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BROMOFORM

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Bromoform is a brominated trihalomethane, a low-molecular-weight halogenated hydrocarbon. It is in the chemical family of brominated alkanes. The trihalomethanes (chloroform, bromoform, bromodichloromethane, dibromochloromethane) are formed as by-products of chlorine disinfection and are found to occur in combination in drinking water supplies. Bromoform is a mild anesthetic and is found as a contaminant in drinking water supplies. When heated to decomposition, it emits highly toxic fumes of bromine.

Specific Substances

    1) Bromoforme
    2) Formyl tribromide
    3) Methane, tribromo-
    4) Methenyl tribromide
    5) Methyl tribromide
    6) Tribromomethane
    7) Molecular Formula: C-H-Br3
    8) CAS 75-25-2
    9) BROMOFORMIO
    10) TRIBROMMETHAAN
    11) TRIBROMMETHAN
    12) TRIBROMOMETAN
    1.2.1) MOLECULAR FORMULA
    1) C-H-Br3

Available Forms Sources

    A) FORMS
    1) The commercial preparation is generally preserved by the addition of 3% to 4% alcohol (Budavari, 1996). Bromoform is a colorless to yellow, nonflammable, heavy liquid, or hexagonal crystals, with a chloroform-like odor and a sweetish chloroform-like taste. The odor should not be considered as a warning property (Bingham et al, 2001). Although bromoform will not burn, its fumes will be a toxicity problem if involved in a fire caused by other materials or if heated past its boiling point.
    B) SOURCES
    1) Bromoform can be prepared from a reaction between acetone and sodium hypobromite. It is also produced by adding bromine to a heated solution of acetone and sodium carbonate; also prepared by treating chloroform with aluminum bromide or by electrolysis of potassium bromide in ethyl alcohol (HSDB , 2001). Bromoform is the major organohalide produced by chlorination of seawater during desalination. It is a major component of the organohalides produced by marine algae.
    2) Bromine, a brominated trihalomethane, is also formed as a by-product of chlorine disinfection and is found to occur in combination with other trihalomethanes in drinking water supplies (da Silva et al, 1999).
    C) USES
    1) Bromoform is used in separating mixtures of minerals. Therapeutically, it was formerly used as a sedative, hypnotic, and antitussive (OHM/TADS , 2001; Bingham et al, 2001; Budavari, 1996).
    2) It is also used in organic synthesis of pharmaceuticals, and as a solvent for waxes, greases, and oils (OHM/TADS , 2001; Lewis, 1993). It is used in the shipbuilding, aircraft and aerospace industries; it is used in fire extinguishers (HSDB , 2001; ACGIH, 1991; Hathaway et al, 1991).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) Bromoform is toxic by ingestion, inhalation, and skin absorption. It is a central nervous system depressant. Accidental ingestion of the liquid has produced central nervous system depression with coma and loss of reflexes. With very large doses, death may occur and is usually due to respiratory failure. Smaller doses have led to listlessness, headache, and vertigo. The major route of human exposure is from drinking water.
    B) Inhalation may cause irritation of the respiratory tract, pharynx, and larynx, producing salivation. Inhalation may be fatal as a result of spasm, inflammation, and edema of the larynx and bronchi, chemical pneumonitis and pulmonary edema.
    1) It has anesthetic properties similar to those of chloroform, but is not sufficiently volatile for inhalation purposes and is too toxic for human use.
    C) Exposure to vapors or dust may cause burning of the eyes and lacrimation.
    D) Bromoform is a skin and eye irritant. Repeated or prolonged contact may cause dermatitis.
    E) Chronic effects have not been reported from industrial exposure, but have been reported following oral abuse.
    F) In animal studies, target organs of toxicity are the skin, liver, kidneys, respiratory system, lungs and central nervous system.
    G) Chronic oral abuse of bromoform may result in bromism.
    0.2.5) CARDIOVASCULAR
    A) In extreme cases of poisoning resulting in severe CNS depression, shock may occur.
    0.2.6) RESPIRATORY
    A) Inhalation may be fatal as a result of spasm, inflammation, and edema of the larynx and bronchi, chemical pneumonitis and acute lung injury.
    0.2.7) NEUROLOGIC
    A) Bromoform is a CNS depressant. Bromoform-induced anesthesia and sedation may persist for days in poisoned animals. The principal cause of death in animals following acute oral exposures is CNS and respiratory depression. Seizures may occur.
    0.2.20) REPRODUCTIVE
    A) No reproductive adverse effects have been reported in humans. Developmental toxicity in the absence of maternal toxicity has been reported in rat studies.

