The following information has been extracted from our CHEMINFO database, which also contains hazard control and regulatory information. [More about...] [Sample Record]

Access the complete CHEMINFO database by contacting CCOHS Client Services.

 
SECTION 1. CHEMICAL IDENTIFICATION

CHEMINFO Record Number: 643
CCOHS Chemical Name: Bromoform

Synonyms:
Methane tribromide
Methenyl tribromide
Methyl tribromide
Tribromomethane

Chemical Name French: Bromoforme
Chemical Name Spanish: Bromoformo
CAS Registry Number: 75-25-2
UN/NA Number(s): 2515
RTECS Number(s): PB5600000
EU EINECS/ELINCS Number: 200-854-6
Chemical Family: Halogenated aliphatic hydrocarbon / saturated halogenated hydrocarbon / halocarbon / halogenated alkane / haloalkane / trihaloalkane / haloform / bromoalkane / tribromoalkane / brominated methane
Molecular Formula: C-H-Br3
Structural Formula: CHBr3

SECTION 2. DESCRIPTION

Appearance and Odour:
Colourless to yellow liquid with a sweet, suffocating, chloroform-like odour.(21,25) Lachrymator (vapour irritates the eyes and causes tears).(1)

Odour Threshold:
A wide range of values have been reported; 0.19 to 15 ppm.(21)

Warning Properties:
NOT RELIABLE - odour threshold equal to or greater than the TLV.

Composition/Purity:
Bromoform is available commercially in grades of greater than 95% to greater than 99%. Bromoform frequently contains stabilizers to prevent oxidation by air and light. The most common stabilizers used include ethanol (up to 3-4%), amylenes (0.05%), and diphenylamine.(7,22,23)

Uses and Occurrences:
Bromoform has only limited uses. It is used in geological assaying for mineral ore separation; in the electronics industry in quality assurance programs, and as a laboratory reagent. It has been used as a catalyst, initiator, or sensitizer in polymer reactions and in the vulcanization of rubber; as a solvent for waxes, greases, oils, liquid-solvent extractions and nuclear magnetic resonance.(5,7)
It was formerly used as an ingredient in fire-resistant chemicals and gauge fluids; as a chemical intermediate in organic synthesis; and a sedative, antitussive agent and an antiseptic.(4,5)


SECTION 3. HAZARDS IDENTIFICATION

EMERGENCY OVERVIEW:
Colourless to yellow liquid with a sweet, suffocating, chloroform-like odour. Lachrymator. Will not burn. Can decompose at high temperatures forming toxic and corrosive gases such as hydrogen bromide and bromine. Closed containers may rupture and explode if heated, releasing toxic gases or vapours. Forms impact sensitive compounds with alkali metals, such as lithium, potassium, sodium or sodium-potassium alloy. TOXIC. May be harmful if swallowed. The vapour may irritate the nose and upper respiratory tract. May be a mild central nervous system depressant. High vapour concentrations may cause headache, nausea, dizziness, drowsiness, incoordination and confusion. May cause skin and eye irritation.



POTENTIAL HEALTH EFFECTS

Effects of Short-Term (Acute) Exposure

Inhalation:
The vapour may irritate the nose and throat, based on limited human information. High concentrations may cause symptoms of mild central nervous depression (tiredness, headache, dizziness and unconsciousness) and liver injury, based on very limited animal information.
A historical report indicates the vapour caused local irritation of the respiratory tract and throat.(1)

Skin Contact:
The liquid may cause moderate irritation, based on limited animal information. There is no human information available.
Limited animal information suggests that bromoform can be absorbed through the skin. It is not known if harmful effects would occur due to exposure by this route.

Eye Contact:
The liquid may be a moderate irritant, based on limited animal information. A historical report indicates the vapour can irritate the eye causing tearing (lachrymation).(1)

Ingestion:
There are case reports involving ingestion of bromoform by children. Central nervous system (CNS) depression characterized by listlessness, headache and dizziness was observed. In severe cases, coma and loss of reflexes has occurred. Respiratory failure and death may follow severe exposure.(1) Ingestion is not a common route of exposure in the workplace.

Effects of Long-Term (Chronic) Exposure

There are no reported long-term effects in humans. However, information from animal studies suggests that bromoform may cause liver injury.

Carcinogenicity:

There is no relevant human information available. The International Agency for Research on Cancer (IARC) has determined there is limited evidence of the carcinogenicity of bromoform to experimental animals.(2)

The International Agency for Research on Cancer (IARC) has concluded that this chemical is not classifiable as to its carcinogenicity to humans (Group 3).

The American Conference of Governmental Industrial Hygienists (ACGIH) has designated this chemical as an animal carcinogen (A3).

The US National Toxicology Program (NTP) has not listed this chemical in its report on carcinogens.

