ATSDR: Camp Lejeune, and tetrachloroethylene (PCE)

Camp Lejeune, North Carolina

Agency for Toxic Substances and Disease Registry, 4770 Buford Hwy NE, Atlanta, GA 30341 / Contact CDC: 800-232-4636 / TTY: 888-232-6348

Reported health effects linked with trichloroethylene (TCE), tetrachloroethylene (PCE), benzene, and vinyl chloride (VC) exposure

Reported health effects linked with TCE, PCE, benzene, and VC exposure in people

Q: What did the 1998 ATSDR health study “Volatile Organic Compounds in Drinking Water and Adverse Pregnancy Outcomes” at Camp Lejeune find?

A: Overall, the study found a link between PCE-contaminated drinking water and lower birth weights for infants of older mothers and mothers with histories of fetal loss. PCE-contaminated drinking water was also linked with small-for-gestational-age infants for older mothers and mothers with two or more prior fetal losses. This study could not look at fetal deaths because existing records were not complete. Because of errors in the exposure information available at that time, ATSDR will reanalyze this study when the water modeling is completed.

Q: What have other studies found about the persistent health effects of TCE, PCE, benzene, and VC?

A: The effects of exposure to any chemical depend on—

• When you are exposed (during pregnancy, in infancy),
• How much you are exposed to,
• How long you are exposed,
• How you are exposed (breathing, drinking), and
• What your personal traits and habits are.

Therefore, not everyone who is exposed to TCE, PCE, benzene, or VC will develop a health problem.

A limited number of studies have been done that looked at the health problems in children and adults related to drinking water contaminated with TCE and PCE. Only one study (in New Jersey) has looked at the health problems in children related to drinking water contaminated with benzene or VC. However, too few children were exposed to benzene or VC in that study to reach any conclusion about health problems. No studies have looked at the health problems in adults related to drinking water contaminated with benzene and VC.

A much larger number of studies have looked at health problems among workers exposed to TCE, PCE, benzene, and VC. Below is a list of the types of health outcomes that have been found to be linked to TCE, PCE, benzene, and VC. The numbers in parentheses indicate the reference for the study. All of the references are listed at the end.

Reported health problems in children who were exposed in the womb from their mother drinking water contaminated with TCE and/or PCE include—

• Leukemia (1-3)
• Small for gestational age (4-6)
• Low birth weight (6-8)
• Fetal death (4, 7, 9)
• Major heart defects (7, 10)
• Neural tube defects (4, 7, 9)
• Oral cleft defects (including cleft lip) (4, 7, 9)
• Chonal atresia (nasal passages blocked with bone or tissue) (4, 9)
• Eye defects (4, 9)

Reported health problems in children who were exposed in the womb from their mother working with TCE and/or PCE include—

• Low birth weight (11)
• Miscarriage (12, 13)
• Major malformations (11)

Reported health problems in people of all ages from drinking water contaminated with TCE and/or PCE include—

• Non-Hodgkins lymphoma (1, 12)
• Leukemia (1, 17)
• Rectal cancer (14)
• Bladder cancer (17)
• Breast cancer (18)
• Lung cancer (14)

Reported health problems in people of all ages from working with TCE and/or PCE include—

• Hodgkins disease (15)
• Non-Hodgkins lymphoma (15)
• Cervical cancer (15)
• Esophageal cancer (15, 30, 31)
• Kidney cancer (15)
• Liver/biliary cancer (15)
• Ovarian cancer (15)
• Prostate cancer (15)
• End-stage renal disease (29)
• Neurological effects (delayed reaction times problems with short-term memory, visual perception, attention, and color vision) (13)
• Severe, generalized hypersensitivity skin disorder (an autoimmune-related disease) (32)
• Scleroderma (32)

Reported health problems in people of all ages from working with benzene include—

• Non-Hodgkin’s lymphoma (19, 20)
• Leukemias (21, 22)
• Multiple myeloma (23)
• Aplastic anemia (24)
• Miscarriage (24)

Reported health problems in people of all ages from working with VC include—

• Liver cancer (25, 26)
• Soft tissue sarcoma (26)
• Brain cancer (26)
• Lung cancer (27)
• Liver cirrhosis (28)

Workers are exposed to much higher levels of TCE, PCE, benzene, and VC than are people who drink contaminated water. Therefore, the health problems seen in people who worked with TCE, PCE, benzene, and VC may not be seen in people who drank contaminated water.

For health problems not listed in the tables—

• Studies, so far, do not support a link with the particular health outcome and TCE, PCE, benzene, or VC exposure, or
• There is not enough information to see if the outcome is linked to TCE, PCE, benzene, or VC exposure.

Q: How are studies in animals and people different?

A: In studies done in laboratory animals, such as mice, the animals are exposed to much higher levels of chemicals than are people. Animals are also exposed in different ways than are people. In animal studies, we know the exact types and levels of chemicals the animals are exposed to. We can’t tell for certain the exact levels people are exposed to. Also, people are usually exposed to multiple chemicals. Medications, alcohol intake, and lifestyle factors also play a role in how these chemicals affect people.

Reported health effects linked with TCE, PCE, benzene, and VC exposure in animals

Q: What health effects are seen in animal studies of PCE exposure?