Laboratory Monitoring

    A) Urinalysis, electrolytes, liver and renal function tests, chest x-ray, ECG and cardiac monitoring may be useful in symptomatic patients following exposure to bromoform. Bromine may cause elevation in the measured serum chloride concentration.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) Treatment is symptomatic and supportive.
    B) ACTIVATED CHARCOAL: Administer charcoal as a slurry (240 mL water/30 g charcoal). Usual dose: 25 to 100 g in adults/adolescents, 25 to 50 g in children (1 to 12 years), and 1 g/kg in infants less than 1 year old.
    C) GASTRIC LAVAGE: Consider after ingestion of a potentially life-threatening amount of poison if it can be performed soon after ingestion (generally within 1 hour). Protect airway by placement in the head down left lateral decubitus position or by endotracheal intubation. Control any seizures first.
    1) CONTRAINDICATIONS: Loss of airway protective reflexes or decreased level of consciousness in unintubated patients; following ingestion of corrosives; hydrocarbons (high aspiration potential); patients at risk of hemorrhage or gastrointestinal perforation; and trivial or non-toxic ingestion.
    D) HYPOTENSION: Infuse 10 to 20 mL/kg isotonic fluid. If hypotension persists, administer dopamine (5 to 20 mcg/kg/min) or norepinephrine (ADULT: begin infusion at 0.5 to 1 mcg/min; CHILD: begin infusion at 0.1 mcg/kg/min); titrate to desired response.
    E) SEIZURES: Administer a benzodiazepine; DIAZEPAM (ADULT: 5 to 10 mg IV initially; repeat every 5 to 20 minutes as needed. CHILD: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed) or LORAZEPAM (ADULT: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist. CHILD: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue).
    1) Consider phenobarbital or propofol if seizures recur after diazepam 30 mg (adults) or 10 mg (children greater than 5 years).
    2) Monitor for hypotension, dysrhythmias, respiratory depression, and need for endotracheal intubation. Evaluate for hypoglycemia, electrolyte disturbances, and hypoxia.
    0.4.3) INHALATION EXPOSURE
    A) INHALATION: Move patient to fresh air. Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with an inhaled beta2-adrenergic agonist. Consider systemic corticosteroids in patients with significant bronchospasm.
    B) ACUTE LUNG INJURY: Maintain ventilation and oxygenation and evaluate with frequent arterial blood gases and/or pulse oximetry monitoring. Early use of PEEP and mechanical ventilation may be needed.
    0.4.4) EYE EXPOSURE
    A) DECONTAMINATION: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, the patient should be seen in a healthcare facility.
    B) Treatment is symptomatic and supportive; there is no specific antidote.
    0.4.5) DERMAL EXPOSURE
    A) OVERVIEW
    1) DECONTAMINATION: Remove contaminated clothing and jewelry and place them in plastic bags. Wash exposed areas with soap and water for 10 to 15 minutes with gentle sponging to avoid skin breakdown. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).
    2) Treatment is symptomatic and supportive; there is no specific antidote.
    3) Bromoform may be absorbed through the skin and it can penetrate rubber gloves. Observe patient for delayed toxicity.

Range Of Toxicity

    A) Human toxicity data is limited. The lowest published lethal dose of bromoform for humans via ingestion is 143 mg/kg.
    B) An oral human dose of 250 to 500 mg/kg is speculated to be lethal to a child.
    C) The principal cause of death in animals following acute oral exposures is CNS depression.

Clinical Effects

Summary Of Exposure

    A) Bromoform is toxic by ingestion, inhalation, and skin absorption. It is a central nervous system depressant. Accidental ingestion of the liquid has produced central nervous system depression with coma and loss of reflexes. With very large doses, death may occur and is usually due to respiratory failure. Smaller doses have led to listlessness, headache, and vertigo. The major route of human exposure is from drinking water.
    B) Inhalation may cause irritation of the respiratory tract, pharynx, and larynx, producing salivation. Inhalation may be fatal as a result of spasm, inflammation, and edema of the larynx and bronchi, chemical pneumonitis and pulmonary edema.
    1) It has anesthetic properties similar to those of chloroform, but is not sufficiently volatile for inhalation purposes and is too toxic for human use.
    C) Exposure to vapors or dust may cause burning of the eyes and lacrimation.
    D) Bromoform is a skin and eye irritant. Repeated or prolonged contact may cause dermatitis.
    E) Chronic effects have not been reported from industrial exposure, but have been reported following oral abuse.
    F) In animal studies, target organs of toxicity are the skin, liver, kidneys, respiratory system, lungs and central nervous system.
    G) Chronic oral abuse of bromoform may result in bromism.

Heent

    3.4.3) EYES
    A) Exposure to liquid, fumes or dust may result in eye irritation with lacrimation (Material Data Safety Sheet, 1997; Grant & Schuman, 1993). Inhalation of small amounts causes flow of tears and saliva (Lewis, 2000).
    B) Both miosis and mydriasis (more rare) have been reported in children exposed to bromoform, likely related to depth of CNS depression (HSDB , 2001; Grant & Schuman, 1993; von Oettingen, 1955).
    C) RABBITS - Exposure to undiluted liquid was moderately irritating to rabbit eyes, with healing complete in 1 to 2 days (HSDB , 2001).
    D) Lacrimation was reported in all rats treated orally with bromoform (Agarwal & Mehendale, 1983).
    3.4.6) THROAT
    A) Exposure to vapor may result in irritation of the respiratory tract, pharynx and larynx (HSDB , 2001). Exposures may cause coughing and difficult breathing. Inhalation of small amounts causes flow of tears and saliva (Lewis, 2000).
    B) Because bromoform is partly excreted via the lungs, poisoning victims usually have a characteristic odor of the breath (von Oettingen, 1955).
    C) Ingestion is followed by a burning sensation in the mouth (von Oettingen, 1955).

Cardiovascular

    3.5.1) SUMMARY
    A) In extreme cases of poisoning resulting in severe CNS depression, shock may occur.
    3.5.2) CLINICAL EFFECTS
    A) HYPOTENSIVE EPISODE
    1) In extreme cases of poisoning resulting in severe CNS depression, shock may occur (HSDB , 2001).

Respiratory

    3.6.1) SUMMARY
    A) Inhalation may be fatal as a result of spasm, inflammation, and edema of the larynx and bronchi, chemical pneumonitis and acute lung injury.
    3.6.2) CLINICAL EFFECTS
    A) ACUTE RESPIRATORY INSUFFICIENCY
    1) Respiratory depression with possible respiratory failure may result following severe poisoning (inhalation or ingestion) with CNS depression (HSDB , 2001). Following oral doses for whooping cough in children, profound CNS depression occurred, with death usually the result of respiratory failure (Bingham et al, 2001; von Oettingen, 1955).
    B) IRRITATION SYMPTOM
    1) Inhalation of high concentrations may cause respiratory tract irritation (HSDB , 2001; Material Data Safety Sheet, 1997).
    C) ACUTE LUNG INJURY
    1) Severe inhalation of fumes may result in acute lung injury (HSDB , 2001). Inhalation may be fatal as a result of spasm, inflammation, and edema of the larynx and bronchi, chemical pneumonitis and acute lung injury (Bingham et al, 2001). Significant ingestions have resulted in rales and signs of incipient acute lung injury (von Oettingen, 1955).
    D) SMELL OF BREATH - FINDING
    1) Because bromoform is partly excreted via the lungs, poisoning victims usually have a characteristic odor of the breath (von Oettingen, 1955).

