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 Rosmarie A. Faust, Ph.D, who is a member of the Chemical Hazard Evaluation Group in the Biomedical and Environmental Information Analysis Section, Health Sciences Research Division, *.
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.
1,1,2-Trichloroethane (CAS Reg. No. 79-00-5), also known as vinyl trichloride, is a nonflammable liquid that is used in the manufacture of 1,1-dichloroethene; as a solvent for fats, waxes, resins, and alkaloids; and in organic synthesis (Budavari et al. 1989, EPA 1980).
1,1,2-Trichloroethane is released to the environment as a result of anthropogenic activity. The chemical has been identified in the United States at 45 of 1177 hazardous waste sites on the National Priorities List. Based on release patterns of related chemicals, it is estimated that 70-90% of the total release is to air, 10-30% to land, and a few percent to water. Removal of 1,1,2-trichloroethane from the atmosphere is thought to occur by reaction with photochemically produced hydroxyl radicals (estimated half-life 49 days) and from washout by precipitation; however, most of the 1,1,2-trichloroethane removed by washout is expected to reenter the atmosphere by volatilization. If released to soil, 1,1,2-trichloroethane is expected to partially leach into groundwater and to partially volatilize. In surface water, volatilization is the primary removal process (ATSDR 1989).
1,1,2-Trichloroethane is rapidly absorbed, widely distributed in organs and tissues, and extensively metabolized. Major metabolites include chloroacetic acid, S-carboxymethylcysteine, and thiodiacetic acid. 1,1,2-Trichloroethane and/or its metabolites are primarily excreted through the lungs and urine (Morgan et al. 1970, 1972; Kronevi et al. 1977; Mitoma et al. 1985).
Very limited human data were available to evaluate the toxicity of 1,1,2-trichloroethane. The chemical exerts a narcotic action at "low" concentrations and is irritating to the eyes and mucous membranes of the respiratory tract. When in contact with skin, 1,1,2-trichloroethane may cause cracking and erythema (IARC 1979).
The oral LD50 for mice (378-491 mg/kg) (White et al. 1985) indicates that in animals the acute oral toxicity of 1,1,2-trichloroethane is moderate. 1,1,2-Trichloroethane is a central nervous system depressant, inducing sedation in mice at oral doses of 378 mg/kg (White et al. 1985) and drowsiness, incoordination, and narcosis in dogs at 289 mg/kg (Wright and Schaffer 1932). Male and female CD-1 mice ingesting 384 mg/kg in drinking water for 90 days exhibited alterations in serum enzyme and hepatic microsomal enzyme activities, indicating adverse liver effects. In addition, depressed immune function in both sexes and decreased hemoglobin and hematocrit values in females were noted (Sanders et al. 1985, White et al. 1985). Decreased survival was reported in female B6C3F1 mice exposed to 195 or 390 mg/kg/day for 78 weeks (NCI 1978).
Bonnet et al. (1980) reported an inhalation LC50 of 1654 ppm for rats exposed to 1,1,2-trichloroethane for 6 hours, while another study found that a single 7-hour exposure to 250 or 500 ppm resulted in the death of more than half of the exposed female rats, with surviving animals exhibiting marked liver and kidney damage (Torkelson 1994). As noted previously, 1,1,2-trichloroethane is a central nervous system depressant inducing narcosis; death results from respiratory arrest (ACGIH 1991). In mice, a concentration of 3750 ppm for 30 minutes produced central nervous system depression and significantly increased liver enzyme activity within 18 minutes and death in half the animals within 10 hours (Gehring 1968). No adverse effects were observed in rats, guinea pigs, and rabbits exposed to 15 ppm for 7 hours/day, 5 days/week for 6 months, but female rats exposed to 30 ppm (16 exposures; 7 hours/day, 5 days/week) exhibited minor hepatic effects (Torkelson 1994). Repeated topical applications of 0.1 mL 1,1,2-trichloroethane produced erythema, edema, fissuring, and scaling of rabbit and guinea pig skin (Wahlberg 1984b).