A: Results of animal studies showed that PCE can cause liver and kidney damage. The studies also showed that PCE can cause liver cancer in animals. Exposure at very high levels of PCE can be harmful to the unborn pups of pregnant rats and mice. Changes in behavior were seen in the offspring of rats that breathed high levels of the chemical while they were pregnant. Behavioral changes included being hyperactive. Various neurological problems were seen in both the mother and offspring. Neurological problems included being unable to coordinate muscles and decreased movement.

Q: What health effects are seen in animals from TCE exposure?

A: Results of animal studies showed that TCE may cause liver, kidney, or lung cancer. The studies also showed that TCE can cause neurological problems and liver and kidney damage in animals. Neurological problems included being unable to coordinate muscles and decreased movement.

Q: What health effects are seen in animals from benzene exposure?

A: Results of animal studies showed that benzene may cause Zymbal-gland (ear canal) carcinoma, oral-cavity tumors, skin cancer, lymphoma, lung tumors, ovarian tumors, and mammary-gland carcinoma.

Q: What health effects are seen in animals from VC exposure?

A: Results of animal studies showed that VC may cause tumors in the liver, lung,
mammary-gland, Zymbal-gland (ear canal), kidney, skin, and stomach, and angiosarcoma (blood-vessel tumors) and adenocarcinoma (tumors of the linings of organs) at various sites. VC also caused genetic damage including mutations, DNA damage, chromosome damage or loss, chromosomal aberrations (changes in chromosome structure or number), and sister chromatid exchange.

Reported health effects linked with TCE, PCE, benzene, and VC exposure in both people and animals

Q: What health effects are seen in both people and animals from TCE, PCE, benzene, and VC exposure?

A: When there are studies in people, results of animal studies are used to help support any observed links. Results of animal studies are used when there are no studies in people. Reported health effects seen in both people and animals include—

• Lung cancer
• Kidney cancer
• Liver cancer
• Lymphoma
• Breast cancer
• Neurological effects

Some health effects seen in people cannot be tested for in animals.

References

1. Cohn P, Klotz J, Bove F, Fagliano J. 1994. Drinking water contamination and the incidence of leukemia and non-Hodgkin’s lymphoma. Environ Health Perspect 102:556-61.

2. Costas K, Knorr RS, Condon SK. 2002. A case-control study of childhood leukemia in Woburn, Massachusetts: the relationship between leukemia incidence and exposure to public drinking water. Sci Total Environ 300:23-35.

3. New Jersey Department of Health and Senior Services. 2003. Case-control study of childhood cancers in Dover Township (Ocean Country), New Jersey. Trenton, New Jersey: New Jersey Department of Health and Senior Services.

4. Massachusetts Department of Public Health, Centers for Disease Control and Prevention, Massachusetts Health Research Institute. 1996. Final report of the Woburn environmental and birth study. Boston, Massachusetts: Massachusetts Department of Public Health.

5. Agency for Toxic Substances and Disease Registry. 1998. Volatile organic compounds in drinking water and adverse pregnancy outcomes: U.S. Marine Corps Camp Lejeune, North Carolina. Atlanta: US Department of Health and Human Services.

6. Sonnenfeld N, Hertz-Picciotto I, Kaye WE. 2001. Tetrachloroethylene in drinking water and birth outcomes at the US Marine Corps Base at Camp Lejeune, North Carolina. Am J Epidemiol 154(10):902-8.

7. Bove FJ, Fulcomer MC, Klotz JB, Esmart J, et al. 1995. Public drinking water contamination and birth outcomes. Am J Epidemiol 141:850-62.

8. Rodenbeck SE, Sanderson LM, Rene A. 2000. Maternal exposure to trichloroethylene in drinking water and birthweight outcomes. Arch Environ Health 55:188–194.

9. Bove F, Shim Y, Zeitz P. 2002. Drinking water contaminants and adverse pregnancy outcomes: a Review. Environ Health Perspect 110(S): 61-73.

10. Goldberg SJ, Lebowitz MD, Graver EJ, Hicks S. 1990. An association of human congenital cardiac malformations and drinking water contaminants. J Am Coll Cardiol 16:155–164.

11. Khattak S, K-Moghtader G, McMartin K, Barrera M, et al. 1999. Pregnancy outcome following gestational exposure to organic solvents: a prospective controlled study. JAMA 281(12): 1106-09.

12. Pesticide and Environmental Toxicology Section, Office of Environmental Health Hazard Assessment, California Environmental Protection Agency. 1999. Public health goal for trichloroethylene in drinking water. Sacramento, California.

13. Pesticide and Environmental Toxicology Section, Office of Environmental Health Hazard Assessment, California Environmental Protection Agency. 2001. Public health goal for tetrachloroethylene in drinking water. Sacramento, California.

14. Paulu C, Aschengrau A, Ozonoff D. 1999. Tetrachloroethylene-contaminated drinking water in Massachusetts and the risk of colon-rectum, lung, and other cancers. Environ Health Perspect 107(4):265-71.

15. Wartenberg D, Reyner D, Scott CS. 2000. Trichloroethylene and cancer: epidemiologic evidence. Environ Health Perspect 108(S2):161-176.

