Chlorobenzene (Monochlorobenzene) CAS No. 108-90-7
1,2-Dichlorobenzene (o-dichlorobenzene) CAS No. 95-50-1
1,3-Dichlorobenzene (m-dichlorobenzene) CAS No. 541-73-1
1,4-Dichlorobenzene (p-dichlorobenzene, Paradichlorobenzene) CAS No. 106-46-7
Chlorobenzene (monochlorobenzene) and the three dichlorobenzenes are halogenated aromatic hydrocarbons pirmarily used in industrial and chemical synthetic processes. Chlorobenzene has been used to produce DDT, phenol, and nitrobenzene. The dichlorobenzenes are also chemical intermediates in synthesis of dyes, pesticides, and other industrial products. The chlorobenzenes have sometimes been used as solvents for pesticides and auto parts degreasers (ATSDR, 2007). 1,4-Dichlorobenzene (1,4-DCB; paradichlorobenzene) is used also as a moth repellent and as a deodorizer (ATSDR, 2007).
Ambient air is the primary source of chlorobenzene exposure for the general population. Indoor air levels of 1,4-DCB may exceed outdoor levels when moth repellents or deodorizers are in use (Wallace et al., 1987, 1991). Dietary sources are negligible (Schaum et al., 2003), and chlorobenzenes generally are not detected in drinking water or groundwater in the United States (USGS, 2006), but may be detected where industrial waste containing these chemicals has been discharged (IPCS, 2004). Chlorobenzenes volatilize from soil and water (ATSDR, 2007, 2008). People involved in the production or use of chlorobenzenes may be exposed by inhalation or dermal contact. Chlorobenzenes are well absorbed after inhalation and ingestion. 1,4-DCB is not appreciably absorbed through intact skin. Within a few hours following exposure, these chemicals are eliminated from tissues via oxidative hepatic metabolism followed by conjugation or oxidation. The major urinary metabolites are dichlorophenols (ATSDR, 2007, 2006).
Human health effects from chlorobenzenes at low environmental doses or at biomonitored levels from low environmental exposures are unknown. In humans, high air levels of 1,2- or 1,4-dichlorobenzenes cause eye and nasal irritation, and prolonged or repeated contact with concentrated solutions of either chemical may cause skin irritation or sensitization (Elovaara, 1998). Asthma and reduced pulmonary function have been associated with recent exposure to aromatic chemicals, including 1,4-DCB, but causation is unclear (Arif and Shah, 2007; Elliott et al., 2006). Laboratory animals exposed to high levels of chlorobenzene may demonstrate liver enlargement and serum transaminase elevations, renal tubular cell damage, and central nervous system depression. High doses of 1,2- or 1,3-dichlorbenzenes can result in centrilobular liver necrosis and decreased thyroid hormone levels and, among male animals, renal tubular degeneration (ATSDR, 2007; Elovaara, 1998; NTP, 1987). 1,4-DCB is not as acutely hepatotoxic or thyrotoxic as the other dichlorobenzene isomers (den Besten et al., 1991, 1992; Stine et al., 1991). In animal studies, 1,4-DCB is not considered to be a reproductive or developmental toxicant (ATSDR, 2007, 2008; Elovaara, 1998). Animals fed high doses of 1,4-DCB demonstrated an increased incidence of renal and hepatic tumors, but no evidence was found of mutagenicity or genotoxicity in vitro (NTP, 1987).
The U.S. EPA and the FDA regulate the levels of 1,2- or 1,4-dichlorobenzene in air and water and in bottled drinking water, respectively. U.S. EPA regulates the monochlorobenzene level in drinking water. NIOSH and ACGIH provide workplace guidelines for 1,2- and 1,4-dichlorobenzenes and monochlorobenzene levels in air. IARC classifies 1,4-dichlorobenze as a possible human carcinogen, and NTP determined that it was reasonably anticipated to be a human carcinogen. However, IARC determined that the human carcinogenicity of 1,2-dichlorobenzene and 1,3-dichlorobenzene was unclassifiable. Additional information about external exposure (i.e., environmental levels) and health effects is available from ATSDR at http://www.atsdr.cdc.gov/toxprofiles/index.asp.
