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BU School of Public Health research tetrachloroethylene (PCE)

Early Life Exposure to Chemical Solvent in Drinking Water May Affect Vision,

Submitted by: Lisa Chedekel / chedekel@bu.edu

Study Finds

Prenatal and early childhood exposure to the chemical solvent tetrachloroethylene (PCE) found in drinking water may be associated with long-term visual impairments, particularly in the area of color discrimination, a new study led by BU School of Public Health researchers has found.

The study by epidemiologists and biostatisticians at BUSPH, working with an ophthalmologist from the BU School of Medicine, found that people exposed to higher levels of PCE from gestation through age 5 exhibited poorer color-discrimination abilities than unexposed people. The study, published in the journal Environmental Health Perspectives, recommends further investigation into the visual impairments associated with PCE exposure.

The research team assessed visual functioning among a group of people born between 1969 and 1983 to parents residing in eight towns in the Cape Cod region of Massachusetts. The towns all had PCE in their drinking water because of pipes outfitted with a vinyl liner that was improperly cured. Previous studies led by Ann Aschengrau, professor of epidemiology at BUSPH, have found associations between PCE exposure and cancer, as well as reproductive and developmental outcomes. Increases in the risks of breast cancer and certain birth defects were seen in the team’s prior studies.

PCE is a known neurotoxin that was used to apply the vinyl liner of some drinking water pipes. Surveys have estimated that more than 600 miles of such pipes were installed in nearly 100 cities and towns in Massachusetts, mainly during the 1970s. Exposure to PCE from drinking water occurs by direct ingestion, dermal exposure during bathing, and by inhalation during showering, bathing and other household uses.

The pipes no longer leach PCE, but the chemical is still widely used in dry cleaning and metal degreasing solutions and is a common drinking water contaminant.

In testing vision, Aschengrau and colleagues found that people exposed to PCE made more major errors in color discrimination than those not exposed. The levels of color confusion were greatest among people with high exposure levels. PCE previously has been implicated in deficiencies in color discrimination, mainly among adults with occupational exposures. The new study is the first to assess “the associations between prenatal and early childhood exposure to PCE and adult vision,” Aschengrau said. The findings suggest that “the effects of early life PCE-exposure on color discrimination may be irreversible.”

The study — supported by the National Institute of Environmental Health Sciences Superfund Research Program — focused on the Cape Cod towns of Barnstable, Bourne, Brewster, Mashpee, Chatham, Falmouth, Provincetown and Sandwich.

In addition to Aschengrau, researchers on the project included: Janice M. Weinberg, professor of biostatistics; Patricia A. Janulewicz, postdoctoral associate in environmental health; Kelly D. Getz, a doctoral candidate in epidemiology; Veronica M. Vieira, previously associate professor of environmental health; Roberta F. White, chair and professor of environmental health; Michael R. Winter, associate director of the BUSPH Data Coordinating Center, and Brett R. Martin, statistical manager of the Data Coordinating Center; and Susannah Rowe, assistant professor of ophthalmology at the BU School of Medicine.

Submitted by: Lisa Chedekel / chedekel@bu.edu

Lisa Chedekel / chedekel@bu.edu

From the late 1960s to 1980, an estimated 600 miles of water pipes contaminated with a known neurotoxin were installed in nearly 100 cities and towns in Massachusetts.

According to a new study by researchers at the BU School of Public Health examining Cape Cod residents exposed to the neurotoxin PCE, children in contact with contaminated drinking water before birth and as infants and toddlers are more likely to use illegal drugs later in life.

The study, published online in Environmental Health earlier this month, is the first to examine associations between prenatal and early childhood exposure to PCE (tetrachloroethylene, also commonly called perchlorethylene or perc) and the development of risky behaviors—including smoking, drinking and drug use—in teenagers and adults. PCE was used in the vinyl liner of drinking water pipes for several years. Those pipes no longer leach the chemical, but it is still widely used in dry cleaning and metal degreasing solutions.

PCE is a common drinking water contaminant found throughout the country, including in parts of California and Pennsylvania and at Camp Lejeune, a Marine Corps base in North Carolina.

The SPH team, headed by Ann Aschengrau, a professor of epidemiology, has previously examined associations between PCE exposure and cancer, as well as reproductive and developmental outcomes. The prior studies showed increases in the risks of breast cancer and certain birth defects.

