Dense Nonaqueous Phase Liquids (DNAPLs)

Halogenated Alkanes

Carbon Tetrachloride

Human Health Toxicity

Exposure of the general population to carbon tetrachloride (CT) might occur via inhalation of ambient air, or ingestion of drinking water. Inhalation and dermal exposure can occur when contaminated water is used for showering. Although banned from consumer products, the general population might still be exposed to background concentrations of CT in air and water. The extremely slow breakdown of this compound in the environment has resulted in its persistence and accumulation; however, there is little evidence of contamination of foodstuffs with CT, and the compound does not appear to bioaccumulate. Occupational exposure to CT in chemical manufacturing plants would most likely occur via inhalation. Residents of areas close to plants engaged in production of the chemical might be exposed to fugitive emissions that result in elevated concentrations in ambient air.

CT is readily absorbed by the gastrointestinal tract after oral exposure, and is also readily absorbed from the lungs. Dermal exposure to the compound results in absorption through the skin, but this is thought to proceed more slowly than absorption from either the gut or lung. Once absorbed, the target organs for CT toxicity in humans and laboratory rodents are the liver, kidneys, and central nervous system. A general pattern of liver and renal toxicity in humans and laboratory animal species is observed independent of the route of exposure.

CT is acutely toxic and was a cause of death by accidental poisoning when domestic use was not subject to regulation. Deaths from accidental poisoning have been reported for both oral and inhalation exposures. Concurrent dermal exposure may have contributed to accidental death in some instances. Autopsy reports of cases of CT poisoning have noted marked necrosis and fatty degeneration of the liver, as well as pulmonary edema (fluid in the lungs), a condition deemed to be secondary to renal failure.

Laboratory rodents exposed to low concentrations of CT vapor showed increased liver weight, alterations in enzyme levels, and lesions of the liver that included fibrosis, cirrhosis, the deposition of ceroid, a wax-like yellow/white pigment, and necrosis. Renal toxicity occurred in these studies at concentrations higher than those required for liver toxicity.

A small number of case studies (individual exposures) implicate CT in the development of human liver cancer. Epidemiological studies provide some suggestion that CT is positively associated with cancer development in exposed individuals; however, the results of these studies are confounded by the likely exposure of the subjects to other carcinogenic solvents and by the lack of definitive evidence of CT exposure. Laboratory rodent studies offer strong evidence that CT is carcinogenic, producing cancerous tumors of the liver, both carcinomas and adenomas, and cancers of the adrenal glands.

EPA's Integrated Risk Information System (IRIS) presents an RfD (an estimated daily oral exposure to a substance that is likely to be without deleterious effects on the general population, including sensitive sub-groups) for CT of 7 x 10-⁴ mg/kg/day. The RfD is based on the results of a study in rats that reported sensitive non-cancer endpoints, such as alterations in enzyme levels and development of lesions in the livers of laboratory animals.

The IRIS record for CT classifies the compound as "B2; Probable human carcinogen" based on its carcinogenicity in laboratory rodents. To calculate the cancer risk from CT-contaminated drinking water, IRIS derived a concentration of 3 µg/L as being applicable to a 1 x 10-⁵ risk level (one additional case of cancer in 100,000). In addition, IRIS provides an Inhalation Unit Risk (IUR), the carcinogenic risk associated with continuous (lifetime) exposure to 1 µg/m³ carbon tetrachloride in air. The IUR value is 1.5 x 10-⁵ per µg/m³. The eleventh Report on Carcinogens states: "Carbon tetrachloride is reasonably anticipated to be a human carcinogen based on sufficient evidence of carcinogenicity in experimental animals" (NTP 2005). In addition, the International Agency for Research on Cancer's (IARC) 1987 evaluation carbon tetrachloride stated: "There is inadequate evidence in humans for the carcinogenicity of carbon tetrachloride," and "There is sufficient evidence in experimental animals for the carcinogenicity of carbon tetrachloride," with the overall evaluation that CT "is possibly carcinogenic in humans (Group 2B)." The 1999 IARC update for CT reiterated these conclusions.

EPA's maximum contaminant level (MCL) for CT in drinking water is 5 µg/L.

