Biomonitoring Summary
Other Halogenated Solvents
Dibromomethane CAS No. 74-95-3
1,1-Dichloroethane CAS No. 75-34-3
1,2-Dichloroethane (Ethylene dichloride) CAS No. 107-06-2
1,1-Dichloroethene (Vinylidene chloride) CAS No. 75-34-3
cis-1,2-Dichloroethene CAS No. 156-59-2
trans-1,2-Dichloroethene CAS No. 156-60-5
1,2-Dichloropropane CAS No. 78-87-5
1,1,1-Trichloroethane (Methyl chloroform) CAS No. 71-55-6
1,1,2-Trichloroethane CAS No. 79-00-5
1,1,2,2-Tetrachloroethane CAS No. 79-34-5
Tetrachloromethane (Carbon tetrachloride) CAS No. 56-23-5
General Information
The halogenated solvents are volatile organic chemicals consisting of a hydrocarbon chain or one hydrocarbon substituted with one or more chlorine or bromine atoms. Most of these chemicals are used as degreasers and solvents in various products such as paints. In the past, 1,1,1-trichloroethane was used as a dry cleaning agent, insect fumigant, and solvent in consumer products; more recently, its U.S. production has been restricted because of its principal use in manufacturing hydrofluorocarbons (Armstrong, et al., 2004; ATSDR, 2006). Production of 1,1,2,2-tetrachloroethane in the U.S. has ceased, and currently, it is only used as a chemical intermediate in the production of several other halogenated solvents (ATSDR, 2008). 1,1,2-trichloroethane, 1,2-dichloroethane and 1,1-dichloroethene are used in the synthesis of other chemicals, such as polyvinylidene. Tetrachloromethane use as a solvent and fumigant has been discontinued due to toxicity concerns, and its other major use, production of chlorofluorocarbon refrigerants, has been restricted as a result of regulations of ozone-depleting chemicals (ATSDR, 2005).
These volatile halogenated solvents may be released into the air from facilities that produce or use them, from contaminated waste water, or from hazardous waste sites. In surveys of U.S. drinking water, 1,1,1-trichloroethane was one of the most frequently detected chlorinated solvents; detected in less than 10 percent of domestic wells (Moran et al., 2007; Rowe et al., 2007). When 1,1,1-trichlorethane was available in consumer products, indoor air concentrations could exceed outdoor air concentrations (Wallace, et al., 1991). Because of their volatility, these halogenated solvents generally do not persist in soil or water. Workers involved in the production or use of these solvents may be exposed by inhalation or by dermal contact with the liquid solvents.
s Inhalation is the most common exposure route for the general population, including indoor sources from such as paints, adhesives, cleaning solutions, and aerosolized insecticide sprays; from industries producing these solvents; and from contaminated waste disposal sites (Armstrong et al., 2004; ATSDR, 2008 and 2001). Drinking water may contribute to exposure due to contaminated underground drinking water supplies. In general, these solvents are well absorbed by inhalation, dermal, or oral exposure. After absorption, small amounts may be exhaled in expired air, and the remaining amount rapidly distributed to tissues. 1,1,1-Trichloroethane is exceptional in that most of a dose is exhaled unchanged in expired air and less than 10 percent of a dose is metabolized (Monster, et al., 1979). Fatty tissues can transiently accumulate these solvents, which are slowly released back into the blood stream. Many of these halogenated solvents are metabolized to more water soluble metabolites that can be excreted in the urine. Hepatic transformation of tetrachloromethane may lead to the generation of reactive intermediate metabolites which may be responsible for liver toxicity (Weber et al., 2003). Other halogenated solvents may undergo similar metabolism to reactive intermediates that contribute to toxicity (Casciola and Ivanetich, 1984; IPCS, 2003; Raucy et al., 1993).
Human health effects from these solvents at low environmental doses or at biomonitored levels from low environmental exposures are unknown. Acute exposure to massive doses by either inhalation or ingestion can cause central nervous system depression and unconsciousness, cardiac dysrhythmias, and hepatic and renal injury. Eye and respiratory tract irritation may occur with exposure to high vapor concentrations of most of these solvents, and allergic contact dermatitis has been reported following 1, 2-dichloroethane dermal exposure (Baruffini et al., 1989). Exposures to vapor concentrations exceeding occupational standards have been associated with fatigue, headache, delayed reactions, and neuropsychological impairment (ATSDR, 2001; Bowler et al., 2003). Epidemiologic studies of workers exposed to various halogenated solvents have found occasional associations between exposure and reduced fertility and spontaneous abortion in women (Figa-Talamanca, 2006). In animal studies, reproductive toxicity has not been consistently demonstrated in the absence of maternal toxicity (IPCS, 1990, 1992, and 1993).
