Biomonitoring Summary
Halogenated Solvents
Dichloromethane (Methylene chloride) CAS No. 75-09-2
Trichloroethene (Trichloroethylene) CAS No. 79-01-6
Tetrachloroethene (Tetrachloroethylene, Perchloroethylene) CAS No. 127-18-4
General Information
Dichloromethane, trichloroethene, and tetrachloroethene are volatile halogenated short-chain hydrocarbons. Dichloromethane is used principally as a solvent in paint removers and thinners, as well as in other household products (cleaners, glues, and adhesives), and also as a degreasing agent. Trichloroethene is used primarily as an industrial degreaser, solvent, and in the synthesis of other chemicals. In the past, it was used in dry cleaning, food processing, household cleaners, and as a general anesthetic. Tetrachloroethene is used in dry cleaning, metal cleaning, the synthesis of other chemicals, and household products such as water repellants, silicone lubricants, and spot removers. All three of these halogenated solvents are produced and used in high volumes in the U.S., and have been detected in urban and ambient air and occasionally, soils, and drinking water most likely contaminated by industrial discharge (Moran et al., 2007; Rowe et al., 2007). Because of their volatility, these solvents do not persist in the soil or water following the discontinuation of contamination.
Inhalation is the most common exposure route for the general population including indoor sources from paints, adhesives, and cleaning solutions. Volatilization from contaminated water (eg., shower water) as well as the use of household products containing these solvents can result in higher indoor than outdoor air concentrations (ATSDR, 1997b; Martin et al., 2005). Nearby dry cleaning establishments, industries producing these solvents, and contaminated waste disposal sites can also contribute to human exposure (Armstrong and Green, 2004; ATSDR, 1997a, b, and 2000; Schreiber et al., 1993; Wallace et al., 1991). Drinking water may contribute to exposure when underground drinking water supplies have been contaminated. Workers in industries such as dry cleaning, aircraft maintenance, electronics manufacturing, and chemical production may be exposed by inhalation or by dermal contact with the liquid solvents. The U.S. EPA has established drinking water standards and other environmental standards for all three solvents, and the FDA regulates tetrachloroethene and trichloroethene as indirect food additives. For all three solvents, workplace standards have been established by OSHA, and ACGIH has recommended occupational guidelines and biological exposure indices for monitoring workers.
All three solvents are well absorbed by ingestion and inhalation, and animal studies have demonstrated that liquid forms can be dermally absorbed. Following absorption, part of the solvent dose is excreted into expired air; for tetrachloroethene, about 97-99% of the dose is eliminated unmetabolized into expired air, though it has an elimination half-life of several days (ATSDR, 1997a; Monster et al., 1986). The retained solvent can undergo hepatic metabolism. Trichloroethene and tetrachloroethene are metabolized to trichloroacetic acid and tricholoroethanol, which are eliminated in the urine. Dichloromethane is partially metabolized to carbon monoxide and carbon dioxide. Elevated carboxyhemoglobin levels in blood have been reported following intentional dichloromethane overdose or exposure to air concentrations greatly exceeding occupational standards (ATSDR, 2000; Hughes and Tracy, 1993).
Human health effects from dichloromethane, tetrachloroethene, and trichloroethene at low environmental doses or at biomonitored levels from low environmental exposures are unknown. Accidental or intentional high dose acute exposure by ingestion or inhalation of any of these solvents can result in loss of motor coordination, somnolence, and unconsciousness. Inhaling high doses of trichloroethene and tetrachloroethene may also produce cardiac arrhythmias attributed to enhanced sensitivity to catecholamines. High dose acute exposure to tetrachloroethene has resulted in reversible kidney impairment, and prolonged, low level exposure to either tetrachloroethene or trichloroethene has been associated with altered renal enzyme excretion and liver enlargement (ATSDR, 1997a, b). Chronic occupational exposure to any of these three solvents may be associated with mild degrees of neurological impairments, including reaction times, verbal skills, cognitive ability and motor function (Armstrong and Green, 2004).
