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U.S. Environmental Protection Agency
U.S. EPA Technology Innovation and Field Services Division

Dense Nonaqueous Phase Liquids (DNAPLs)

Toxicology

Halogenated Alkanes

Bromoform

Human Health Toxicity

Although bromoform is manufactured in the U.S. for laboratory use and for electronics industry applications with possible implications for occupational exposure, the chemical is also generated as a byproduct of water disinfection. The use of chlorine for the disinfection of drinking water results in the formation of trihalomethane (THM) disinfection byproducts, one of which is bromoform. This occurrence can result in exposure to the general population, albeit at very low concentrations. The general population is exposed via ingestion of drinking water, inhalation of vaporized bromoform, and dermal contact when showering or swimming (ATSDR 2005).

Bromoform is well absorbed from the gastrointestinal tract, and is expected to be readily absorbed across the lung and via dermal contact. Once absorbed, it is rapidly distributed throughout the body. Metabolism of bromoform takes place in the liver, by the cytochrome P450 mixed-function oxidase system. It has been suggested that highly reactive metabolites might exert the toxic and carcinogenic effects associated with the compound.

Animal studies indicate that the liver is the critical target organ of bromoform toxicity, with exposure resulting in fatty accumulation in the liver, swelling, and necrosis at higher levels of exposure. At doses higher than those causing liver damage, adverse effects on the kidney have been reported. Bromoform also causes depression of the central nervous system, producing drowsiness, sleepiness and narcosis (ATSDR 2005). EPA's Integrated Risk Information System (IRIS) classifies bromoform as "B2; probable human carcinogen," based on inadequate human data and sufficient evidence of carcinogenicity in animals, namely "an increased incidence of tumors after oral administration of bromoform in rats and intraperitoneal administration in mice."

Epidemiological studies have investigated the effects on pregnancy outcome from exposure to THMs in drinking water; however, the results of such studies are inconclusive as the treated subjects are exposed to a mixture of THMs, and any effect cannot be attributed to one compound. Animal studies suggest that bromoform does not cause histological damage to the reproductive organs, but that high levels of exposure can reduce fertility. It is thought that bromoform might be toxic to the fetus, but data are inconclusive (ATSDR 2005).

Bromoform gives both positive and negative results in both in vitro and in vivo genotoxicity tests (ATSDR 2005). Studies that are positive for the mutagenicity of bromoform support the IRIS classification of the compound as a carcinogen.

As of 2010, EPA has not developed a maximum contaminant level (MCL) for bromoform alone, but the total annual average trihalomethane amount for bromoform, chloroform, bromodichloromethane, and dibromochloromethane together should not exceed 80 µg/L for safe drinking water (EPA 2001).

The Regional Screening Levels (formerly Preliminary Remediation Goals) posted by EPA Region 9 identify risk-based concentrations for bromoform for the following common exposure pathways:

Residential soil 6.1 E+01 mg/kg
Industrial soil 2.2 E+02 mg/kg
Residential air 2.2 E-00 ug/m3
Industrial air 1.1 E+01 ug/m3
Tapwater 8.5 E+00 ug/L

References

Bromoform (CASRN 75-25-2)
U.S. EPA, Integrated Risk Information System (IRIS).

Toxicological Profile for Bromoform and Chlorodibromomethane
Agency for Toxic Substances and Disease Registry (ATSDR), 273 pp, 2005

Stage 1 Disinfectants and Disinfection Byproducts Rule Adobe PDF Logo
U.S. EPA, Office of Water. EPA 816-F-01-014, 4 pp, 2001

For Further Information

Bromoform Hazard Summary
EPA Technology Transfer Network Air Toxics Website, 2000 Update

Health and Environmental Effects Document for BromoformAdobe PDF Logo
EPA 600-8-90-025, 120 pp, 1989

Ecological Toxicity

There are few studies describing the ecotoxicity of bromoform, and those available are limited to the toxicity of the compound to aquatic receptors. The Pesticides Action Network (PAN) Pesticide Database presents summary information for the acute toxicity of bromoform to three groups of organisms: crustaceans, fish, and zooplankton. Bromoform is reported as slightly toxic to all three groups. The database additionally cites studies of the effects of bromoform on amphibians, mollusks and phytoplankton (Kegley et al. 2009).

No toxicity studies for terrestrial receptors were found aside from studies of laboratory animals (IRIS, Faust 1995); however, a terrestrial toxicity reference value (TRV) for the rat has been derived (DOE 1999).

References

Bromoform: Identification, Toxicity, Use, Water Pollution Potential, Ecological Toxicity and Regulatory Information
Kegley, S.E., B.R. Hill, S. Orme, and A.H. Choi.
PAN Pesticide Database. Pesticide Action Network, San Francisco, CA, 2009

Formal Toxicity Summary for Bromoform
Faust, R.A.
Risk Assessment Information System (RAIS), Oak Ridge Reservation Environmental Restoration Program, 1995

Terrestrial Toxicity Reference ValuesAdobe PDF Logo
U.S. DOE
Manual ERD-AG-003 Revision 0 (TRVs), 1999

This 13-page Department of Energy manual provides toxicity reference values for earthworms, various mammals, and various bird species.



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