Substances Included Synonyms

Therapeutic Toxic Class

A)

Specific Substances

1) Tetrachloroethylene
2) Carbon bichloride
3) Carbon dichloride
4) ENT 1,860
5) Ethene, tetrachloro-
6) Ethylene tetrachloride
7) Ethylene, tetrachloro-
8) NCI-c 04580
9) Perc
10) Perchlor
11) Perchlorethylene
12) Perchloroethylene
13) Percosolve
14) Perk
15) Tetrachlorethylene
16) Tetrachloroethene
17) 1,1,2,2-Tetrachloroethylene
18) STCC 4940355
19) NIOSH/RTECS KX 3850000
20) Molecular Formula: C2-Cl4
21) CAS 127-18-4
22) References: RTECS, 1999; HSDB, 2001; Lewis, 1996
23) ETHYLENE, TETRACHLOR0-

1.2.1) MOLECULAR FORMULA
1) C2-Cl4
2) Cl2C:CCl2

Available Forms Sources

A)

1) Tetrachloroethylene is a colorless, clear, heavy, non-flammable, volatile liquid with a sweet ethereal or chloroform-like odor (noticeable on the breath of poisoning victims) (AAR, 2000; (CHRIS , 2001; Gaillard et al, 1995; Lewis, 1997; Lewis, 1998; NIOSH , 1999; Sittig, 1991).
2) Tetrachloroethylene is available in dry cleaning and industrial grades of 95+ percent purity (CHRIS , 2001).
3) Available grades are purified, technical, and USP (as tetrachloroethylene, spectrophotometric) (Lewis, 1997).
4) In the USA, tetrachloroethylene is available in the following grades: purified, technical, USP, spectrophotometric, and dry cleaning. Both the technical and dry cleaning grades meet the technical grade specifications, and differ only in the amounts of stabilizers, such as amines, thymol or mixtures of epoxides and esters. USP grade contains between 99 percent and 99.5 percent tetrachloroethylene, the remainder consisting of ethanol (HSDB , 2002) IARC, 1979).
5) It is also available in food grade (HSDB , 2002).
6) Tetrachloroethylene for veterinary medicinal use is available in the USA in 0.2, 0.5, 1.0, 2.5, and 5.0 milliliter size capsules (NemaWorm(R), Parke-Davis)(HSDB , 2002).
7) In Japan, the technical form of tetrachloroethylene has the following specifications: Max. 0.002% maximum amount of non-volatile matter; 0.0001% maximum amount of acidity (as HCl); pH 6.8 (OHM/TADS , 2001).
8) Tetrachloroethylene, available as DOWCLENE EC, contains 75% methyl chloroform and 25% tetrachloroethylene (OHM/TADS , 2001).

B)

1) Tetrachloroethylene can be manufactured via (Lewis, 1997):

1) Chlorination of hydrocarbons, followed by pyrolysis of the generated carbon tetrachloride;
2) Reaction between acetylene and chlorine (with trichloroethylene as intermediate).

2) It can also be manufactured through (Ashford, 1994; Budavari, 1996; HSDB , 2002):

1) Catalytic oxidation of 1,1,2,2,-tetrachloroethane;
2) Catalytic oxidation of acetylene;
3) Direct chlorination of ethylene (Huels method; yielding 70% tetrachloroethylene, 20% carbon tetrachloride, 10% other products);
4) Simultaneous chlorination and pyrolyzation of hydrocarbons (such as methane, ethane, propane) (yielding over 95% tetrachloroethylene, plus carbon tetrachloride and hydrochloric acid);
5) Oxyhydrochlorination, perchlorination and/or dehydrochlorination of hydrocarbons or chlorinated hydrocarbons (such as 1,2-dichloro- ethane, propylene, propylene dichloride, 1,1,2-trichloroethane).

3) Other manufacturing processes are (Ashford, 1994):

1) Chlorination of ethylene dichloride (also produces trichloroethylene);
2) Thermal dechlorination of carbon tetrachloride.

C)

1) Tetrachloroethylene is a solvent used extensively in dry cleaning and textile industries (ACGIH, 1991; Bingham et al, 2001; (HSIA, 1999); Lewis, 1997; Lewis, 1998).
2) US demand in 1998 was estimated to be 344 million pounds ((HSIA, 1999)).
3) Tetrachloroethylene was introduced as a dry cleaning agent in the late 1930's ((HSIA, 1999)).
4) It has been used as a dry cleaning solvent since then due to its nonflammability and low toxicity ((HSIA, 1999)).
5) It is used in chemical manufacturing (of fluorocarbons), as a drying agent for metals and some other solids, as a fumigant, as a heat transfer medium, and as a degreasing solvent (AAR, 2000; (Bingham et al, 2001; ITI, 1995; Lewis, 1996; Lewis, 1997; Sittig, 1991).
6) Perchloroethylene is a basic raw material in the manufacture of HFC 134a, an alternative to chloroflurocarbon refrigerants ((HSIA, 1999)).
7) It is used for cold cleaning and vapor degreasing of metals and as a drying agent for metals and other solids (HSDB , 2002; Lewis, 1998).
8) It is used as automotive aerosol solvent, and an intermediate in the production of particular fluorinated compounds ((HSIA, 1999)).
9) Tetrachloroethylene is used as an insulating fluid and cooling gas in electrical transformers (HSDB , 2002).
10) Tetrachloroethylene is a general solvent for rubber coatings, printing ink, glues, sealants, polishes, lubricants, and silicones. It is used in the manufacturing of fluorocarbons 113, 114, 115, and 116, in soot removal, as a heat exchange medium, and as a component of typewriter correction fluid (ACGIH, 1991; HSDB , 2002) IARC, 1979).
11) Tetrachloroethylene has been used as an anthelmintic (vermifuge) medication for hookworms and flukes in humans, small animals and ruminants, but more current treatments use drugs that are less toxic and easier to use (HSDB , 2002; Lewis, 1998).

a) Tetrachloroethylene is an effective anthelmintic medication for hookworms and flukes (JEF Reynolds , 1989; Sittig, 1991). It is ineffective against liver flukes and roundworms (JEF Reynolds , 1989).

12) In the past, tetrachloroethylene was used in grain protectant mixtures and liquid grain fumigants, but it is no longer approved for these uses (HSDB , 2002; Lewis, 1998).
13) Consumer products which contain tetrachloroethylene include water repellents, silicone lubricants, fabric finishers, spot removers, adhesives and wood cleaners ((ATSDR, 1997)).
14) Tetrachloroethylene is used in some tire inflation kits in pressurized cans (Isenschmid et al, 1998).
15) Inhalant abuse of this substance has been reported, with death as a result (Isenschmid et al, 1998).
16) "Tetrachloroethylene Draught" is a pharmacological mixture of tetrachlorethylene, acacia, peppermint emulsion and chloroform water (HSDB , 2002).

Overview

Life Support

A)

Clinical Effects

0.2.1)

A) USES: Tetrachloroethylene, also known as perchloroethylene, is a halogenated alkene solvent used extensively in dry cleaning and textile industries. It is a colorless, heavy, non-inflammable and volatile liquid with an ether-like odor (noticeable on the breath of poisoned victims).
B) TOXICOLOGY: Tetrachloroethylene is an anesthetic agent that causes acute CNS and respiratory depression; hypoxic death may occur if exposure is severe and prolonged. It may also decrease the myocardial threshold to the arrhythmogenic action of injected catecholamines.
C) ROUTE OF EXPOSURE: The main route of occupational exposure is by inhalation and it is readily absorbed through the lungs.
D) EPIDEMIOLOGY: Exposure can occur and is usually associated with occupational exposure.
E) WITH POISONING/EXPOSURE

1) ADVERSE EFFECTS: In general, tetrachloroethylene affects the liver, kidneys, and central nervous system. It can cause hepatic failure leading to hepatorenal syndrome and occasionally nephrotoxic renal failure. The liver is a target organ in humans for tetrachloroethylene toxicity.
2) ACUTE EFFECTS: Tetrachloroethylene is irritating to the eyes, skin and mucous membranes. Signs and symptoms of exposure may include CNS depression, malaise, dizziness, headache, lightheadedness, disorientation, seizures, respiratory tract irritation, noncardiogenic pulmonary edema, nausea, vomiting and diarrhea. Eye contact may cause pain, lacrimation and burning. Dermal exposure can cause dermatitis, erythema, burns and vesiculation. Long-term exposure may cause liver, kidney and heart damage. Sudden death has occurred following high concentrations of tetrachloroethylene.
3) CHRONIC EFFECTS: Chronic exposure may affect the liver and kidneys. It can also produce confusion, disorientation, muscle cramps, fatigue, agitation, cardiac dysrhythmias, reduced color perception, impaired vision, contact dermatitis and defatting dermatitis, impaired memory, numbness of the extremities, and peripheral neuropathy.

0.2.4)

A) Eye, nose and throat irritation may occur.

0.2.5)

A) Cardiac dysrhythmias may develop with high exposures.

0.2.6)

A) Upper respiratory tract irritation and noncardiogenic pulmonary edema may occur.

0.2.7)

A) CNS depression, coma and peripheral neuropathies may develop. Optic neuritis has been reported.

0.2.8)

A) Nausea, vomiting and anorexia may be noted acutely. Diarrhea and bloody stools may result from ingestion. Long-term exposure has been associated with abdominal pain and constipation.

0.2.9)

A) Hepatotoxicity with increased enzyme levels may be seen.

0.2.10)

A) Proteinuria, hematuria and oliguric renal failure have occurred.

0.2.14)

A) Dermatitis, a burning sensation and erythema may be seen after dermal exposure. Toxic epidermal necrolysis has occurred after ingestion.

0.2.18)

A) Psychosis, hallucinations and distorted perceptions have been reported with inhalation exposure to tetrachloroethylene. Drug dependence may occur.

0.2.20)

A) Fetotoxicity and developmental abnormalities have been described in experimental animals only.

0.2.21)

A) Tetrachloroethylene is probably carcinogenic to humans. Epidemiologic data suggest a possible increased incidence of liver, esophageal and urinary tract tumors and leukemia in humans, but data are limited.

Laboratory Monitoring

A)

B)

C)

D)

E)

Treatment Overview

0.4.2)

A) SUMMARY

1) The primary route of exposure is via inhalation. See Inhalation Overview for further information.

0.4.3)

A) MANAGEMENT OF MILD TO MODERATE TOXICITY

1) Treatment is symptomatic and supportive. Monitor neurologic and respiratory function. Assess oxygenation and respiratory effort. Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary. Administer 100% humidified supplemental oxygen, perform endotracheal intubation and provide assisted ventilation as required. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Treat bronchospasm with an inhaled beta2-adrenergic agonist. Consider systemic corticosteroids in patients with significant bronchospasm. Monitor renal and liver function.