An oral reference dose of 0.04 mg/kg/day for subchronic exposure (EPA 1995b) and 0.004 mg/kg/day for chronic exposure (EPA 1995a) to 1,1,2-trichloroethane was calculated based on a no observed adverse effects level (NOAEL) of 3.9 mg/kg/day and a lowest observed adverse effects level (LOAEL) of 44 mg/kg/day from a 90-day drinking water study with mice (White et al. 1985, Sanders et al. 1985). Clinical chemistry alterations indicative of liver damage were identified as critical effects. An inhalation reference concentration for 1,1,2-trichloroethane is under review by EPA (EPA 1995a).
No epidemiologic studies or case reports addressing the carcinogenicity of 1,1,2-trichloroethane in humans were available. In a rodent bioassay, 1,1,2-trichloroethane was administered by gavage to Osborne-Mendel rats (46 or 92 mg/kg/day) and B6C3F1 mice (195 or 390 mg/kg/day), 5 days/week for 78 weeks (NCI 1978). No effects on tumor development were noted in rats. Treated mice had significantly (p<0.01) increased incidences of hepatocellular carcinomas. The tumor incidences in treated males were 37% and 76% in the low- and high-dose groups, respectively, compared with 10% in vehicle controls, and 33% and 89% in females, respectively, compared to no observed tumors in vehicle controls. An increased incidence of adrenal pheochromocytomas was also observed in male and female mice. In a cancer initiation/promotion study with rats, 1,1,2-trichloroethane did not exhibit tumor initiating or promoting activity (Story et al. 1986).
Based on United States Environmental Protection Agency (EPA) guidelines, 1,1,2-trichloroethane was assigned to weight-of-evidence group C, possible human carcinogen. For oral exposure, the slope factor is 5.7E-2 (mg/kg/day)-1 and the unit risk for drinking water is 1.6E-6 (µg/L)-1 (EPA 1995a). The inhalation slope factor and unit risk are 5.7E-2 (mg/kg/day)-1 (EPA 1995b) and 1.6E-5 (µg/m3)-1, respectively (EPA 1995a).
1,1,2-Trichloroethane (CAS Reg. No. 79-00-5), also known as vinyl trichloride, is a halogenated aliphatic hydrocarbon with the chemical formula of ClCHCl2. It has a molecular weight of 133.42, a melting point of -35C, a boiling point of 113-114C, and a density of 1.4711 at 20/4C. 1,1,2-Trichloroethane is a nonflammable liquid with a pleasant odor that is insoluble in water and miscible with alcohol, ether, and many other organic liquids (Budavari et al. 1989).
1,1,2-Trichloroethane is used in the manufacture of 1,1-dichloroethene; as a solvent for fats, waxes, natural resins, and alkaloids; and in organic synthesis (Budavari et al. 1989, EPA 1980) and is released to the environment as a result of anthropogenic activity. Effluent monitoring data indicate that high levels of discharge (>100 ppb) are associated with laundries and organic chemicals and mechanical products industries (ATSDR 1989). Small amounts of 1,1,2-trichloroethane are formed during the water chlorination process (EPA 1980). Gaseous releases include vent gas and fugitive emissions from the production and use of 1,1,2-trichloroethane as well as volatilization from wastewater and municipal treatment plants. Releases to soil are expected to result from land filling of sludge and process residues (ATSDR 1989). 1,1,2-Trichloroethane has been detected in urban air at concentrations up to 0.223 µg/m3 (ACGIH 1991). The chemical has been identified in the United States at 45 of 1177 hazardous waste sites on the National Priorities List. Based on release patterns of related chemicals, it is estimated that 70-90% of the total release is to air, 10-30% to land, and a few percent to water (ATSDR 1989).
Removal of 1,1,2-trichloroethane from the atmosphere is thought to occur by reaction with photochemically produced hydroxyl radicals (estimated half-life 49 days) and from washout by precipitation; however, most of the 1,1,2-trichloroethane removed by washout is expected to reenter the atmosphere by volatilization. If released to soil, 1,1,2-trichloroethane is expected to partially leach into groundwater and partially volatilize. In surface water, volatilization is the primary removal process (ATSDR 1989).
No data were available on the oral absorption of 1,1,2-trichloroethane. High oral doses were metabolized by rats and mice (see Sect. 2.3), indicating that the chemical is well absorbed from the gastrointestinal tract.
1,1,2-Trichloroethane is extensively absorbed after inhalation exposure. A volunteer who inhaled one breath of 1,1,2-trichloroethane retained more than 90% of the administered dose in the body after 50 minutes (Morgan et al. 1970, 1972).
