Biomonitoring Summary

Disinfection By-Products (Trihalomethanes)

Bromodichloromethane CAS No. 75-27-4
Dibromochloromethane (Chlorodibromomethane) CAS No. 124-48-1
Tribromomethane (Bromoform) CAS No. 75-25-2
Trichloromethane (Chloroform) CAS No. 57-57-8

General Information

Disinfection by-products (DBP) are a class of chemical by-products also referred to as trihalomethanes (THMs), formed when chlorine or bromine interacts with the natural organic materials found in water. DBPs also include other formed products, such as haloacetic acids, haloacetonitriles, haloketones, and chlorophenols. The composition and levels of specific DBPs are determined by water quality, water treatment conditions, and disinfectant type (IPCS, 2000). Primary sources of DBPs are chlorinated drinking water and recreational water bodies, such as swimming pools.

In drinking water, trichloromethane is the predominant DBP, usually found at much higher levels than bromodichloromethane; tribromomethane is the least abundant (Krasner et al., 1989). DBPs are volatile at room temperature and can be detected in ambient air during activities such as showering, bathing, dishwashing, and swimming (Backer, et al., 2000; Gordon et al., 2006). Trichloromethane has industrial applications and is used to produce refrigerants and feedstock. It may be released into the environment where chlorine-based chemicals are used for bleaching and disinfecting processes or disposed at hazardous waste sites (IPCS, 2004; LaRegina, et al. 1986). Tribromomethane has limited industrial uses, mainly in geological assaying, electronics manufacturing, and as a solvent in laboratory analyses (ATSDR, 2005). DBPs tend not to bioaccumulate in aquatic organisms or persist in open or surface waters or soils, but they can remain in water within closed pipe systems. Workplace exposure may occur during the production of trichloromethane or tribromomethane, or in workplaces where DBPs may be generated, such as pulp or paper manufacturing, swimming pools, and water treatment plants (IPCS, 2004).

General population exposure to DBPs occurs primarily through ingesting chlorinated water and inhaling the water vapor. Dermal absorption also may occur during bathing and swimming (ATSDR, 1997, 2005; Dick, et al., 1995; Leavens et al., 2007). Each of the DBPs is rapidly absorbed and distributed widely throughout the body. In animals, these chemicals undergo hepatic metabolism to reactive chemicals, which can bind to cell macromolecules and be toxic in large amounts (IPCS, 2000). Ultimately, DBPs are metabolized to carbon dioxide, which is eliminated in exhaled air within a few hours. Only a small amount of each DBP is eliminated unchanged in urine. Elimination half-lives for these chemicals are less than four hours (ATSDR, 2005; Leavens et al., 2007).

Human health effects from DBPs at low environmental doses or at biomonitored levels from low environmental exposures are unclear or unknown. Humans exposed to massive levels of trichloromethane or tribromomethane develop central nervous system depression and hepatotoxicity (ATSDR, 2005, 1997). Acute animal toxicity studies of each of these chemicals have found central nervous system depression, liver and renal damage or necrosis, and occasionally, cardiac depression and arrhythmias (IPCS, 2000). In studies of rodents chronically fed high doses of either trichloromethane or bromodichloromethane, carcinomas occurred in the liver and kidney; large intestine tumors and polyps were also noted with bromodichloromethane (NCI, 1976; NTP, 1987). Chronic feeding studies in rodents with either dibromochloromethane or tribromomethane showed inconsistent evidence of carcinogenicity across species and genders. The DBPs did not produce reproductive or developmental effects in animals unless maternal toxicity was present, but bromodichloromethane altered sperm motility (IPCS, 2000). Numerous epidemiologic studies of the relationships between chlorinated water source and various cancers, adverse reproductive outcomes, and cardiovascular disease have been inconclusive (IPCS, 2000). IARC classified trichloromethane and bromodichloromethane as possible human carcinogens, and NTP determined that these chemicals are reasonably anticipated to be human carcinogens. However, IARC found dibromochloromethane and tribromomethane to be unclassifiable regarding human carcinogenicity. The U.S. EPA has established drinking water and environmental standards for "total THMs." OSHA and ACGIH have established workplace standards and guidelines, respectively, for trichloromethane and tribromomethane. Information about external exposure (i.e., environmental levels) and health effects is available from ATSDR at: https://www.atsdr.cdc.gov/toxprofiles/.