Neurologic

    3.7.1) SUMMARY
    A) Bromoform is a CNS depressant. Bromoform-induced anesthesia and sedation may persist for days in poisoned animals. The principal cause of death in animals following acute oral exposures is CNS and respiratory depression. Seizures may occur.
    3.7.2) CLINICAL EFFECTS
    A) CENTRAL NERVOUS SYSTEM DEFICIT
    1) Bromoform poisonings result in CNS depression via the inhalation or oral routes of exposure. Anesthetic properties are similar to those of chloroform, but bromoform is not sufficiently volatile for anesthesia utility. Inhalation of high concentrations have resulted in CNS effects of headache, dizziness, amnesia, unconsciousness, seizures and coma (HSDB , 2001; Lewis, 2000; Material Data Safety Sheet, 1997; von Oettingen, 1955). Ingestions have resulted in pallor, somnolence, stupor, and unconsciousness (von Oettingen, 1955).
    a) In severe poisonings, unconsciousness may be associated with loss of reflexes, trismus, and seizures (von Oettingen, 1955).
    2) Accidental oral overdoses of bromoform, given to children with whooping cough in the early 1900's, resulted in profound CNS depression manifested as unconsciousness, stupor, and loss of reflexes. Death was usually due to respiratory failure. Doses in these cases were estimated to be in the range of 150 to 300 mg/kg daily (Bingham et al, 2001; von Oettingen, 1955). Smaller doses were reported to result in listlessness, headache, and vertigo.
    3) Bromoform-induced anesthesia and sedation in animals may persist for days (Bingham et al, 2001). Chronic exposures may result in CNS damage (Material Data Safety Sheet, 1997).
    B) SEIZURE
    1) Following severe inhalational or oral poisoning, seizures and unconsciousness may occur (OHM/TADS , 2001; HSDB , 2001; von Oettingen, 1955).
    C) SECONDARY PERIPHERAL NEUROPATHY
    1) Daily use of bromoform as an antitussive has resulted in polyneuritis and encephalopathy (Falcy et al, 1989).
    2) CASE REPORT - Following daily, increasing use of an antitussive syrup containing bromoform (up to 5 bottles/day containing 750 mg bromoform and 750 mg codeine), a 47-year-old female was admitted to the ED with vomiting, polyneuritis of the lower limbs and motor imbalance. The patient complained of itching and numbness of the distal extremities. Examination revealed areflexia of all limbs; motor deficit in both lower limbs as well as in the proximal muscles were noted. The patient recovered following symptomatic therapy (Falcy et al, 1989).
    3.7.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) CNS DEPRESSION
    a) DOGS - When exposed to 56,000 ppm of bromoform, dogs became deeply anesthetized after 20 minutes and died after one hour of exposure. In another study, CNS depression occurred in 8 minutes and death in one hour from exposure of dogs to 29,000 ppm (HSDB , 2001).
    b) RATS - When single oral, toxic doses were administered to rats, sedation, flaccid muscle tone, ataxia, piloerection and prostration were reported. On pathologic examination, liver and kidney congestion were noted (HSDB , 2001).
    c) RATS - Following acute oral toxicity studies in rats, death in all cases was secondary to prolonged sedation, with the animals never recovering consciousness (Agarwal & Mehendale, 1983).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) EXCESSIVE SALIVATION
    1) Salivation may occur following exposure to bromoform vapor, even in small amounts (HSDB , 2001; Lewis, 2000; Grant & Schuman, 1993).
    B) GASTRITIS
    1) Ingestion may result in gastrointestinal irritation with nausea, vomiting and diarrhea (Material Data Safety Sheet, 1997). Chronic ingestion of bromoform for antitussive purposes has resulted in vomiting (Falcy et al, 1989).

Hepatic

    3.9.2) CLINICAL EFFECTS
    A) LARGE LIVER
    1) CASE REPORT - Painful hepatomegaly was reported in an adult following chronic and increasing doses of an antitussive syrup containing codeine and bromoform (Falcy et al, 1989).
    3.9.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) HEPATITIS
    a) Although not reported in humans, inhalation studies in animals have shown that bromoform is more toxic to the liver than chloroform (HSDB , 2001; Grant & Schuman, 1993). Moderate chronic liver toxicity has been reported in animal studies (Bingham et al, 2001), although no hepatic damage has been seen following acute toxicity studies in animals (Agarwal & Mehendale, 1983).
    2) HEPATOCELLULAR DAMAGE
    a) DOGS - Severe fatty degeneration of the liver was reported in dogs following bromoform anesthesia. The intensity of the liver damage appeared to increase with the depth of narcosis (von Oettingen, 1955).
    b) MICE - Following administration by gavage to mice, fatty infiltration of the liver was reported (HSDB , 2001).
    c) MICE - Following exposure to 200 mg/kg/day via gavage in mice for 2 weeks, both male and female mice were found to have microscopically varying degrees of hepatocellular degeneration (Anon, 1997).
    d) GUINEA PIGS - Following injections of 100-200 mg/kg/day into guinea pigs for 10 days, pathologic changes in the liver and kidney were reported (HSDB , 2001).
    e) RATS - When single oral, toxic doses were administered to rats, sedation, flaccid muscle tone, ataxia, piloerection and prostration were reported. On pathologic examination, liver and kidney congestion were noted (HSDB , 2001).
    f) RATS - Chronic toxicity studies in rats fed bromoform (2500 ppm) for 90 days demonstrated histologic effects of fatty liver infiltration and a lobular pattern in the liver due to an increase in the cytoplasmic homogeneity and density of the hepatocytes in the periportal area. Following a 90-day recovery period, the histological changes were found to be mild, not significantly different from those of controls (Chu et al, 1982a).
    g) RATS - In a 14-day toxicity study, serum ALT levels were elevated in the highest exposure group (289 mg/kg/day). At the high dose, frequent liver changes were noted, including moderately severe centrilobular cytoplasmic pallor, minimal inflammation, and increased mitotic figures in 2 animals (Condie et al, 1983).