1,1,2-Trichloroethane is also rapidly absorbed through the skin, probably because of the highly lipid soluble character of the compound (Kronevi et al. 1977). In mice, 99.7% of the dose was retained in the body 15 minutes after application of 0.5 mL of 1,1,2-trichloroethane (Tsuruta 1975). The absorption rate was calculated to be 130 nmoles/min/cm2 of skin. From the mouse data, the author estimated that if both hands were exposed to liquid 1,1,2-trichloroethane for 1 minute, total dermal uptake would be 13.9 mg for humans (ACGIH 1991). A single application of 1 mL of 1,1,2-trichloroethane to the skin of guinea pigs was absorbed rapidly, as indicated by the appearance of 3-4 µg/mL of the chemical in the blood within 30 minutes (Jakobson et al. 1977).
One oral study with rats and mice showed that 1,1,2-trichloroethane is distributed to the liver (Mitoma et al., 1985). Following inhalation exposure to 1000 ppm for one hour, 1,1,2-trichloroethane was distributed in fatty tissue (600 µ/g), kidneys and liver (80 µg/g), blood and brain (46-60 µg/g), and heart, spleen, and lungs (20-35 µ/g) of mice (Takahara 1986).
Mice retained 1-3% of an intraperitoneally administered dose of 0.1-0.2 g/kg of 1,1,2-trichloroethane after 3 days (Yllner 1971).
Following gavage administration of 1,1,2-trichloroethane to mice (300 mg/kg) and rats (70 mg/kg), 81% of the administered dose was metabolized by both species (Mitoma et al. 1985). Therefore, mice had a greater body burden than rats but were able to metabolize the same fraction of the dose. The primary metabolites identified in this study were chloroacetic acid, S-carboxymethylcysteine, and thiodiacetic acid. Similar metabolites were identified following intraperitoneal injection of mice with 10-13 g/kg of 1,1,2-trichloroethane (Yllner 1971). The major urinary metabolites (as % of dose) were S-carboxymethylcysteine (29-46% free, 3-10% bound), chloroacetic acid (6-31%), and 2,2-dichloroethanol (38-42%). 2,2,2-Trichloroethanol, oxalic acid, and trichloroacetic acid were also identified. Metabolites identified in the urine of rats following inhalation of 200 ppm for 8 hours or intraperitoneal injection with 2.8 mmol/kg body weight included trichloroacetic acid and trichloroethanol (Ikeda and Ohtsuji 1972).
A volunteer who inhaled one breath of 1,1,2-trichloroethane eliminated 10% of the inspired dose in the alveolar air after 12 seconds and about 0.5% after 40 seconds of breath holding (Morgan et al. 1970, 1972). Excretion in the breath after 1 hour was 2.9% of the administered dose and the excretion rate in the urine was less than 0.01%/minute. From these data, the half life for urinary excretion was estimated to be 70 minutes.
In laboratory animals, 72 to 87% of a single oral, parenteral, or inhaled dose of 1,1,2-trichloroethane was accounted for as urinary metabolites. Urinary elimination of trichloroacetic acid and trichloroethanol by rats was comparable after either inhaling 200 ppm for 8 hours or after a single intraperitoneal injection of 2.8 mmol/kg (Ikeda and Ohtsuji 1972). Following intraperitoneal administration of 0.1-0.2 g/kg of 1,1,2-trichloroethane, mice excreted 73-87% of the dose in urine, 0.1-2% in feces, and 16-22% in expired air (60% as CO2; the remainder unchanged) (Yllner 1971).
Information on the acute oral toxicity of 1,1,2-trichloroethane in humans was not available.
Oral LD50s listed for rats are 0.58 mL (Smyth et al. 1969) and 100-200 mg/kg (Torkelson 1994). For male and female mice, oral LD50 values are 378 and 491 mg/kg, respectively (White et al. (1985). All mice receiving 450 mg/kg became sedated within an hour, and 10% of these mice lost their righting reflex (White et al. 1985). The ED50 for motor impairment (dose that produced motor impairment in one half of the test animals) was 128 mg/kg in mice. The peak effect occurred within 5 minutes of dosing (Borcelleca 1983). Drowsiness, incoordination, and partial narcosis was seen in dogs 12 to 50 minutes after oral dosing with 289 or 722 mg/kg of 1,1,2-trichloroethane (Wright and Schaffer 1932). Oral administration of 0.75 g/kg was lethal to dogs, and fatty degeneration of the liver was seen in dogs dying two or more days following dosing (ACGIH 1986).