Teratogenicity and Embryotoxicity:
There is insufficient information available to to conclude that bromoform is a developmental toxin.
There are two human studies that examined pregnancy outcomes in relation to bromoform and other trihalomethane levels in the drinking water. No significant associations were found between bromoform levels and the risk of premature babies or miscarriages.(19,47) A number of studies have examined the association between reproductive outcomes and trihalomethane exposure in drinking water. However, no bromoform exposure data is provided, so these studies are not reviewed here. The limited animal information available suggests that bromoform may cause developmental effects in the presence of maternal toxicity.

Reproductive Toxicity:
There is insufficient information available to conclude that bromoform is a reproductive toxin.
No conclusions can be drawn from a limited human study where the relationship between trihalomethanes in the drinking water and menstrual cycle function was examined.(48) This study is limited by exposure to other trihalomethanes. No significant reproductive effects were observed in the absence of toxicity in the parents in one 2-generation mouse study.
A number of studies have examined the association between reproductive outcomes and trihalomethane exposure in drinking water. However, no bromoform exposure data is provided, so these studies are not reviewed here.

Mutagenicity:
It is not possible to conclude that bromoform is mutagenic based on the available information. For live animals, there are negative results from studies in rats and mice and positive results from 2 limited studies in rats and mice. There have been several positive results but also some negative results from tests in cultured mammalian cells and bacteria. Positive and negative results have been obtained in fruit flies.

Toxicologically Synergistic Materials:
There is no information available.

Potential for Accumulation:
Bromoform is unlikely to accumulate. Bromoform is probably rapidly absorbed following oral and inhalation exposure and distributed to the liver, brain, kidneys, blood, lung, stomach and fat. Some bromoform is metabolized to tribromomethanol, which decomposes to dibromocarbonyl (the bromine analogue of phosgene). Dibromocarbonyl is highly reactive, and may undergo a number of reactions, including reaction with cellular nucleophiles to yield covalent adducts, hydrolysis to form carbon dioxide and reaction with glutathione to yield carbon monoxide. Absorbed bromoform is mainly eliminated unchanged or as carbon dioxide in the expired air. Small amounts (1-5% in rats) are eliminated as metabolites in the urine. The amount eliminated as carbon dioxide varies with the dose and the species. With oral exposure of rats, 67% bromoform was eliminated unchanged and 4% as carbon dioxide in expired air. With mice, 6% was eliminated unchanged and 40% as carbon dioxide in expired air.(4-7)


SECTION 4. FIRST AID MEASURES

Inhalation:
Remove source of contamination or move victim to fresh air. Obtain medical attention immediately.

Skin Contact:
As quickly as possible, flush with lukewarm, gently flowing water for at least 20 minutes or until the chemical is removed. Under running water, remove contaminated clothing, shoes and leather goods (e.g. watchbands, belts). Obtain medical attention immediately. Completely decontaminate clothing, shoes and leather goods before re-use or discard.

Eye Contact:
Immediately flush the contaminated eye(s) with lukewarm, gently flowing water for 20 minutes or until the chemical is removed, while holding the eyelid(s) open. Take care not to rinse contaminated water into the unaffected eye or onto the face. Obtain medical attention immediately.

Ingestion:
NEVER give anything by mouth if victim is rapidly losing consciousness, is unconscious or is convulsing. Have victim rinse mouth thoroughly with water. DO NOT INDUCE VOMITING. Have victim drink 240 to 300 mL (8 to 10 oz) of water to dilute material in stomach. If vomiting occurs naturally, rinse mouth and repeat administration of water. Obtain medical attention immediately.

First Aid Comments:
Provide general supportive measures (comfort, warmth, rest).
Consult a doctor and/or the nearest Poison Control Centre for all exposures except minor instances of inhalation or skin contact.
All first aid procedures should be periodically reviewed by a doctor familiar with the material and its conditions of use in the workplace.



SECTION 5. FIRE FIGHTING MEASURES

Flash Point:
Not flammable (does not burn).(20)

Lower Flammable (Explosive) Limit (LFL/LEL):
Not applicable

Upper Flammable (Explosive) Limit (UFL/UEL):
Not applicable

Autoignition (Ignition) Temperature:
Not applicable

Sensitivity to Mechanical Impact:
Probably not sensitive; normally stable material.

Sensitivity to Static Charge:
Bromoform will not accumulate static charge since it has a high electrical conductivity and is considered to be a conductive material.(22) Bromoform will not be ignited by a static discharge because it does not burn.

Electrical Conductivity:
Less than 2 X 10(6) pS/m at 25 deg C (24)

Combustion and Thermal Decomposition Products:
Hydrogen bromide and bromine gases, carbon monoxide, carbon dioxide, and other toxic and irritating compounds.

Fire Hazard Summary:
Bromoform does not burn. During a fire, toxic and/or corrosive gases, such as hydrogen bromide, bromine and carbon monoxide, may be generated. Closed containers may explode if exposed to excess heat for a sufficient period of time releasing large quantities of toxic gases or vapours.