Experimental animals exposed chronically to high doses of each of these solvents developed tumors of the liver, lung, and kidney. In addition, lymphoid and hematopoietic tumors were observed with 1,2-dichloroethane and 1,1,1-trichloroethane; mammary gland tumors were observed with tetrachloromethane, 1,2-dichloroethane, and 1,1-dichloroethene. IARC has determined that the dichloroethanes and tetrachloromethane are possible human carcinogens; the other halogenated solvents in this section are not classifiable regarding human carcinogenicity. NTP has determined that tetrachloromethane and 1,2-dichloroethane are reasonably anticipated to be human carcinogens. With the exception of dibromomethane, the U.S. EPA has established drinking water standards and other environmental criteria. The FDA regulates several of these solvents in bottled water and as indirect food additives. Occupational standards and guidelines are available for most of these chemicals from OSHA and ACGIH, respectively. Further information on the halogenated solvents is available from ATSDR at: https://www.atsdr.cdc.gov/toxprofiles/index.asp.
Biomonitoring Information
Levels of halogenated solvents in blood reflect recent exposure. With the exception of tetrachloromethane in the NHANES 2001-2002 subsample, the other ten halogenated solvents were detectable few or none of the participants in the NHANES 2003-2004 and 2005-2006 subsamples. In a non-representative sample of adults in NHANES III (1988-1994), blood levels were also non-detectable or detected in <10% of samples, except for 1,1,1-trichloroethane which was detected in a majority of samples with a median of 0.13 µg/L (Ashley et al., 1994; Churchill et al., 2001). 1,1,1-Trichloroethane was not detected in children who underwent periodic blood testing as part of an environmental exposure study (Sexton et al, 2005 and 2006). In a study of German residents, 1,1,1-trichloroethane levels were of similar magnitude to the NHANES III study (Hajimiragha et al., 1986).
Finding a measurable amount of any of these halogenated solvents in blood does not imply that the level of the solvent causes an adverse health effect. Biomonitoring studies of blood halogenated solvents 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 halogenated solvents 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 carbon tetrachloride. Atlanta GA. 2005 [online]. Available at URL: https://www.atsdr.cdc.gov/toxprofiles/tp.asp?id=196&tid;=35. 8/3/12
Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological profile for 1,2-dichloroethane update. Atlanta GA. 2001 [online]. Available at URL: https://www.atsdr.cdc.gov/toxprofiles/tp.asp?id=592&tid;=110. 8/3/12
Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological profile for 1,1,1-trichloroethane. Atlanta GA. 2006 [online}. Available at URL: https://www.atsdr.cdc.gov/toxprofiles/tp.asp?id=432&tid;=76. 8/3/12
Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological profile for 1,1,2,2-tetracholoroethane. Atlanta GA. 2008 [online]. Available at URL: https://www.atsdr.cdc.gov/toxprofiles/tp.asp?id=801&tid;=156. 8/3/12
Armstrong SR, Green LC. Chlorinated hydrocarbon solvents. Clin Occup Environ Med 2004;4(3):481-496, vi.
Baruffini A, Cirla AM, Pisati G, Ratti R, Zedda S. Allergic contact dermatitis from 1,2-dichloropropane. Contact Dermatitis 1989;20(5):379-380.
Bell BP, Franks P, Hildreth N, et al. Methylene chloride exposure and birthweight in Monroe County, New York. Environ Res 1991:55:31-39.
Bove FJ, Fulcomer MC, Klotz JB, Esmart J, Dufficy EM, Savrin JE. Public drinking water contamination and birth outcomes.Am J Epidemiol 1995 May 1;141(9):850-62.
Bowler RM, Gysens S, Hartney C. Neuropsychological effects of ethylene dichloride exposure. Neurotoxicology 2003;24(4-5):553-562.
Casciola LA, Ivanetich KM. Metabolism of chloroethanes by rat liver nuclear cytochrome P-450. Carcinogenesis 1984;5(5):543-548.