B) MANAGEMENT OF SEVERE TOXICITY

1) Treatment is symptomatic and supportive. Following a significant exposure, endotracheal intubation and ventilatory assistance with supplemental oxygen may be required if CNS and respiratory depression are present. Monitor renal and liver function. ACUTE LUNG INJURY: Maintain ventilation and oxygenation and evaluate with frequent arterial blood gases and/or pulse oximetry monitoring. Early use of PEEP and mechanical ventilation may be needed.

C) DECONTAMINATION

1) PREHOSPITAL: INHALATION: Immediately move patient from the toxic environment to fresh air. Monitor for respiratory distress. Assess respiratory effort and pulse oximetry. Begin oxygen therapy as indicated. DERMAL: Exposed skin and eyes should be flushed with copious amounts of water.
2) HOSPITAL: INHALATION: Assess respiratory effort. If cough or difficulty in breathing develops, evaluate for hypoxia, respiratory tract irritation, bronchitis, or pneumonitis. DERMAL: Exposed skin and eyes should be flushed with copious amounts of water.

D) ANTIDOTE

1) There is no known antidote.

E) AIRWAY MANAGEMENT

1) Endotracheal intubation and ventilatory assistance with supplemental oxygen may be required if CNS and respiratory depression are present.

F) CARDIOVASCULAR FINDING

1) Some halogenated hydrocarbons sensitize the myocardium to catecholamines, but this effect has not been substantiated for tetrachloroethylene. Epinephrine or other beta-adrenergic agents should be used only with caution and only when clearly indicated. Careful ECG monitoring for the possible induction of arrhythmias should be done, and resuscitation medications and equipment should be readily available. Begin therapy with the lowest effective doses of these agents is advisable.

G) PATIENT DISPOSITION

1) HOME CRITERIA: Since most exposures occur outside the home, there is no role for home management following an exposure to tetrachloroethylene.
2) OBSERVATION CRITERIA: Patients with a deliberate or significant overdose should be sent to a healthcare facility for evaluation. Those who are symptomatic, need to be monitored until they are clearly improving and clinically stable.
3) ADMISSION CRITERIA: Patients should be closely monitored and may require an intensive care setting if severe respiratory distress is present. Closely monitor respiratory and CNS function until the patient is clearly improving.
4) CONSULT CRITERIA: Consult a pulmonologist, medical toxicologist and/or poison center for assistance in managing patients with an overdose.

0.4.4)

A) DECONTAMINATION: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, the patient should be seen in a healthcare facility.

0.4.5)

A) OVERVIEW

1) DECONTAMINATION: Remove contaminated clothing and jewelry and place them in plastic bags. Wash exposed areas with soap and water for 10 to 15 minutes with gentle sponging to avoid skin breakdown. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).
2) Treat dermal irritation or burns with standard topical therapy. Patients developing dermal hypersensitivity reactions may require treatment with systemic or topical corticosteroids or antihistamines.

Range Of Toxicity

A)

Clinical Effects

Summary Of Exposure

A)

B)

C)

D)

E)

1) ADVERSE EFFECTS: In general, tetrachloroethylene affects the liver, kidneys, and central nervous system. It can cause hepatic failure leading to hepatorenal syndrome and occasionally nephrotoxic renal failure. The liver is a target organ in humans for tetrachloroethylene toxicity.
2) ACUTE EFFECTS: Tetrachloroethylene is irritating to the eyes, skin and mucous membranes. Signs and symptoms of exposure may include CNS depression, malaise, dizziness, headache, lightheadedness, disorientation, seizures, respiratory tract irritation, noncardiogenic pulmonary edema, nausea, vomiting and diarrhea. Eye contact may cause pain, lacrimation and burning. Dermal exposure can cause dermatitis, erythema, burns and vesiculation. Long-term exposure may cause liver, kidney and heart damage. Sudden death has occurred following high concentrations of tetrachloroethylene.
3) CHRONIC EFFECTS: Chronic exposure may affect the liver and kidneys. It can also produce confusion, disorientation, muscle cramps, fatigue, agitation, cardiac dysrhythmias, reduced color perception, impaired vision, contact dermatitis and defatting dermatitis, impaired memory, numbness of the extremities, and peripheral neuropathy.

Heent

3.4.1)

A) Eye, nose and throat irritation may occur.

3.4.3)

A) IRRITATION

1) Ocular splash exposure to the eyes is expected to cause pain, lacrimation and burning, but no permanent damage (Rowe & McCollister, 1952; Bingham et al, 2001).
2) The vapors are irritating to the eyes, nose, and throat at high concentrations (Browning, 1965; Bingham et al, 2001; Grant & Schuman, 1993).
3) Very mild irritation is reported after exposure to 106 ppm (ACGIH, 1996).
4) Mild irritation was reported after a 7-hour exposure to 100 ppm (Hathaway et al, 1996).

B) One study demonstrated that dry-cleaners exposed to tetrachloroethylene were more likely to have subclinical color vision loss, mainly in the blue-yellow range (Cavalleri et al, 1994). A dose-response relationship was found between workplace tetrachloroethylene concentrations (TWA) and effects on color vision.
C) Impaired vision has resulted from prolonged exposure to tetrachloroethylene (Hathaway et al, 1996).
D) Severe bilateral optic neuritis with residual tunnel vision, with high levels of tetrachloroethylene in blood and chloroform in urine, has been reported in a 57-year-old woman following perchloroethylene exposure in a dry cleaning shop. She developed headache, blindness (with residual light perception), and retroorbital pain one day after spending more than 9 hours ironing clothes immediately after removing them from the dry cleaning machine. A recreation of the work scenario suggested that perchloroethylene concentrations in steam rising from the iron may have reached 1716 mg/m3 (252 ppm) (Onofrj et al, 1999).

3.4.5)

A) The vapors are irritating to the nose at high concentrations (Browning, 1965; Bingham et al, 2001).
B) Mild irritation occurred after exposure to 100 ppm for 7 hours (Hathaway et al, 1996).

3.4.6)

A) The vapors are irritating to the throat at high concentrations (Browning, 1965; Clayton & Clayton, 1994).
B) Mild irritation occurred after a 7-hour exposure to 100 ppm (Hathaway et al, 1996).

Cardiovascular

3.5.1)

A) Cardiac dysrhythmias may develop with high exposures.

3.5.2)

A) DEAD - SUDDEN DEATH

1) WITH POISONING/EXPOSURE

a) Exposure may decrease the myocardial threshold to the arrhythmogenic action of catecholamines.
b) Two cases of sudden death in patients exposed to high concentrations of tetrachloroethylene have been reported (ACGIH, 1991). The mechanism may have been myocardial sensitization to catecholamines or respiratory depression.

B) VENTRICULAR ARRHYTHMIA

1) WITH POISONING/EXPOSURE

a) CASE REPORT: Multiple ventricular premature beats occurred in a worker with chronic exposure and tetrachloroethylene detected in the blood. No dysrhythmia was noted one month after this patient discontinued tetrachloroethylene exposure (Abedin et al, 1980).

C) CARDIOMYOPATHY

1) WITH POISONING/EXPOSURE

a) In a case of fatal chronic overexposure, autopsy findings included fatty degeneration of the myocardium (Trense & Zimmerman, 1969).

3.5.3)

A) ANIMAL STUDIES

1) HEART DISORDER

a) Exposure may decrease the myocardial threshold to the arrhythmogenic action of catecholamines, as demonstrated in a dog model with exposure to highly anesthetic levels of tetrachloroethylene (5,000 to 10,000 ppm) (Reinhardt et al, 1973).

1) However, exposure to concentrations of 5,000 to 10,000 ppm did not produce dysrhythmias in dogs without injection of exogenous epinephrine (Hathaway et al, 1996), and the significance of these findings for humans exposed to allowable concentrations is questionable (Clayton & Clayton, 1994).

Respiratory

3.6.1)

A) Upper respiratory tract irritation and noncardiogenic pulmonary edema may occur.

3.6.2)

A) IRRITATION SYMPTOM

1) WITH POISONING/EXPOSURE

a) Upper respiratory tract irritation may occur with exposure to high airborne concentrations (Clayton & Clayton, 1994; Harbison, 1998).

B) ACUTE LUNG INJURY

1) WITH POISONING/EXPOSURE

a) CHRONIC EXPOSURE: In a case of fatal chronic overexposure, autopsy findings included hemorrhagic pneumonitis and pulmonary edema (Trense & Zimmerman, 1969).

C) RESPIRATORY FAILURE

1) WITH POISONING/EXPOSURE

a) CASE REPORT: A 13-month-old toddler with sickle cell trait ingested and aspirated a dry cleaning solution containing perchloroethylene. He initially became unconscious and experienced a brief generalized seizure; he subsequently developed pneumonia and respiratory failure. On admission he was intubated and stabilized with mechanical ventilation. The patient stabilized during the second day and he was taken off the ventilator on day four (Algren & Rodgers, 1992).
b) Cases of fatal central nervous system and respiratory depression have occurred from using sleeping bags recently dry cleaned with tetrachloroethylene and not thoroughly aired to remove all of the solvent (Baxter et al, 2000; Finkel, 1983).

Neurologic

3.7.1)

A) CNS depression, coma and peripheral neuropathies may develop. Optic neuritis has been reported.

3.7.2)

A) CENTRAL NERVOUS SYSTEM DEFICIT

1) WITH POISONING/EXPOSURE

a) Ingestion and inhalation will produce central nervous system depression, dizziness, inebriation, lightheadedness, mental dullness, frontal headache, sleepiness, slurred speech, difficulty walking and speaking, and incoordination (HSDB , 2002; Bingham et al, 2001; Baselt, 2000; Browning, 1965; Hathaway et al, 1996; Hayes & Laws, 1991) (Stewart, 1976).

1) At 216 ppm, sleepiness and dizziness were reported (ACGIH, 1996).
2) Studies suggest that symptoms such as dizziness, headache, incoordination and sleepiness occur at concentrations of 100 to 200 ppm for 5.5- to 7-hour exposures (ACGIH, 1996).
3) Exposure to 280 ppm for 2 hours or to 600 ppm for 10 minutes resulted in loss of motor coordination (ACGIH, 1996).

b) Incoordination is often the first noted effect with exposure to low concentrations. Dizziness, lightheadedness and vertigo may also occur (ACGIH, 1991).

1) Lightheadedness begins at concentrations of 200 ppm or slightly higher (Bingham et al, 2001).

c) CNS depression ranging from mild narcosis to coma with respiratory depression and death may occur (ACGIH, 1991; Hathaway et al, 1996).