Extinguishing Media:
Bromoform is not combustible. Use extinguishing media suitable for surrounding fire.

Fire Fighting Instructions:
If a fire occurs in the vicinity of containers of bromoform, evacuate area and fight fire from a safe distance or a protected location. Approach fire from upwind to avoid toxic bromoform and/or its decomposition products.
If possible, isolate materials not yet involved in the fire, move containers from the fire area if this can be done without risk, and protect personnel. Otherwise, fire-exposed containers or tanks should be cooled by application of water spray. Application should begin as soon as possible (within the first 5 minutes) and should concentrate on any unwetted portions of the container. Apply water from the side and from a safe distance until well after the fire is out. Stay away from the ends of tanks involved in the fire, but be aware that flying material from ruptured tanks may travel in any direction. Withdraw immediately in case of rising sound from venting safety device or any discolouration of tank due to fire. Water spray may be used to flush spills away and prevent exposure.
For a massive fire, it may be prudent to use unmanned hose holders or monitor nozzles and evacuate the area.

Protection of Fire Fighters:
The thermal decomposition products of bromoform are toxic and corrosive. Do not enter without wearing specialized protective equipment suitable for the situation. Firefighter's normal protective equipment (Bunker Gear) will not provide adequate protection. Chemical protective clothing (e.g. chemical splash suit) and positive pressure self-contained breathing apparatus (NIOSH approved or equivalent) may be necessary.



NATIONAL FIRE PROTECTION ASSOCIATION (NFPA) HAZARD IDENTIFICATION

NFPA - Comments:
NFPA has no listing for this chemical in Codes 49 or 325.


SECTION 9. PHYSICAL AND CHEMICAL PROPERTIES

Molecular Weight: 252.77

Conversion Factor:
1 ppm = 10.3 mg/m3; 1 mg/m3 = 0.097 ppm at 25 deg C (calculated)

Physical State: Liquid
Melting Point: 8.0-8.5 (46.4-47.3 deg F) (5,38)
Boiling Point: 149.5 deg C (301 deg F) (23,27)
Relative Density (Specific Gravity): 2.90 at 15 deg C (26); 2.89 at 20 deg C (23,29); 2.88 at 25 deg C (29) (water = 1)
Solubility in Water: Slightly soluble (approximately 300 mg/100 g at 20-25 deg C) (28,38)
Solubility in Other Liquids: Soluble all proportions in ethanol, acetone, diethyl ether, methanol, petroleum ether, and ligroin; soluble in benzene, chloroform and solvent naphtha.(4,5,24,35)
Coefficient of Oil/Water Distribution (Partition Coefficient): Log P(oct) = 2.40 (experimental) (30)
pH Value: Not available
Viscosity-Dynamic: 2.15 mPa.s (2.15 centipoises) at 15 deg C; 1.74 mPa.s (1.74 centipoises) at 30 deg C (24,29)
Viscosity-Kinematic: 0.74 mm2/s (0.74 centistokes) at 15 deg C (calculated)
Saybolt Universal Viscosity: 28.1 Saybolt Universal Seconds at 37.8 deg C (100 deg F) (calculated)
Surface Tension: 46.18 mN/m (46.18 dynes/cm) at 15 deg C; 44.87 mN/m (44.87 dynes/cm) at 25 deg C (31)
Vapour Density: 8.72 (air = 1) (calculated)
Vapour Pressure: 0.667 kPa (5 mm Hg) at 20 deg C (28); 0.747 kPa (5.6 mm Hg) at 25 deg C (27)
Saturation Vapour Concentration: 6600 ppm (0.66%) at 20 deg C; 7400 ppm (0.74%) at 25 deg C (calculated)
Evaporation Rate: Not available
Henry's Law Constant: 68 Pa.m3/mol (cited as log H = -1.56 (dimensionless)) at 25 deg C (experimental) (37); 43.6 Pa.m3/mol at 20 deg C (experimental) (38); log H = -1.75 (dimensionless constant; calculated)

Other Physical Properties:
DIELECTRIC CONSTANT: 4.39 at 20 deg C (24)


SECTION 10. STABILITY AND REACTIVITY

Stability:
Stable under normal conditions. Gradually decomposes on standing, acquiring a yellow colour. Air, light and or heat accelerate the decomposition.(35) Normally stabilized to prevent oxidation.

Hazardous Polymerization:
Does not occur.

Incompatibility - Materials to Avoid:

NOTE: Chemical reactions that could result in a hazardous situation (e.g. generation of flammable or toxic chemicals, fire or detonation) are listed here. Many of these reactions can be done safely if specific control measures (e.g. cooling of the reaction) are in place. Although not intended to be complete, an overview of important reactions involving common chemicals is provided to assist in the development of safe work practices.


