported: runs of very sharp spikes of short
duration followed by a short wave. Myoclonic
jerks coincide these polyspike and wave
complexes (Hustinx et al, 1993). Uncini et
al (1990) were able to show that the status
mioclonicus as seen in some cases of serious
methyl bromide poisoning may represent a form
of cortical reflex myoclonus.
Brain stem damage was described in a man who
died 30 days after unconsciousness following
methyl bromide exposure. At postmorten
examination the brain showed mild generalized
swelling, normal ventricles and well defines
symmetrical lesions, including loss of
neurones in the mammilary bodies and inferior
colliculi. The cerebellar dentate nuclei had
occasional foci of neuronal loss;other brain
regions were normal. The spinal cord was
normal but dorsal root ganglia had scattered
nodules of neuronal loss (Cavanagh,
1992)
9.4.3.2 Peripheral nervous system
Distal muscular weakness, painful
plantar dysaesthesia and alteration of tendon
reflexes due to axonal neuropathy have been
described after acute poisoning (Hustinx et
al, 1993).
Low-level subacute exposure to the vapour
have produced a syndrome of polyneuropathy
characterized by persistent numbness in the
and legs, impaired superficial sensation,
muscle weakness, unsteadiness of gait and
absent or hypoactive distal tendon reflexes
(Kantarjian, 1963).
9.4.3.3 Autonomic nervous system
No data available
9.4.3.4 Skeletal and smooth muscle
High serum CPK has been seen
returning to normal soon after suppression of
seizures (Hustinx et al, 1993)
9.4.4 Gastrointestinal
Acute exposure may cause: nausea, vomiting,
abdominal pain.
9.4.5 Hepatic
Rise in ALAT - ASAT and LDH have been described
several days after an acute episode suggestive of
mild hepatotoxicity (Verberk et al, 1979).
9.4.6 Urinary
9.4.6.1 Renal
Transient proteinuria has been
described (Hustinx et al, 1993). Renal
failure due to tubular necrosis may be a late
sequela, but this is uncommon and usually
mild (Benatt, 1948).
9.4.6.2 Others
No data available
9.4.7 Endocrine and reproductive systems
No data available
9.4.8 Dermatological
Methyl bromide is a potent skin irritant and an
intense vesicant. Prolonged skin contact may cause
blisters and vesicles resembling a second-degree burn
(Gosselin et al, 1984; CCOHS, 1992).
9.4.9 Eye, ears, nose, throat: local effects
Methyl bromide has local irritant effects. It
is a severe eye, nose, skin and mucous membrane
irritant.
Various visual disturbances have been described:
blurring of vision, diplopia, lacrymation and
accommodative disturbance
Burning sensation of the throat has also been
reported.
9.4.10 Hematological
Varying degrees of leucocytosis with or
without left shift have been described (Hustinx et al,
1993).
9.4.11 Immunological
No data available
9.4.12 Metabolic
9.4.12.1 Acid-base disturbances
Metabolic acidosis has been
observed in moderate and severe
poisoning.
9.4.12.2 Fluid and electrolyte disturbances
Raise in serum chloride
concentrations has been observed in some
patients (Hustinx et al, 1993).
9.4.12.3 Allergic reactions
No data available
9.4.14 Other clinical effects
An employee habitually not wearing a mask in a
fumigating plant spraying fruits and vegetables was
initially treated for psychosis as the early symptoms
of methyl bromide poisoning are similar (Zatuchni and
Hong, 1981)
9.4.15 Special risks
No data available
9.5 Others
No data available
10. MANAGEMENT
10.1 General Principles
Exposed people should be monitored for a minimum of 24
to 48 hours to detect delayed symptoms especially pulmonary
edema.
Management is primarily supportive.
In case of respiratory and cadiac arrest initiate
cardiopulmonary resuscitation immediately.
Administer supplemental oxygen and treat bronchospasm,
pulmonary edema, seizures and coma.
High dose thiopental anaesthesia seems effective in the
treatment of CH3Br induced generalised seizures that have
proved to be unresponsive to regular treatment with
antiepileptic drugs.