1) Very light narcosis was reported in subjects not acclimated who had been exposed to tetrachloroethylene at concentrations of 2,000 ppm or more for a few minutes (Hayes & Laws, 1991).

d) CASE SERIES: In a series of 29 cases of tetrachloroethylene poisoning resulting from the use of coin-operated dry cleaning machines, transient loss of consciousness occurred in three patients. Two adults suffered a loss of consciousness lasting 5 hours (Garnier et al, 1996).
e) CASE SERIES: McCarthy and Jones (1983) reviewed 44 cases of tetrachloroethylene occupational poisoning reported to Her Majesty's Factory Inspectorate in the United Kingdom between 1961 and 1980. Three cases were fatalities (McCarthy & Jones, 1983):

1) Seventeen of these 44 workers were rendered unconscious, 22 were conscious but had CNS symptoms or signs, 9 had nausea or vomiting and 1 had hepatic effects (slightly increased SGPT in an otherwise asymptomatic patient).
2) No cardiac effects were attributed to tetrachloroethylene exposure.
3) Operations involving tetrachloroethylene that were associated with fatality or unconsciousness (31 total cases) included maintaining or servicing degreasing baths (1 case; none were associated with operating degreasing baths), use as a portable cold form (3 cases), dry-cleaning (17 cases) and miscellaneous uses (10 cases).

f) CASE REPORT: A 13-month-old toddler with sickle cell trait ingested and aspirated a dry cleaning solution containing perchloroethylene. He initially became unconscious and experienced a brief generalized seizure; he subsequently developed pneumonia and respiratory failure (Algren & Rodgers, 1992).

B) NEUROPATHY

1) WITH POISONING/EXPOSURE

a) CASE SERIES: In one study, 101 employees of dry cleaning shops with long- term tetrachloroethylene exposure to a TWA of 205 mg/m(3) were compared with an unexposed control group with a battery of neuropsychological tests. The author concluded that the presence of subtle neurobehavioral deficits could not be excluded, even in employees exposed for several years only to tetrachloroethylene concentrations below 50 ppm (Seeber, 1989).

1) ETHANOL INTERACTION: Although it has been postulated that alcohol consumption may be a predisposing factor in tetrachloroethylene toxicity (Sittig, 1985), alcohol use did not account for differences in subtle neurobehavioral defects in tetrachloroethylene-exposed dry cleaning workers in this study (Seeber, 1989).

b) In another study, women with long-term low-level exposure to tetrachloroethylene had prolonged reaction times on neurobehavioral tests (Ferroni et al, 1992).

C) ELECTROENCEPHALOGRAM ABNORMAL

1) WITH POISONING/EXPOSURE

a) EEG abnormalities have been demonstrated in 4 of 16 factory workers with exposure to 60 to 450 ppm of tetrachloroethylene for periods of 2 to more than 20 years (Hathaway et al, 1996).

D) HEADACHE

1) WITH POISONING/EXPOSURE

a) Headache may be noted (ACGIH, 1991; Bingham et al, 2001; Hathaway et al, 1996).

E) SECONDARY PERIPHERAL NEUROPATHY

1) WITH POISONING/EXPOSURE

a) CHRONIC EXPOSURE: Peripheral neuropathy has been described after chronic exposure (Baselt, 2000; Hathaway et al, 1996).

F) OPTIC NEURITIS

1) WITH POISONING/EXPOSURE

a) CASE REPORT: Severe bilateral optic neuritis occurred in a 57-year-old woman who owned a dry-cleaning shop. Perchloroethylene (PCE) vapors were increased 5 times over normal limits when ironing freshly dry-cleaned fabrics. Complete blindness was reported in the left and right eyes for 9 and 11 days, respectively. Bright phosphenes and pain were reported on eye rotation. The patient had persistent visual field defects and abnormal color vision one year after exposure. The PCE concentration in blood samples taken 48 hours after the onset of blindness was increased (1.08 mg/g), and chloroform was present in her urine (Onofrj et al, 1999).

Gastrointestinal

3.8.1)

A) Nausea, vomiting and anorexia may be noted acutely. Diarrhea and bloody stools may result from ingestion. Long-term exposure has been associated with abdominal pain and constipation.

3.8.2)

A) NAUSEA AND VOMITING

1) WITH POISONING/EXPOSURE

a) Nausea and vomiting may occur following exposure (Bingham et al, 2001; Lewis, 1998).

B) DIARRHEA

1) WITH POISONING/EXPOSURE

a) Diarrhea and bloody stools may occur if this compound is ingested (Sittig, 1991).

C) LOSS OF APPETITE

1) WITH POISONING/EXPOSURE

a) Anorexia may occur after exposure (Bingham et al, 2001).

D) ABDOMINAL PAIN

1) WITH POISONING/EXPOSURE

a) CHRONIC EXPOSURE: Long-term exposure above 200 ppm can cause abdominal pain and constipation (Sittig, 1991).

Hepatic

3.9.1)

A) Hepatotoxicity with increased enzyme levels may be seen.

3.9.2)

A) LIVER DAMAGE

1) Liver damage may result from chronic or severe acute exposure (JEF Reynolds , 1989; Stewart, 1967; Lachnit & Pietschmann, 1960; Hathaway et al, 1996) (ACGIH, 1993). Increased serum levels of hepatic enzymes may be noted (Lachnit & Pietschmann, 1960). The liver is a target organ in humans for tetrachloroethylene toxicity (Lash & Parker, 2001).

a) Other reports indicate that the effect high levels of tetrachloroethylene have on liver function are mild and transient (Harbison, 1998).

2) Chronic occupational exposure has resulted in hepatitis, confusion, disorientation, muscle cramps, fatigue, agitation, and damage to liver, kidneys and spleen (Baselt, 2000).
3) In a study of tetrachloroethylene-exposed workers, none had clinical evidence of liver disease or increases in AST, ALT, alkaline phosphatase or GGT (Gennari et al, 1992). However, the pattern of GGT isoenzymes differed in exposed workers and controls (increased GGT-2).
4) In a study comparing dry-cleaning operators chronically exposed to low levels of tetrachloroethylene with a control group of unexposed laundry workers, mean hepatic transaminase levels were minimally higher in the dry-cleaning group than in the control group. Diffuse parenchymal changes in echogenicity, determined by liver ultrasonography, were increased almost two-fold in the dry-cleaners (Brodkin et al, 1995). Hepatotoxicity is believed to be a consequence of tetrachloroethylene metabolism by P450 enzymes (Lash & Parker, 2001).
5) CASE REPORT: A worker developed severe liver injury and elevated serum levels of SGOT and aldolase following acute tetrachloroethylene poisoning (Lachnit & Pietschmann, 1960).
6) CASE REPORT: A woman developed hepatitis after inhalation exposure to tetrachloroethylene in a dry-cleaning facility. Six months after discontinuing exposure, her liver was still enlarged, although jaundice had cleared (Meckler & Phelps, 1966).

B) LARGE LIVER

1) WITH POISONING/EXPOSURE

a) Liver enlargement was still present 6 months after removal from exposure in one chronic occupational poisoning case (Meckler & Phelps, 1966).

C) HEPATIC NECROSIS

1) WITH POISONING/EXPOSURE

a) In a case of fatal chronic overexposure, autopsy findings included lobular necrosis of the liver (Trense & Zimmerman, 1969).

3.9.3)

A) ANIMAL STUDIES

1) HEPATOCELLULAR DAMAGE

a) In experimental animals, hepatic and renal injury have been demonstrated (Mazza, 1972; Brancaccio et al, 1971).

Genitourinary

3.10.1)

A) Proteinuria, hematuria and oliguric renal failure have occurred.

3.10.2)

A) ALBUMINURIA

1) WITH POISONING/EXPOSURE

a) Proteinuria and hematuria may occur after massive acute exposure with unconsciousness (ACGIH, 1986).

B) RENAL FAILURE SYNDROME

1) WITH POISONING/EXPOSURE

a) Acute oliguric uremia has occurred from inhalation exposure to vapors from a self-service dry-cleaning machine (HSDB , 2002).
b) Some reports suggest that exposure to high levels of tetrachloroethylene results in only mild and transient effects on kidney function (Harbison, 1998).

C) RENAL TUBULAR DISORDER

1) WITH POISONING/EXPOSURE

a) Several studies have found evidence of subclinical renal tubular damage (urinary albumin, beta-2-microglobulin, retinol-binding protein, brush border antigens; blood laminin fragments) in workers chronically exposed to tetrachloroethylene (Mutti et al, 1992; Price et al, 1994; Lash & Parker, 2001).
b) Other studies have not confirmed these findings (Vyskocil et al, 1990; Solet & Robins, 1991).

D) DISORDER OF MENSTRUATION

1) WITH POISONING/EXPOSURE

a) A small preliminary study of 592 laundry or dry-cleaner workers found a higher incidence of dysmenorrhea, unusual cycle length, menorrhagia and premenstrual syndrome in women exposed to tetrachloroethylene (Zielhius et al, 1989).

3.10.3)

A) ANIMAL STUDIES

1) RENAL FUNCTION ABNORMAL

a) Rats and rabbits exposed to 2,280 ppm, 4 hours daily, 6 days per week for 45 days developed significant reductions in glomerular filtration, renal plasma flow and maximum tubular excretion (Branccacio et al, 1971).
b) These effects have not been described in exposed humans.

Hematologic

3.13.2)

A) HEMOLYSIS

1) CASE REPORT: A 13-month-old toddler with sickle cell trait showed evidence of intravascular hemolysis within 24 hours of ingestion and aspiration of perchloroethylene (Algren & Rodgers, 1992).

Dermatologic

3.14.1)

A) Dermatitis, a burning sensation and erythema may be seen after dermal exposure. Toxic epidermal necrolysis has occurred after ingestion.

3.14.2)

A) DERMATITIS

1) WITH POISONING/EXPOSURE

a) Chronic direct skin exposure may cause reddening and chapping (Morgan, 1969; Sittig, 1985).
b) A dry, scaly, fissured dermatitis may occur with repeated direct skin contact (Sittig, 1985).
c) Dermatitis due to defatting of the skin occurs with contact to concentrated tetrachloroethylene (Lewis, 1998) or when contact is prolonged or frequently repeated (HSDB , 2002; Lewis, 2000).

B) LYELL'S TOXIC EPIDERMAL NECROLYSIS, SUBEPIDERMAL TYPE

1) WITH POISONING/EXPOSURE

a) Ingestion of tetrachloroethylene was associated with the development of toxic epidermal necrolysis (Potter, 1960).

C) BULLOUS ERUPTION

1) WITH POISONING/EXPOSURE

a) Dermal burns, blistering and vesiculation may result with direct skin contact with liquid perchloroethylene (Baselt, 2000; Harbison, 1998).
b) Erythema and a severe burning sensation may occur if the liquid material is left on the skin for 40 minutes or longer (Hathaway et al, 1996).