ALKALI METALS (e.g. lithium, potassium, sodium or sodium-potassium alloy) - form shock-sensitive mixtures which can explode with great violence on light impact.(32,33)
ACETONE/POTASSIUM HYDROXIDE - acetone mixed with bromoform in the presence of a powdered strong base, such as potassium hydroxide, can react violently, giving off heat.(32)
REACTIVE METAL POWDERS (e.g. aluminum, magnesium, zinc and their alloys) - can react explosively.(22)
NITROMETHANE or CYCLIC POLYETHYLENE OXIDES/POTASSIUM HYDROXIDE - mixtures can explode.(32)

Hazardous Decomposition Products:
No information available.

Conditions to Avoid:
Excessive heat, open flames, hot surfaces, welding arc, electric arc, or other high temperature sources which may cause thermal decomposition, sunlight, depletion of stabilizers

Corrosivity to Metals:
Dry, stabilized bromoform is not corrosive to any of the common construction materials. Cast iron, steel, stainless steel (e.g. types 304, 316, 12 Cr and 17 Cr), aluminum, copper, bronze, brass, nickel and its alloys, tantalum, titanium and zirconium have good resistance (less than 0.5 mm/year (less than 20 mils/year)).(34) Wet bromoform is corrosive to steel and gray cast iron at 25 deg C (corrosion rate of greater than 1.270 mm/year (50 mils/year)).(34)

Corrosivity to Non-Metals:
Bromoform attacks plastics, like polyvinyl chloride (PVC), chlorinated polyvinyl chloride (CPVC), polypropylene, nylon, high-density polyethylene (HDPE), polystyrene and polysulfone.(49) Bromoform does not attack Teflon and other fluorocarbons, like polyvinylidene fluoride (Kynar), and polyvinylidene chloride (Saran).(49)


SECTION 11. TOXICOLOGICAL INFORMATION

Lethal concentration (rat): 437 ppm (4-hour exposure); cited as 4500 mg/m3 (4-hour exposure) (8, unconfirmed)

LD50 (oral, rat): 933 mg/kg (4)
LD50 (oral, mouse): 707 mg/kg (4)

Eye Irritation:

Unconfirmed information suggests that bromoform is a moderate irritant.

Undiluted liquid was moderately irritating to rabbits; complete healing occurred within 1 to 2 days.(8 citing unpublished data)

Skin Irritation:

Unconfirmed information suggests that bromoform is a moderate irritant.

Repeated contact with bromoform was moderately irritating to rabbit skin.(8, unconfirmed)

Effects of Short-Term (Acute) Exposure:

Bromoform has caused central nervous system (CNS) depression in animals exposed to oral doses of 600 mg/kg/day and higher. Liver injury has been observed following oral exposure to doses as low as 200 mg/kg/day for 9 days or 60 mg/kg/day for 1 month. Kidney injury has been observed following oral exposure to 145 mg/kg/day for 14 days. Limited information suggests that similar effects would occur following inhalation or skin contact with high concentrations.

Inhalation:
A dog exposed by inhalation to 20 mL of bromoform in an enclosed area (reported to produce a saturated atmosphere of 7000 ppm) became very excited initially, then became unconscious after 8 minutes, and died within 60 minutes. Similar effects were observed in a dog given two exposures. Examination of the dead animals revealed liver injury and signs of respiratory irritation.(9) Bromoform was described as a narcotic when rabbits were exposed to 11-13 mg/L (1070-1270 ppm), for an unspecified durations. Bromoform was described as a narcotic when rabbits were exposed once to 1064-1741 ppm for an unspecified duration.(8) In a study, which is not available in English, exposure of rats to 240 ppm for 10 days resulted in central nervous system effects, dystrophic and vascular changes in the liver and kidney. There were changes in liver metabolism and in filtration capacity of the kidneys.(5,8-unconfirmed)

Skin Contact:
A 2000 mg/kg dose of undiluted bromoform was held against the unbroken skin of rabbits for 24 hours. No deaths occurred but tiredness (lethargy) and a slight weight loss were noted.(8, unconfirmed)