A single gavage dose of 60 mg/kg of 1,1,2-trichloroethane produced significantly increased serum glutamic oxalacetic transaminase and serum glutamic pyruvic transaminase activities in 50% of male rats tested (ED50) (Tyson et al. 1983). Seven daily doses of 1,1,2-trichloroethane (300 mg/kg/day) given by gavage resulted in the death of all seven mice tested. Single doses up to 100 mg/kg did not cause mortality in this study (Kallman et al. 1983). The same investigators reported that 1,1,2-trichloroethane administered to mice by gavage produced a dose-related taste aversion to saccharin in drinking water in mice. An ED50 (dose that produced taste aversion in half of the test animals) of 32 mg/kg was calculated.
In a range-finding study, male mice were administered up to 38 mg/kg/day of 1,1,2-trichloroethane by gavage for 14 days (Sanders et al. 1985, White et al. 1985). Mice receiving 38 mg/kg/day exhibited significantly decreased serum lactic dehydrogenase activity and significantly increased absolute brain, thymus, and testes weights. No definite effects on humoral or cell-mediated immune response to sheep red blood cells were observed.
Information on the subchronic oral toxicity of 1,1,2-trichloroethane in humans was not available.
Male and female CD-1 mice were exposed to 1,1,2-trichloroethane in drinking water (4.4, 46, or 305 mg/kg for males and 3.9, 44, or 384 mg/kg for females) for 90 days (Sanders et al. 1985, White et al. 1985). Exposure to 1,1,2-trichloroethane produced dose-dependent alterations in serum enzyme levels and hepatic microsomal enzyme activities, indicating adverse liver effects. Specific effects included decreased liver glutathione and increased serum alkaline phosphatase activity (males); increased glutathione, serum glutamic oxalacetic transaminase, and serum glutamic pyruvic transaminase activities; increased fibrinogen levels; decreased cytochrome P-450 and aniline hydroxylase activities; and increased liver weights (females). Significantly decreased hemoglobin and hematocrit values (at 384 mg/kg) were also seen in females (White et al. 1985). Cell-mediated immunity was unaltered in both sexes at 44 and 384 mg/kg, while humoral immune status was depressed in both sexes, particularly when it was determined by hemagglutination titers. Macrophage function was depressed only in males (Sanders et al. 1985).
Information on the chronic toxicity of 1,1,2-trichloroethane in humans following oral exposure was not available.
In a carcinogenicity bioassay, B6C3F1 mice and Osborne-Mendel rats (50 animals/sex/dose) were treated by gavage with 195 or 390 mg/kg/day (mice) or 46 or 92 mg/kg/day (rats), 5 days/week for 78 weeks, followed by an observation period up to 35 weeks for rats and up to 13 weeks for mice (NCI 1978, see also Sect. 4.1.2.). Survival of male and female rats and male mice was not affected by treatment with 1,1,2-trichloroethane, but survival of female mice was reduced, particularly in the low-dose group. Some of the deaths occurred early in the experiment (8 died in week 36 and 11 in week 55), were not tumor-related, and did not appear to have a common cause. Except for mortality data, the report did not provide information for noncancer effects.
Information on the developmental and reproductive toxicity of 1,1,2-trichloroethane in humans following oral exposure was not available.
In a developmental toxicity screen, pregnant mice were treated by gavage with 350 mg/kg/day of 1,1,2-trichloroethane in corn oil on days 8 to 12 of gestation. Survival and weight of offspring was not affected by treatment (Seidenberg et al. 1986, Seidenberg and Becker 1986).
ORAL REFERENCE DOSE: 4E-2 mg/kg/day (EPA 1995b)
NOAEL: 3.9 mg/kg/day
UNCERTAINTY FACTOR: 100
PRINCIPAL STUDIES: White et al. (1985), Sanders et al. (1985)
COMMENTS: The subchronic reference dose was based on the same studies as the chronic oral reference dose. An uncertainty factor of 10 each was applied for inter- and intraspecies variation.