D) SYSTEMIC SCLEROSIS

1) WITH POISONING/EXPOSURE

a) CASE REPORT: A 26-year-old woman developed local scleroderma after inhalation exposure to tetrachloroethylene and other solvents. Plaques resembling morphea appeared on the volar surfaces of the forearms and on the dorsal surfaces of the ankles after approximately 1 year of solvent exposure (Czirjak et al, 1994).

E) SKIN ABSORPTION

1) WITH POISONING/EXPOSURE

a) Although some dermal absorption may occur, skin exposure is not expected to result in substantial absorption at airborne concentrations up to at least 600 ppm (Bingham et al, 2001).

Endocrine

3.16.2)

A) HYPERPROLACTINEMIA

1) WITH POISONING/EXPOSURE

a) In one study, women with long-term low-level exposure to tetrachloroethylene had increased levels of prolactin during the proliferative stage of the menstrual cycle, compared with controls (Ferroni et al, 1992).

3.16.3)

A) ANIMAL STUDIES

1) ENDOCRINE DISORDER

a) RABBITS exposed to 15 mg/L, 1 hour daily for 15 days developed gradual increases in plasma and urine concentrations of corticosteroids, epinephrine, norepinephrine and 3-methyl-1-hydroxymandelic acid (Brancaccio et al, 1971). These effects lasted for 30 days after exposure ended.
b) Similar effects have not been reported in exposed humans.

Reproductive

3.20.1)

A) Fetotoxicity and developmental abnormalities have been described in experimental animals only.

3.20.2)

A) HUMANS

1) In a large Scandinavian study, perchloroethylene was mentioned as one of many solvents linked to an increased risk of central nervous system and structural defects in the children of women exposed during pregnancy. This has not been confirmed, and the problem of mixed exposures makes it impossible to attribute these effects to perchloroethylene alone (Kurppa, 1983).
2) A case-control study of female dry-cleaning workers, with laundry workers as controls, did not find increases in spontaneous abortions, perinatal deaths, congenital malformations or low birth weights. However, the number of exposed women was small (Ahlborg, 1990).
3) No reports of teratogenicity associated with tetrachloroethylene were found in humans (Schardein, 1993).

B) ANIMAL STUDIES

1) Five aliphatic chlorinated hydrocarbons were tested for teratogenic potential in fertilized chicken eggs. The following decreasing order of potential was found (Elovaara et al, 1979):

1) 1,1,1-Trichloroethane
2) Trichloroethylene
3) Methylene chloride
4) Tetrachloroethylene
5) 1,1,2-Trichloroethane
6) Olive oil (control)

2) Inhalation exposure led to skeletal anomalies in rats (Schardein, 2000). When pregnant rats were exposed to 100, 300 or 900 ppm tetrachloroethylene on days 6 through 15 of gestation, developmental toxicity was evident at some doses (ACGIH, 1986).
3) An increased number of resorptions, delayed skull ossification, subcutaneous edema and sternal malformations were found in the offspring of rats exposed to 300 ppm of tetrachloroethylene, 7 hours per day on days 6 through 15 of pregnancy (Hathaway et al, 1996; Schwetz et al, 1975).
4) When given to female rats during pregnancy, perchloroethylene caused the following symptoms in offspring: fetotoxicity, developmental abnormalities of the musculoskeletal system, effects on the live birth index, effects on growth statistics, biochemical and metabolic effects, behavioral effects, and post-implantation mortality (RTECS , 2002).
5) Developmental delays and embryotoxicity have been reported (Bingham et al, 2001). Fetotoxicity, musculoskeletal system abnormalities and homeostasis occurred in the offspring of female mice exposed to perchloroethylene during pregnancy (RTECS , 2002).
6) Malformations in offspring, including kinked tails and eye defects, full-litter resorption and delayed parturition, were produced after exposure of female rats to perchloroethylene on gestation days 6 to 19 (Narotsky & Kavlock, 1995).
7) Perchloroethylene was teratogenic in chickens when injected into the eggs, but the relevance of this study to human occupational exposure is unclear (Elovaara et al, 1979). TRICHLOROACETIC ACID, a metabolite of perchloroethylene, has been found in the amniotic fluid of exposed mice (Ghantous, 1986).
8) LACK OF EFFECT

a) Perchloroethylene was not teratogenic in several rodent studies with exposure to 300 ppm on days 6 to 15 of pregnancy in rats and mice, 100 or 500 ppm in rats and rabbits, 100 ppm on days 14 to 20, or 900 ppm on days 7 to 13 in rats (Beliles, 1980; Nelson, 1979; Schwetz et al, 1975).

3.20.3)

A) HUMANS

1) ABORTION

a) High exposure to tetrachloroethylene during pregnancy was associated with a higher risk of spontaneous abortion (odds ratio 3.4) in a case-control study of laundry and dry-cleaner workers (Kyyronen et al, 1989).

B) ANIMAL STUDIES

1) In rats, perchloroethylene is able to cross the placenta and will be metabolized to trichloroacetic acid in the placenta or fetus. Although perchloroethylene seems to have little toxicity in developing rabbits and rats, one study showed delayed fetal development in mice exposed to high atmospheric concentrations (IARC , 1997).
2) Perchloroethylene and its metabolites are embryotoxic and induce morphologic abnormalities in the explanted rat embryo (Saillenfait et al, 1995). The addition of S-9 microsomal activity to the system reduces the effects of perchloroethylene.

3.20.4)

A) HUMANS

1) BREAST MILK

a) Obstructive jaundice in breast-fed newborn infants was associated with tetrachloroethylene excretion in breast milk (Bagnell & Ellenberger, 1977).

Carcinogenicity

3.21.1)

A) IARC Carcinogenicity Ratings for CAS127-18-4 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):

1) IARC Classification

a) Listed as: Tetrachloroethylene
b) Carcinogen Rating: 2A

1) The agent (mixture) is probably carcinogenic to humans. The exposure circumstance entails exposures that are probably carcinogenic to humans. This category is used when there is limited evidence of carcinogenicity in humans and sufficient evidence of carcinogenicity in experimental animals. In some cases, an agent (mixture) may be classified in this category when there is inadequate evidence of carcinogenicity in humans and sufficient evidence of carcinogenicity in experimental animals and strong evidence that the carcinogenesis is mediated by a mechanism that also operates in humans. Exceptionally, an agent, mixture or exposure circumstance may be classified in this category solely on the basis of limited evidence of carcinogenicity in humans.

3.21.2)

A) Tetrachloroethylene is probably carcinogenic to humans. Epidemiologic data suggest a possible increased incidence of liver, esophageal and urinary tract tumors and leukemia in humans, but data are limited.

3.21.3)

A) SUMMARY

1) In 2014, the International Agency for Research on Cancer (IARC) classified tetrachloroethylene as Group 2A (probably carcinogenic to humans) (International Agency for Research on Cancer, 2015).

B) HEPATIC CARCINOMA

1) Two limited epidemiologic studies on the mortality of individuals with occupational tetrachloroethylene exposure in dry-cleaning and laundering operations have been done, and indicate an increase in liver cancer in women, but not men (ACGIH, 1996).

a) However, these studies are not satisfactory for reaching definite conclusions about the potential for tetrachloroethylene carcinogenicity in humans; these individuals were also exposed to trichlorofluoromethane, 1,1,2-trichloro-1,2,2-trifluoroethane, and white spirits (Hathaway et al, 1996).
b) Follow-up of one cohort study found that dry-cleaners who were exposed only to tetrachloroethylene had no increase in incidence of cancer (Harbison, 1998).

C) BLADDER CARCINOMA

1) In a meta-analysis of 7 studies of dry cleaning workers, a significant risk of bladder cancer was observed. The mean relative risk for dry clean workers (n=139) was 1.47 (95% CI: 1.16, 1.85) and the mean relative risk among tetrachloroethylene workers (n=463; 3 studies) was 1.08 (95% CI: 0.82, 1.42). In addition, the relative risk for smoking (a known risk for bladder cancer) adjusted studies (n=4 case-controlled studies) was 1.5 (95% CI: 0.8, 2.84). Although dry clean workers are exposed to a mix of chemicals and solvents, tetrachloroethylene is the only component that has the potential to be a bladder carcinogen (Vlaanderen et al, 2014).
2) A 1987 cohort mortality study of dry-cleaning workers with exposure to tetrachloroethylene as well as other petroleum-based solvents detected an increased incidence of urinary tract cancers (Brown & Kaplan, 1987). The significance of this study for workers exposed only to tetrachloroethylene is unclear. No liver cancers were found among these workers.
3) In a cohort study, dry-cleaning workers exposed to tetrachloroethylene and other solvents had an increased mortality from bladder cancer (SMR 2.14) (Ruder et al, 1994).
4) An increased incidence of bladder cancer was found in a case-control study of individuals who had been exposed to tetrachloroethylene in drinking water for up to 10 years (Goldfrank, 1998).

D) BRAIN CARCINOMA

1) Association between "likely" occupational exposure to tetrachloroethylene and astrocytic brain cancer was seen in a case-control study in white males (Heineman et al, 1994).

E) ESOPHAGEAL CARCINOMA

1) In a cohort study, dry-cleaning workers exposed to tetrachloroethylene only with 5 years of exposure and 20 or more years since first exposure had an increased mortality from esophageal cancer (SMR 7.17) (Ruder et al, 1994).

F) LEUKEMIA

1) In a population-based case-control study exposure to high level of tetrachloroethylene in drinking water was associated with an increased risk of leukemia (adjusted odds ratio 5.84 when a latency period of 5 years between exposure and development of leukemia was taken into account) (Aschengrau et al, 1993).