Ingestion:
Signs of central nervous system (CNS) depression (e.g. lethargy, sedation, muscular incoordination) and minor organ injury (enlarged and congested livers and kidneys) were seen in a rat LD50 study (oral doses of 546-2100 mg/kg).(10) CNS depression was noted in rats and mice exposed to 600 mg/kg/day and higher in corn oil by gavage for up to 14 days. All rats given 600 mg/kg/day and higher died by day 7. Liver effects were reported in female rats exposed to 200 mg/kg/day for 9 days, while kidney effects were reported in male mice exposed to 145 mg/kg/day for 14 days.(4) Mice were given 50, 125 or 250 mg/kg/day bromoform by gavage for 14 days. At 125 mg/kg/day and higher, there was a significant increase in liver weight in males. At 250 mg/kg/day, there was a significant increase in liver weight in females and for both sexes in an enzyme that indicates liver damage.(11) Female mice were given 200 or 500 mg/kg/day bromoform by gavage in corn oil for 9 of 11 days or 300 mg/kg/day in drinking water for 11 days. For gavage administration, there was a dose-related increase in relative liver weight, which was significant at both doses. In the drinking water, there was no increase in relative liver weight. A dose-related increase in liver toxicity was significant for all doses/administrations of bromoform.(39) Male mice were given 0, 72, 145 or 289 mg/kg/day bromoform in corn oil by gavage for 14 days. Mice given 280 mg/kg for 14 days had focal inflammation in the liver and a significant increase in an enzyme indicating liver damage. At 145 and 280 mg/kg/day, there was kidney injury (degenerative changes, enlargement in the kidneys and a significant decrease in the uptake of organic ions).(40) No toxic effects, except a slight increase in kidney weight in the high dose group, were observed in male rats following ingestion, for 28 days, of drinking water containing 5-500 ppm (estimated doses of 0.7-80 mg/kg/day).(12) In a one month study, bromoform was administered in the diet of rats, microencapsulated in gelatin-starch syrup to compensate for its low solubility. Estimated doses were 60, 190 and 620 mg/kg for males and 60, 210 and 730 mg/kg for females. Liver lesions (vacuolization and swelling of liver cells) were significantly increased in both sexes of all groups.(13)

Effects of Long-Term (Chronic) Exposure:

The available information suggests that long-term inhalation or ingestion exposure could result in liver injury. In one study, significant liver injury (fatty degeneration, chronic inflammation) was observed in rats given oral doses of 100 mg/kg/day for 103 weeks.

Inhalation:
In a study, which is not available in English, exposure of rats to 24 ppm for 2 months resulted in decreased blood clotting, impaired glycogen metabolism in the liver and in impaired kidney function. Exposure to 2.4 ppm for 2 months caused no effects.(5,8,unconfirmed)

Ingestion:
In a 13-week study, minor liver injury (vacuolization of liver cells) was observed in male rats given oral doses of 50-200 mg/kg/day and in male mice given 200 or 400 mg/kg/day. Similar effects were not observed in female rats or mice. All male rats exposed to 100 or 200 mg/kg/day and all female rats exposed to 200 mg/kg/day were lethargic. More severe liver injury (fatty degeneration, chronic inflammation) was seen in male and female rats given oral doses of 100 or 200 mg/kg/day for 103 weeks. Liver tissue death (necrosis) incidence was increased in male rats but decreased in females at the 200 mg/kg dose level.(4) Male F344 rats and male B6C3F1 mice developed changes indicative of kidney injury (glomerular and proximal tubule damage) following exposure to bromoform in drinking water (approximately 20, 100 and 200 mg/kg/day; cited as 0.12, 0.6 and 1.2 g/L - rats; approximately 20, 90 and 170 mg/kg/day; cited as 0.08, 0.4 or 0.8 g/L - mice) for 52 weeks.(14) This study is reported in an abstract and no further details are available.

Carcinogenicity:
The International Agency for Research on Cancer (IARC) has determined that there is limited evidence for the carcinogenicity of bromoform to experimental animals.(2)
Some evidence (a large number of tumours in the large intestine) of carcinogenicity was observed in male rats given daily oral doses of bromoform, and clear evidence of carcinogenicity was observed in female rats given daily oral doses of bromoform for 2 years. No evidence of carcinogenicity was seen in mice similarly dosed for 2 years.(4) Repeated injections (3 injections a week for a total of 24) into the stomach cavity of mice produced a significant increase in lung tumours.(15) No conclusions can be drawn from this study since the relevance of this route of exposure is not relevant.

Teratogenicity, Embryotoxicity and/or Fetotoxicity:
The limited information available suggests that bromoform may cause developmental effects in the presence of maternal toxicity.
Oral doses of 50, 100 or 200 mg/kg/day given in corn oil during days 6-15 of pregnancy did not cause teratogenic effects or maternal toxicity in rats. Some fetotoxicity (skeletal abnormalities) was observed in pups from the high dose group.(16) A statistical analysis of the data was not reported, however an independent analysis indicated a significant increase in aberrations of the segments of the sternum (sternebra).(5) These are considered to be minor skeletal variations. In a study reported by abstract, female mice were orally dosed with 0, 25, 50, 100, 200, 400, 600 or 800 mg/kg/day from day 6-15 of pregnancy. Maternal toxicity, as evidenced by decreased motor activity, was present at 200 mg/kg/day and higher. Reduced pup weights at 6 days after birth were noted following exposure to 800 mg/kg/day. At 400 and 800 mg/kg/day, there were individual cases of pups with the brain outside the skull (exencephaly).(41) There are insufficient details available to evaluate this report.