16. Morgan RW, Kelsh MA, Zhao K, Heringer S. 1998. Mortality of aerospace workers exposed to trichloroethylene. Epidemiology 9(4):424-31.

17. Aschengrau A, Ozonoff D, Paulu C, Coogan P, Vezina R, Heeren T, Zhang Y. 1993. Cancer risk and tetrachloroethylene-contaminated drinking water in Massachusetts. Arch Environ Health. 48:284-92.

18. Aschengrau A, Rogers S, Ozonoff D. 2003. Perchloroethylene-contaminated drinking water and the risk of breast cancer: additional results from Cape Cod, Massachusetts, USA. Environ Health Perspect 111(2):167-73.

19. Steinmaus C, Smith AH, Jones RM, Smith MT. 2008. Meta-analysis of benzene exposure and non-Hodgkin’s lymphoma: Biases could mask an important association. Occup. Environ. Med. 65(6):371-8.

20. Mehlman MA. 2006. Causal relationship between non-Hodgkin’s lymphoma and exposure to benzene and benzene-containing solvents. Ann. N.Y. Acad. Sci. 1076:120–128.

21. Rinsky RA, Hornung RW, Silver SR, Tseng CY. 2002. Benzene exposure and hematopoietic mortality: A long-term epidemiologic risk assessment. Am J Ind Med. 42(6):474-80

22. Glass DC, Gray CN, Jolley DJ, Gibbons C, et al. 2003. Leukemia risk associated with low-level benzene exposure. Epidemiology. 14(5):569-577.

23. Infante PF. 2006. Benzene Exposure and Multiple Myeloma: A Detailed Meta-analysis of Benzene Cohort Studies. Ann. N.Y. Acad. Sci. 1076:90–109.

24. Khan HA. 2007. Short Review: Benzene’s toxicity: a consolidated short review of human and animal studies. Hum Exp Toxicol. 26; 677-685.

25. Bosetti C, La Vecchia C, Lipworth L, McLaughlin JK. 2003. Occupational exposure to vinyl chloride and cancer risk: a review of the epidemiologic literature. European Journal of Cancer Prevention. 12:427–430.

26. Boffetta P, Matisane L, Mundt KA, Dell LD. 2003. Meta-analysis of studies of occupational exposure to vinyl chloride in relation to cancer mortality. Scand J Work Environ Health. 29:220-229.

27. Scelo G, Constantinescu V, Csiki I, Zaridze D, et al. 2004. Occupational exposure to vinyl chloride, acrylonitrile and styrene and lung cancer risk (Europe). Cancer Causes Control. 15:445-452.

28. Grosse Y, Baan R, Straif K, Secretan B, et al. 2007. Carcinogenicity of 1,3-butadiene, ethylene oxide, vinyl chloride, vinyl fluoride, and vinyl bromide. Oncology: The Lancet. 8:679-680.

29. Calvert GM, Ruder AM, Petersen MR. 2010. Mortality and end-stage renal disease incidence among dry cleaning workers. OEM [Epub ahead of print, Dec 16, 2010]

30. U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program 2005. Report on Carcinogens, Eleventh Edition.

31. Mundt KA, Birk T, Burch MT. 2003. Critical review of the epidemiological literature on occupational exposure to perchloroethylene and cancer. Int Arch Occup Environ Health. 76:473-91.

32. Cooper GS, Makris SL, Nietert PJ, Jinot J. 2009. Evidence of Autoimmune-Related Effects of Trichloroethylene Exposure from Studies in Mice and Humans. Environ Health Perspect 117:696–702.

You can find more information in:

EPA and tetrachloroethylene (perchloroethylene)

Hazard Summary-Created in April 1992; Revised in January 2000

Tetrachloroethylene is widely used for dry-cleaning fabrics and metal degreasing operations. The main effects of tetrachloroethylene in humans are neurological, liver, and kidney effects following acute (short-term) and chronic (long-term) inhalation exposure. Adverse reproductive effects, such as spontaneous abortions, have been reported from occupational exposure to tetrachloroethylene; however, no definite conclusions can be made because of the limitations of the studies. Results from epidemiological studies of dry-cleaners occupationally exposed to tetrachloroethylene suggest increased risks for several types of cancer. Animal studies have reported an increased incidence of liver cancer in mice, via inhalation and gavage (experimentally placing the chemical in the stomach), and kidney and mononuclear cell leukemia in rats. In the mid-1980s,

EPA considered the epidemiological and animal evidence on tetrachloroethylene as intermediate between a probable and possible human carcinogen (Group B/C). The Agency is currently reassessing its potential carcinogenicity.

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 and the RfD, and the Agency for Toxic Substances and Disease Registry’s (ATSDR’s) Toxicological Profile for Tetrachloroethylene. Another secondary source is EPA’s Health Effects Assessment for Tetrachloroethylene.