G) CARCINOMA

1) A case-control study conducted in Montreal, Canada of occupational exposures to any of 6 chlorinated solvents (carbon tetrachloride, methylene chloride, 1,1,1-trichloroethane, chloroform, trichloroethylene, and tetrachloroethylene) and association with cancer found an increased risk of prostate cancer with tetrachloroethylene exposure and an increased risk of melanoma with trichloroethylene exposure. The analysis that included 3730 cancer cases (occurring from 1979 to 1985) and 533 population controls focused on the following 11 cancer types: esophagus, stomach, colon, rectum, liver, pancreas, prostate, bladder, kidney, melanoma, and non-Hodgkin lymphoma. An association was observed between tetrachloroethylene exposure and risk of prostate cancer (odds ratio [OR], 2.2; 95% CI, 0.8 to 5.7 for any exposure and OR, 4.3; 95% CI, 1.4 to 13 for substantial exposure), as well as between trichloroethylene exposure and melanoma risk (OR, 3; 95% CI, 1.2 to 7.2 for any exposure and OR, 3.2; 95% CI, 1 to 9.9 for substantial exposure). There was also an association between substantial exposure to chlorinated alkenes (ie, trichloroethylene and tetrachloroethylene) in general and melanoma risk (OR, 2.6; 95% CI, 1 to 7.1). Substantial exposure was defined as a degree of confidence that the exposure actually occurred of probable or definite, a medium or high solvent concentration and frequency of exposure, and a duration of exposure that was greater than 5 years. While an association between substantial exposure to chloroform and risk of pancreatic cancer exists (OR, 10.6; 95% CI, 1.2 to 93), this was based on only 2 exposed workers. The majority of ORs were close to null or like the chloroform and pancreatic association, were based on very small numbers, thereby providing limited power to detect real risk (Christensen et al, 2013).
2) In a retrospective epidemiological study of 330 laundry and dry-cleaner workers, there were some excess cancers of the lung, cervix, uterus and skin as causes of death; however, these subjects were also exposed to CARBON TETRACHLORIDE and TRICHLOROETHYLENE (Blair, 1979).
3) A NIOSH industry-wide study of approximately 1,600 people was carried out over many years. In 1980, this study found excess cancers of the colon, pancreas and urinary tract (p 26). In 1985, the conclusion of excess urinary tract cancers seems have been 'softened' somewhat and also complicated by exposures to petroleum solvents (Brown & Kaplan, 1985). An association between "likely" occupational exposure to perchloroethylene and astrocytic brain cancer was seen in a case-control study in white males (Heineman et al, 1994).

H) LACK OF EFFECT

1) In a review article of 44 epidemiological studies on occupational exposure to perchloroethylene (PCE) and cancer, it was determined that there were no evidence of an association between breast, prostate, skin or brain cancer and exposure to PCE. In addition, a relationship between PCE and cancer of the oral cavity, liver, pancreas, cervix, and lung was considered unlikely, and scientific evidence was inadequate for laryngeal, kidney, esophageal and bladder cancers (Mundt et al, 2003).

3.21.4)

A) CARCINOMA

1) NCI Carcinogenesis Bioassays (RTECS , 2001)

a) MOUSE: Gavage; Clear Evidence
b) RAT: Gavage; Inadequate Studies

2) NTP Carcinogenesis Studies

a) MOUSE: Inhalation; Clear Evidence
b) RAT: Inhalation; Clear Evidence

3) Laboratory Animals

a) Tetrachloroethylene is carcinogenic in laboratory animals (Hathaway et al, 1996).

1) An increased incidence of hepatocellular carcinomas was found in mice given gavage doses of 500 or 1,000 mg/kg/day for 78 weeks (Baselt, 2000; Hathaway et al, 1996).

b) An increased incidence of mononuclear cell leukemia was seen in rats inhaling 200 to 400 ppm for 2 years (Hathaway et al, 1996).
c) Repeated exposure of mice to 100 or 200 ppm resulted in an increased incidence of carcinomas and hepatocellular adenomas (Hathaway et al, 1996).
d) The ACGIH regards perchloroethylene as an animal carcinogen (Group A3) (ACGIH, 1996a).
e) When tested for lung adenomas in strain A cancer-susceptible mice, perchloroethylene was found to be inactive. This compound did not produce cancer of the skin or of distant sites when applied to the skin of mice in different ways (Bingham et al, 2001).
f) Perchloroethylene caused liver cancers when given orally to mice at doses of 536 or 1,072 mg/kg/day for 78 weeks (Anon, 1977). Another carcinogenicity study in rats and mice exposed by inhalation found liver tumors in mice, kidney tumors in male rats and leukemia in rats (p 5).

Genotoxicity

A)

Laboratory Monitoring

Monitoring Parameters Levels

4.1.1)

A) Closely monitor level of consciousness, respiratory function and oxygenation.
B) Monitor liver and renal function tests and urinalysis in patients with significant exposure.
C) Obtain a baseline ECG and institute continuous cardiac monitoring as indicated.
D) Expired air tetrachloroethylene or urinary metabolite measurements may be useful for monitoring chronically exposed workers.
E) Tetrachloroethylene is radiopaque, abdominal radiographs may be useful to assess decontamination following ingestion.

4.1.2)

A) BLOOD/SERUM CHEMISTRY

1) Blood tetrachloroethylene levels have been shown to be useful for biological surveillance of exposed workers (Baselt, 1997).
2) Monitor liver and renal function tests and urinalysis in patients with significant exposure.

4.1.3)

A) URINARY LEVELS

1) Daily urine thioether measurements might be useful in monitoring occupational exposure to tetrachloroethylene (LaFuente & Mallol, 1986), although analysis for tetrachloroethylene in expired air is likely more useful (Bingham et al, 2001).
2) Monitoring the urinary concentrations of chlorinated metabolites of tetrachloroethylene is of only limited utility, because saturation of the metabolic pathways occurs at air levels greater than 50 ppm and there is no correlation between amounts of urinary metabolites and exposure at higher air concentrations (Baselt, 1997).
3) In one study, urinary concentration of tetrachloroethylene showed a linear relationship with the environmental time-weighted average (TWA) (Imbriani et al, 1988). The urinary tetrachloroethylene concentration corresponding to a TWA of 335 mg/m3 was 120 mcg/L, with a lower confidence limit of 100 mcg/L.

B) URINALYSIS

1) Proteinuria and hematuria may occur after massive acute exposures (ACGIH, 1986). Monitor urinalysis in patients with significant acute poisoning.

4.1.4)

A) OTHER

1) BREATH ANALYSIS

a) Alveolar sampling seemed to provide a valid estimate of tetrachloroethylene concentration in mixed venous blood and arterial blood (Opdam & Smolders, 1986).
b) Measured breath tetrachloroethylene concentrations after the conclusion of exposure correlate well with the amount absorbed and with blood levels (Baselt, 1997), and are generally considered more useful for monitoring workers with chronic exposure (Clayton & Clayton, 1994).

1) With chronic exposure, breath levels taken at the same time each day will generally increase only by 20% (Baselt, 1997).
2) Immediately after termination of exposure to 100 ppm for 7 hours, breath concentrations averaged 20 ppm (Baselt, 1997).

Radiographic Studies

A)

1) Tetrachloroethylene is radiopaque in vitro (Dally et al, 1987). Abdominal radiographs may be useful to assess the efficacy of decontamination after ingestion.

Methods

A)

1) Tetrachloroethylene can be measured in air by adsorption onto charcoal, workup with carbon disulfide and measurement by gas chromatography with flame ioization (Sittig, 1991; NIOSH , 2001).
2) A gas chromatographic method exists for measurement of tetrachloroethylene in expired breath (Baselt, 1997).
3) Tetrachloroethylene can be measured in water by inert purging followed by gas chromatography with halide-specific detection or gas chromatography-mass spectrometry. EPA methods 601 or 624 are appropriate (Sittig, 1991).
4) Detection of tetrachloroethylene in urine and blood after ingestion has been reported (Koppel et al, 1985).

a) A gas chromatographic method exists for measurement of tetrachloroethylene in blood (Baselt, 1997).
b) Gaillard et al (1995) described a gas chromatography/mass spectrometry method for determination of tetrachloroethylene in blood, urine and body tissues.

Treatment

Life Support

A)

Patient Disposition

6.3.3)

6.3.3.1) ADMISSION CRITERIA/INHALATION

A) Patients should be closely monitored and may require an intensive care setting if severe respiratory distress is present. Closely monitor respiratory and CNS function until the patient is clearly improving.

6.3.3.2) HOME CRITERIA/INHALATION

A) Since most exposures occur outside the home, there is no role for home management following an exposure to tetrachloroethylene.

6.3.3.3) CONSULT CRITERIA/INHALATION

A) Consult a pulmonologist, medical toxicologist and/or poison center for assistance in managing patients with an overdose.

6.3.3.5) OBSERVATION CRITERIA/INHALATION

A) Patients with a deliberate or significant overdose should be sent to a healthcare facility for evaluation. Those who are symptomatic, need to be monitored until they are clearly improving and clinically stable.

Monitoring

A)

B)

C)

D)

E)

Oral Exposure

6.5.1)

A) EMESIS/NOT RECOMMENDED

1) Emesis is not recommended because of the potential for CNS depression.

B) ACTIVATED CHARCOAL

1) PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION

a) Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).

1) In patients who are at risk for the abrupt onset of seizures or mental status depression, activated charcoal should not be administered in the prehospital setting, due to the risk of aspiration in the event of spontaneous emesis.
2) The addition of flavoring agents (cola drinks, chocolate milk, cherry syrup) to activated charcoal improves the palatability for children and may facilitate successful administration (Guenther Skokan et al, 2001; Dagnone et al, 2002).

2) CHARCOAL DOSE

a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).

1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).

b) ADVERSE EFFECTS/CONTRAINDICATIONS

1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).

6.5.2)

A) EMESIS/NOT RECOMMENDED

1) Emesis is not recommended because of the potential for CNS depression.

B) ACTIVATED CHARCOAL

1) CHARCOAL ADMINISTRATION

a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.

2) CHARCOAL DOSE

a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).

1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).

b) ADVERSE EFFECTS/CONTRAINDICATIONS

1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).

6.5.3)

A) SUPPORT

1) The primary route of exposure is via inhalation. See Inhalation Overview for further information.

Inhalation Exposure

6.7.1)

A) Immediately move patient from the toxic environment to fresh air. Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for hypoxia, respiratory tract irritation, bronchitis, or pneumonitis. Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary. Administer 100% humidified supplemental oxygen, perform endotracheal intubation and provide assisted ventilation as required.

6.7.2)

A) SUPPORT

1) MANAGEMENT OF MILD TO MODERATE TOXICITY

a) Treatment is symptomatic and supportive. Monitor neurologic and respiratory function. Assess oxygenation and respiratory effort. Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis.
b) INITIAL TREATMENT: Administer 100% humidified supplemental oxygen, perform endotracheal intubation and provide assisted ventilation as required. Administer inhaled beta-2 adrenergic agonists, if bronchospasm develops. Consider systemic corticosteroids in patients with significant bronchospasm (National Heart,Lung,and Blood Institute, 2007).

2) MANAGEMENT OF SEVERE TOXICITY

a) Treatment is symptomatic and supportive. Following a significant exposure, endotracheal intubation and ventilatory assistance with supplemental oxygen may be required if CNS and respiratory depression are present. Monitor renal and liver function. ACUTE LUNG INJURY: Maintain ventilation and oxygenation and evaluate with frequent arterial blood gases and/or pulse oximetry monitoring. Early use of PEEP and mechanical ventilation may be needed.

B) MONITORING OF PATIENT

1) Closely monitor level of consciousness, respiratory function and oxygenation.
2) Monitor liver and renal function in patients with a significant exposure.
3) Obtain a baseline ECG and institute continuous cardiac monitoring as indicated.