Reproductive Toxicity:
No significant reproductive effects were observed in the absence of toxicity in the parents in one 2-generation ingestion study using mice.
In a 2-generation study, mice were given bromoform in corn oil orally at doses of 0, 50, 100 or 200 mg/kg. There were no adverse effects on fertility. A slight decrease in neonatal survival (F1) was observed in the high dose group, only in the first 4 days after birth. This dose also produced toxicity in the parents.(17) No effects on the reproductive organs of rats and mice were observed in a 2-year study with oral doses of 100 or 200 mg/kg/day.(4) Male rats orally given 190 or 380 mg/kg/day bromoform in a polyoxyethylated vegetable oil for 7 days showed a significant decrease in testosterone levels at 380 mg/kg/day.(42) There was no evaluation of the effect on fertility and this dose is expected to produce liver toxicity.

Mutagenicity:
It is not possible to conclude that bromoform is mutagenic based on the available information. For live animals, there are negative results from studies using rats and mice and positive results from 2 limited studies using rats and mice. There have been several positive results but also some negative results from tests using cultured mammalian cells and bacteria. Positive and negative results have been obtained in fruit flies.
Negative results (micronuclei in mouse bone marrow cells, unscheduled DNA synthesis in rat liver cells) were obtained following single oral doses of 0, 250, 500 or 1000 mg/kg in mice and 0, 324 or 1080 mg/kg in rats.(43) Negative results (DNA strand breaks in kidney cells) were obtained in rats orally dosed with 190 or 380 mg/kg/day for 7 days.(42) Positive results (sister chromatid exchanges (SCEs) in bone marrow cells) were obtained in mice exposed orally to 25 or 200 mg/kg/day bromoform in olive oil for 4 days.(3) This study is limited by the small numbers of animals (4/group). Positive results (chromosomal aberrations in bone marrow cells) were obtained in a study where male rats were orally exposed to 2.5, 25 or 253 mg/kg/day for 5 days. There was a dose-related increase with significance at 253 mg/kg/day.(18) This study is limited by low animal numbers (3/group). Intraperitoneal exposure caused an increase in SCEs and micronuclei, but not chromosomal aberrations, in bone marrow cells in mice.(4) This exposure route is not relevant to occupational exposure.
There have been several in vitro studies with bromoform with mixed results. Positive results (DNA damage, SCEs) were obtained in cultured human cells, without metabolic activation.(3,44) Positive results (SCEs) were also obtained in cultured mammalian cells, with and without metabolic activation. However, the response was reduced by metabolic activation.(4,45) Positive results (gene mutation, SCEs, chromosome aberrations) were obtained in cultured mammalian cells, in the absence of metabolic activation. In the presence of metabolic activation, positive results were still obtained for gene mutations but not for SCEs or chromosome aberrations.(4) Positive and negative results (gene mutation) have been obtained in bacteria, with and without metabolic activation. (4,5-unconfirmed,46)
Positive and negative results have been obtained in fruit flies (Drosophila).(4,5-unconfirmed)