The usage of Dimercaprol (BAL) and acetylcysteine have not
been critically tested in controlled studies and their
reported effectiveness concerned only less severely poisoned
patients.
10.2 Relevant laboratory analyses and other investigations
10.2.1 Sample collection
10.2.2 Biomedical analysis
The following analysis may be useful in the
management of CH3Br poisoning :
Arterial blood gases
Acid base balance
Serum electrolytes
Urine analysis
Creatinine
Total haemoglobin, blood cell count
Hepatic enzymes
Chest x-ray
ECG
EEG
10.2.3 Toxicological analysis
Measurement of blood CH3Br and serum bromide
(Br-) by induction coupled plasma mass spectrometry
should be performed (Hustinx et al, 1993).
Methyl bromide itself has been detected in human
tissue on only one occasion. This observation may be
due to the absence of methyl bromide or more probably
its very short half-life in tissues as well as
difficulties in analysis (EHC 1994). Data on
concentrations of bromide in various human tissues
after methyl bromide poisoning are scarce.
There is an inconsistency in the data as to whether
there is a correlation between bromide levels and the
symptoms of methyl bromide. Serum Br- concentrations
are considered by some authors to correlate poorly
with clinical symptoms and outcome (Bradford,
1990)
Cases of fatal CH3Br poisoning have reportedly
occurred in association with serum Br- concentrations
of only 30 mg/L whereas concentrations of more than
200 mg/L were found in professional fumigators
without any accompanying symptoms (Hustinx et al,
1993).
In four lethal cases of people exposed to methyl
bromide, Marraccini et al (1983) found bromide ion
concentrations in serum or plasma ranging from 40 to
583 mg/L. Methyl bromide was detected in the brain of
one patient (detection limit < 1 ppm).
10.2.4 Other investigations
Haemoglobin adducts as a biological index to
methyl bromide exposureMethyl bromide reacts with
cysteine to form S-methylcysteine (MeCys) in
haemoglobin. Iwasaki and Kagawa (1989) determined the
haemoglobin adduct in methyl bromide manufacturing
workers and examined its effectiveness as a biological
index of exposure to methyl bromide. Haemoglobin
adducts have a life span of about 2 months, so workers
only intermittently exposed to methyl bromide would
also be detected in such a survey.
10.3 Life supportive procedures and sympomatic treatment
Treatment with diazepam, clonazepam, diphenylhydantoin
or paraldehyde is often not sufficient to supress convulsive
activity. In these cases high dose thiopental anaesthesia
seems to be effective.
The drug resistant status epilepticus , also described by
some authors as status myoclonicus is associated with a high
mortality (Hustinx et al, 1993).
10.4 Decontamination
Measures for decontamination. In case of inhalation
remove the source of contamination or remove victim from
exposure to the fresh air. Take proper precaution to ensure
the rescuers their own safety before attempting recue. e.g.
wear appropriate protective equipment. Use breathing
apparatus.
Remove all contaminated clothing and wash affected skin with
soap and water.
Irrigate exposed eyes with copious water.
10.5 Elimination
No data indicating the benefit of forced diuresis,
alkalinization, haemodialysis or haemoperfusion is
available.
10.6 Antidote treatment
10.6.1 Adults
Although BAL has been used for treating methyl
bromide poisoning there is no evidence that it was
beneficial (Hayes and Laws, 1991).
10.6.2 Children
No data available
10.7 Management discussion
In the past chelating agents as Dimercaprol and N-
acetylcysteine have been used. None of these drugs were used
in the context of controlled prospective trials and their
reported effectiveness concerned only less severely poisoned
patients (Hustinx et al, 1993).
11. ILLUSTRATIVE CASES
11.1 Case reports from literature
Systemic methyl bromide (CH3Br) poisoning with signs
and symptoms of varying severity developed in nine greenhouse
workers after acute inhalational exposure on two consecutive
days.
Measurements of CH3Br, carried out at the site within hours
after the accident suggest that exposure on the second day
may have been in excess of 200 ppm (800 mg/m3). All workers
were admitted for observation. Seven of them were discharged
after an uneventful overnight observation and residual
symptoms if any, subsided within three weeks of the
accident. Two patients needed intensive care for several
weeks because of severe reactive myoclonus and tonic-clonic
generalised convulsions. These conditions were unresponsive
to repeated doses of diazepam, clonazepam and
diphenylhydantoin but could be suppressed effectively by
induction of a thiopental coma that had to be continued for
three weeks.