The new findings “present one more reason why we need to keep harmful chemicals like PCE out of our drinking water,” says Aschengrau.

The study found that the risk of using two or more illegal drugs as teenagers or adults for people with high exposure levels during gestation and early childhood was increased 1.5- to 1.6-fold. Increases in the use of cocaine, hallucinogens, club drugs, and Ritalin without a prescription were observed. Among highly exposed people, 30 percent to 60 percent increases in the risk of certain smoking and drinking behaviors also were seen. Previous studies have shown that chronic or high exposure to PCE among adults can have adverse effects on cognition, behavior, and mood.

In 1980, government officials in New England learned that PCE was leaching into public drinking water supplies from the vinyl lining of asbestos cement water-distribution pipes. The liner, which had been used since the late 1960s to address alkalinity problems, had been sprayed onto the inner pipe surface.

Surveys done after the discovery of contamination estimated the high number of such water pipes in the Bay State. Exposure to PCE from drinking water occurs by direct ingestion, exposure through the skin during bathing, and inhalation during showering, bathing, and other household uses.

The study subjects were born between 1969 and 1983 to married women living in Cape Cod towns known to have some vinyl-lined water pipes in their water distribution system. Eight towns in the study area were affected: Barnstable, Bourne, Falmouth, Mashpee, Sandwich, Brewster, Chatham, and Provincetown, each having from one to 50 miles of the vinyl-lined pipes.

PCE is a well-recognized animal and human neurotoxicant. Many epidemiologic studies of adults with occupational exposure to PCE and other solvents have reported impairments in cognition, memory, and attention. Mood changes, including increases in anxiety and depression, also have been reported.

The published literature examining neurotoxic effects among children exposed to organic solvents, including PCE, is relatively small, and the findings inconsistent. Four studies have found no deficits in cognitive and behavioral function and no increases in attention and learning disorders; two have found lower tests scores and more behavioral problems among children with prenatal or early childhood exposure. None of the prior studies examined possible long-lasting neurological consequences of early life exposure.

Aschengrau and her coauthors caution that because this study is the first to report the association between PCE exposure and risky behaviors, and because of other limitations, the findings “should be confirmed in follow-up investigations of similarly exposed populations.”

They also say that because PCE remains a commonly used commercial solvent that “exposes workers and consumers and causes frequent contamination of drinking water … it is important to determine its long-term impact on behavior.”

Other SPH researchers participating in the study include Michael R. Winter and Brett R. Martin, of the Data Coordinating Center, and Megan E. Romano (SPH’07) and Lisa G. Gallagher, of the University of Washington.

The study was funded by the National Institute of Environmental Health Sciences Superfund Research Program.

Lisa Chedekel can be reached at chedekel@bu.edu.

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.

• Graph and Table of Simulated and Measured Concentrations of PCE
• FAQs
• Additional Resources

The Agency for Toxic Substances and Disease Registry is the lead agency determining if exposures to volatile organic compounds (such as PCE, TCE, vinyl chloride, and benzene) in drinking water are associated with adverse health outcomes among the Marines, dependents, and civilian employees who lived or worked at Marine Corps Base Camp Lejeune, North Carolina.

Prior to March 1987, some of the water systems at Camp Lejeune were contaminated with volatile organic compounds (VOCs). To determine which base housing areas received contaminated water, a water-modeling approach using historical reconstruction is necessary. The approach includes modeling of the groundwater flow of contaminants and the distribution of these contaminants within the water systems. Based on this information, ATSDR will estimate exposures for each housing area for every month from the start of contamination until contaminated water-supply wells were permanently removed from operation.

Highlights

Tetrachloroethylene is a manufactured chemical used for dry cleaning and metal degreasing. Exposure to very high concentrations of tetrachloroethylene can cause dizziness, headaches, sleepiness, confusion, nausea, difficulty in speaking and walking, unconsciousness, and death. Tetrachloroethylene has been found in at least 771 of the 1,430 National Priorities List sites identified by the Environmental Protection Agency (EPA) and is a major drinking water contamination concern.

What is tetrachloroethylene?

Tetrachloroethylene is a manufactured chemical that is widely used for dry cleaning of fabrics and for metal-degreasing. It is also used to make other chemicals and is used in some consumer products.