ORAL REFERENCE DOSE: 4E-3 mg/kg/day (EPA 1995a)
NOAEL: 3.9 mg/kg/day
LOAEL: 44 mg/kg/day
UNCERTAINTY FACTOR: 1000
Data Base: Medium
Reference Dose: Medium
VERIFICATION DATE: 5/26/88
PRINCIPAL STUDIES: White et al. (1985), Sanders et al. (1985)
COMMENTS: The chronic reference dose is based on clinical chemistry alterations indicative of adverse effects on the liver in male and female mice exposed to 1,1,2-trichloroethane in drinking water for 90 days. An uncertainty factor of 10 each was applied for inter- and intraspecies variation and for extrapolation to lifetime exposure from an intermediate exposure duration.
1,1,2-Trichloroethane exerts a narcotic action at "low" concentrations and is irritating to the eyes and mucous membranes of the respiratory tract (IARC 1979).
Inhalation of 13,600 ppm 1,1,2-trichloroethane for 2 hours was fatal to laboratory animals (species not given) (ACGIH 1991). For a 6-hour exposure, Bonnet et al. (1980) reported an LC50 of 1654 ppm for rats, while other studies showed mortality at lower concentrations. Smyth et al. (1969) found that exposure to 500 ppm for 8 hours was fatal to 4/6 rats. In an unpublished Dow Chemical study reported by Torkelson (1994), it was shown that single 7-hour exposures to 250 or 500 ppm resulted in the death of more than half of exposed female rats. Surviving animals exhibited marked liver and kidney damage. Rats exposed to 250 ppm for 4 hours survived, but showed liver and kidney necrosis. Exposures for 1 or 2 hours to 250 ppm did not produce gross or microscopic lesions of the liver or kidney, and all rats survived a 7-hour exposure to 100 ppm (not examined microscopically).
1,1,2-Trichloroethane is a central nervous system depressant inducing narcosis; death results from respiratory arrest. As a central nervous system depressant, 1,1,2-trichloroethane is considerably more potent than chloroform. Narcotic concentrations also produce respiratory tract and eye irritation. Concentrations producing deep narcosis followed by respiratory arrest were on the order of 13,600 ppm for a 2-hour exposure (species not given) (ACGIH 1991). A concentration of 3750 ppm for 30 minutes produced central nervous system depression and significantly increased serum glutamic oxalacetic transaminase activity in mice (Gehring 1968). At this exposure concentration, the ET50 (time required to produce a specific effect in half the animals) for serum glutamic oxalacetic transaminase elevation was 17.5 minutes, the ET50 for anesthesia was 18 minutes, and the LT50 (time required to cause death in one half of the mice) was 10 hours.
Information on the subchronic toxicity of 1,1,2-trichloroethane in humans following inhalation exposure was not available.
In an unpublished Dow Chemical study reported by Torkelson (1994), rats, guinea pigs, and rabbits were exposed to 30 ppm 1,1,2-trichloroethane, 7 hours/day, 5 days/week for 16 exposures or 15 ppm, 7 hours/day, 5 days/week for 6 months. No effects were observed on organ weights, hematology, or clinical chemistry parameters at 15 ppm, but female rats exposed to 30 ppm exhibited minor fatty changes and cloudy swelling in the liver.
Long-term exposure to 1,1,2-trichloroethane vapor (concentration not reported) has caused chronic gastric symptoms, fat deposition in the kidneys, and damage to the lungs (IARC 1979). Further details were not provided.
Information on the chronic toxicity of 1,1,2-trichloroethane in animals following inhalation exposure was not available.
Information on the developmental and reproductive toxicity of 1,1,2-trichloroethane in humans or animals following inhalation exposure was not available.
An inhalation reference concentration for 1,1,2-trichloroethane is under review by the EPA (1995a).
When in contact with skin, 1,1,2-trichloroethane produces cracking and erythema (IARC 1979). Stinging, burning, and transient whitening of the skin was reported in an individual who had received a topical application of 1.5 mL of 1,1,2-trichloroethane on 3.1 cm2 skin under occlusion for 5 minutes (Wahlberg 1984a). In an open test with the same individual, application of 0.1 mL of 1,1,2-trichloroethane produced no erythema. No visible skin reactions were found in another study, in which a volunteer was given daily open applications of 0.1 mL of 1,1,2-trichloroethane for 15 days (Wahlberg 1984b).