Genitourinary

    3.10.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) RENAL FUNCTION ABNORMAL
    a) RATS - A single intraperitoneal dose of 3 mmol/kg given to rats has been shown to produce renal dysfunction, characterized by a reduction in glomerular filtration rate, reduced renal concentrating ability and elevated blood urea nitrogen levels (Kroll et al, 1994).
    b) RATS - When single oral, toxic doses were administered to rats, sedation, flaccid muscle tone, ataxia, piloerection and prostration were reported. On pathologic examination, liver and kidney congestion were noted (HSDB , 2001).
    c) RATS - When single non-lethal doses (3 mmol/kg) of bromoform were administered intraperitoneally to rats, elevations of BUN and reduced renal concentrating ability were reported. Glomerular filtration rate was also significantly reduced. Maximal renal effects were noted at 21 to 24 hours post-treatment (Kroll et al, 1994).
    d) MICE - Following administration by gavage to mice, signs of hemorrhage in the kidney were reported (HSDB , 2001).
    e) GUINEA PIGS - Following injections of 100-200 mg/kg/day into guinea pigs for 10 days, pathologic changes in the liver and kidney were reported (HSDB , 2001).

Hematologic

    3.13.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) LEUKOPENIA
    a) Chronic toxicity studies in rats fed bromoform (2500 ppm) for 90 days demonstrated decreased lymphocyte counts, which were reversible when exposure was terminated (Chu et al, 1982a). Chu et al (1982) reported decreased lymphocyte counts in acute toxicity studies in rats.

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) SKIN IRRITATION
    1) Dermal exposures may result in skin irritation and may be absorbed through the skin in harmful amounts (HSDB , 2001; Material Data Safety Sheet, 1997). Inhalation may cause reddening of the face (Lewis, 2000). Repeated or prolonged contact may result in dermatitis (Bingham et al, 2001).

Reproductive

    3.20.1) SUMMARY
    A) No reproductive adverse effects have been reported in humans. Developmental toxicity in the absence of maternal toxicity has been reported in rat studies.
    3.20.2) TERATOGENICITY
    A) ANIMAL STUDIES
    1) Following orally administered bromoform to rats, evidence of developmental toxicity in the absence of maternal toxicity was demonstrated (IARC, 1999). Following gavage studies in pregnant rats from days 6 to 15 of gestation, slight increases in several skeletal anomalies were observed, with no other significant maternal toxicity, fetotoxicity, or teratogenicity (Bingham et al, 2001).
    2) When bromoform was administered to rats by gavage from day 6 to day 15 of gestation, at doses of 50, 100, or 200 mg/kg/day, evidence of a fetotoxic response was observed. No teratogenic effects were noted. No dose-related histopathological changes were noted in mothers or fetuses. No maternal toxicity was noted (Ruddick et al, 1983).
    3.20.3) EFFECTS IN PREGNANCY
    A) ANIMAL STUDIES
    1) When bromoform was administered to rats by gavage from day 6 to day 15 of gestation, at doses of 50, 100, or 200 mg/kg/day, no maternal toxicity was observed (Ruddick et al, 1983).

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS75-25-2 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):
    1) IARC Classification
    a) Listed as: Bromoform
    b) Carcinogen Rating: 3
    1) The agent (mixture or exposure circumstance) is not classifiable as to its carcinogenicity to humans. This category is used most commonly for agents, mixtures and exposure circumstances for which the evidence of carcinogenicity is inadequate in humans and inadequate or limited in experimental animals. Exceptionally, agents (mixtures) for which the evidence of carcinogenicity is inadequate in humans but sufficient in experimental animals may be placed in this category when there is strong evidence that the mechanism of carcinogenicity in experimental animals does not operate in humans. Agents, mixtures and exposure circumstances that do not fall into any other group are also placed in this category.
    3.21.4) ANIMAL STUDIES
    A) CARCINOMA
    1) In experimental animals, there is limited evidence for the carcinogenicity of bromoform (IARC, 1999). Animal studies indicate a probable carcinogenic response in rats, but not mice (Bingham et al, 2001).
    2) In a two-year rat and mice study, neoplasms of the large intestine were reported in male and female rats following treatment with bromoform (Dunnick & Melnick, 1993).

Genotoxicity

    A) Bromoform is genotoxic in several assay systems. It has been shown to be mutagenic when tested against three strains of Salmonella typhimurium.
    B) Bromoform induced mitotic arrest in plants, mutations in insects and in cultured mammalian cells and sister chromatid exchange in human lymphocytes. Chromosomal aberrations were induced in cultured mammalian cells. In single studies in rodents in vivo, bromoform did not bind to DNA or cause chromosomal aberrations. Sister chromatid exchange was induced in rodents in vivo.

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Urinalysis, electrolytes, liver and renal function tests, chest x-ray, ECG and cardiac monitoring may be useful in symptomatic patients following exposure to bromoform. Bromine may cause elevation in the measured serum chloride concentration.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) Monitor fluid and electrolyte levels in patients with persistent vomiting. Bromine may cause elevations in measurement of serum chloride.
    2) Liver and renal function tests, INR or PT/PTT should be monitored in symptomatic patients.
    4.1.3) URINE
    A) URINALYSIS
    1) Obtain urinalysis in symptomatic patients.
    4.1.4) OTHER
    A) OTHER
    1) ECG
    a) Monitor ECG in symptomatic patients.

Radiographic Studies

    A) CHEST RADIOGRAPH
    1) Chest x-ray may be of value if pulmonary function is compromised.

Methods

    A) CHROMATOGRAPHY
    1) Bromoform has been measured in rat blood by means of headspace gas chromatography and an electron capture detector (da Silva et al, 1999).
    2) McNeal et al (1995) reported a purge-and-trap capillary gas chromatography with mass selective detection method for the detection and quantification of bromoform in water and commercial beverages.