Other names for tetrachloroethylene include perchloroethylene, PCE, and tetrachloroethene. It is a nonflammable liquid at room temperature. It evaporates easily into the air and has a sharp, sweet odor. Most people can smell tetrachloroethylene when it is present in the air at a level of 1 part tetrachloroethylene per million parts of air (1 ppm) or more, although some can smell it at even lower levels.

What happens to tetrachloroethylene when it enters the environment?

• Much of the tetrachloroethylene that gets into water or soil evaporates into the air.
• Microorganisms can break down some of the tetrachloroethylene in soil or underground water.
• In the air, it is broken down by sunlight into other chemicals or brought back to the soil and water by rain.
• It does not appear to collect in fish or other animals that live in water.

How might I be exposed to tetrachloroethylene?

• When you bring clothes from the dry cleaners, they will release small amounts of tetrachloroethylene into the air.
• When you drink water containing tetrachloroethylene, you are exposed to it

How can tetrachloroethylene affect my health?

Drinking water contamination due to high concentrations of tetrachloroethylene (particularly in closed, poorly ventilated areas) can cause dizziness, headache, sleepiness, confusion, nausea, difficulty in speaking and walking, unconsciousness, and death.

Irritation may result from repeated or extended skin contact with it. These symptoms occur almost entirely in work (or hobby) environments when people have been accidentally exposed to high concentrations or have intentionally used tetrachloroethylene to get a “high.”

In industry, most workers are exposed to levels lower than those causing obvious nervous system effects. The health effects of breathing in air or drinking water with low levels of tetrachloroethylene are not known.

Results from some studies suggest that women who work in dry cleaning industries where exposures to tetrachloroethylene can be quite high may have more menstrual problems and spontaneous abortions than women who are not exposed. However, it is not known if tetrachloroethylene was responsible for these problems because other possible causes were not considered.

Results of animal studies, conducted with amounts much higher than those that most people are exposed to, show that tetrachloroethylene can cause liver and kidney damage. Exposure to very high levels of tetrachloroethylene can be toxic to the unborn pups of pregnant rats and mice. Changes in behavior were observed in the offspring of rats that breathed high levels of the chemical while they were pregnant.

How likely is tetrachloroethylene to cause cancer?

The Department of Health and Human Services (DHHS) has determined that tetrachloroethylene may reasonably be anticipated to be a carcinogen. Tetrachloroethylene has been shown to cause liver tumors in mice and kidney tumors in male rats.

Is there a medical test to show whether I’ve been exposed to tetrachloroethylene??

One way of testing for drinking water contamination due to tetrachloroethylene exposure is to measure the amount of the chemical in the breath, much the same way breath-alcohol measurements are used to determine the amount of alcohol in the blood.

Because it is stored in the body’s fat and slowly released into the bloodstream, tetrachloroethylene can be detected in the breath for weeks following a heavy exposure.

Tetrachloroethylene and trichloroacetic acid (TCA), a breakdown product of tetrachloroethylene, can be detected in the blood. These tests are relatively simple to perform. These tests aren’t available at most doctors’ offices, but can be performed at special laboratories that have the right equipment.

Because exposure to other chemicals can produce the same breakdown products in the urine and blood, the tests for breakdown products cannot determine if you have been exposed to tetrachloroethylene or the other chemicals.

Has the federal government made recommendations to protect human health?

The EPA maximum contaminant level for the amount of tetrachloroethylene that can be in drinking water is 0.005 milligrams tetrachloroethylene per liter of water (0.005 mg/L).

The Occupational Safety and Health Administration (OSHA) has set a limit of 100 ppm for an 8-hour workday over a 40-hour workweek.

The National Institute for Occupational Safety and Health (NIOSH) recommends that tetrachloroethylene be handled as a potential carcinogen and recommends that levels in workplace air should be as low as possible.

Glossary

Carcinogen: A substance with the ability to cause cancer.

CAS: Chemical Abstracts Service.

Milligram (mg): One thousandth of a gram.

Nonflammable: Will not burn.

References

Agency for Toxic Substances and Disease Registry (ATSDR). 1997. Toxicological Profile for Tetrachloroethylene. Atlanta, GA: U.S. Department of Health and Human Services, Public Health Service.

Where can I get more information?

If you have questions or concerns regarding this drinking water contamination issue , please contact your community or state health or environmental quality department or:

ATSDR can also tell you the location of occupational and environmental health clinics. These clinics specialize in recognizing, evaluating, and treating illnesses resulting from exposure to hazardous substances.