Uses

• Tetrachloroethylene is used for dry cleaning and textile processing, as a chemical intermediate, and for vapor degreasing in metal-cleaning operations. (1)

Sources and Potential Exposure

• Prior to 1981, tetrachloroethylene was detected in ambient air at average levels of 0.16 parts per billion (ppb) in rural and remote areas, 0.79 ppb in urban and suburban areas, and 1.3 ppb in areas near emission sources. (1)
• Tetrachloroethylene has also been detected in drinking water; one survey prior to 1984 of water supplies from groundwater sources reported a median concentration of 0.75 ppb for the samples in which tetrachloroethylene was detected, with a maximum level of 69 ppb. (1)
• Occupational exposure to tetrachloroethylene may occur, primarily in dry cleaning establishments and at industries manufacturing or using the chemical. (1)

Assessing Personal Exposure

• Tetrachloroethylene can be measured in the breath, and breakdown products of tetrachloroethylene can be measured in the blood and urine. (1)

Health Hazard Information

Acute Effects:

• Effects resulting from acute, inhalation exposure of humans to tetrachloroethylene vapors include irritation of the upper respiratory tract and eyes, kidney dysfunction, and at lower concentrations, neurological effects, such as reversible mood and behavioral changes, impairment of coordination, dizziness, headache, sleepiness, and unconciousness. (1)
• Animal studies have reported effects on the liver, kidney, and central nervous system (CNS) from acute inhalation exposure to tetrachloroethylene. (1)
• Acute animal tests in mice have shown tetrachloroethylene to have low toxicity from inhalation and oral exposure. (1)

Chronic Effects (Noncancer):

• The major effects from chronic inhalation exposure to tetrachloroethylene in humans are neurological effects, including sensory symptoms such as headaches, impairments in cognititve and motor neurobehavioral functioning and color vision decrements. Other effects noted in humans include cardiac arrhythmia, liver damage, and possible kidney effects. (1,5)
• Animal studies have reported effects on the liver, kidney, and CNS from chronic inhalation exposure to tetrachloroethylene. (1,5)
• EPA has not established a Reference Concentration (RfC) for tetrachloroethylene. (4)
• The Reference Dose (RfD) for tetrachloroethylene is 0.01 milligrams per kilogram body weight per day (mg/kg/d) based on hepatotoxicity in mice and weight gain in rats. The RfD is an estimate (with uncertainty spanning perhaps an order of magnitude) of a daily oral exposure to the human population (including sensitive subgroups) that is likely to be without appreciable risk of deleterious noncancer effects during a lifetime. It is not a direct estimator of risk, but rather a reference point to gauge the potential effects. At exposures increasingly greater than the RfD, the potential for adverse health effects increases. Lifetime exposure above the RfD does not imply that an adverse health effect would necessarily occur. (4)
• EPA has medium confidence in the RfD based on low confidence in the study on which the RfD was based due to the lack of complete histopathological examination at the no-observed-adverse-effect level (NOAEL) in the mouse; and medium confidence in the database because it is relatively complete but lacks studies of reproductive and teratology endpoints subsequent to oral exposure. (4)
• ATSDR has calculated a chronic-duration inhalation minimal risk level (MRL) of 0.04 parts per million (ppm) (0.3 milligrams per cubic meter, mg/m³) for tetrachloroethylene based on neurological effects in humans. The MRL is an estimate of the daily human exposure to a hazardous substance that is likely to be without appreciable risk of adverse noncancer health effects over a specified duration of exposure. (1)
• Repeated skin contact may cause irritation. (1)

Reproductive/Developmental Effects:

• Some adverse reproductive effects, such as spontaneous abortions, menstrual disorders, altered sperm structure, and reduced fertility, have been reported in studies of workers occupationally exposed to tetrachloroethylene. However, no definitive conclusions can be made because of the limitations of the studies. (1)
• In one study of residents exposed to drinking water contaminated with tetrachloroethylene and other solvents, there was a suggestion that birth defects were associated with exposure. However, no firm conclusions can be drawn from this study due to multiple chemical exposures and problems with the analysis. (1)
• Increased fetal resorptions and effects to the fetus have been reported in animals exposed to high levels of tetrachloroethylene by inhalation. (1)

Cancer Risk:

• Epidemiological studies of dry cleaning workers exposed to tetrachloroethylene and other solvents suggest an increased risk for a variety of cancers (esophagus, kidney, bladder, lung, pancreas, and cervix). These studies are complicated by potential exposure to other chemicals and personal lifestyle factors such as alcohol consumption and smoking were not taken into account. (1,5,6)
• One human study reported that there was a potential association between drinking water contaminated with tetrachloroethylene and other chemicals and an increased risk of childhood leukemia. The statistical significance of the incidence of leukemia has not been resolved. (1)
• Animal studies have reported an increased incidence of liver tumors in mice, from inhalation and gavage (experimentally placing the chemical in the stomach) exposure, and kidney and mononuclear cell leukemias in rats, via inhalation exposure. (1,5,6)
• Less than 5 percent of absorbed tetrachloroethylene is metabolized by humans to trichloroacetic acid (TCA), with the remainder being exhaled unchanged. TCA is classified as a Group C, possible human carcinogen based on limited evidence of liver tumors in mice (but not rats). (4,7)
• EPA does not currently have a classification for the carcinogenicity of tetrachloroethylene. The International Agency for Research on Cancer (IARC) has classified tetrachloroethylene as probably carcinogenic to humans.
• EPA uses mathematical models, based on animal studies, to estimate the probability of a person developing cancer from breathing air containing a specified concentration of a chemical. EPA has calculated a provisional inhalation unit risk estimate of 5.8 × 10^-7 (µg/m³)^-1. A provisonal value is one which has not received Agency-wide review. (7)
• EPA has calculated a provisional oral cancer slope factor of 0.051 (mg/kg/d)^-1. (5)