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.3) DISPOSITION/INHALATION EXPOSURE
    6.3.3.1) ADMISSION CRITERIA/INHALATION
    A) Symptomatic patients should be admitted and observed.
    6.3.5) DISPOSITION/DERMAL EXPOSURE
    6.3.5.5) OBSERVATION CRITERIA/DERMAL
    A) Bromoform may be absorbed through the skin. Observe patient for delayed toxicity.

Monitoring

    A) Urinalysis, electrolytes, liver and renal function tests, chest x-ray, ECG and cardiac monitoring may be useful in symptomatic patients following exposure to bromoform. Bromine may cause elevation in the measured serum chloride concentration.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) EMESIS/NOT RECOMMENDED -
    1) Induction of emesis is not recommended because the patient may become rapidly obtunded.
    B) ACTIVATED CHARCOAL -
    1) No data were found to indicate that bromoform is adsorbed to charcoal. However, until definitive quantitative data are available, use of activated charcoal is recommended.
    2) PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION
    a) Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).
    1) In patients who are at risk for the abrupt onset of seizures or mental status depression, activated charcoal should not be administered in the prehospital setting, due to the risk of aspiration in the event of spontaneous emesis.
    2) The addition of flavoring agents (cola drinks, chocolate milk, cherry syrup) to activated charcoal improves the palatability for children and may facilitate successful administration (Guenther Skokan et al, 2001; Dagnone et al, 2002).
    3) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.2) PREVENTION OF ABSORPTION
    A) EMESIS/NOT RECOMMENDED
    1) Since the patient may rapidly become obtunded, ipecac-induced emesis is NOT recommended.
    B) ACTIVATED CHARCOAL
    1) No data were found to indicate that bromoform is adsorbed to charcoal. However, until definitive quantitative data are available, use of activated charcoal is recommended.
    2) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    3) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    C) GASTRIC LAVAGE
    1) INDICATIONS: Consider gastric lavage with a large-bore orogastric tube (ADULT: 36 to 40 French or 30 English gauge tube {external diameter 12 to 13.3 mm}; CHILD: 24 to 28 French {diameter 7.8 to 9.3 mm}) after a potentially life threatening ingestion if it can be performed soon after ingestion (generally within 60 minutes).
    a) Consider lavage more than 60 minutes after ingestion of sustained-release formulations and substances known to form bezoars or concretions.
    2) PRECAUTIONS:
    a) SEIZURE CONTROL: Is mandatory prior to gastric lavage.
    b) AIRWAY PROTECTION: Place patients in the head down left lateral decubitus position, with suction available. Patients with depressed mental status should be intubated with a cuffed endotracheal tube prior to lavage.
    3) LAVAGE FLUID:
    a) Use small aliquots of liquid. Lavage with 200 to 300 milliliters warm tap water (preferably 38 degrees Celsius) or saline per wash (in older children or adults) and 10 milliliters/kilogram body weight of normal saline in young children(Vale et al, 2004) and repeat until lavage return is clear.
    b) The volume of lavage return should approximate amount of fluid given to avoid fluid-electrolyte imbalance.
    c) CAUTION: Water should be avoided in young children because of the risk of electrolyte imbalance and water intoxication. Warm fluids avoid the risk of hypothermia in very young children and the elderly.
    4) COMPLICATIONS:
    a) Complications of gastric lavage have included: aspiration pneumonia, hypoxia, hypercapnia, mechanical injury to the throat, esophagus, or stomach, fluid and electrolyte imbalance (Vale, 1997). Combative patients may be at greater risk for complications (Caravati et al, 2001).
    b) Gastric lavage can cause significant morbidity; it should NOT be performed routinely in all poisoned patients (Vale, 1997).
    5) CONTRAINDICATIONS:
    a) Loss of airway protective reflexes or decreased level of consciousness if patient is not intubated, following ingestion of corrosive substances, hydrocarbons (high aspiration potential), patients at risk of hemorrhage or gastrointestinal perforation, or trivial or non-toxic ingestion.
    6.5.3) TREATMENT
    A) SUPPORT
    1) Treatment is symptomatic and supportive.
    B) AIRWAY MANAGEMENT
    1) Ventilatory assistance may be necessary if there is profound CNS depression or acute respiratory distress.
    C) HYPOTENSIVE EPISODE
    1) SUMMARY
    a) Infuse 10 to 20 milliliters/kilogram of isotonic fluid and keep the patient supine. If hypotension persists, administer dopamine or norepinephrine. Consider central venous pressure monitoring to guide further fluid therapy.
    2) DOPAMINE
    a) DOSE: Begin at 5 micrograms per kilogram per minute progressing in 5 micrograms per kilogram per minute increments as needed (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). If hypotension persists, dopamine may need to be discontinued and a more potent vasoconstrictor (eg, norepinephrine) should be considered (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
    b) CAUTION: If ventricular dysrhythmias occur, decrease rate of administration (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). Extravasation may cause local tissue necrosis, administration through a central venous catheter is preferred (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
    3) NOREPINEPHRINE
