The Risk Assessment Information System

Toxicity Profiles

Condensed Toxicity Summary for TETRACHLOROETHYLENE

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.

MARCH 1993

Prepared by: Mary Lou Daugherty, M.S., Chemical Hazard Evaluation Group, Biomedical Environmental Information Analysis Section, Health and Safety Research Division, Oak Ridge National Laboratory*, Oak Ridge, Tennessee.

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.

Tetrachloroethylene (CAS No. 127-18-4) is a halogenated aliphatic hydrocarbon with a vapor pressure of 17.8 mm Hg at 25C (U.S. EPA, 1982). The chemical is used primarily as a solvent in industry and, less frequently, in commercial dry-cleaning operations (ATSDR, 1990). Occupational exposure to tetrachloroethylene occurs via inhalation, resulting in systemic effects, and via dermal contact, resulting in local effects. Exposure to the general population can occur through contaminated air, food and water (ATSDR, 1990).

The respiratory tract is the primary route of entry for tetrachloroethylene (NTP, 1986; U.S. EPA, 1988). The chemical is rapidly absorbed by this route and reaches an equilibrium in the blood within 3 hours after the initiation of exposure (Hake and Stewart, 1977). Tetrachloroethylene is also significantly absorbed by the gastrointestinal (g.i.) tract, but not through the skin (Koppel et al., 1985; ATSDR, 1990). The chemical accumulates in tissues with high lipid content, where the half-life is estimated to be 55 hours (Stewart, 1969; ATSDR, 1990), and has been identified in perirenal fat, brain, liver, placentofetal tissue, and amniotic fluid (Savolainen et al., 1977). The proposed first step for the biotransformation of tetrachloroethylene is the formation of an epoxide thought to be responsible for the carcinogenic potential of the chemical (Henschler and Hoos, 1982; Calabrese and Kenyon, 1991). Tetrachloroethylene is excreted mainly unchanged through the lungs, regardless of route of administration (NTP, 1986). The urine and feces comprise secondary routes of excretion (Monster et al., 1979; Ohtsuki et al., 1983). The major urinary metabolite of tetrachloroethylene, trichloroacetic acid, is formed via the cytochrome P-450 system (ATSDR, 1990).

The main targets of tetrachloroethylene toxicity are the liver and kidney by both oral and inhalation exposure, and the central nervous system by inhalation exposure. Acute exposure to high concentrations of the chemical (estimated to be greater than 1500 ppm for a 30-minute exposure) may be fatal to humans (Torkelson and Rowe, 1981). Chronic exposure causes respiratory tract irritation, headache, nausea, sleeplessness, abdominal pains, constipation, cirrhosis of the liver, hepatitis, and nephritis in humans; and microscopic changes in renal tubular cells, squamous metaplasia of the nasal epithelium, necrosis of the liver, and congestion of the lungs in animals (Chmielewski et al., 1976; Coler and Rossmiller, 1953; Stewart et al., 1970; von Ottingen, 1964; Stewart, 1969; NTP, 1986).

Some epidemiology studies have found an association between inhalation exposure to tetrachloroethylene and an increased risk for spontaneous abortion, idiopathic infertility, and sperm abnormalities among dry-cleaning workers, but others have not found similar effects (Kyyronen et al, 1989; van der Gulden and Zielhuis, 1989). The adverse effects in humans are supported in part by the results of animal studies in which tetrachloroethylene induced fetotoxicity (but did not cause malformations) in the offspring of treated dams (Schwetz et al., 1975; Beliles et al., 1980; Nelson et al., 1980).

Reference doses (RfDs) for subchronic and chronic oral exposure to tetrachloroethylene are 1E-1 mg/kg/day and 1E-2 mg/kg/day, respectively (Buben and Flaherty, 1985; U.S. EPA, 1990; 1992a). These values are based on hepatotoxicity observed in mice given 100 mg tetrachloroethylene/kg body weight for 6 weeks and a no-observed-adverse effect level (NOAEL) of 20 mg/kg.

Epidemiology studies of dry cleaning and laundry workers have demonstrated excesses in mortality due to various types of cancer, including liver cancer, but the data are regarded as inconclusive because of various confounding factors (Lynge and Thygesen, 1990; U.S. EPA, 1988). The tenuous finding of an excess of liver tumors in humans is strengthened by the results of carcinogenicity bioassays in which tetrachloroethylene, administered either orally or by inhalation, induced hepatocellular tumors in mice (NCI, 1977; NTP, 1986). The chemical also induced mononuclear cell leukemia and renal tubular cell tumors in rats. Tetrachloroethylene was negative for tumor initiation in a dermal study and for tumor induction in a pulmonary tumor assay (Van Duuren et al., 1979; Theiss et al., 1977).

Although U.S. EPA's Science Advisory Board recommended a weight-of-evidence classification of C-B2 continuum (C = possible human carcinogen; B2 = probable human carcinogen), the agency has not adopted a current position on the weight-of-evidence classification (U.S. EPA, 1992b). In an earlier evaluation, tetrachloroethylene was assigned to weight-of-evidence Group B2, probable human carcinogen, based on sufficient evidence from oral and inhalation studies for carcinogenicity in animals and no or inadequate evidence for carcinogenicity to humans (NCI, 1977; NTP, 1986; U.S. EPA, 1987). The unit risk and slope factor values for tetrachloroethylene have been withdrawn from IRIS and HEAST. The upper bound risk estimates from the 1985 Health Assessment Document (U.S. EPA, 1985) as amended by inhalation values from the 1987 addendum (U.S. EPA, 1987) have not yet been verified by the IRIS-CRAVE Workgroup. For oral exposure, the slope factor is 5.2E-2 (mg/kg/day)-1; the unit risk is 1.5E-6 (µg/L)-1. For inhalation exposure, the slope factor is 2.0E-3 (mg/kg/day)-1; the unit risk ranges from 2.9E-7 to 9.5E-7 (µg/m3)-1 with a geometric mean of 5.8E-7 (µg/m3)-1 (U.S. EPA, 1987). When the Agency makes a decision about weight-of-evidence, the CRAVE-IRIS verification will be completed and the information put on IRIS (U.S. EPA, 1992b).

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