The Risk Assessment Information System

Toxicity Profiles

Condensed Toxicity Summary for BROMOFORM

May 1995

NOTE: Although the toxicity values presented in these toxicity profiles were correct at the time they were produced, these values are subject to change. Users should always refer to the Toxicity Value Database for the current toxicity values.

Prepared by: Rosmarie A. Faust, Ph.D., Chemical Hazard Evaluation Group, Biomedical and Environmental Information Analysis Section, Health Sciences Research Division, *, Oak Ridge, Tennessee.


*Managed by Lockheed Martin Energy Systems, Inc., for the U.S. Department of Energy under Contract No. DE-AC05-84OR21400.

Bromoform (CAS No. 75-25-2), also referred to as tribromomethane, is a halogenated aliphatic hydrocarbon with a molecular formula of CHBr3 (Budavari et al., 1989). Bromoform is formed as a byproduct during water chlorination when chlorine reacts with endogenous organic materials such as humic and fulvic acid and bromide ions. The principal route of human exposure is from the ingestion of contaminated drinking water (ATSDR, 1990).

Bromoform is readily absorbed from the gastrointestinal tract (Mink et al., 1986) and, by analogy to related compounds, is expected to be absorbed from the respiratory tract. It is distributed to various tissues, with highest levels in adipose tissue and blood (Parra et al., 1986). Bromoform is metabolized in the liver by cytochrome P-450 oxidases; carbon monoxide and carbon dioxide are the primary metabolites (Stevens and Anders, 1979, 1981; Ahmed et al., 1977). Bromoform and its metabolites are excreted primarily through the lungs and to some extent in the urine (Mink et al., 1986).

In humans, accidental ingestion of bromoform has led to listlessness, headache, and vertigo and at higher doses to central nervous system depression, coma, and death. The estimated lethal dose for a 10- to 20-kg child is 250 to 500 mg/kg. Exposure to bromoform vapor has caused irritation of the respiratory tract, pharynx, and larynx, as well as lacrimation and salivation (von Oettingen, 1955).

In animals, the liver, kidneys, and central nervous system are the primary target organs for bromoform toxicity. The principal cause of death following acute oral exposure is central nervous system depression (Chu et al., 1980). An oral dose of 1 g/kg has produced ataxia, sedation, and anesthesia within 30 minutes in mice (Bowman et al., 1978) and oral LD50 values for rodents range from 1.14 to 1.55 g/kg (Chu et al., 1980; Bowman et al. 1978). Subchronic and chronic oral exposures (100 mg/kg by gavage for 13 weeks or 2 years) have caused lethargy in rats (NTP, 1989). Hepatic effects observed in rats and/or mice following subchronic (14-90 days) or chronic (2-year) exposure to bromoform at oral doses ranging from 50 to 200 mg/kg/day include vacuolization of hepatocytes, fat accumulation, liver enzyme changes, and increased liver weight (NTP, 1989; Chu et al., 1982; Munson et al., 1982). Kidney effects, characterized by histopathologic changes in the epithelial tubules and glomeruli and altered enzyme levels, were seen in mice exposed to bromoform by gavage at doses of >=145 mg/kg/day for 14 days (Condie et al., 1983). Additional effects following oral administration of bromoform include immune depression in mice treated with 250 mg/kg/day for 14 days (Munson et al., 1982) and fetotoxic effects (minor skeletal abnormalities) in rats treated with 100 mg/kg/day during gestation (Ruddick et al., 1983).

Acute inhalation exposure may produce severe central nervous system depression in animals. Inhalation of >=7000 ppm bromoform has caused deep anesthesia in dogs after 8 minutes and death after 1 hour (ACGIH, 1991). Central nervous system effects were also observed in rabbits exposed to 240 ppm for 10 days (Dykan, 1964), and impaired liver and kidney function has been reported in rats following exposure to 24 ppm for 2 months (Dykan, 1962). Bromoform is moderately irritating to rabbit skin and eyes (Torkelson, 1994).

Based on liver lesions seen in rats in a 13-week gavage study, an oral reference dose (RfD) of 2.00E-02 mg/kg/day was derived for chronic exposure (EPA, 1995a) and 2.00E-01 mg/kg/day for subchronic exposure to bromoform (EPA, 1995b). An inhalation reference concentration (RfC) has not been calculated for bromoform.

The epidemiological evidence for an association between ingestion of chlorinated drinking water containing bromoform and increased cancer risk is inadequate (EPA, 1989). One long-term oral study and a lung tumor assay provide evidence of carcinogenicity for bromoform in animals. An increased incidence of intestinal tumors (adenomatous polyps and adenocarcinomas) was seen in female rats receiving 200 mg/kg/day for 2 years (NTP, 1989), and an increased incidence of lung tumors was seen in male mice administered intraperitoneal injections of 4-100 mg/kg (3 times weekly for a total of 18-24 injections) of bromoform (Theiss et al., 1977).

Based on EPA guidelines, bromoform was assigned to weight-of-evidence group B2, probable human carcinogen (EPA, 1995a). For oral exposure, the slope factor and unit risk are 7.90E-03 (mg/kg/day)-1 and 2.3E-07 (ug/L) -1 (EPA, 1995a), and for inhalation exposure, the slope factor and unit risk are 3.90E-03 (mg/kg/day)-1 (EPA, 1995b) and 1.10E-06 (ug/m3)-1, respectively (EPA, 1995a). Retrieve Toxicity Profiles Formal Version

Last Updated 8/29/97

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