    a) PREPARATION: 4 milligrams (1 amp) added to 1000 milliliters of diluent provides a concentration of 4 micrograms/milliliter of norepinephrine base. Norepinephrine bitartrate should be mixed in dextrose solutions (dextrose 5% in water, dextrose 5% in saline) since dextrose-containing solutions protect against excessive oxidation and subsequent potency loss. Administration in saline alone is not recommended (Prod Info norepinephrine bitartrate injection, 2005).
    b) DOSE
    1) ADULT: Dose range: 0.1 to 0.5 microgram/kilogram/minute (eg, 70 kg adult 7 to 35 mcg/min); titrate to maintain adequate blood pressure (Peberdy et al, 2010).
    2) CHILD: Dose range: 0.1 to 2 micrograms/kilogram/minute; titrate to maintain adequate blood pressure (Kleinman et al, 2010).
    3) CAUTION: Extravasation may cause local tissue ischemia, administration by central venous catheter is advised (Peberdy et al, 2010).
    D) SEIZURE
    1) Seizures may rarely occur following exposure.
    2) SUMMARY
    a) Attempt initial control with a benzodiazepine (eg, diazepam, lorazepam). If seizures persist or recur, administer phenobarbital or propofol.
    b) Monitor for respiratory depression, hypotension, and dysrhythmias. Endotracheal intubation should be performed in patients with persistent seizures.
    c) Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or, if immediate bedside glucose testing is not available, treat with intravenous dextrose).
    3) DIAZEPAM
    a) ADULT DOSE: Initially 5 to 10 mg IV, OR 0.15 mg/kg IV up to 10 mg per dose up to a rate of 5 mg/minute; may be repeated every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
    b) PEDIATRIC DOSE: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
    c) Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after repeated doses of diazepam .
    4) NO INTRAVENOUS ACCESS
    a) DIAZEPAM may be given rectally or intramuscularly (Manno, 2003). RECTAL DOSE: CHILD: Greater than 12 years: 0.2 mg/kg; 6 to 11 years: 0.3 mg/kg; 2 to 5 years: 0.5 mg/kg (Brophy et al, 2012).
    b) MIDAZOLAM has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. ADULT DOSE: 0.2 mg/kg IM, up to a maximum dose of 10 mg (Brophy et al, 2012). PEDIATRIC DOSE: INTRAMUSCULAR: 0.2 mg/kg IM, up to a maximum dose of 7 mg (Chamberlain et al, 1997) OR 10 mg IM (weight greater than 40 kg); 5 mg IM (weight 13 to 40 kg); INTRANASAL: 0.2 to 0.5 mg/kg up to a maximum of 10 mg/dose (Loddenkemper & Goodkin, 2011; Brophy et al, 2012). BUCCAL midazolam, 10 mg, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).
    5) LORAZEPAM
    a) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 mg/min (Brophy et al, 2012; Prod Info lorazepam IM, IV injection, 2008).
    b) ADULT DOSE: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist (Manno, 2003; Brophy et al, 2012).
    c) PEDIATRIC DOSE: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sreenath et al, 2010; Chin et al, 2008).
    6) PHENOBARBITAL
    a) ADULT LOADING DOSE: 20 mg/kg IV at an infusion rate of 50 to 100 mg/minute IV. An additional 5 to 10 mg/kg dose may be given 10 minutes after loading infusion if seizures persist or recur (Brophy et al, 2012).
    b) Patients receiving high doses will require endotracheal intubation and may require vasopressor support (Brophy et al, 2012).
    c) PEDIATRIC LOADING DOSE: 20 mg/kg may be given as single or divided application (2 mg/kg/minute in children weighing less than 40 kg up to 100 mg/min in children weighing greater than 40 kg). A plasma concentration of about 20 mg/L will be achieved by this dose (Loddenkemper & Goodkin, 2011).
    d) REPEAT PEDIATRIC DOSE: Repeat doses of 5 to 20 mg/kg may be given every 15 to 20 minutes if seizures persist, with cardiorespiratory monitoring (Loddenkemper & Goodkin, 2011).
    e) MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation (Loddenkemper & Goodkin, 2011; Manno, 2003).
    f) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over the next 12 to 24 hours. Therapeutic serum concentrations of phenobarbital range from 10 to 40 mcg/mL, although the optimal plasma concentration for some individuals may vary outside this range (Hvidberg & Dam, 1976; Choonara & Rane, 1990; AMA Department of Drugs, 1992).
    7) OTHER AGENTS
    a) If seizures persist after phenobarbital, propofol or pentobarbital infusion, or neuromuscular paralysis with general anesthesia (isoflurane) and continuous EEG monitoring should be considered (Manno, 2003). Other anticonvulsants can be considered (eg, valproate sodium, levetiracetam, lacosamide, topiramate) if seizures persist or recur; however, there is very little data regarding their use in toxin induced seizures, controlled trials are not available to define the optimal dosage ranges for these agents in status epilepticus (Brophy et al, 2012):
    1) VALPROATE SODIUM: ADULT DOSE: An initial dose of 20 to 40 mg/kg IV, at a rate of 3 to 6 mg/kg/minute; may give an additional dose of 20 mg/kg 10 minutes after loading infusion. PEDIATRIC DOSE: 1.5 to 3 mg/kg/minute (Brophy et al, 2012).
    2) LEVETIRACETAM: ADULT DOSE: 1000 to 3000 mg IV, at a rate of 2 to 5 mg/kg/min IV. PEDIATRIC DOSE: 20 to 60 mg/kg IV (Brophy et al, 2012; Loddenkemper & Goodkin, 2011).
    3) LACOSAMIDE: ADULT DOSE: 200 to 400 mg IV; 200 mg IV over 15 minutes (Brophy et al, 2012). PEDIATRIC DOSE: In one study, median starting doses of 1.3 mg/kg/day and maintenance doses of 4.7 mg/kg/day were used in children 8 years and older (Loddenkemper & Goodkin, 2011).
    4) TOPIRAMATE: ADULT DOSE: 200 to 400 mg nasogastric/orally OR 300 to 1600 mg/day orally divided in 2 to 4 times daily (Brophy et al, 2012).