Physical Properties

• Tetrachloroethylene is a nonflammable colorless liquid with a sharp sweet odor; the odor threshold is 1 ppm. (1)
• The chemical formula for tetrachloroethylene is C₂Cl₄, and the molecular weight is 165.83 g/mol. (1)
• The vapor pressure for tetrachloroethylene is 18.47 mm Hg at 25 °C, and it has a log octanol/water partition coefficient (log K_ow) of 3.40. (1)

Conversion Factors:
To convert concentrations in air (at 25°C) from ppm to mg/m³: mg/m³ = (ppm) × (molecular weight of the compound)/(24.45). For tetrachloroethylene: 1 ppm = 6.78 mg/m³. To convert concentrations in air from µg/m³ to mg/m³: mg/m³ = (µg/m³) × (1 mg/1,000 µg).

AIHA ERPG–American Industrial Hygiene Association’s emergency response planning guidelines. ERPG 1 is the maximum airborne concentration below which it is believed nearly all individuals could be exposed up to one hour without experiencing other than mild transient adverse health effects or perceiving a clearly defined objectionable odor; ERPG 2 is the maximum airborne concentration below which it is believed nearly all individuals could be exposed up to one hour without experiencing or developing irreversible or other serious health effects that could impair their abilities to take protective action.
ACGIH STEL–American Conference of Governmental and Industrial Hygienists’ short-term exposure limit; 15-min time-weighted-average exposure that should not be exceeded at any time during a workday even if the 8-h time-weighted-average is within the threshold limit value.
ACGIH TLV–American 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)–A 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.
NIOSH IDLH– National Institute of Occupational Safety and Health’s immediately dangerous to life or health concentration; NIOSH recommended exposure limit to ensure that a worker can escape from an exposure condition that is likely to cause death or immediate or delayed permanent adverse health effects or prevent escape from the environment.
OSHA PEL–Occupational 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.

The health and regulatory values cited in this factsheet were obtained in December 1999.
^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. OSHA numbers are regulatory, whereas NIOSH, ACGIH, and AIHA numbers are advisory.
^cThe LOAEL is from the critical study used as the basis for the ATSDR chronic inhalation MRL.

References

1. Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological Profile for Tetrachloroethylene (Update). U.S. Public Health Service, U.S. Department of Health and Human Services, Atlanta, GA. 1997.
2. American Conference of Governmental and Industrial Hygienists (ACGIH). 1999 TLVs and BEIs: Threshold Limit Values for Chemical Substances and Physical Agents, Biological Exposure Indices. Cincinnati, OH. 1999.
3. Occupational Safety and Health Administration (OSHA). Occupational Safety and Health Standards, Toxic and Hazardous Substances. Code of Federal Regulations 29 CFR 1910.1000. 1998.
4. U.S. Environmental Protection Agency. Integrated Risk Information System (IRIS) on Tetrachloroethylene. National Center for Environmental Assessment, Office of Research and Development, Washington, DC. 1999.
5. U.S. Environmental Protection Agency. Health Effects Assessment for Tetrachloroethylene. EPA/600/8-89-096. Environmental Criteria and Assessment Office, Office of Health and Environmental Assessment, Office of Research and Development, Cincinnati, OH. 1988.
6. U.S. Environmental Protection Agency. Updated Health Assessment Document for Tetrachloroethylene. EPA/600/8-82/005B. Environmental Criteria and Assessment Office, Office of Health and Environmental Assessment, Office of Research and Development, Cincinnati, OH. 1988.
7. U.S. Environmental Protection Agency. Risk Assessment Issue Paper for Carcinogenicity Information for Tetrachloroethylene (Perchloroethylene, PERC) (CASRN 127-18-4). Superfund Technical Support Center, National Center for Environmental Assessment, Cincinnati, OH. nd.
8. National Institute for Occupational Safety and Health (NIOSH). Pocket Guide to Chemical Hazards. U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention. Cincinnati, OH. 1997.
9. American Industrial Hygiene Association (AIHA). The AIHA 1998 Emergency Response Planning Guidelines and Workplace Environmental Exposure Level Guides Handbook. 1998.
10. U.S. Environmental Protection Agency. National Emission Standards for Hazardous Air Pollutants: Wood Furniture Manufacturing Operations. Federal Register 63 FR 34336-346. June 24, 1998.

Tetrachloroethylene, also known under its systematic name tetrachloroethene and many other names, is a chlorocarbon with the formula Cl₂C=CCl₂. It is a colourless liquid widely used for dry cleaning of fabrics, hence it is sometimes called “dry-cleaning fluid.” It has a sweet odor detectable by most people at a concentration of 1 part per million (1 ppm). Worldwide production was about 1 megatonne in 1985.^[1]

Production

Michael Faraday first synthesized tetrachloroethylene in 1821 by thermal decomposition of hexachloroethane.

C₂Cl₆ → C₂Cl₄ + Cl₂

Most tetrachloroethene is produced by high temperature chlorinolysis of light hydrocarbons. The method is related to Faraday’s discovery since hexachloroethane is generated and thermally decomposes.^[1] Side products include carbon tetrachloride, hydrogen chloride, and hexachlorobutadiene.