The Regional Screening Levels (formerly Preliminary Remediation Goals) posted by EPA Region 9 identify risk-based concentrations for chloroform for the following common exposure pathways:

Residential soil	2.5 E-01 mg/kg
Industrial soil	1.2 E-00 mg/kg
Residential air	1.6 E-01 µg/m3
Industrial air	8.2 E-01 µg/m3
Tapwater	2.0 E-01 µg/L

References

Carbon Tetrachloride
World Health Organization, Geneva. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Vol. 71, p 401-432, 1987

Carbon Tetrachloride, CAS No. 56-23-5
Report on Carcinogens, Twelfth Edition. U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program (NTP), 2011

Carbon Tetrachloride (CASRN 56-23-5)
U.S. EPA, Integrated Risk Information System (IRIS)

Carbon Tetrachloride (Group 2B)
World Health Organization, Geneva. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Vol. 71, 1999

Public Health Goals for Carbon Tetrachloride in Drinking Water
Parker, T.
California EPA, Office of Environmental Health Hazard Assessment, 39 pp, 2000

Toxicological Profile for Carbon Tetrachloride
Agency for Toxic Substances and Disease Registry (ATSDR), 361 pp, 2005

For Further Information

Scope of the Risk Evaluation for Carbon Tetrachloride (Methane, Tetrachloro-)
EPA 740-R-17-010, 65 pp, 2017

EPA presents the occupational scenarios in which workers and occupational non-users might be exposed to carbon tetrachloride during conditions of use, such as manufacturing, processing, repackaging, and recycling. EPA believes that workers and bystanders as well as certain other groups of individuals may experience greater exposures to carbon tetrachloride than the general population. The report is accompanied online by a separate extensive bibliography of literature concerning the chemical's fate, exposure, and environmental and human health hazards.

Toxicological Review for Carbon Tetrachloride (CAS No. 56-23-5) in Support of Summary Information on the Integrated Risk Information System (IRIS)
U.S. EPA, Washington, DC. EPA 635-R-08-005F, 473 pp, 2010

Ecological Toxicity

Few studies were found that describe the response of ecological receptors to CT, and those that do generally are range-finding studies, performed to determine a range of toxic concentrations that might adversely impact a particular species. The endpoint chosen for such studies is often the death of a predetermined percentage of the organisms under test. For example, an LC₅₀ (lethal concentration) study determines the median concentration that will kill 50 percent of the test organisms. Usually the time-period taken to kill the organisms is stated; however, times for the LC₅₀ studies reported here have not been readily available. LC₅₀ studies have been performed to determine the effect of CT on aquatic species, including invertebrates, fish, and amphibians. CT is moderately toxic to the water flea, Moina macrocarpa, with an LC₅₀ of 2.3 mg/L, slightly toxic to the scud, Gammarus pseudolimnaeus (LC₅₀ 11.1 mg/L), and not acutely toxic to three other species: the brine shrimp, the rotifer, and the water flea Daphnia magna (LC₅₀ 280 mg/L). An invertebrate species that is sensitive to CT is the flatworm Dugesia japonica, with an LC₅₀ value of 0.2 mg/L (Kegley et al. 2009).

Eight studies using various species of fish suggest that the chemical is slightly toxic to the zebra danio, bluegill, golden orfe, fathead minnow, and sole, with LC₅₀ values reported between 13 and 63.3 mg/L. CT is not acutely toxic to carp, inland silverside, and medaka, with LC₅₀ values of 283.5, 150, and 637 mg/L respectively.

The larval stage (fertilization to 4 days after hatching) of the bullfrog, Rana catesbeiara, appears to be particularly susceptible to CT, with a reported LC₅₀ value of 0.92 mg/L.

Although few studies are available that document investigation of the toxicity of CT to terrestrial wildlife, there is concern for the potential toxicity of VOCs toward burrowing animals, such as snakes, tortoises, gophers, ground squirrels, rats, moles, voles, coyotes, badgers, and foxes, as well as birds such as the burrowing owl. Subsurface soil contaminated with VOCs presents a risk from inhalation exposure as in a burrow the contaminant may disperse poorly to the external atmosphere. Some species spend most of their lives within their burrows, and many burrowing species rear their young in nurseries constructed within them (Roy et al. 2009).

References

1,1,1-Trichloroethane
Irwin, R. et al.
Environmental Contaminants Encyclopedia, National Park Service, 1997

Carbon Tetrachloride
Irwin, R. et al.
Environmental Contaminants Encyclopedia, National Park Service, 1997

Carbon Tetrachloride Health and Safety Guide
World Health Organization, Geneva. International Programme on Chemical Safety, Health and Safety Guide 108, 1998

Carbon Tetrachloride: Identification, Toxicity, Use, Water Pollution Potential, Ecological Toxicity and Regulatory Information
Kegley, S.E., B.R. Hill, S. Orme, and A.H. Choi.
PAN Pesticide Database. Pesticide Action Network, San Francisco, CA, 2009

Evaluating Vapor Risk Intrusion in Ecological Risk Assessment
Roy M., S. Smith, and B. Elkland.
2009 DoD Environmental Monitoring & Data Quality Workshop, San Antonio, Texas, March 30 - April 3, 2009

Dichloroethane-1,2 (EDC 1,2-Dichloroethane)
Irwin, R. et al.
Environmental Contaminants Encyclopedia, National Park Service, 1997