Inhalation Exposure

    6.7.1) DECONTAMINATION
    A) Move patient from the toxic environment to fresh air. Monitor for respiratory distress. If cough or difficulty in breathing develops, evaluate for hypoxia, respiratory tract irritation, bronchitis, or pneumonitis.
    B) OBSERVATION: Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    C) INITIAL TREATMENT: Administer 100% humidified supplemental oxygen, perform endotracheal intubation and provide assisted ventilation as required. Administer inhaled beta-2 adrenergic agonists, if bronchospasm develops. Consider systemic corticosteroids in patients with significant bronchospasm (National Heart,Lung,and Blood Institute, 2007). Exposed skin and eyes should be flushed with copious amounts of water.
    6.7.2) TREATMENT
    A) SUPPORT
    1) Treatment is symptomatic and supportive.
    B) AIRWAY MANAGEMENT
    1) Ventilatory assistance may be necessary if there is profound CNS depression or acute respiratory distress.
    C) ACUTE LUNG INJURY
    1) ONSET: Onset of acute lung injury after toxic exposure may be delayed up to 24 to 72 hours after exposure in some cases.
    2) NON-PHARMACOLOGIC TREATMENT: The treatment of acute lung injury is primarily supportive (Cataletto, 2012). Maintain adequate ventilation and oxygenation with frequent monitoring of arterial blood gases and/or pulse oximetry. If a high FIO2 is required to maintain adequate oxygenation, mechanical ventilation and positive-end-expiratory pressure (PEEP) may be required; ventilation with small tidal volumes (6 mL/kg) is preferred if ARDS develops (Haas, 2011; Stolbach & Hoffman, 2011).
    a) To minimize barotrauma and other complications, use the lowest amount of PEEP possible while maintaining adequate oxygenation. Use of smaller tidal volumes (6 mL/kg) and lower plateau pressures (30 cm water or less) has been associated with decreased mortality and more rapid weaning from mechanical ventilation in patients with ARDS (Brower et al, 2000). More treatment information may be obtained from ARDS Clinical Network website, NIH NHLBI ARDS Clinical Network Mechanical Ventilation Protocol Summary, http://www.ardsnet.org/node/77791 (NHLBI ARDS Network, 2008)
    3) FLUIDS: Crystalloid solutions must be administered judiciously. Pulmonary artery monitoring may help. In general the pulmonary artery wedge pressure should be kept relatively low while still maintaining adequate cardiac output, blood pressure and urine output (Stolbach & Hoffman, 2011).
    4) ANTIBIOTICS: Indicated only when there is evidence of infection (Artigas et al, 1998).
    5) EXPERIMENTAL THERAPY: Partial liquid ventilation has shown promise in preliminary studies (Kollef & Schuster, 1995).
    6) CALFACTANT: In a multicenter, randomized, blinded trial, endotracheal instillation of 2 doses of 80 mL/m(2) calfactant (35 mg/mL of phospholipid suspension in saline) in infants, children, and adolescents with acute lung injury resulted in acute improvement in oxygenation and lower mortality; however, no significant decrease in the course of respiratory failure measured by duration of ventilator therapy, intensive care unit, or hospital stay was noted. Adverse effects (transient hypoxia and hypotension) were more frequent in calfactant patients, but these effects were mild and did not require withdrawal from the study (Wilson et al, 2005).
    7) However, in a multicenter, randomized, controlled, and masked trial, endotracheal instillation of up to 3 doses of calfactant (30 mg) in adults only with acute lung injury/ARDS due to direct lung injury was not associated with improved oxygenation and longer term benefits compared to the placebo group. It was also associated with significant increases in hypoxia and hypotension (Willson et al, 2015).
    D) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Eye Exposure

    6.8.1) DECONTAMINATION
    A) EYE IRRIGATION, ROUTINE: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, an ophthalmologic examination should be performed (Peate, 2007; Naradzay & Barish, 2006).

Dermal Exposure

    6.9.1) DECONTAMINATION
    A) DERMAL DECONTAMINATION
    1) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

Enhanced Elimination

    A) SUMMARY
    1) No studies have addressed the utilization of extracorporeal elimination techniques in poisoning with this agent.

Range Of Toxicity

Summary

    A) Human toxicity data is limited. The lowest published lethal dose of bromoform for humans via ingestion is 143 mg/kg.
    B) An oral human dose of 250 to 500 mg/kg is speculated to be lethal to a child.
    C) The principal cause of death in animals following acute oral exposures is CNS depression.

Minimum Lethal Exposure

    A) ACUTE
    1) HUMAN - The lowest published lethal dose of bromoform for humans via ingestion is 143 mg/kg (RTECS , 2001; Hathaway et al, 1991).
    2) An oral human dose of 250 to 500 milligrams/kilogram is speculated to be lethal to a child, with death due to CNS depression (Bingham et al, 2001).
    3) Accidental oral overdoses of bromoform, given to children with whooping cough in the early 1900's, resulted in profound CNS depression manifested as unconsciousness, stupor, and loss of reflexes. Death was usually due to respiratory failure. Doses in these cases were estimated to be in the range of 150 to 300 milligrams/kilogram daily (Bingham et al, 2001).
    4) ANIMAL - A saturated atmosphere of 7000 ppm or more produced death in dogs in 60 minutes (Hathaway et al, 1991).

Maximum Tolerated Exposure

    A) ACUTE
    1) The maximum tolerated human exposure to bromoform has not been delineated.
    B) ANIMAL DATA
    1) Undiluted bromoform was moderately irritating to rabbit eyes, but healing was complete in 1 to 2 days. Repeated skin contact caused moderate irritation to rabbit skin (HSDB , 2001; ACGIH, 1991).
    2) Chronic exposure of rats to 25 ppm bromoform, 4 hours/day for 2 months caused unspecified adverse effects in the liver and kidneys (HSDB , 2001; ACGIH, 1991).
    3) A saturated atmosphere of 7000 ppm or more produced anesthesia in dogs in 8 minutes and death in 60 minutes (HSDB , 2001; Hathaway et al, 1991).

Serum Plasma Blood Concentrations

    7.5.2) TOXIC CONCENTRATIONS
    A) TOXIC CONCENTRATION LEVELS
    1) CHRONIC
    a) CASE REPORT - Initial serum bromine levels of 1940 milligrams/liter were reported in a female adult following the chronic abuse of an antitussive syrup containing codeine and bromoform. Daily use had gradually increased to a maximum of 5 bottles/day (750 mg bromoform and 750 mg codeine) (Falcy et al, 1989).

