Biomonitoring Summary
Chlorobenzenes
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
General Information
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 https://www.atsdr.cdc.gov/toxprofiles/index.asp.
Biomonitoring Information
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 imply 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.
References
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Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological profile for chlorobenzene. Atlanta GA [updated 2008 August 08] Available at URL: https://www.atsdr.cdc.gov/toxprofiles/tp.asp?id=489&tid=87. 8/3/12
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