Costas K, Knorr RS, Condon SK. A case-control study of childhood leukemia in Woburn, Massachusetts: the relationship between leukemia incidence and exposure to public drinking water. Sci Total Environ 2002;300(1-3):23-35.
Croen LA, Shaw GM, Sanbonmatsu L, et al. 1997. Maternal residential proximity to hazardous waste sites and risk for selected congenital malformations. Epidemiology 1997;8:347-354.
Eskenazi B, Fenster L, Hudes M, Wyrobek AJ, Katz DF, Gerson J, et al. A study of the effect of perchloroethylene exposure on the reproductive outcomes of wives of dry cleaning workers. Am J Ind Med 1991a; 20:593-600.
Eskenazi B, Wyrobek AJ, Fenster L, Katz DF, Sadler M, Lee J, et al. A study of the effect of perchloroethylene exposure on semen quality in dry cleaning workers. Am J Ind Med 1991b;20:575- 591.
Figa-Telemanca I. Occupational risk factors and reproductive health of women. Occup Med (Lond) 2006;56(8):521-531.
Hajimiragha H, Ewers U, Jansen-Rosseck R, Brockhaus A. Human exposure to volatile halogenated hydrocarbons from the general environment. Int Arch Occup Environ Health. 1986;58(2):141-50.
Hill RH Jr, Ashley DL, Head SL, Needham LL, Pirkle JL. p-Dichlorobenzene exposure among 1,000 adults in the United States. Arch Environ Health 1995;50(4):277-280.
International Programme on Chemical Safety (IPCS). Concise International Chemical Assessment Document 51. 1,1-Dicholoroethene (vinylidene chloride). 2003 [online]. Available at URL: http://www.inchem.org/documents/cicads/cicads/cicad51.htm. 4/21/09
International Programme on Chemical Safety (IPCS). Environmental Health Criteria 146. 1,3-Dichloropropene, 1,2-Dichloropropane & Mixtures. 1993 [online]. Available at URL: http://www.intox.org/databank/documents/chemical/dichlorp/ehc146.htm. 4/21/09
International Programme on Chemical Safety (IPCS). Environmental Health Criteria 136. 1,1,1-Trichloroethane. 1992 [online]. Available at URL: http://www.inchem.org/documents/ehc/ehc/ehc136.htm. 4/21/09
International Programme on Chemical Safety (IPCS). Environmental Health Criteria 100. Vinylidene chloride. 1990 [online]. Available at URL: http://www.inchem.org/documents/ehc/ehc/ehc100.htm. 4/21/09
Monster AC, Boersma G, Steenweg H. Kinetics of tetrachloroethylene in volunteers: influence of exposure concentration and work load. Int Arch Occup Environ Health 1979;42:303-309.
Moran MJ, Zogorski JS, Squillace PJ. Chlorinated solvents in groundwater of the United States. Environ Sci Technol 2007;41:74-81.
Raucy JL, Kraner JC, Lasker JM. Bioactivation of halogenated hydrocarbons by cytochrome P4502E1. Crit Rev Toxicol 1993;23(1):1-20.
Rodenbeck SE, Sanderson LM, Rene A. Maternal exposure to trichloroethylene in drinking water and birth-weight outcomes. Arch Environ Health 2000;55(3):188-194.
Rowe BL, Toccalino PL, Moran MJ, Zogorski JS, Price CV. Occurrence and potential human-health relevance of volatile organic compounds in drinking water from domestic wells in the United States. Environ Health Perspect 2007;115(11):1539-1546.
Sexton K, Adgate JL, Church TR, Ashley DL, Needham LL, Ramachandran G, et al. Children's exposure to volatile organic compounds as determined by longitudinal measurements in blood. Environ Health Perspect 2005;113(3):342-349.
Sexton K, Adgate JL, Fredrickson AL, Ryan AD, Needham LL, Ashley DL. Using biologic markers in blood to assess exposure to multiple environmental chemicals for inner-city children 3-6 years of age. Environ Health Perspect 2006;114(3):453-459.
Weber LW, Boll M, Stampfl A. Hepatotoxicity and mechanism of action of haloalkanes: carbon tetrachloride as a toxicological model. Crit Rev Toxicol 2003;33(2):105-136.
Windham GC, Shusterman D, Swan SH, Fenster L, Eskenazi B. Exposure to organic solvents and adverse pregnancy outcome. Am J Ind Med. 1991;20(2):241-259.