Smyth et al. (1969) reported a dermal LD50 of 3.73 mL/kg for rabbits. Topical application of 465 mg/cm2 of 1,1,2-trichloroethane produced pyknotic nuclei in epidermal cells of guinea pigs within 15 minutes. Skin damage progressed to vesicle formation and separation of skin layers with increased duration of exposure (Kronevi et al. 1977). A single topical application of 1 or 2 g of 1,1,2-trichloroethane/kg killed 1/4 rabbits; similar treatment with 0.5 kg caused signs of intoxication, delayed recovery, and liver and kidney injury (ACGIH 1991). Daily open applications of 0.1 mL for 10 days produced increased skin-fold thickness, marked erythema and edema, and fissuring and scaling in guinea pigs and rabbits (Wahlberg 1984b). Following topical application of 0.5 or 2.0 mL, all 20 guinea pigs died within 3 days, whereas only 5/20 animals died after treatment with 0.25 mL. Surviving animals gained weight more slowly than controls (Wahlberg 1976).
1,1,2-Trichloroethane applied directly to the eye did not produce significant corneal necrosis in rabbits (Smyth et al. 1969). The chemical was classified as a slight eye irritant, producing moderate conjunctivitis and epithelial abrasion in rabbits (Duprat et al. 1976).
Intraperitoneal LD50s for mice and dogs are 0.35 mL/kg and 0.45 mL/kg, respectively (Klaassen and Plaa 1967). Near lethal doses produced kidney necrosis in both species and liver necrosis in dogs. The reported ED50 for kidney necrosis was 0.17 mL/kg for mice and 0.4 mL/kg for dogs examined 24 hours after dosing.
Divicenzo and Kravasage (1974) administered 1,1,2-trichloroethane by intraperitoneal injection at doses of 200 or 400 mg/kg to guinea pigs. Serum ornithine carbamyl transferase activity as an indicator of hepatotoxicity was measured 24 hours later. Ornithine carbamyl transferase activity was increased at both doses indicating moderate hepatotoxicity according to the authors' classification. Liver damage was confirmed by histopathological examination showing liver necrosis and, at the higher dose, lipid deposition.
Information on the subchronic toxicity of 1,1,2-trichloroethane by other routes of exposure in humans or animals was not available.
Information on the chronic toxicity of 1,1,2-trichloroethane by other routes of exposure in humans or animals was not available.
Information on the developmental or reproductive toxicity of 1,1,2-trichloroethane by other routes of exposure in humans or animals was not available.
1. Liver: Subchronic exposure has produced effects on liver enzymes in mice.
2. Immune system: Subchronic exposure has resulted in effects on immune function in mice.
1. Hematopoietic system: Decreased hemoglobin and hematocrit values were reported in female mice following subchronic exposure.
2. Nervous system: Sedation, drowsiness, incoordination, and taste aversion to saccharin were reported in acutely exposed animals, but longer-term studies did not report neurological effects.
The available data do not permit determination of primary target organs. Long-term human exposure to 1,1,2-trichloroethane vapor has been reported to cause chronic gastric symptoms, fat deposition in the kidneys, and damage to the lungs. However, further details were not provided. In animals, short-term exposure to high concentrations has produced central nervous system depression as well as liver and kidney damage.
No other target organs were identified.
Skin: When in contact with skin, 1,1,2-trichloroethane produces cracking and erythema.
Information on the carcinogenicity of 1,1,2-trichloroethane in humans following oral exposure was not available.
Groups of B6C3F1 mice or Osborne-Mendel rats (50 animals/sex/dose) were treated by gavage with 46 or 92 mg/kg/day (rats) and with 195 or 390 mg/kg/day (mice), 5 days/week for 78 weeks, followed by an observation period up to 35 weeks for rats and up to 13 weeks for mice (NCI 1978). No effects on tumor development were noted in rats. Treated mice had significantly (p < 0.01) increased incidences of hepatocellular carcinomas. The incidences were 2/17, 0/20, 18/49, and 37/49 (males) and 0/20, 2/20, 16/48, and 40/45 (females) for the vehicle control, untreated control, low-dose, and high-dose groups, respectively. High-dose male and female mice also had increased incidences of adrenal pheochromocytomas (8/48 for males and 12/43 for females), tumors that were not seen at the lower doses or in controls.