Several other methods have been developed. When 1,2-dichloroethane is heated to 400 °C with chlorine, tetrachloroethene is produced by the chemical reaction:

ClCH₂CH₂Cl + 3 Cl₂ → Cl₂C=CCl₂ + 4 HCl

This reaction can be catalyzed by a mixture of potassium chloride and aluminium chloride or by activated carbon. Trichloroethylene is a major byproduct, which is separated by distillation.

According to an EPA report of 1976, the quantity of Tetrachloroethylene (also known as perchloroethylene or PCE) produced in the United States in just one year 1973, totaled 706 million pounds (320,000 metric tons). Diamond Shamrock, Dow Chemical Company, E.I DuPont and Vulcan Materials Company (Chemical Division) were among the top eight producers nationwide. ^[2]

Uses

Tetrachloroethylene is an excellent solvent for organic materials. Otherwise it is volatile, highly stable, and nonflammable. For these reasons, it is widely used in dry cleaning. Usually as a mixture with other chlorocarbons, it is also used to degrease metal parts in the automotive and other metalworking industries. It appears in a few consumer products including paint strippers and spot removers.

Historical applications

Tetrachloroethene was once extensively used as an intermediate in the manufacture of HFC-134a and related refrigerants. In the early 20th century, tetrachloroethene was used for the treatment for hookworm infestation.^[3]

Health and safety

The International Agency for Research on Cancer has classified tetrachloroethene as a Group 2A carcinogen, which means that it is probably carcinogenic to humans.^[4] Like many chlorinated hydrocarbons, tetrachloroethene is a central nervous system depressant and can enter the body through respiratory or dermal exposure.^[5] Tetrachloroethene dissolves fats from the skin, potentially resulting in skin irritation.

Animal studies and a study of 99 twins by Dr. Samuel Goldman and researchers at the Parkinson’s Institute in Sunnyvale, California determined there is a “lot of circumstantial evidence” that exposure to tetrachloroethene increases the risk of developing Parkinson’s disease ninefold. Larger population studies are planned.^[6]

At temperatures over 600 °F (316 °C), such as in welding, tetrachloroethylene can decompose into phosgene, an extremely poisonous gas.^[7][8] Tetrachloroethylene should not be used near welding operations, flames, or hot surfaces.^[9]

Testing for exposure

Tetrachloroethene exposure can be evaluated by a breath test, analogous to breath-alcohol measurements. Because it is stored in the body’s fat and slowly released into the bloodstream, tetrachloroethene can be detected in the breath for weeks following a heavy exposure. Tetrachloroethylene and trichloroacetic acid (TCA), a breakdown product of tetrachloroethene, can be detected in the blood.

In Europe, the Scientific Committee on Occupational Exposure Limits (SCOEL) recommends for tetrachloroethylene an occupational exposure limit (8h time-weighted average) of 20 ppm and a short-term exposure limit (15 min) of 40 ppm.^[10]

Environmental contamination

Tetrachloroethene is a common soil contaminant. With a specific gravity greater than 1, tetrachloroethylene will be present as a dense nonaqueous phase liquid if sufficient quantities of liquid are spilled in the environment. Because of its mobility in groundwater, its toxicity at low levels, and its density (which causes it to sink below the water table), cleanup activities are more difficult than for oil spills. Recent research has focused on the in place remediation of soil and ground water pollution by tetrachloroethylene. Instead of excavation or extraction for above-ground treatment or disposal, tetrachloroethylene contamination has been successfully remediated by chemical treatment or bioremediation. Bioremediation has been successful under anaerobic conditions by reductive dechlorination by Dehalococcoides sp. and under aerobic conditions by cometabolism by Pseudomonas sp.^[11][12] Partial degradation daughter products include trichloroethylene, cis-1,2-dichloroethene and vinyl chloride; full degradation converts tetrachloroethylene to ethene and hydrogen chloride dissolved in water.

Estimates state that 85% of tetrachloroethylene produced is released into the atmosphere; while models from OECD assumed that 90% is released into the air and 10% to water. Based on these models, its distribution in the environment is estimated to be in the air (76.39% – 99.69%), water (0.23% – 23.2%), soil (0.06-7%), with the remainder in the sediment and biota. Estimates of lifetime in the atmosphere vary, but a 1987 survey estimated the lifetime in the air has been estimated at about 2 months in the Southern Hemisphere and 5–6 months in the Northern Hemisphere. Degradation products observed in a laboratory include phosgene, trichloroacetyl chloride, hydrogen chloride, carbon dioxide, and carbon monoxide. Tetrachloroethylene is degraded by hydrolysis, and is also persistent under aerobic conditions. This compound is degraded by reductive dechlorination with anaerobic conditions present, with the degradation products like trichloroethene, dichloroethene, vinyl chloride, ethene, and ethane.^[13]

References

Further reading

• “Toxicological Profile for Tetrachloroethene”. Agency for Toxic Substances and Disease Registry. 1997.