Workplace Standards

    A) ACGIH TLV Values for CAS75-25-2 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Editor's Note: The listed values are recommendations or guidelines developed by ACGIH(R) to assist in the control of health hazards. They should only be used, interpreted and applied by individuals trained in industrial hygiene. Before applying these values, it is imperative to read the introduction to each section in the current TLVs(R) and BEI(R) Book and become familiar with the constraints and limitations to their use. Always consult the Documentation of the TLVs(R) and BEIs(R) before applying these recommendations and guidelines.
    a) Adopted Value
    1) Bromoform
    a) TLV:
    1) TLV-TWA: 0.5 ppm
    2) TLV-STEL:
    3) TLV-Ceiling:
    b) Notations and Endnotes:
    1) Carcinogenicity Category: A3
    2) Codes: Not Listed
    3) Definitions:
    a) A3: Confirmed Animal Carcinogen with Unknown Relevance to Humans: The agent is carcinogenic in experimental animals at a relatively high dose, by route(s) of administration, at site(s), of histologic type(s), or by mechanism(s) that may not be relevant to worker exposure. Available epidemiologic studies do not confirm an increased risk of cancer in exposed humans. Available evidence does not suggest that the agent is likely to cause cancer in humans except under uncommon or unlikely routes or levels of exposure.
    c) TLV Basis - Critical Effect(s): Liver dam; URT and eye irr
    d) Molecular Weight: 252.73
    1) For gases and vapors, to convert the TLV from ppm to mg/m(3):
    a) [(TLV in ppm)(gram molecular weight of substance)]/24.45
    2) For gases and vapors, to convert the TLV from mg/m(3) to ppm:
    a) [(TLV in mg/m(3))(24.45)]/gram molecular weight of substance
    e) Additional information:

    B) NIOSH REL and IDLH Values for CAS75-25-2 (National Institute for Occupational Safety and Health, 2007):
    1) Listed as: Bromoform
    2) REL:
    a) TWA: 0.5 ppm (5 mg/m(3))
    b) STEL:
    c) Ceiling:
    d) Carcinogen Listing: (Not Listed) Not Listed
    e) Skin Designation: [skin]
    1) Indicates the potential for dermal absorption; skin exposure should be prevented as necessary through the use of good work practices and gloves, coveralls, goggles, and other appropriate equipment.
    f) Note(s):
    3) IDLH:
    a) IDLH: 850 ppm
    b) Note(s): Not Listed

    C) Carcinogenicity Ratings for CAS75-25-2 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): A3 ; Listed as: Bromoform
    a) A3 :Confirmed Animal Carcinogen with Unknown Relevance to Humans: The agent is carcinogenic in experimental animals at a relatively high dose, by route(s) of administration, at site(s), of histologic type(s), or by mechanism(s) that may not be relevant to worker exposure. Available epidemiologic studies do not confirm an increased risk of cancer in exposed humans. Available evidence does not suggest that the agent is likely to cause cancer in humans except under uncommon or unlikely routes or levels of exposure.
    2) EPA (U.S. Environmental Protection Agency, 2011): B2 ; Listed as: Bromoform
    a) B2 : Probable human carcinogen - based on sufficient evidence of carcinogenicity in animals.
    3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): 3 ; Listed as: Bromoform
    a) 3 : The agent (mixture or exposure circumstance) is not classifiable as to its carcinogenicity to humans. This category is used most commonly for agents, mixtures and exposure circumstances for which the evidence of carcinogenicity is inadequate in humans and inadequate or limited in experimental animals. Exceptionally, agents (mixtures) for which the evidence of carcinogenicity is inadequate in humans but sufficient in experimental animals may be placed in this category when there is strong evidence that the mechanism of carcinogenicity in experimental animals does not operate in humans. Agents, mixtures and exposure circumstances that do not fall into any other group are also placed in this category.
    4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed ; Listed as: Bromoform
    5) MAK (DFG, 2002): Category 3B ; Listed as: Tribromomethane
    a) Category 3B : Substances for which in vitro or animal studies have yielded evidence of carcinogenic effects that is not sufficient for classification of the substance in one of the other categories. Further studies are required before a final decision can be made. A MAK value can be established provided no genotoxic effects have been detected. (Footnote: In the past, when a substance was classified as Category 3 it was given a MAK value provided that it had no detectable genotoxic effects. When all such substances have been examined for whether or not they may be classified in Category 4, this sentence may be omitted.)
    6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

    D) OSHA PEL Values for CAS75-25-2 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Listed as: Bromoform
    2) Table Z-1 for Bromoform:
    a) 8-hour TWA:
    1) ppm: 0.5
    a) Parts of vapor or gas per million parts of contaminated air by volume at 25 degrees C and 760 torr.
    2) mg/m3: 5
    a) Milligrams of substances per cubic meter of air. When entry is in this column only, the value is exact; when listed with a ppm entry, it is approximate.
    3) Ceiling Value:
    4) Skin Designation: Yes
    5) Notation(s): Not Listed

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) References: HSDB, 2001 Lewis, 1992 RTECS, 2001
    1) LD50- (INTRAPERITONEAL)MOUSE:
    a) 1274 mg/kg
    2) LD50- (ORAL)MOUSE:
    a) 1072 mg/kg
    b) 1400 mg/kg
    c) Female, 1500 mg/kg
    3) LD50- (SUBCUTANEOUS)MOUSE:
    a) 1820 mg/kg
    4) LD50- (INTRAPERITONEAL)RAT:
    a) 414 mg/kg
    5) LD50- (ORAL)RAT:
    a) 933 mg/kg
    b) 1147 mg/kg
    c) Female, 1147 mg/kg
    d) Male, 2500 mg/kg -- 10% solution in corn oil
    e) Male, 1388 mg/kg

Pharmacology Toxicology

Pharmacologic Mechanism

    A) Bromoform is a central nervous system depressant producing anesthesia, analgesia, stupor, and narcosis.

Physicochemical

Physical Characteristics

    A) Bromoform is a heavy, volatile liquid with a chloroform odor and a sweetish taste (OHM/TADS , 2001; Budavari, 1996).
    B) Bromoform is a solid below 8.3 degrees C (47 degrees F) (NIOSH , 2001).
    C) Colorless liquid or hexagonal crystals (Lewis, 2000).
    D) Bromoform gradually decomposes, acquiring a yellow color (Budavari, 1996).

Ph

    1) No information found at the time of this review.

Molecular Weight

    A) 252.77 (Budavari, 1996)

References

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