C) CARDIOVASCULAR FINDING

1) Some halogenated hydrocarbons sensitize the myocardium to catecholamines, but this effect has not been substantiated for tetrachloroethylene. Epinephrine or other beta-adrenergic agents should be used only with caution and only when clearly indicated.
2) Begin therapy with the lowest effective dose of these agents is advisable.
3) Careful ECG monitoring for the possible induction of dysrhythmias should be done, and resuscitation medications and equipment should be readily available.

D) ACUTE LUNG INJURY

1) ONSET: Onset of acute lung injury after toxic exposure may be delayed up to 24 to 72 hours after exposure in some cases.
2) NON-PHARMACOLOGIC TREATMENT: The treatment of acute lung injury is primarily supportive (Cataletto, 2012). Maintain adequate ventilation and oxygenation with frequent monitoring of arterial blood gases and/or pulse oximetry. If a high FIO2 is required to maintain adequate oxygenation, mechanical ventilation and positive-end-expiratory pressure (PEEP) may be required; ventilation with small tidal volumes (6 mL/kg) is preferred if ARDS develops (Haas, 2011; Stolbach & Hoffman, 2011).

a) To minimize barotrauma and other complications, use the lowest amount of PEEP possible while maintaining adequate oxygenation. Use of smaller tidal volumes (6 mL/kg) and lower plateau pressures (30 cm water or less) has been associated with decreased mortality and more rapid weaning from mechanical ventilation in patients with ARDS (Brower et al, 2000). More treatment information may be obtained from ARDS Clinical Network website, NIH NHLBI ARDS Clinical Network Mechanical Ventilation Protocol Summary, http://www.ardsnet.org/node/77791 (NHLBI ARDS Network, 2008)

3) FLUIDS: Crystalloid solutions must be administered judiciously. Pulmonary artery monitoring may help. In general the pulmonary artery wedge pressure should be kept relatively low while still maintaining adequate cardiac output, blood pressure and urine output (Stolbach & Hoffman, 2011).
4) ANTIBIOTICS: Indicated only when there is evidence of infection (Artigas et al, 1998).
5) EXPERIMENTAL THERAPY: Partial liquid ventilation has shown promise in preliminary studies (Kollef & Schuster, 1995).
6) CALFACTANT: In a multicenter, randomized, blinded trial, endotracheal instillation of 2 doses of 80 mL/m(2) calfactant (35 mg/mL of phospholipid suspension in saline) in infants, children, and adolescents with acute lung injury resulted in acute improvement in oxygenation and lower mortality; however, no significant decrease in the course of respiratory failure measured by duration of ventilator therapy, intensive care unit, or hospital stay was noted. Adverse effects (transient hypoxia and hypotension) were more frequent in calfactant patients, but these effects were mild and did not require withdrawal from the study (Wilson et al, 2005).
7) However, in a multicenter, randomized, controlled, and masked trial, endotracheal instillation of up to 3 doses of calfactant (30 mg) in adults only with acute lung injury/ARDS due to direct lung injury was not associated with improved oxygenation and longer term benefits compared to the placebo group. It was also associated with significant increases in hypoxia and hypotension (Willson et al, 2015).

E) EXPERIMENTAL THERAPY

1) CONTROLLED HYPERVENTILATION

a) Based on limited experience, controlled hyperventilation enhanced pulmonary elimination of tetrachloroethylene in a child who had ingested 8 to 10 mL of this tetrachloroethylene (Koppel et al, 1985).
b) While there is little clinical experience with this treatment modality, it is physiologically attractive and most likely safe in patients requiring endotracheal intubation and mechanical ventilation for CNS and respiratory depression. Monitor arterial blood gases and avoid pH greater than 7.55.

F) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Eye Exposure

6.8.1)

A) EYE IRRIGATION, ROUTINE: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, an ophthalmologic examination should be performed (Peate, 2007; Naradzay & Barish, 2006).

Dermal Exposure

6.9.1)

A) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

6.9.2)

A) CHEMICAL BURN

1) APPLICATION

a) These recommendations apply to patients with MINOR chemical burns (FIRST DEGREE; SECOND DEGREE: less than 15% body surface area in adults; less than 10% body surface area in children; THIRD DEGREE: less than 2% body surface area). Consultation with a clinician experienced in burn therapy or a burn unit should be obtained if larger area or more severe burns are present. Neutralizing agents should NOT be used.

2) DEBRIDEMENT

a) After initial flushing with large volumes of water to remove any residual chemical material, clean wounds with a mild disinfectant soap and water.
b) DEVITALIZED SKIN: Loose, nonviable tissue should be removed by gentle cleansing with surgical soap or formal skin debridement (Moylan, 1980; Haynes, 1981). Intravenous analgesia may be required (Roberts, 1988).
c) BLISTERS: Removal and debridement of closed blisters is controversial. Current consensus is that intact blisters prevent pain and dehydration, promote healing, and allow motion; therefore, blisters should be left intact until they rupture spontaneously or healing is well underway, unless they are extremely large or inhibit motion (Roberts, 1988; Carvajal & Stewart, 1987).

3) TREATMENT

a) TOPICAL ANTIBIOTICS: Prophylactic topical antibiotic therapy with silver sulfadiazine is recommended for all burns except superficial partial thickness (first-degree) burns (Roberts, 1988). For first-degree burns bacitracin may be used, but effectiveness is not documented (Roberts, 1988).
b) SYSTEMIC ANTIBIOTICS: Systemic antibiotics are generally not indicated unless infection is present or the burn involves the hands, feet, or perineum.
c) WOUND DRESSING:

1) Depending on the site and area, the burn may be treated open (face, ears, or perineum) or covered with sterile nonstick porous gauze. The gauze dressing should be fluffy and thick enough to absorb all drainage.
2) Alternatively, a petrolatum fine-mesh gauze dressing may be used alone on partial-thickness burns.

d) DRESSING CHANGES:

1) Daily dressing changes are indicated if a burn cream is used; changes every 3 to 4 days are adequate with a dry dressing.
2) If dressing changes are to be done at home, the patient or caregiver should be instructed in proper techniques and given sufficient dressings and other necessary supplies.

e) Analgesics such as acetaminophen with codeine may be used for pain relief if needed.

4) TETANUS PROPHYLAXIS

a) The patient's tetanus immunization status should be determined. Tetanus toxoid 0.5 milliliter intramuscularly or other indicated tetanus prophylaxis should be administered if required.

B) IRRITATION SYMPTOM

1) Treat dermal irritation or burns with standard topical therapy. Patients developing dermal hypersensitivity reactions may require treatment with systemic or topical corticosteroids or antihistamines.

C) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Abstracts

Case Reports

A)

1) FATALITY: A dry cleaning worker died following chronic exposure. Tetrachloroethylene concentrations in the small (72-cubic-meter) workspace were 250 ppm. The initial symptoms were anorexia, coughing and shortness of breath, followed by vomiting, hemoptysis and sweating. Miliary tuberculosis was also diagnosed in this individual. Dyspnea and hemoptysis later developed, and the worker died in cardiac arrest after developing circulatory failure. Autopsy findings were hemorrhagic pneumonitis, pulmonary edema, lobular necrosis of the liver and fatty degeneration of the myocardium (Trense & Zimmerman, 1969).
2) CASE REPORT: A 33-year-old man attempting to clear a plugged line in a dry-cleaning facility and was found lying unconscious in a machine 20 minutes later. The victim was pronounced dead on arrival to the hospital. Blood, tissue and urine were sampled for tetrachloroethylene, and showed 4.4 mg/dL in blood, 36 mg/100 g in brain, and 0.3 mg/100 g in lung. No tetrachloroethylene was detected in the urine or stomach contents, and no trichloroacetic acid (a metabolite) was present in the urine(Lukaszewski, 1979)
3) Cases of fatal central nervous system and respiratory depression have occurred from using sleeping bags recently dry-cleaned with tetrachloroethylene and not thoroughly aired to remove all of the solvent (Baselt, 2000; Finkel, 1983).
4) LIVER INJURY: A worker developed severe liver injury and increased serum levels of SGOT and aldolase after acute tetrachloroethylene poisoning (Lachnit & Pietschmann, 1960).
5) CASE REPORT: A woman developed hepatitis after inhalation exposure to tetrachloroethylene in a dry-cleaning facility. Six months after discontinuing exposure, her liver was still enlarged, although jaundice had cleared (Meckler & Phelps, 1966).

B)

1) McCarthy and Jones (1983) reviewed 44 cases of tetrachloroethylene occupational poisoning reported to Her Majesty's Factory Inspectorate in the UK between 1961 and 1980. Three cases were fatalities.

a) Seventeen of these 44 workers were rendered unconscious, 22 were conscious but had CNS symptoms or signs, 9 had nausea or vomiting and 1 had hepatic effects (slightly increased SGPT in an otherwise asymptomatic patient).
b) No cardiac effects were attributed to tetrachloroethylene exposure.
c) Operations involving tetrachloroethylene that were associated with fatality or unconsciousness (31 total cases) included maintaining or servicing degreasing baths (1 case; none were associated with operating degreasing baths), use as a portable cold form (3 cases), dry-cleaning (17 cases) and miscellaneous uses (10 cases).

C)

1) A 13-month-old toddler with sickle cell trait ingested and aspirated a dry-cleaning solution containing perchloroethylene. He initially became unconscious and experienced a brief generalized seizure; he subsequently developed pneumonia and respiratory failure. On admission he was intubated and stabilized with mechanical ventilation. Over 24 hours, his serum hemoglobin concentration fell 3.5 grams/dL. However, a sickle-cell screen was positive. The patient stabilized during the second day; no further hemolysis was observed and he was taken off the ventilator on day four (Algren & Rodgers, 1992).

Range Of Toxicity

Summary

A)

Therapeutic Dose

7.2.1)

A) DISEASE STATE

1) ANTHELMINTIC -

a) Single Dose - 0.1 to 0.12 milliliter/kilogram orally, up to a maximum of 5 milliliters (JEF Reynolds , 1989). Treatment may be repeated in 4 to 7 days if necessary.
b) Treatment schedules on alternate-day or on 3 consecutive days have also been given (JEF Reynolds , 1989).
c) Patient should be kept in bed for 4 hours after treatment (JEF Reynolds , 1989).
d) Alcohol and fats should be avoided for 24 hours before and after treatment (JEF Reynolds , 1989).

7.2.2)

A) DISEASE STATE

1) ANTHELMINTIC -

a) Single Dose - 0.1 milliliter/kilogram orally, up to a maximum of 4 milliliters (JEF Reynolds , 1989).
b) Patient should be kept in bed for 4 hours after treatment (JEF Reynolds , 1989).
c) Alcohol and fats should be avoided for 24 hours before and after treatment (JEF Reynolds , 1989).