• Doherty, R.E. (2000). “A History of the Production and Use of Carbon Tetrachloride, Tetrachloroethylene, Trichloroethylene and 1,1,1-Trichloroethane in the United States: Part 1 – Historical Background; Carbon Tetrachloride and Tetrachloroethylene”. Environmental Forensics 1 (2): 69–81. DOI:10.1006/enfo.2000.0010.

External links

• ATSDR Case Studies in Environmental Medicine: Tetrachloroethylene Toxicity U.S. Department of Health and Human Services
• Australian National Pollutant Inventory (NPI) page
• “Toxic Fumes May Have Made Gunman Snap”, by Julian Kesner, New York Daily News, April 20, 2007.

67-66-3

Hazard Summary-Created in April 1992; Revised in January 2000

Chloroform may be released to the air as a result of its formation in the chlorination of drinking water, wastewater and swimming pools. Other sources include pulp and paper mills, hazardous waste sites, and sanitary landfills. The major effect from acute (short-term) inhalation exposure to chloroform is central nervous system depression. Chronic (long-term) exposure to chloroform by inhalation in humans has resulted in effects on the liver, including hepatitis and jaundice, and central nervous system effects, such as depression and irritability. Chloroform has been shown to be carcinogenic in animals after oral exposure, resulting in an increase in kidney and liver tumors. EPA has classified chloroform as a Group B2, probable human carcinogen.

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 and the RfD, and the carcinogenic effects of chloroform including the unit cancer risk for inhalation exposure, and the Agency for Toxic Substances and Disease Registry’s (ATSDR’s) Toxicological Profile for Chloroform.

Uses

• The vast majority of the chloroform produced in the United States is used to make HCFC-22. The rest is produced for export and for miscellaneous uses. (1)
• Chloroform was used in the past as an extraction solvent for fats, oils, greases, and other products; as a dry cleaning spot remover; in fire extinguishers; as a fumigant; and as an anesthetic. However, chloroform is no longer used in these products. (1)

Sources and Potential Exposure

• Chloroform may be released to the air from a large number of sources related to its manufacture and use, as well as its formation in the chlorination of drinking water, wastewater, and swimming pools. Pulp and paper mills, hazardous waste sites, and sanitary landfills are also sources of air emissions. The background level of chloroform in ambient air in the early 1990s was estimated at 0.00004 parts per million (ppm). (1)
• Human exposure to chloroform may occur through drinking water, where chloroform is formed as a result of the chlorination of naturally occurring organic materials found in raw water supplies. Measurements of chloroform in drinking water during the 1970s and 1980s ranged from 0.022 to 0.068 ppm. (1)
• Chloroform may also be found in some foods and beverages, largely from the use of tap water during production processes. (1)

Assessing Personal Exposure

• Chloroform can be detected in blood, urine, and body tissues. However, these methods are not very reliable because chloroform is rapidly eliminated from the body, and the tests are not specific for chloroform. (1)

Health Hazard Information

Acute Effects:

• The major effect from acute inhalation exposure to chloroform in humans is central nervous system depression. At very high levels (40,000 ppm), chloroform exposure may result in death, with concentrations in the range of 1,500 to 30,000 ppm producing anesthesia, and lower concentrations (<1,500 ppm) resulting in dizziness, headache, tiredness, and other effects. (1,2)
• Effects noted in humans exposed to chloroform via anesthesia include changes in respiratory rate, cardiac effects, gastrointestinal effects, such as nausea and vomiting, and effects on the liver and kidney. Chloroform is not currently used as a surgical anesthetic. (1,2)
• In humans, a fatal oral dose of chloroform may be as low as 10 mL (14.8 g), with death due to respiratory or cardiac arrest. (1,2)
• Tests involving acute exposure of animals have shown chloroform to have low acute toxicity from inhalation exposure and moderate acute toxicity from oral exposure. (3)

Chronic Effects (Noncancer):

• Chronic exposure to chloroform by inhalation in humans is associated with effects on the liver, including hepatitis and jaundice, and central nervous system effects, such as depression and irritability. Inhalation exposures of animals have also resulted in effects on the kidney. (1,2)
• Chronic oral exposure to chloroform in humans has resulted in effects on the blood, liver, and kidney. (1,2)
• EPA has not established a Reference Concentration (RfC) for chloroform. (4)
• The California Environmental Protection Agency (CalEPA) has established a chronic reference exposure level of 0.3 milligrams per cubic meter (mg/m³) for chloroform based on exposures resulting in kidney and liver effects in rats. The CalEPA reference exposure level is a concentration at or below which adverse health effects are not likely to occur. It is not a direct estimator of risk, but rather a reference point to gauge the potential effects. At lifetime exposures increasingly greater than the reference exposure level, the potential for adverse health effects increases. (5)
• ATSDR has established an acute inhalation minimal risk level (MRL) of 0.5 mg/m³ (0.1 ppm) based on exposures resulting in liver effects in mice, an intermediate inhalation MRL of 0.2 mg/m³ (0.05 ppm) based on worker exposures resulting in liver effects in humans, and a chronic inhalation MRL of 0.1 mg/m³ (0.02 ppm) also based on liver effects in humans. The MRL is an estimate of the daily human exposure to a hazardous substance that is likely to be without appreciable risk of adverse noncancer health effects over a specified duration of exposure. (1)
• The Reference Dose (RfD) for chloroform is 0.01 milligrams per kilogram per day (mg/kg/d) based on exposures resulting in fatty cyst formation in the livers of dogs. The RfD is an estimate (with uncertainty spanning perhaps an order of magnitude) of a daily oral exposure to the human population (including sensitive subgroups) that is likely to be without appreciable risk of deleterious noncancer effects during a lifetime. (4)
• EPA has medium to low confidence in the RfD due to: medium confidence in the critical study on which the RfD was based because only two treatment doses were used, and a no-observed-effect level (NOEL) was not determined; and medium to low confidence in the database because several studies support the choice of a lowest-observed-adverse-effect level (LOAEL), but a NOEL was not found. (4)