SECTION 16. OTHER INFORMATION

Selected Bibliography:
(1) Von Oettingen, W.F. Bromoform. In: The halogenated aliphatic, olefinic, cyclic, aromatic and aliphatic-aromatic hydrocarbons including the halogenated insecticides: their toxicity and potential dangers. US Government Printing Office (1955). p. 65-67
(2) International Agency for Research on Cancer (IARC). Bromoform. In: IARC monographs on the evaluation of carcinogenic risks to humans. Vol. 71, parts 1, 2 and 3. Re-evaluation of some organic chemicals, hydrazine and hydrogen peroxide. World Health Organization, 1999. p. 1309-1316
(3) Morimoto, K., et al. Trihalomethanes induce sister chromatid exchanges in human lymphocytes in vitro and mouse bone marrow cells in vivo. Environmental Research. Vol. 32 (1983). p. 72-79
(4) US National Toxicology Program (NTP). NTP technical report on the toxicology and carcinogenesis studies of tribromomethane (bromoform) (CAS No. 75-25-2) in F344/N rats and B6C3F1 mice. NTP TR 350. US Department of Health and Human Services, May 1989
(5) Agency for Toxic Substances and Disease Registry. Draft toxicological profile for bromoform and dibromochloromethane. US Department of Health and Human Services, Sept. 2003
(6) Ahmed, A.E., et al. Halogenated methanes : metabolism and toxicity. Federation Proceedings. Vol. 39, no. 13 (Nov. 1980). p. 3150-3155
(7) International Agency for Research on Cancer (IARC). Bromoform. In: IARC monographs on the evaluation of carcinogenic risks to humans. Vol. 52. Chlorinated drinking-water; chlorination by-products; some other halogenated compounds; cobalt and cobalt compounds. World Health Organization, 1991. p. 213-242
(8) Reid, J.B. Saturated methyl halogenated aliphatic hydrocarbons. In: Patty's toxicology. 5th ed. Edited by E. Bingham, et al. Vol. 5. (Chapter 62). John Wiley and Sons, 2001
(9) Marzbach, L. The pharmacology of methyl bromide and related compounds. Zeitschrift fuer die Gesamte Experimentelle Medizin. Vol. 63, no. 3/4 (1929). p. 383- 392
(10) Chu, I., et al. The acute toxicity of four trihalomethanes in male and female rats. Toxicology and Applied Pharmacology. Vol. 52, no. 2 (Feb. 1980). p. 351- 353
(11) Munson, A.E., et al. Toxicology of organic drinking water contaminants: trichloromethane, bromodichloromethane, dibromochloromethane and tribromomethane. Environmental Health Perspectives. Vol. 46 (1982). p. 117-126
(12) Chu, I., et al. Toxicity of trihalomethanes: I. The acute and subacute toxicity of chloroform, bromodichloromethane, chlorodibromomethane and bromoform in rats. Journal of Environmental Science and Health (Part B). Vol. B17, no. 3 (Sept. 30, 1982). p. 205-224
(13) Aida, Y., et al. Toxicities of microencapsulated tribromomethane, dibromochloromethane and bromodichloromethane administered in the diet to Wistar rats for one month. The Journal of Toxicological Sciences. Vol. 17 (1992). p. 119-133
(14) Moore, T.C., et al. Renal toxicity of bromodichloromethane (BDCM) and bromoform (TBM) administered chronically to rats and mice in drinking water. Abstract. Toxicologist. Vol. 14 (1994). p. 281
(15) Theiss, J.C., et al. Test for carcinogenicity of organic contaminants of United States drinking waters by pulmonary tumor response in strain A mice. Cancer Research. Vol. 37, no. 8 (1977). p. 2717-2720
(16) Ruddick, J.A., et al. A teratological assessment of four trihalomethanes in the rat. Journal of Environmental Science and Health. Vol. B18, no. 3 (July 21, 1983). p. 333-349
(17) Chapin, R.E., et al. Reproductive assessment by continuous breeding: evolving study design and summaries of ninety studies. Environmental Health Perspectives. Vol. 105, suppl. 1 (Feb. 1997). p. 199-205, 277-278
(18) Fujie, K., et al. Acute and subacute cytogenetic effects of the trihalomethanes on rat bone marrow cells in vivo. Mutation Research. Vol. 242 (1990). p. 111-119
(19) Kramer, M.D., et al. The association of waterborne chloroform with intrauterine growth retardation. Epidemiology. Vol. 3, no. 5 (1992). p. 407-413
(20) Bromoform. Hawley's condensed chemical dictionary. [CD-ROM]. 14th ed. Edited by R.J. Lewis, Sr. John Wiley and Sons, Inc., 2002
(21) Odor thresholds for chemicals with established occupational health standards. American Industrial Hygiene Association, 1989. p. 13, 47
(22) Britton, LG. Using material data in static hazard assessment. Plant/Operations Progress. Vol. 11, no. 2 (Apr. 1992). p. 56-70
(23) Ioffe, D., et al. Bromine, organic compounds: aliphatic bromine compounds: tribromomethane. In: Kirk-Othmer encyclopedia of chemical technology. John Wiley and Sons, 2002. Available at: <mrw.interscience.wiley.com/kirk/kirk_search_fs.html> (Subscription required)
(24) Dean, J.A. Lange's handbook of chemistry. 15th ed. McGraw-Hill, Inc., 1999. p. 1.326, 5.103, 5.127, 8.161
(25) Bromoform. In: NIOSH pocket guide to chemical hazards. National Institute for Occupational Safety and Health, June 1997
(26) Forsberg, K., et al. Quick selection guide to chemical protective clothing. 4th ed. Van Nostrand Reinhold, 2002