In some of the patients previous subchronic exposure to CH3Br
as shown by their occupational histories and high serum
bromide concentrations is likely to have been a factor
contributing to the severity of their symptoms. A direct
association between serum bromide concentrations and the
severity of neurological symptoms, however, seemed to be
absent. An on site investigation into the circumstances
leading to the accident showed the presence of an empty and
out of use drainage system that covered both sections of the
greenhouse. This was probably the most important factor
contributing to the rapid and inadvertent spread of CH3Br
(Hustinx et al, 1993).
11.2 Internally extracted data on cases
11.3 Internal cases
12. ADDITIONAL INFORMATION
12.1 Availability of antidotes
No antidote available.
12.2 Specific preventive measures
Personal protective equipment: Wear suitable personal
protective equipment including approved respiratory
protection.
Have appropriate equipment available for use in emergencies
such as spills or fire. Respiratory protection: NIOSH
recommendations: positive pressure, full-facepiece SCBA; or
positive pressure, full-facepiece SCBA.
Eye/face protection: Chemical safety goggles. A face shield
may also be necessary.
Skin protection: Impervious gloves, coveralls, boots and/or
other resistant protective clothing. Have a safety
shower/eye-wash fountain readily available in the immediate
work area.
Personal protection comments: Remove contaminated clothing
promptly. Keep contaminated clothing in closed containers.
Discard or launder before rewearing. Inform laundry personnel
of contaminant's hazards. Discard contaminated leather goods
(shoes,belt, watchband).
Do not smoke, eat or drink in work areas.
Wash hands thoroughly after handling this material. Maintain
good housekeeping (CCOHS, 1992).
12.3 Other
Spill and leak procedures: Precautions
Restrict access to area until completion of clean-up. Ensure
clean-up is conducted by trained personnel only. Wear
adequate personal protective equipment. Ventilate area.
Extinguish or remove all ignition sources.
Clean-up: Do not touch spilled material. Prevent material
from entering sewers or confined spaces. Stop or reduce leak
if safe to do so. Contain spilled liquid with earth, sand or
absorbent material which does not react with spilled
material.
Large spills: Contact fire and emergency services and
supplier for advice.
13. REFERENCES
ACGIH (1986) Threshold limit values for chemical substances
and physical changes and biological exposure indices. Cincinnati,
Ohio, American Conference of Governmental Industrial Hygienist,
pp 26.
Alexeef GV, Kilgore WW (1983) Methyl bromide In: Gunther FA., &
Gunther JD., ed. Residue reviews. Residues of pesticides and other
contaminants in the total environment, Vol 88, New York,Springer
Verlag , pp 102-153.
Baselt R (1982) Disposition of Toxic Drugs and Chemicals in Man,
2nd. Ed. Biochemical Publications, Davis, California,
pp 516-517.
Benatt, AJ,Courtney TRB (1948) Uraemia in methyl bromide
poisoning. A case report. Brit. J. Ind. Med. 5: 21-25
Bradford JC (1990) Methyl bromide and related compounds. In:
Haddad LM and Winchester JF, eds. Clinical Management of
Poisoning and Drug Overdose. 2nd. ed. Philadelphia: W B Saunders
Company.
Cavanagh JB (1992) Methyl bromide intoxication and acute energy
deprivation syndromes . Neuropathol. Appl. Neurobiol,
18: 573-578.
Chavez CT, Hepler RS, Straatsma BR (1985) Methyl Bromide optic
atrophy. Am J Ophthalmol 99: 715-19
CCOHS (1992) CHEMINFO Canadian Centre for Occupational Health and
Safety
EHC (1994) Environmental Health Criteria (EHC) for Methyl
bromide, draft for Editor, IPCS/UNEP/ILO/WHO
Ellenhorn MJ & Barceloux DG (1988) Medical Toxicology. Diagnosis
and Treatment of Human Poisoning. New York, Elsevierr, p957.
