Carbon tetrachloride [factsheet]

CARBON TETRACHLORIDE

Please Note: The main sources of information for this fact sheet are EPA's Integrated Risk Information System (IRIS), which contains information on oral chronic toxicity of carbon tetrachloride and the RfD, and the carcinogenic effects of carbon tetrachloride including the unit cancer risk for inhalation exposure, and the Agency for Toxic Substances and Disease Registry's (ATSDR's) Toxicological Profile for Carbon Tetrachloride. Other secondary sources include the Hazardous Substances Data Bank (HSDB), a database of summaries of peer-reviewed literature, and the Registry of Toxic Effects of Chemical Substances (RTECS), a database of toxic effects that are not peer reviewed.

Environmental/Occupational Exposure

* Individuals may be exposed to carbon tetrachloride in the air from accidental releases from production and uses, and from its disposal in landfills. (1)

* Carbon tetrachloride is also a common contaminant of indoor air; the sources of exposure appear to be building materials or products, such as cleaning agents, used in the home. (1)

* Workers involved in the manufacture or use of carbon tetrachloride are most likely to have significant exposures to carbon tetrachloride. (1)

* Individuals may also be exposed to carbon tetrachloride by drinking contaminated water. (1,2)

* In the past, ingestion of bread or other products made with carbon tetrachloride-fumigated grain may have contributed to dietary exposure, but this route of exposure is no longer believed to be of significance. (2)

Assessing Personal Exposure

* Measurement of carbon tetrachloride in exhaled breath has been the most convenient medium to determine exposure; measurements in blood, fat, or other tissues have also been used as indicators of exposure. However, these tests are not routinely available and cannot be used to predict whether any health effects will result. (1)

Health Hazard Information

Acute Effects:

* Acute (short-term) inhalation and oral exposures to carbon tetrachloride have been observed primarily to damage the liver and kidneys of humans. Depression of the central nervous system has also been reported. Symptoms of acute exposure in humans include headache, weakness, lethargy, nausea, and vomiting. (1-6)

* Delayed pulmonary edema has been observed in humans exposed to carbon tetrachloride by inhalation and ingestion, but this is believed to be due to injury to the kidney rather than direct action of carbon tetrachloride on the lung. (1)

* Acute animal exposure tests, such as the LC₅₀ and LD₅₀ tests in rats, mice, rabbits, and guinea pigs, have demonstrated carbon tetrachloride to have low toxicity from inhalation exposure, low-to-moderate toxicity from ingestion, and moderate toxicity from dermal exposure. (7)

Chronic Effects (Noncancer):

* Chronic (long-term) inhalation or oral exposure to carbon tetrachloride produces liver and kidney damage in humans and animals. (1,3,6,8)

* EPA has not established an RfC for carbon tetrachloride. (9)

* The RfD for carbon tetrachloride is 0.0007 mg/kg/d based on liver lesions in rats. (9)

* EPA has high confidence in the principal study on which the RfD was based because the study was well conducted and good dose-response was observed in the liver, which is the target organ for carbon tetrachloride toxicity; medium confidence in the database because four additional subchronic studies support the RfD, but reproductive and teratology endpoints are not well investigated; and, consequently, medium confidence in the RfD.

Reproductive/Developmental Effects:

* No information is available on the reproductive or developmental effects of carbon tetrachloride in humans.

* Decreased fertility in rats, decreased sperm production in male rats, degenerative changes in the testes, and a decreased survival rate of newborns have been observed in animals exposed to carbon tetrachloride orally and by inhalation. (1,6)

* Birth defects have not been observed in animals exposed to carbon tetrachloride by inhalation or ingestion. (1,2,8)

Cancer Risk:

* Occasional reports have noted the occurrence of liver cancer in workers who had been exposed to carbon tetrachloride by inhalation exposure; however, the data are not sufficient to establish a cause-and-effect relationship. (1,6,8-10)

* Liver tumors have developed in animals exposed to carbon tetrachloride by gavage (experimentally placing the chemical in their stomachs). (1-4,6,8-11)

* EPA has classified carbon tetrachloride as a Group B2, probable human carcinogen. (8,9)

* EPA uses mathematical models, based on human and animal studies, to estimate the probability of a person developing cancer from breathing air containing a specified concentration of a chemical. EPA calculated an inhalation unit risk of 1.5 H 10^-5 (m g/m³)^-1. EPA estimates that, if an individual were to breathe air containing carbon tetrachloride at 0.07 m g/m³* over his or her entire lifetime, that person would theoretically have no more than a one-in-a-million increased chance of developing cancer as a direct result of breathing air containing this chemical. Similarly, EPA estimates that breathing air containing 0.7 m g/m³ would result in not greater than a one-in-a-hundred thousand increased chance of developing cancer, and air containing 7.0 m g/m³ would result in not greater than a one-in-a-ten thousand increased chance of developing cancer. (9)

* EPA's Office of Air Quality Planning and Standards, for a hazard ranking under Section 112(g) of the Clean Air Act Amendments, has ranked carbon tetrachloride in the nonthreshold category. The 1/ED₁₀ value is 0.34 per (mg/kg)/d and this would place it in the low category under Superfund's ranking for carcinogenic hazard. (12)

Physical Properties

* The chemical formula for carbon tetrachloride is CCl₄, and its molecular weight is 153.8 g/mol. (1,2)

* Carbon tetrachloride is a clear, nonflammable liquid which is almost insoluble in water. (1)

