NOTE: Although the toxicity values presented in these toxicity profiles were correct at the time they were produced, these values are subject to change. Users should always refer to the Toxicity Value Database for the current toxicity values.
Prepared by: James C. Norris, Ph.D, Chemical Hazard Evaluation Group in the Biomedical and Environmental Information Analysis Section, Health Sciences Research Division, Oak Ridge National Laboratory*.
Prepared for: Oak Ridge Reservation Environmental Restoration Program.
*Managed by Martin Marietta Energy Systems, Inc., for the U.S. Department of Energy under Contract No. DE-AC05-84OR21400.
1,4-Dichlorobenzene (CAS 106-46-7), also referred to as para-DCB, p-DCB, paracide, Paramoth®, Parazene®, PDB, and Santochlor®, has a benzene ring with two chlorine atoms attached at the 1 and 4 carbon atoms; it does not occur naturally (ATSDR 1993). 1,4-Dichlorobenzene is used to make mothballs, deodorant blocks used in restrooms, and in animal holding facilities to control odors (ATSDR 1993). It also has applications in fumigants, insecticides, lacquers, paints, and seed disinfection products (Leber and Benya 1994). Of the 1300 sites on the United States Environmental Protection Agency's National Priorities List, 1,4-dichlorobenzene has been identified on at least 244 sites. Drinking water samples from U.S. surface water sources, environmental hazardous waste sites, and food have been reported to contain 1,4-dichlorobenzene (ATSDR 1993).
Detectable concentrations of 1,4-dichlorobenzene were found in adipose tissue and blood samples taken from Tokyo residents (Morita and Ohi 1975, Morita et al. 1975). A national survey of various volatile organic chemicals demonstrated 1,4-dichlorobenzene in the three adipose tissues sampled. In addition, studies have shown that babies can receive 1,4-dichlorobenzene from mother's milk (ATSDR 1993). 1,4-Dichlorobenzene is absorbed by experimental animals via inhalation, gavage, or subcutaneous injection (Hawkins et al. 1980). Data from oral administration of 1,4-dichlorobenzene to rabbits indicated oxidation to 2,5-dichlorophenol, which was found in the urine as a conjugate of glucuronic and sulfuric acids (Azouz et al. 1955). Other metabolites identified in the blood and urine of rats were 2,5-dichlorophenyl methyl sulfoxide and 2,5-dichlorophenyl methyl sulfone.
Severe hypochromic, microcytic anemia with excessive polychromasia, marginal nuclear hypersegmentation of the neutrophils, and a small number of red blood cells with Heinz bodies developed in a pregnant woman (21 years old) who consumed 1-2 blocks of 1,4-dichlorobenzene toilet air freshener per week throughout her pregnancy (Campbell and Davidson 1970). A 19-year-old female who consumed 4-5 moth pellets containing 1,4-dichlorobenzene on a daily basis for 2.5 years developed symmetrical, well-demarcated areas of increased pigmentation over various parts of her body, which disappeared over a 4-month period after discontinuing the ingestion (Frank and Cohen 1961).
In rats, 13-week gavage studies resulted in decreased hematocrit levels, red blood cell counts, and hemoglobin concentrations at 300 mg/kg/day (NTP 1987). Oral administration of 1200 and 1500 mg/kg/day resulted in degeneration and necrosis of rat hepatocytes. Increased incidences of hepatocellular degeneration and individual cell necrosis were observed in male and female mice gavaged with 600-1800 mg/kg/day.
Rats exposed via inhalation to 96-341 ppm of 1,4-dichlorobenzene intermittently for 5-7 months had cloudy swelling and degeneration of hepatic parenchymal cells in the central zone of the liver. Increased liver weights in the male and/or female rats occurred above 96 ppm (Hollingsworth et al. 1956). During a 2-generation study, adult rats exposed to 538 ppm exhibited tremors, ataxia, and hyperactivity; decreased grooming behavior; and an unkempt appearance (Tyl and Neeper-Bradley 1989). Both generations of offspring in the 538 ppm group had lower body weights at lactation day 4, and average litter size and survival were decreased. Selected animals from the first filial generation still had reduced body weights at 5 weeks postexposure.
No epidemiologic studies or case reports addressing the carcinogenicity of 1,4-dichlorobenzene in humans were available. In a 2-year study, female rats and male and female mice were gavaged with 300 and 600 mg/kg/day and male rats were gavaged with 150 and 300 mg/kg/day (NTP 1987). Nephropathy, epithelial hyperplasia of the renal pelvis, mineralization of the collecting tubules in the renal medulla, and focal hyperplasia of the renal tubular epithelium were noted in male rats receiving 150 and 300 mg/kg/day. Female rats gavaged with 300 and 600 mg/kg/day had an increased incidence of nephropathy and minimal hyperplasia of the renal pelvis or tubules. The following tumors were described as being present in the animals: renal tubular adenocarcinomas in male rats (controls, 2%; low dose, 6%; high dose, 14%), a marginal increase in mononuclear cell leukemia in male rats (control, 10%; low dose, 14%; high dose, 22%), hepatocellular carcinomas in male mice (controls, 28%; low dose, 22.5%; high dose, 64%) and in female mice (controls, 10%; low dose, 10.4%; high dose, 38%), and hepatocellular adenomas in male mice (controls, 10%; low dose, 26.2%; high dose, 32%) and in female mice (controls, 20%; low dose, 12.5%; high dose, 42%). In this NTP study, the tumor incidence in female controls was higher than the historical control. In both male and female mice, hepatocellular degeneration with resultant initiation of tissue repair was present. These findings resulted in a speculation by NTP (1987) that 1,4-dichlorobenzene was acting as a tumor promotor for liver tumors in male and female mice.
Reference concentrations (RfC) of 2.5 mg/m3 (0.42 ppm) for subchronic inhalation exposure (EPA 1995b) and 0.8 mg/m3 (0.13 ppm) for chronic inhalation exposure for 1,4-dichlorobenzene were derived (EPA 1995a) based on increased liver weights in the P1 males exposed via inhalation to 1,4-dichlorobenzene from the study of Tyl and Neeper-Bradley (1989). The No Observed Adverse Effects Level (NOAEL) was 301 mg/m3 (50 ppm). The Lowest Observed Adverse Effects Level (LOAEL) was 902 mg/m3 (150 ppm) (EPA 1995a). 1,4-Dichlorobenzene has been classified as C, possible carcinogen to humans (EPA 1995b). For oral exposure, the slope factor was 0.024 (mg/kg/day)-1, and the unit risk was 6.8E-7 (µg/L)-1 (EPA 1995 b).Retrieve Toxicity Profiles Formal Version
Last Updated 8/29/97