Levels of chlorobenzene, 1,2-dichlorobenzene, 1,3-dichlorobenzene, and 1,4-dichlorobenzene in blood reflect recent exposure. Generally, blood levels of chlorobenzene, 1,2-dichlorobenzene, 1,3-dichlorobenzene were below the detection limit in NHANES 2003-2006 and were detected in less than 10% of the U.S. general population samples in earlier surveys (Ashley et al., 1994; Elliott et al., 2006). For 1,4-dichlorobenzene, a nonrepresentative sample of adults from the National Health and Nutrition Examination Survey (NHANES) III (1988–1994) demonstrated a median level of 1,4-DCB level of 0.33 µg/L (Hill et al., 1995), or equivalent to the 75th percentile of the NHANES 2003-2004 subsample, and about three times higher than levels found in a sample of Midwestern adults and children (Bonanno et al., 2001). A small study of urban, low-income children monitored over a two year period reported that median 1,4-DCB blood levels were slightly lower than NHANES III (Sexton et al., 2005, 2006). Ambient air and blood levels have been shown to correlate reasonably well (Lin et al., 2008; Sexton et al., 2005). Residential construction and cleaning activities, including the recent use of toilet bowl deodorants, may contribute to elevated indoor air and blood levels of 1,4-DCB (Bonanno et al., 2001; Churchill et al., 2001).
Finding a measurable amount of chlorobenzenes in the urine does not mean that the level of chlorobenzene causes an adverse health effect. Biomonitoring studies of urinary chlorobenzenes can provide physicians and public health officials with reference values so that they can determine whether people have been exposed to higher levels of chlorobenzenes than are found in the general population. Biomonitoring data can also help scientists plan and conduct research on exposure and health effects.
Arif AA, Shah SM. Association between personal exposure to volatile organic compounds and asthma among US adult population. Int Arch Occup Environ Health 2007;80(8):711-719.
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.
Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological profile for dichlorobenzenes update. Atlanta GA [updated 2007 October 19] Available at URL: http://www.atsdr.cdc.gov/toxprofiles/tp.asp?id=704&tid=126. 8/3/12
Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological profile for chlorobenzene. Atlanta GA [updated 2008 August 08] Available at URL: http://www.atsdr.cdc.gov/toxprofiles/tp.asp?id=489&tid=87. 8/3/12
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.
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.
Den Besten C, Ellenbroek M, van der Ree MAE, Rietjens IMCM, van Bladeren PJ. The involvement of primary and secondary metabolism in the covalent bainding of 1,2- and 1,4-dichlorobenzenes. Chem Biol Interact 1992;84:259-275.
Den Besten C, Vet JJRM, Besselink HT, Kiel FS, van Berke BJM, Beems R, et al. The liver, kidney, and thyroid toxicity of chlorinated benzenes. Toxicol Appl Pharmacol 1991;111:69-81.
Elliott L, Longnecker MP, Kissling GE, London SJ. Volatile organic compounds and pulmonary function in the Third National Health and Nutrition Examination Survey, 1988-1994. Environ Health Perspect 2006;114(8):1210-1214.
Elovaara E. 122. Dichlorobenzenes, The Nordic Expert Group for Criteria Documentation of Health Risks from Chemicals. The National Institute for Working Life. Stockholm, Sweden. 1998. Available at URL: http://www.inchem.org/documents/kemi/kemi/ah1998_04.pdf. 8/3/12
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). Chlorobenzenes other than hexachlorobenzene: environmental aspects (Cicads 60). Geneva, Switzerland. 2004. Available at URL: http://www.inchem.org/documents/cicads/cicads/cicad60.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 Expo Sci Environ Epidemiol 2008 Jul;18(4):421-9.
National Toxicology Program (NTP). Toxicology and carcinogenesis studies of 1,4-dichlorobenzene in F344/N rats and B6C3F1 mice (gavage studies), NTP TR 319, NIH Publication No. 87-2575. Research Triangle Park NC. 1987. Available at URL: http://ntp.niehs.nih.gov/ntp/htdocs/lt_rpts/tr255.pdf. 8/3/12
Schaum J, Schuda L, Wu C, Sears R, Ferrario J, Andrews K. A national survey of persistent, bioaccumulative, and toxic (PBT) pollutants in the United States milk supply. J Exp Anal Environ Epidemiol 2003;13:177-186.
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.
Stine ER, Gunawardhana L, Sipes IG. The acute hepatotoxicity of the isomers of dichlorobenzene in Fischer-344 and Sprague-Dawley rats: isomer-specific and strain-specific differential toxicity. Toxicol Appl Pharmacol 1991;42:197-208.
United States Geological Survey (USGS). Volatile organic compounds in the nation's ground water and drinking-water supply wells. Reston VA [updated 2006 August 28] Available at URL: http://pubs.usgs.gov/circ/circ1292/. 8/3/12
Wallace L, Pellizzari E, Hartwell T, et al.. The TEAM study: personal exposures to toxic substances in air, drinking water, and breath of 400 residents of New Jersey, North Carolina, and North Dakota. Environ Res 1987;43:290–307.
Wallace L, Nelson W, Ziegenfus R, et al.. The Los Angeles team study: personal exposures, indoor-outdoor air concentrations, and breath concentrations of 25 volatile organic compounds. J Exposure Anal Environ Epidemiol 1991;1:157–92.