* Carbon tetrachloride has a sweet characteristic odor, with an odor threshold above 10 ppm. (1)

* The vapor pressure for carbon tetrachloride is 91.3 mm Hg at 20 EC, and its log octanol/water partition coefficient (log K_ow) is 2.64. (1)

Uses

* Carbon tetrachloride has been produced in large quantities to make refrigerants and propellants for aerosol cans; production of fluorocarbon propellants is being phased out due to their effect on the ozone layer and this use of carbon tetrachloride is currently declining. (1)

* Carbon tetrachloride is used as a solvent for oils, fats, lacquers, varnishes, rubber waxes, and resins and as a starting material in the manufacture of organic compounds. (5,12)

* Carbon tetrachloride was formerly used as a dry cleaning agent, fire extinguisher, grain fumigant, and pesticide. (1,5,12)

Health Data from Inhalation Exposure

Concentration (mg/m³)	Health numbers^a	Regulatory, advisory numbers^b	Reference
100,000.0
_ _ _ _ 10,000.0	* LC₅₀ (mice) (59,938 mg/m³) * LC₅₀ (rats) (50,336 mg/m³)		7 7
_ _ _ _ 100.0
_ _ _ _ 10.0		* MSHA standard (63 mg/m³) * ACGIH TLV (31 mg/m³) * OSHA PEL and NIOSH REL (12.6 mg/m³)	7 7 7
_ _ _ _ 1.0
_ _ _ _ 0.1
_ _ _ _ 0.01
_ _ _ _ 0.001
_ _ _ _ 0.0001
_ _ _ _ 0.00001	* EPA Cancer Risk Level (1-in-a-million excess lifetime risk)^c (7 H 10^-5 mg/m³)		9

See notes on following page.

ACGIH TLVCAmerican Conference of Governmental and Industrial Hygienists' threshold limit value expressed as a time-weighted average; the concentration of a substance to which most workers can be exposed without adverse effects.

LC₅₀ (Lethal Concentration₅₀)CA calculated concentration of a chemical in air to which exposure for a specific length of time is expected to cause death in 50% of a defined experimental animal population.

MSHACMine Safety and Health Administration.

NIOSH RELCNational Institute of Occupational Safety and Health's recommended exposure limit; NIOSH-recommended exposure limit for an 8- or 10-h time-weighted-average exposure and/or ceiling.

OSHA PELCOccupational Safety and Health Administration's permissible exposure limit expressed as a time-weighted average; the concentration of a substance to which most workers can be exposed without adverse effect averaged over a normal 8-h workday or a 40-h workweek.

^a Health numbers are toxicological numbers from animal testing or risk assessment values developed by EPA.

^b Regulatory numbers are values that have been incorporated in Government regulations, while advisory numbers are nonregulatory values provided by the Government or other groups as advice.

^c These cancer risk estimates were derived from oral data and converted to provide the estimated inhalation risk.

References

1. Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological Profile for Carbon Tetrachloride (Draft). U.S. Public Health Service, U.S. Department of Health and Human Services, Atlanta, GA. 1992.

2. U.S. Environmental Protection Agency. Carbon Tetrachloride Health Advisory. Office of Drinking Water, Washington, DC. 1987.

3. U.S. Department of Health and Human Services. Hazardous Substances Databank (HSDB, online database). National Toxicology Information Program, National Library of Medicine, Bethesda, MD. 1993.

4. International Agency for Research on Cancer (IARC). IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans: Some Halogenated Hydrocarbons. Volume 20. World Health Organization, Lyon. 1979.

5. M. Sittig. Handbook of Toxic and Hazardous Chemicals and Carcinogens. 2nd ed. Noyes Publications, Park Ridge, NJ. 1985.

6. U.S. Environmental Protection Agency. Health Affects Document for Carbon Tetrachloride. EPA/600/8-82-001F. Environmental Criteria and Assessment Office, Office of Health and Environmental Assessment, Office of Research and Development, Cincinnati, OH. 1984.

7. U.S. Department of Health and Human Services. Registry of Toxic Effects of Chemical Substances (RTECS, online database). National Toxicology Information Program, National Library of Medicine, Bethesda, MD. 1993.

8. U.S. Environmental Protection Agency. Updated Health Effects Assessment for Carbon Tetrachloride. EPA/600/8-89/088. Environmental Criteria and Assessment Office, Office of Health and Environmental Assessment, Office of Research and Development, Cincinnati, OH. 1989.

9. U.S. Environmental Protection Agency. Integrated Risk Information System (IRIS) on Carbon Tetrachloride. Environmental Criteria and Assessment Office, Office of Health and Environmental Assessment, Office of Research and Development, Cincinnati, OH. 1993.

10. International Agency for Research on Cancer (IARC). IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans: Chemicals, Industrial Processess and Industries Associated with Cancer in Humans. Supplement 4. World Health Organization, Lyon. 1982.

11. International Agency for Research on Cancer (IARC). IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Volume 1. World Health Organization, Lyon. 1972.

12. The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals. 11th ed. Ed. S. Budavari. Merck and Co. Inc., Rahway, NJ. 1989.

13. U.S. Environmental Protection Agency. Technical Background Document to Support Rulemaking Pursuant to the Clean Air ActCSection 112(g). Ranking of Pollutants with Respect to Hazard to Human Health. EPAB450/3-92-010. Emissions Standards Division, Office of Air Quality Planning and Standards, Research Triangle Park, NC. 1994.