In a cancer initiation/promotion study, Story et al. (1986) gave rats a single oral dose of 69 mg/kg of 1,1,2-trichloroethane, followed by treatment for 8 weeks with phenobarbital (as promoter of hepatocellular carcinomas). In the promotion experiment, diethylnitrosamine was used as the initiator and 1,1,2-trichloroethane as the possible promoter. No evidence was observed that 1,1,2-trichloroethane was a tumor initiator or promoter, using liver foci with altered enzyme levels as preneoplastic markers.
Information on the carcinogenicity of 1,1,2-trichloroethane in humans or animals following inhalation exposure was not available.
Information on the carcinogenicity of 1,1,2-trichloroethane in humans by other routes of exposure was not available.
Subcutaneous injection of 15.4 or 46.8 µmol of 1,1,2-trichloroethane in dimethylsulfoxide once a week for 2 years had no effect on the incidence of benign mesenchymal and epithelial tumors in rats (Norpoth et al. 1988). The incidence of sarcomas (predominantly of the extremities) increased with dose and was significantly increased in high-dose rats compared to untreated controls. As stated in ATSDR (1989), the lack of sarcomas in the untreated controls was unusual for this strain, and when compared to the spontaneous incidence of sarcomas reported in the literature, this increase was no longer significant. In addition, the sarcoma incidence was not increased when compared to vehicle controls.
Classification--C, possible human carcinogen (EPA 1995a)
Basis--Based on hepatocellular carcinomas and adrenal pheochromocytomas in one strain of mice. Carcinogenicity was not shown in rats. 1,1,2-Trichloroethane is structurally related to 1,2-dichloroethane, a probable human carcinogen (Group B2).
SLOPE FACTOR: 5.7E-2 (mg/kg/day)-1 (EPA 1995a)
UNIT RISK: 1.6E-6 (µg/L)-1 (EPA 1995a)
PRINCIPAL STUDY: NCI (1978)
COMMENT: The doses are time-weighted-averages adjusted for frequency of exposure (5/7 days). The weight of mice was assumed to be 0.033 kg.
SLOPE FACTOR: 5.7E-2 (mg/kg/day)-1 (EPA 1995b)
UNIT RISK: 1.6E-5 (µg/m3)-1 (EPA 1995a)
PRINCIPAL STUDY: NCI (1978)
COMMENT: The inhalation slope factor is based on route-to-route extrapolation.
ACGIH (American Conference of Governmental Industrial Hygienists). 1991. Documentation of the Threshold Limit Values and Biological Exposure Indices, 6th Ed. ACGIH, Cincinnati, Ohio, pp. 1607-1610.
ACGIH. 1986. Documentation of the Threshold Limit Values and Biological Exposure Indices, 5th Ed. ACGIH, Cincinnati, Ohio, p. 594.
ATSDR (Agency for Toxic Substances and Disease Registry). 1989. Toxicological Profile for 1,1,2-Trichloroethane. ATSDR/TP-89/24, prepared by Syracuse Research Corporation, under Subcontract to Clement Associates, Inc., Contract No. 205-88-0608, U.S. Public Health Service.
Bonnet, P., Francin, J. M., Gradiski, D., et al. 1980. "Determination of the median lethal concentration of principal chlorinated aliphatic hydrocarbons in the rat," Arch. Mal. Prof. Med. Trav. Secur. Soc. 41:317-321 (French; cited in ATSDR 1989).
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Duprat, P., L. Delsaut, and D. Gradsiki. 1976. "Irritating power of the principal aliphatic chloride solvents on the skin and ocular mucosa of the rabbit," Eur. J. Toxicol. Environ. 9: 171-177 (French; cited in ATSDR 1989).
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EPA. 1995a. Integrated Risk Information System (IRIS). Environmental Criteria and Assessment Office, Office of Health and Environmental Assessment, Cincinnati, Ohio.
EPA. 1995b. Health Effects Assessment Summary Tables. Annual FY-95. Prepared for the Office of Health and Environmental Assessment, Environmental Criteria and Assessment Office, Cincinnati, Ohio, for the Office of Emergency and Remedial Response, Washington, D.C.
Gehring, P. J. 1968. "Hepatotoxic potency of various chlorinated hydrocarbon vapors relative to their narcotic and lethal potencies in mice," Toxicol. Appl. Pharmacol. 13: 287-298.
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