Various epidemiologic studies of chronic tetrachloroethene exposure in dry cleaning workers found increased incidences of esophageal and cervical cancers and non-Hodgkin's lymphoma, but confounding exposures (e.g., other solvents and trichloroethene) were likely (IPCS, 2006). In animals studies, tetrachloroethene and trichloroethene each induced kidney and liver tumors; tetrachloroethene also caused leukemia, and trichloroethene caused lung and testicular tumors (IARC, 1995). Animal studies of inhaled dichloromethane have reported increased incidences of lung and hepatocellular cancers, and in female animals, mammary gland tumors (NTP, 2011). Trichloroethene and tetrachloroethene are classified as probable human carcinogens by IARC, and dichloromethane is classified as a possible human carcinogen by IARC. All three are classified as reasonably anticipated to be human carcinogens by NTP. Additional information about these 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. In the NHANES 2003-2004 subsample, the level of blood tetrachloroethene for adults at the 75th percentile of the U.S. population appear similar to the levels at the 75th percentile reported for non-smoking adults in a subsample of NHANES 1999-2000 participants (Lin et al., 2008) and were similar or slightly less that levels reported in a nonrepresentative subsample of the earlier NHANES III (1988-1994) (Ashley et al., 1994; Churchill et al., 2001). A recent study of low income, urban children in the Midwest reported slightly lower median tetrachloroethene levels (Sexton et al., 2005; Sexton et al., 2006) than the NHANES III levels (Ashley et al., 1994; Churchill et al., 2001). Other population studies have reported similarly low tetrachloroethene levels (Begerow et al., 1996; Bonanno et al., 2001). Population studies in Italy and Germany have reported multifold higher tetrachloroethene and trichloroethene blood levels than the U.S. surveys (Brugnone et al., 1994; Hajimiragha et al., 1986). Blood levels of trichloroethene and dichloromethane were detected infrequently in previous U.S. surveys and were generally not detected in the NHANES 2003-2004 subsample.
Comparatively higher blood levels of tetrachloroethene and trichloroethene have been noted for urban and industrial residential settings than for rural settings (Barkley et al., 1980; Begerow et al., 1996; Brugnone et al., 1994). Residing near dry-cleaning facilities or storing recently dry-cleaned clothes at home can contribute to increased blood tetrachloroethene levels (Begerow et al., 1996; Popp et al., 1992). In contrast, tetrachloroethene blood levels in occupationally exposed workers have been reported to be many thousand times higher than the unexposed general population (Begerow et al., 1996; Furuki et al., 2000; Monster et al., 1983). The occupational biological exposure index associated with an 8-hour exposure of 25 ppm is 500 µg/L tetrachloroethene in blood (ACGIH, 2007). Non-occupational exposures are usually well below this level.
Finding a measurable amount of any of these 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
ACGIH. TLVs and BEIs Based on the documentation of the threshold limit values for chemical substances and physical agents and biological exposure indices. 2007. Signature Publications. Cincinnati, OH. p.104.
Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological profile for trichloroethylene update. 1997b [online]. Available at URL: https://www.atsdr.cdc.gov/toxprofiles/tp.asp?id=173&tid;=30. 8/3/12
Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological profile for tetrachloroethylene update. 1997a [online]. Available at URL: https://www.atsdr.cdc.gov/toxprofiles/tp.asp?id=265&tid;=48. 8/3/12
Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological profile for Methylene chloride update. 2000 [online]. Available at URL: https://www.atsdr.cdc.gov/toxprofiles/tp.asp?id=234&tid;=42. 8/3/12
Armstrong SR, Green LC. Chlorinated hydrocarbon solvents. Clin Occup Environ Med 2004;4(3):481-496.
Ashley DL, Bonin MA, Cardinali FL, McCraw JM, Wooten JV. Blood concentrations of volatile organic compounds in a nonoccupationally exposed US population and in groups with suspected exposure. Clin Chem 1994;40(7 Pt 2):1401-1404.