(27) Mackay, D., et al. Physical-chemical properties and fate of volatile organic compounds: an application of the fugacity approach. In: Significance and treatment of volatile organic compounds in water supplies. Edited by N.M. Ram, et al. Lewis Publishers Inc., 1990. p. 183-204
(28) Mabey, W., et al. Aquatic fate process data for organic priority pollutants. EPA Report, No. 440/4-81-14. US Environmental Protection Agency, 1982. p. 183-184
(29) Riddick, J.A., et al. Organic solvents: physical properties and methods of purification. Techniques of chemistry. Vol. II. 4th ed. John Wiley and Sons, 1986. p. 539-541
(30) Syracuse Research Corporation. Interactive LogKow (KowWin) Database Demo. Date unknown. Available at: <syrres.com/esc/kowdemo.htm>
(31) Jasper, J.J. Surface tension of pure liquid compounds. In: Compilation of data of some 2200 pure liquid compounds. Journal of Physical and Chemical Reference Data. Vol. 1, no. 4 (1972). p. 859
(32) Bretherick's reactive chemical hazards database. [CD-ROM]. 6th ed. Version 3.0. Edited by P.G. Urben. Butterworth-Heinemann Ltd., 1999
(33) Fire protection guide to hazardous materials. 13th ed. Edited by A.B. Spencer, et al. National Fire Protection Association, 2002. NFPA 491
(34) Corrosion data survey: metals section. 6th ed. National Association of Corrosion Engineers, 1985. p. 24-3 to 25-3
(35) Bromoform. The Merck index: an encyclopedia of chemicals, drugs and biologicals. Edited by M.J. O'Neil, et al. 13th ed. Merck and Company, 2001. p. 237
(36) European Communities. Commission Directive 96/54/EC. July 30, 1996
(37) Hine, J. et al. The intrinsic hydrophilic character of organic compounds. Correlations in terms of structural contributions. Journal of Organic Chemistry. Vol. 40, no. 3 (1975). p. 292-298
(38) Mackay, D. et al. Physical-chemical properties & environmental fate handbook. [CD-ROM]. Chapman & Hall/CRCnetBase, 2000
(39) Coffin, J.C., et al. Effect of trihalomethanes on cell proliferation and DNA methylation in female B6C3F1 mouse liver. Toxicological Sciences. Vol. 58, no. 2 (2000). p. 243-252
(40) Condie, L.W., et al. Comparative renal and hepatotoxicity of halomethanes: bromodichloromethane, bromoform, chloroform, dibromochloromethane and methylene chloride. Drug and Chemical Toxicology. Vol. 6, no. 6 (1983). p. 563-578
(41) Narotsky, M.G., et al. Developmental effects of disinfectant by-products bromoform, bromodichloromethane, bromodichloroacetic acid and bromochloroacetic acid in mice. [Abstract]. Teratology. Vol. 63, no. 6 (2001). p. 279
(42) Potter, C.L., et al. Effects of four trihalomethanes on DNA strand breaks, renal hyaline droplet formation and serum testosterone in male F-344 rats. Cancer Letters. Vol. 106 (1996). p. 235-242
(43) Stocker, K.J., et al. Assessment of the potential in vivo genotoxicity of three halomethanes: chlorodibromomethane, bromodichloromethane and bromoform. Mutagenesis. Vol. 12, no. 3 (1997). p. 169-173
(44) Landi, S., et al. Induction of DNA strand breaks by trihalomethanes in primary human lung epithelial cells. Genetic Toxicology and Environmental Mutagenesis. Vol. 538 (2003). p. 41-50
(45) Fujie, K., et al. Sister-chromatid exchanges induced by trihalomethanes in rat erythroblastic cells and their suppression by crude catechin extracted from green tea. Mutation research. Vol. 300 (1993). p. 241-246
(46) Kargalioglu, Y., et al. Analysis of the cytotoxicity and mutagenicity of drinking water disinfection by-products in Salmonella typhimurium. Teratogenesis, Carcinogenesis, and Mutagenesis. Vol. 22 (2002). p. 113-128
(47) Waller, K., et al. Trihalomethanes in drinking water and spontaneous abortion. Epidemiology. Vol. 9, no. 2 (1998). p. 134-140
(48) Windham, G.C., et al. Chlorination by-products in drinking water and menstrual cycle length. Environmental Health Perspectives. Vol. 111, no. 7 (June 2003). p. 935-941
(49) Pruett, K.M. Chemical resistance guide for plastics: a guide to chemical resistance of engineering thermoplastics, fluoroplastics, fibers and thermoset resins. Compass Publications, 2000. p. 62-73
(50) Occupational Safety and Health Administration (OSHA). Organic Vapour. In: OSHA Analytical Methods Manual. Revision Date: Oct. 31, 2001. Available at: <osha-slc.gov/dts/sltc/methods/toc.html>
(51) National Institute for Occupational Safety and Health (NIOSH). Hydrocarbons, halogenated. In: NIOSH Manual of Analytical Methods (NMAM(R)). 4th ed. Edited by M.E. Cassinelli, et al. DHHS (NIOSH) Publication 94-113. Aug. 1994. Available at: <cdc.gov/niosh/nmam/nmammenu.html>

Information on chemicals reviewed in the CHEMINFO database is drawn from a number of publicly available sources. A list of general references used to compile CHEMINFO records is available in the database Help.


Review/Preparation Date: 2005-02-15



©2007 Canadian  Centre  for  Occupational  Health  &  Safety  
www.ccohs.ca  E-mail: clientservices@ccohs.ca  Fax: (905) 572-2206  Phone: (905) 572-2981  
Mail:  250  Main  Street  East,  Hamilton  Ontario  L8N  1H6