Reproductive/Developmental Effects:

• Little information is available on the reproductive or developmental effects of chloroform in humans, via any route of exposure. A possible association between certain birth outcomes (e.g., low birth weight, cleft palate) and consumption of contaminated drinking water was reported. However, because multiple contaminants were present, the role of chloroform is unclear. (1)
• Animal studies have demonstrated developmental effects, such as decreased fetal body weight, fetal resorptions, and malformations in the offspring of animals exposed to chloroform via inhalation. (1)
• Reproductive effects, such as decreased conception rates, decreased ability to maintain pregnancy, and an increase in the percentage of abnormal sperm were observed in animals exposed to chloroform through inhalation. (1)
• Animal studies have noted decreased fetal weight, increased fetal resorptions, but no evidence of birth defects, in animals orally exposed to chloroform. (1)

Cancer Risk:

• No information is available regarding cancer in humans or animals after inhalation exposure to chloroform. (1)
• Epidemiologic studies suggest an association between cancer of the large intestine, rectum, and/or bladder and the constituents of chlorinated drinking water, including chloroform. However, there are no epidemiologic studies of water containing only chloroform. (1)
• Chloroform has been shown to be carcinogenic in animals after oral exposure, resulting in an increase in kidney and liver tumors. (1)
• EPA considers chloroform to be a probable human carcinogen and has ranked it in EPA’s Group B2. (4)
• EPA has determined that although chloroform is likely to be carcinogenic to humans by all routes of exposure under high-exposure conditions that lead to cell death and regrowth in susceptible tissues, chloroform is not likely to cause cancer in humans by any route of exposure under exposure conditions that do not cause cell death and regrowth. Therefore, EPA has not derived either an oral carcinogenic potency slope or an inhalation unit risk for chloroform.

Physical Properties

• Chloroform is a colorless liquid that is not very soluble in water and is very volatile. (1,6)
• Chloroform has a pleasant, nonirritating odor; the odor threshold is 85 ppm. (1)
• The chemical formula for chloroform is CHCl₃, and it has a molecular weight of 119.38 g/mol. (1)
• The vapor pressure for chloroform is 159 mm Hg at 20 °C, and it has a log octanol/water partition coefficient (log K_ow) of 1.97. (1)

Conversion Factors:
To convert concentrations in air (at 25°C) from ppm to mg/m³: mg/m³ = (ppm) × (molecular weight of the compound)/(24.45). For chloroform: 1 ppm = 4.88 mg/m³. To convert concentrations in air from µg/m³ to mg/m³: mg/m³ = (µg/m³) × (1 mg/1,000 µg).

ACGIH TLV–American 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)–A 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.
NIOSH REL–National 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 PEL–Occupational 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.

The health and regulatory values cited in this factsheet were obtained in December 1999.
^aHealth 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. OSHA numbers are regulatory, whereas NIOSH and ACGIH numbers are advisory.
^cThese cancer risk estimates were derived from oral data and converted to provide the estimated inhalation risk.
^dThe LOAEL is from the critical study used as the basis for the CalEPA chronic reference exposure level.

References

1. Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological Profile for Chloroform. Public Health Service, U.S. Department of Health and Human Services, Atlanta, GA. 1997.
2. U.S. Department of Health and Human Services. Hazardous Substances Data Bank (HSDB, online database). National Toxicology Information Program, National Library of Medicine, Bethesda, MD. 1993.
3. 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.
4. U.S. Environmental Protection Agency. Integrated Risk Information System (IRIS) on Chloroform. National Center for Environmental Assessment, Office of Research and Development, Washington, DC. 1999.
5. California Environmental Protection Agency (CalEPA). Technical Support Document for the Determination of Noncancer Chronic Reference Exposure Levels. Draft for Public Comment. Office of Environmental Health Hazard Assessment, Berkeley, CA. 1997.
6. The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals. 11th ed. Ed. S. Budavari. Merck and Co. Inc., Rahway, NJ. 1989.
7. Occupational Safety and Health Administration (OSHA). Occupational Safety and Health Standards, Toxic and Hazardous Substances. Code of Federal Regulations. 29 CFR 1910.1000. 1998.
8. American Conference of Governmental Industrial Hygienists (ACGIH). 1999 TLVs and BEIs. Threshold Limit Values for Chemical Substances and Physical Agents. Biological Exposure Indices. Cincinnati, OH. 1999.
9. National Institute for Occupational Safety and Health (NIOSH). Pocket Guide to Chemical Hazards. U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention. Cincinnati, OH. 1997.