Barkley J, Bunch J, Bursey JT, Castillo N, Cooper SD, Davis JM, et al. Gas chromatography mass spectrometry computer analysis of volatilie halogenated hydrocarbons in man and his environment—a multimedia environmental study. Biomed Mass Spectrom 1980;7(4):139-147.
Begerow J, Jermann E, Keles T, Freier I, Ranft U, Dunemann L. Internal and external tetrachloroethene exposure of persons living in differently polluted areas of Northrhine-Westphalia (Germany). Zentralbl Hyg Umweltmed. 1996;198(5):394-406.
Bonanno LJ, Freeman NCG, Greenberg M, Lioy PJ. Multivariate analysis on levels of selected metals, particulate matter, VOC, and household characteristics and activities from the Midwestern states NHEXAS. Appl Occup Environ Hyg 2001;16(9):859-874.
Brugnone F, Perbellini L, Guiliari C, Cerpelloni M, Soave M. Blood and urine concentrations of chemical pollutants in the general population. Med Lav 1994;8(5):370-389.
Churchill JA, 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.
Furuki K, Ukai H, Okamoto S, Takada S, Kawai T, Miyama Y, Mitsuyoshi K, et al. Monitoring of occupational exposure to tetrachloroethene by analysis for unmetabolized tetrachloroethene in blood and urine in comparison with urinalysis for trichloroacetic acid. Int Arch Occup Environ Health. 2000;73(4):221-227.
Hughes NJ, Tracey JA. A case of methylene chloride (nitromors) poisoning, effects on carboxyhaemoglobin levels. Hum Exp Toxicol 1993;12(2):159-60.
International Programme on Chemical Safety (IPCS). Concise International Chemical Assessment Document 68-Tetrachloroethene. 2006 [online]. Available at URL: http://www.inchem.org/documents/cicads/cicads/cicad68.htm. 8/3/12
Lin YS, Egeghy PP, Rappaport SM. Relationships between levels of volatile organic compounds in air and blood from the general population. J Exp Sci Environ Epidemiol 2008;18:421-429.
Martin SA, Simmons MB, Ortiz-Serrano M, Kendrick C, Gallo A, Campbell J, et al. Environmental exposure of a community to airborne trichloroethylene. Arch Environ Occup Health 2005;60(6):341-316.
Monster AC. Biological monitoring of chlorinated hydrocarbon solvents. J Occup Med 1986;28:583-588.
Monster AC, Regouin-Peeters W, Van Schijndel A, van der Tuin J. Biological monitoring of occupational exposure to tetrachloroethene. Scand J Work Environ Health 1983;9:273-281.
Moran MJ, Zogorski JS, Squillace PJ. Chlorinated solvents in groundwater of the United States. Environ Sci Technol 2007;41:74-81.
National Toxicology Program (NTP). 12th Report on Carcinogens, RoC. 2011. [online]. Available at URL: https://ntp.niehs.nih.gov/?objectid=03C9AF75-E1BF-FF40-DBA9EC0928DF8B15. 8/3/12
Popp W, Muller G, Baltes-Schmitz B, Wehner B, Vahrenholz C, Schmieding W, et al. concentrations of tetrachloroethene in blood and trichloroacetic acid in urine in workers and neighbours of dry-cleaning shops. Int Arch Occup Environ Health 1992;63:393-395.
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.
Schreiber JS, House S, Prohonic E, Smead G, Hudson C, Styk M, et al. An investigation of indoor air contamination in residences above dry cleaners. Risk Anal 1993;13(3):335-344.
Sexton K, Adgate JL, Church TR, Ashley DL, Needham LL, Ramachandran, 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.
Wallace L, Nelson W, Ziegenfus R, Pellizzari E, Michael L, Whitmore R, et al. The Los Angeles TEAM Study: Personal exposures, indoor-outdoor air concentrations, and breath concentrations of 25 volatile organic compounds. J Exp Anal Environ Epidemiol 1991;1(2):157-192.