Minimum Lethal Exposure

A)

1) The published LDLo for a man is 2857 mg/kg by the inhalation route. This caused central nervous system and pulmonary effects (Lewis, 2000).

B)

1) ADULT: A 27-year-old woman, with a history of borderline personality disorder, was found dead by her family following acute-on-chronic abuse of tetrachloroethylene. The patient had 2 prior hospitalizations secondary to inhalation of volatile substances. The patient was found with 2 cotton swabs dipped with tetrachloroethylene (confirmed by laboratory analysis) in each nostril. The concentration in cardiac blood was 145 mg/L and 4915 mg/kg in adipose tissue. Toxicology screening for drugs of abuse or medications were negative (Amadasi et al, 2015).
2) INFANT: A 2-year-old boy died following a 1.5 hour inhalation exposure to tetrachloroethylene (TCE) from a pair of curtains that were very recently dry-cleaned and left in the child's room with no ventilation. An investigation (repeat dry-cleaning of curtains with a coin-operated machine) showed that 3 pairs of curtains retained 6 kg of TCE when dry cleaned using the same process (Garnier et al, 1996).

Maximum Tolerated Exposure

A)

1) ORAL

a) Humans have been reported to survive oral doses of 500 mg/kg (NIOSH, 1976) (ACGIH, 1986). Ingestion of 12 to 16 g of tetrachloroethylene by a 6-year-old boy resulted in coma (Koppel et al, 1985).
b) When used as an anthelmintic, doses of 2.8 to 4 mL (about 4.6 to 6 g) did not cause fatalities, but resulted in CNS depression, a sense of exhilaration and drunkenness (ACGIH, 1986). No liver function test abnormalities were produced by doses of 1 to 8 mL (1.5 to 12 g) (ACGIH, 1986).

2) ACUTE INHALATION EXPOSURE

a) COMA

1) Two individuals rendered unconscious after acute tetrachloroethylene poisoning had breath concentrations of 85 and 110 ppm. One of these individuals had been exposed to 1,100 ppm tetrachloroethylene for 30 minutes (Baselt, 2000).
2) In humans, unconsciousness has occurred with exposure to 1,470 ppm for 3.5 hours and 2,000 ppm for 1.5 minutes or longer (ACGIH, 1986).

b) OTHER CNS EFFECTS

1) The threshold for neurologic effect in humans for acute exposures is in the range of 100 to 200 ppm (ACGIH, 1996).
2) In human experiments, concentrations of 1000 ppm were tolerated for 1.5 hours, whereas inhalation of 1500 ppm rapidly caused dizziness and a faint feeling (Baselt, 2000).
3) At a concentration of 216 ppm for 2 hours, humans developed difficulty with motor coordination, a thick tongue sensation, eye burning, frontal sinus congestion and lightheadedness (ACGIH, 1986).
4) In human inhalation studies, prolonged exposure to 200 ppm caused early signs of CNS depression, whereas a 7-hour-per-day exposure to 100 ppm did not cause these effects (ACGIH, 1986).

3) IRRITATION

a) Exposure to 500 ppm for 50 minutes has caused tightness in the frontal sinuses, a metallic taste, excessive sweating of the hands and feet, increased salivation and eye irritation in humans (ACGIH, 1986).
b) Humans exposed to 100 ppm for 4 hours have complained of mild conjunctivitis (ACGIH, 1986).
c) The lowest reported toxic dose (TCLo) in man for a 10-minute exposure period was 600 ppm. This exposure produced conjunctival irritation (RTECS , 2001).
d) At exposures greater than 600 ppm, symptoms of dizziness, confusion, nausea, irritation of the mucous membranes such as eyes, and headaches are intensified ((HSIA, 1999)).
e) The lowest reported toxic dose (TCLo) in humans for a 7-hour exposure period was 96 ppm. This exposure produced local anesthetic effect, conjunctival irritation, hallucinations and distorted perceptions (RTECS , 2001).

4) CHRONIC OCCUPATIONAL EXPOSURES

a) Dry-cleaning workers with exposure to airborne concentrations ranging up to 300 ppm had CNS depression and some effects on the autonomic nervous system, but no liver function abnormalities (Hathaway et al, 1996).
b) Electrodiagnostic and neurologic rating scores were abnormal in 20 dry-cleaning workers exposed to airborne levels between 1 and 40 ppm for an average of 7.5 years (Hathaway et al, 1996).
c) EEG recordings were abnormal in 4 of 16 factory workers exposed to airborne concentrations between 60 and 450 ppm for periods ranging from 2 to greater than 20 years (Hathaway et al, 1996).

B)

1) AIR CONCENTRATIONS: Industrial experience and human studies showed responses based on various concentrations (Clayton & Clayton, 1994):

CONCENTRATION (ppm)	RESPONSE
50	Odor threshold (faint); no physiological effects over an 8-hour exposure.
100	Faint to not perceptible odor; no physiological effects over an 8-hour exposure.
200	Definite odor; faint to moderate eye irritation; minimal lightheadedness.
400	Strong unpleasant odor; definite eye irritation; slight nasal irritation; incoordination after 2 hours.
600	Tolerable but very unpleasant odor; eye and nasal irritation; dizziness, loss of inhibitions after 10 minutes.
1000	Intense, irritating odor; eye and respiratory tract irritation; significant dizziness after 2 minutes.
1500	"Gagging", almost intolerable odor; almost intolerable eye and nasal irritation; complete incoordination within minutes, unconsciousness after 30 minutes.

2) INHALATION EXPOSURE (Hathaway et al, 1996):

a) At 2000 ppm, mild CNS depression occurred within 5 minutes.
b) Numbness around the mouth, along with dizziness and some incoordination, was reported after a 10-minute exposure to 600 ppm.
c) A 7-hour exposure to 100 ppm caused headache, somnolence, slurred speech, flushing of the face and neck, and mild irritation of eyes, nose, and throat.

C)

1) Rabbits exposed to 2,790 ppm, 4 hours daily, 5 days per week for 45 days developed fairly significant liver damage and increases in hepatic enzyme levels, particularly after the 15th day (Mazza, 1972).
2) Rats and rabbits exposed to 2,280 ppm, 4 hours daily, 6 days per week for 45 days developed significant reductions in glomerular filtration, renal plasma flow and maximum tubular excretion (Brancaccio et al, 1971).
3) Rabbits exposed to 15 mg/L, one hour daily for 15 days, developed gradual increases in the plasma and urine concentrations of corticosteroids, epinephrine, norepinephrine and 3-methyl-1-hydroxymandelic acid (Brancaccio et al, 1971). These effects lasted for 30 days after exposure ended.
4) Mice exposed up to 1072 mg/kg, 5 days a week for 78 weeks, showed an increase in liver tumors in both sexes ((HSIA, 1999)).
5) Rats exposure to 0, 300, and 600 ppm, 6 hours per day, 5 days per week for 52 weeks, showed no significant carcinogenic effects/differences between the control group and the exposed group ((HSIA, 1999)).
6) Rats and mice exposed to 300 ppm during gestation had mild fetotoxicity in the presence of maternal toxicity. Additional studies in rats and rabbits showed no teratogenic effect at doses of 100 and 500 ppm ((HSIA, 1999)).

Serum Plasma Blood Concentrations

7.5.2)

A) TOXIC CONCENTRATION LEVELS

1) CASE REPORTS

a) ADULT

1) Blood concentration of tetrachloroethylene was 4.4 mg/100 mL in a 33-year-old worker found dead after being left alone for 20 minutes to work on a dry-cleaning machine (Lukaszewski, 1979).

a) Tissue and urine were also sampled for tetrachloroethylene, and showed 36 mg/100 grams in brain and 0.3 mg/100 grams in lung. No tetrachloroethylene was detected in the urine or stomach contents, and no trichloroacetic acid (a metabolite) was present in the urine (Lukaszewski, 1979).

2) A blood concentration of 62 mg/L was measured by headspace GC-ECD analysis after the death of a 26-year-old male subsequent to inhalation of tetrachloroethylene (in a closed plastic bag) for the purpose of an autoerotic sexual experience (Isenschmid et al, 1998).
3) A blood concentration of perchloroethylene of 1.08 mg/g was reported in a 57-year-old female 48 hours after the onset of optic neuritis (bilateral blindness). Thirty-two hours after the first level was drawn, the blood concentration had decreased to 0.65 mg/g (Onofrj et al, 1998).

b) INFANT

1) A 2-year-old boy died after a 1.5-hour inhalation exposure to tetrachloroethylene (TCE) from one pair of curtains that were very recently dry-cleaned and left in the child's room with no ventilation. The post-mortem blood tetrachloroethylene concentration was 66 mg/L (Garnier et al, 1996).

a) Concentrations in brain, heart and lung were 79, 31 and 46 mg/kg, respectively (Garnier et al, 1996).

2) CONCENTRATION LEVEL

a) CONTROLLED EXPOSURES -

1) In normal subjects, exposure to a concentration of 194 ppm for 3 hours resulted in an average peak blood level of 2.6 mg/L. By 30 minutes after exposure ended, tetrachloroethylene was no longer detectable in the blood (Baselt, 2000) Baxter, 2000).

a) Blood concentrations were noted to be correlated with both the concentration of tetrachloroethylene in the breathing atmosphere and an individual's degree of physical activity (Baselt, 2000).

2) The alveolar breath concentrations may approach 50 percent of the breathing atmosphere concentrations with constant exposure (Baselt, 2000).

a) In normal subjects breathing an atmosphere containing 100 ppm tetrachloroethylene, breath concentrations were: 15 ppm at 1 hour, 8 ppm at 15 hours and 4.5 ppm at 71 hours (Baselt, 2000).

3) Chlorinated tetrachloroethylene metabolites (trichloroacetic acid and others) in general are not present at greater than 100 mg/L in the urine of individuals occupationally exposed to ambient air concentrations of up to 400 ppm (Baselt, 1988).

a) The urinary metabolites of trichloroacetic acid and another unknown compound accounted for less than 3 percent of a dose over a 67-hour period (Baselt, 2000).

4) The concentration of tetrachloroethylene in the urine of workers exposed to 50 ppm of the chemical for 4 hours averaged 0.12 mg/L (Baselt, 2000).

b) SYMPTOMATIC EXPOSURE -

1) Two individuals rendered unconscious after acute tetrachloroethylene poisoning had breath concentrations of 85 and 110 ppm. One of these individuals had been exposed to 1,100 ppm tetrachloroethylene for 30 minutes (Baselt, 2000).
2) Two adults who lost consciousness after inhalation exposure to tetrachloroethylene had urinary levels of trichloroacetic acid of 28 mg/L and 13 mg/g creatinine and urinary trichloroethanol levels of 5 mg/L and 26.4 mg/g creatinine 5 hours after exposure ended (Garnier et al, 1996).