Biomonitoring Information

Levels of blood DBPs reflect recent exposure. Geometric mean blood trichloromethane levels were 0.039 and 0.043 ng/mL among non-smoking and smoking adults, respectively, in a subsample of NHANES 1999–2000 participants (Lin et al., 2008), which were at least twice as high as comparable levels in NHANES 2001–2002 and 2003–2004. In a non-representative sample of NHANES III (1988–1994) participants, the geometric mean and median blood trichloromethane levels, respectively, were 0.043 and 0.023 µg/L (Churchill et al., 2001). Similar median blood trichloromethane levels were reported in smaller studies of U.S adults (Ashley et al., 2005; Backer et al., 2000; Buckley et al., 1997) and in the Fourth Report. Immediately following bathing or showering with chlorinated water, median blood levels of trichloromethane, dibromochloromethane, and bromodichloromethane can increase two to four times over baseline levels, and then return to baseline rapidly during the next one to two hours (Ashley et al., 2005; Backer et al., 2000).

Finding a measurable amount of one or more of these THMs in blood does not imply that the level of THMs causes an adverse health effect. Biomonitoring studies of blood THMs can provide physicians and public health officials with reference values so that they can determine whether or not people have been exposed to higher levels of THMs than levels found in the general population. Biomonitoring data can also help scientists plan and conduct research on exposure and health effects.

References

Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological profile for chloroform update. 1997 [online]. Available at URL: https://www.atsdr.cdc.gov/toxprofiles/tp.asp?id=53&tid;=16. 4/26/09

Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological profile for bromoform and chlorodibromomethane. 2005 [online]. Available at URL: https://www.atsdr.cdc.gov/toxprofiles/tp.asp?id=713&tid;=128. 4/26/09

Ashley DL, Blount BC, Singer PC, Depaz E, Wilkes C, Gordon S, et al. Changes in blood trihalomethanes concentrations resulting from differences in water quality and water use activities. Arch Environ Occup Health 2005;60(1):7-15.

Backer LC, Ashley DL, Bonin MA, Cardinali FL, Kieszak SM, Wooten JV. Household exposures to drinking water disinfection by-products: whole blood trihalomethane levels. J Expo Anal Environ Epidemiol 2000;10(4):321-326.

Buckley TJ, Liddle J, Ashley DL, Paschal DC, Burse VW, Needham LL. Environmental and biomarker measurements in nine homes in the lower Rio Grande Valley: multimedia results for pesticides, metals, PAHs and VOCs. Environ Int 1997;23(5):705-732.

Churchill JE, Ashley DL, Kaye WE. Recent chemical exposures and blood volatile organic compound levels in a large population-based sample. Arch Environ Health 2001;56(2):157-166.

Dick D, Ng KM, Sauder DN, Chu I. In vitro and in vivo percutaneous absorption of 14C-chloroform in humans. Hum Exp Toxicol 1995;14: 260-265.

Gordon SM, Brinkman MC, Ashley DL, Blount BC, Lyu C, Masters J, Singer PC. Changes in breath trihalomethane levels resulting from household water-use activities. Environ Health Perspect 2006;114(4):514-521.

International Programme on Chemical Safety (IPCS). Environmental Health Criteria 216. Disinfectants and Disinfectant By-Products. 2000 [online]. Available at URL: http://www.inchem.org/documents/ehc/ehc/ehc216.htm. 4/26/09

International Programme on Chemical Safety (IPCS). Concise International Chemical Assessment Document 58. Chloroform. 2004 [online]. Available at URL: http://www.inchem.org/documents/cicads/cicads/cicad58.htm. 4/26/09

Krasner SW, McGuire MJ, Jacaugelo JG, Patania NL, Reagan KM, Aieta EM. The occurrence of disinfection by-products in US drinking water. J Am Water Works Assoc 1989;81:41–53.

LaRegina J, Bozzelli JW, Harkov R, Gianti S. Volatility organic compounds at hazardous waste sites and a sanitary landfill in New Jersey. An up-to-date review of the present situation. Environ Prog 1986;5:18-27.

Leavens TL, Blount BC, De Marini DM, Madden MC, Valentine JL, Case MW, et al. Disposition of bromodichloromethane in humans following oral and dermal exposure. Toxicol Sci 2007;99(2):432-445.

Lin YS, Egeghy PP, Rappaport SM. Relationships between levels of volatile organic compounds in air and blood from the general population. J Expo Sci Environ Epidemiol 2008;18(4):421-9.

National Cancer Institute (NCI). Report on the carcinogenesis bioassay of chloroform (CAS No. 67-66-3). National Cancer Institute Carcinogenesis Technical Report Series March 1, 1976. [online]. Available at URL: https://ntp.niehs.nih.gov/ntp/htdocs/LT_rpts/trChloroform.pdf. 4/26/09

National Toxicology Program (NTP). Carcinogenesis studies of bromodichloromethane (CAS No. 75-27-4) in F344/N rats and B6C31F mice (gavage studies). Technical Report Series No. 321. 1987 [online]. Available at URL: https://ntp.niehs.nih.gov/ntp/htdocs/LT_rpts/tr321.pdf. 4/26/09