FAO/WHO (1988a) Pesticide residues in food. Report of the Joint
Meeting of the FAO Panel of Experts on Pesticide Residues in Food
and the Environment and the WHO Expert Group on Pesticide
Residues. FAO Plant Production and Protection Paper 92.
FAO/WHO (1988b) Pesticide residues in food - 1988 evaluations.
Part II- Toxicology. FAO Plant Production and Protection Paper
93/2.
Gosselin RE, Smith RP and Hodge HC (1984) Clinical toxicology of
commercial products . 5th ed. William & Wilkins,
pp III-280, III-284, II-158.
Hayes W Jr, Laws E Jr (1991) Handbook of Pesticide Toxicology,
Vol 2 , Chapter 14, Academic Press Inc, pp 668-671.
Hine CH (1969) Methyl bromide poisoning - a review of ten cases.
J. Occup. Med, 11(1): 1-10.
Honma T., Miyagawa M, Sato M, & Hasegawa H (1985) Neurotoxicity
and metabolism of methyl bromide in rats. Toxicol. Appl.
Pharmacol., 81: 183-191
Hustinx WNM, Van de Laar RTH, Van Huffelen AC, Verwey JC,
Meulenbelt J, Savelkoul TJF (1993) Systemic effects of
inhalational methyl bromide poisoning: a study ot nine cases
occupationally exposed due to inadvertent spread during
fumigation. Br J Indus Med, 50: 155-159
IARC (1986) Monographs on the evaluation of the carcinogenic risk
of chemicals to humans: some halogenated hydrocarbons and
pesticide exposure Vol 41, pp 187-212.
Iwasaki K, Ito I, Kagawa J (1989) Biological exposure monitoring
of methyl bromide workers by determination of haemoglobin adducts.
Indust. Health 27, pp 181-183
Kantarjian AD, Shaheen AS (1963) Methyl bromide poisoning with
nervous system manifestation resembling polyneuropathy. Neurology
13: 1054-1058.
Marraccini JV, Thomas GE, Ongley JP, Pfaffenberger D, Davis JH,
Bednarczyk LR (1983) Death and injury caused by methyl bromide,
an insecticide fumigant. J. Foren. Sci. Soc. 28: 601-607
NIOSH (1984) Current Intelligence Bulletin : monohalomethanes:
methyl chloride, methyl bromide, methyl iodide. National Institute
for Occupational Safety and Health, 42: 1-22 Sept. 27
Raabe OG (1986) Inhalation uptake of selected vapors by people.
Laboratory for Energy-related Health Research, University of
California, Davis, (ISS ARB-R 88/338) Order-No PB-88 202726 Final
Report August 1986 - March 1988) 94 pages
Uncini A, Basciani M, Di Muzio A, Antonini D, Onofri M (1990)
Methyl bromide myoclonus: an electro physiological study. Acta
Neurol Scand. 81: 159-164
Verberk MM, Rooyakkers-Beemster T, De Vlieger M, Van Vliet AGM
(19??) Bromine in blood, EEG and transaminases in methyl bromide
workers. Br. J. Ind. Med. 36: 59-62
Windholz M (1983) Merck Index: an encyclopedia of chemicals,
drugs, and biologicals. 10th Edition, Merck & Co., Inc. Rahway,
N.J.
Zatuchni J, Hong K (1981) Methyl bromide poisoning seen initially
as psychosis. Arch Neurol, 38:529-530
14. AUTHOR(S), REVIEWER(S), ADDRESS(ES), UPDATE(S)
Author: Dr M.C. Alonzo
Departamento de Toxicologia & Centro de Informacion y
Asesoramiento Toxicologico
Hospital de Clinicas "Dr. M. Quintela"
7°piso
Avda. Italia s/n
Montevideo
Uruguay
Tel: 598-2-470300/804000
Fax: 598-2-470300
Date: March 1995
Peer review: Cardiff, United Kingdom, March 1995
(Group members: Dr C. Alonzo, Dr M. Balali-
Mood,
Dr R. Fernando, Dr Z. Kolacinski, Ms M.
McFarland,
Dr J. Szajewski, Dr W. Temple)
Finalised: IPCS, September 1996