Workplace Standards

A)

1) Editor's Note: The listed values are recommendations or guidelines developed by ACGIH(R) to assist in the control of health hazards. They should only be used, interpreted and applied by individuals trained in industrial hygiene. Before applying these values, it is imperative to read the introduction to each section in the current TLVs(R) and BEI(R) Book and become familiar with the constraints and limitations to their use. Always consult the Documentation of the TLVs(R) and BEIs(R) before applying these recommendations and guidelines.

a) Adopted Value

1) Tetrachloroethylene

a) TLV:

1) TLV-TWA: 25 ppm
2) TLV-STEL: 100 ppm
3) TLV-Ceiling:

b) Notations and Endnotes:

1) Carcinogenicity Category: A3
2) Codes: BEI
3) Definitions:

a) A3: Confirmed Animal Carcinogen with Unknown Relevance to Humans: The agent is carcinogenic in experimental animals at a relatively high dose, by route(s) of administration, at site(s), of histologic type(s), or by mechanism(s) that may not be relevant to worker exposure. Available epidemiologic studies do not confirm an increased risk of cancer in exposed humans. Available evidence does not suggest that the agent is likely to cause cancer in humans except under uncommon or unlikely routes or levels of exposure.
b) BEI: The BEI notation is listed when a BEI is also recommended for the substance listed. Biological monitoring should be instituted for such substances to evaluate the total exposure from all sources, including dermal, ingestion, or non-occupational.

c) TLV Basis - Critical Effect(s): CNS impair
d) Molecular Weight: 165.8

1) For gases and vapors, to convert the TLV from ppm to mg/m(3):

a) [(TLV in ppm)(gram molecular weight of substance)]/24.45

2) For gases and vapors, to convert the TLV from mg/m(3) to ppm:

a) [(TLV in mg/m(3))(24.45)]/gram molecular weight of substance

e) Additional information:

B) NIOSH REL and IDLH Values for CAS127-18-4 (National Institute for Occupational Safety and Health, 2007):

1) Listed as: Tetrachloroethylene
2) REL:

a) TWA:
b) STEL:
c) Ceiling:
d) Carcinogen Listing: (Ca) NIOSH considers this substance to be a potential occupational carcinogen (See Appendix A in the NIOSH Pocket Guide to Chemical Hazards).
e) Skin Designation: Not Listed
f) Note(s): Minimize workplace exposure concentrations; See Appendix A

3) IDLH:

a) IDLH: 150 ppm
b) Note(s): Ca

1) Ca: NIOSH considers this substance to be a potential occupational carcinogen (See Appendix A).

C) Carcinogenicity Ratings for CAS127-18-4 :

1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): A3 ; Listed as: Tetrachloroethylene

a) A3 :Confirmed Animal Carcinogen with Unknown Relevance to Humans: The agent is carcinogenic in experimental animals at a relatively high dose, by route(s) of administration, at site(s), of histologic type(s), or by mechanism(s) that may not be relevant to worker exposure. Available epidemiologic studies do not confirm an increased risk of cancer in exposed humans. Available evidence does not suggest that the agent is likely to cause cancer in humans except under uncommon or unlikely routes or levels of exposure.

2) EPA (U.S. Environmental Protection Agency, 2011): Not Assessed under the IRIS program. ; Listed as: Tetrachloroethylene
3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): 2A ; Listed as: Tetrachloroethylene

a) 2A : The agent (mixture) is probably carcinogenic to humans. The exposure circumstance entails exposures that are probably carcinogenic to humans. This category is used when there is limited evidence of carcinogenicity in humans and sufficient evidence of carcinogenicity in experimental animals. In some cases, an agent (mixture) may be classified in this category when there is inadequate evidence of carcinogenicity in humans and sufficient evidence of carcinogenicity in experimental animals and strong evidence that the carcinogenesis is mediated by a mechanism that also operates in humans. Exceptionally, an agent, mixture or exposure circumstance may be classified in this category solely on the basis of limited evidence of carcinogenicity in humans.

4) NIOSH (National Institute for Occupational Safety and Health, 2007): Ca ; Listed as: Tetrachloroethylene

a) Ca : NIOSH considers this substance to be a potential occupational carcinogen (See Appendix A in the NIOSH Pocket Guide to Chemical Hazards).

5) MAK (DFG, 2002): Category 3B ; Listed as: Tetrachloroethylene

a) Category 3B : Substances for which in vitro or animal studies have yielded evidence of carcinogenic effects that is not sufficient for classification of the substance in one of the other categories. Further studies are required before a final decision can be made. A MAK value can be established provided no genotoxic effects have been detected. (Footnote: In the past, when a substance was classified as Category 3 it was given a MAK value provided that it had no detectable genotoxic effects. When all such substances have been examined for whether or not they may be classified in Category 4, this sentence may be omitted.)

6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): R ; Listed as: Tetrachloroethylene (Perchloroethylene)

a) R : RAHC = Reasonably anticipated to be a human carcinogen

D) OSHA PEL Values for CAS127-18-4 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):

1) Listed as: Perchloroethylene (Tetrachloroethylene)
2) Table Z-1 for Perchloroethylene (Tetrachloroethylene):

a) 8-hour TWA:

1) ppm:

a) Parts of vapor or gas per million parts of contaminated air by volume at 25 degrees C and 760 torr.

2) mg/m3:

a) Milligrams of substances per cubic meter of air. When entry is in this column only, the value is exact; when listed with a ppm entry, it is approximate.

3) Ceiling Value:
4) Skin Designation: No
5) Notation(s): Not Listed

3) Table Z-2 for Tetrachloroethylene (Z37.22-1967):

a) 8-hour TWA:100 ppm
b) Acceptable Ceiling Concentration: 200 ppm
c) Acceptable Maximum Peak above the Ceiling Concentration for an 8-hour Shift:

1) Concentration: 300 ppm
2) Maximum Duration: 5 min. in any 3 hrs

d) Notation(s): Not Listed

Toxicity Information

7.7.1)

A) (ACGIH, 1996; ATSDR, 1997 Bingham et al, 2001 Hayes & Laws, 1991 IRIS, 2001 ITI, 1995 Lewis, 2000 OHM/TADS, 2001 RTECS, 2001

1) LD50- (INTRAPERITONEAL)MOUSE:

a) 4600-5700 mg/kg (Bingham et al, 2001)
b) 4643-5672 mg/kg (Hayes & Laws, 1991)

2) LD50- (ORAL)MOUSE:

a) 8.85 g/kg (Budavari, 1996)
b) 0.109 -- undiluted (Hayes, 1991)
c) 8100 mg/kg -- General anesthetic
d) 8139 mg/kg (ATSDR, 1997)
e) 8850 mg/kg (Bingham et al, 2001; OHM/TADS, 2001)
f) 8800-10,800 mg/kg for 24H (ACGIH, 1996)

3) LD50- (SUBCUTANEOUS)MOUSE:

a) 65 g/kg -- Behavioral effects (sleep, ataxia)
b) Male, 390 mg/kg (Bingham et al, 2001)

4) LD50- (INTRAPERITONEAL)RAT:

a) 4678 mg/kg
b) 4800 mg/kg (OHM/TADS, 2001)

5) LD50- (ORAL)RAT:

a) 2629 mg/kg
b) 2600 mg/kg (Bingham et al, 2001)
c) Male, 3835 mg/kg (Bingham et al, 2001)
d) Female, 3005 mg/kg (ATSDR, 1997; Bingham et al, 2001)
e) 13,000 mg/kg for 24H (ACGIH, 1991)
f) 5000 mg/kg (ATSDR, 1997)
g) 3835 mg/kg (ATSDR, 1997)

6) TCLo- (INHALATION)HUMAN:

a) 96 ppm for 7H -- Local anesthetic; conjunctive irritation; hallucinations and distorted perceptions
b) 230 ppm -- Systemic effects (ITI, 1995)
c) Male, 600 ppm for 10M -- Conjunctive irritation; general anesthetic

7) TCLo- (INHALATION)MOUSE:

a) Male, 500 ppm for 7H at 5D prior to mating -- Affected spermatogenesis
b) Female, 300 ppm for 7H at 6-15D of pregnancy -- Fetotoxicity; developmental abnormalities in musculoskeletal system and homeostasis
c) 100 ppm for 6H/2Y intermittent -- Carcinogenic by RTECS criteria; Liver tumors
d) 200 ppm for 4H/8W intermittent -- Fatty liver degeneration
e) 1750 ppm for 6H/14D intermittent -- Fatty liver degeneration
f) 1600 ppm for 6H/13W intermittent -- Changes in kidney tubules and other changes in kidney, ureter, and bladder; death

8) TCLo- (INHALATION)RAT:

a) 200 ppm for 6H/2Y-Intermittent -- Carcinogenic effect (Lewis, 2000)
b) 900 ppm for 7H at 7-13D of pregnancy -- Reproductive effects (Lewis, 2000)
c) Female, 1000 ppm for 24H at 14D pre/1-22D of pregnancy -- Developmental abnormalities in musculoskeletal system
d) Female, 1000 ppm for 24H at 1-22D of pregnancy -- Fetotoxicity
e) Female, multigeneration, 1000 ppm for 6H -- Affected live birth index, viability index on post-natal day 4, and growth statistics
f) Female, 900 ppm for 7H at 7-13D of pregnancy -- Affected live birth index; resulted in biochemical, metabolic and behavioral changes
g) Female, 300 ppm for 7H at 6-15D of pregnancy -- Post-implantation mortality
h) 200 ppm for 6H/2Y intermittent -- Carcinogenic by RTECS criteria; Testicular tumors; Leukemia
i) 19,300 mg/m(3) for 24H/94D continuous -- Affected recordings from specific areas of CNS; true cholinesterase
j) 7000 ppm for 8H/50D intermittent -- Diffuse hepatocellular necrosis; changes in blood vessels or in circulation of kidney; changes in spleen
k) 1750 ppm for 6H/14D intermittent -- Death
l) 200 ppm for 4W continuous -- Affected hepatic microsomal mixed oxidase and other oxidoreductases and transaminases

Pharmacology Toxicology

Pharmacologic Mechanism

A)

Toxicologic Mechanism

A)

B)

C)

D)

Physicochemical

Physical Characteristics

A)

B)

C)

D)

Molecular Weight

A)

Animal Toxicology

References

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TETRACHLOROETHYLENE

Classification | Detailed evidence-based information

Therapeutic Toxic Class

Specific Substances

Available Forms Sources

Life Support

Clinical Effects

Laboratory Monitoring

Treatment Overview

Range Of Toxicity

Summary Of Exposure

Heent

Cardiovascular

Respiratory

Neurologic

Gastrointestinal

Hepatic

Genitourinary

Hematologic

Dermatologic

Endocrine

Reproductive

Carcinogenicity

Genotoxicity

Monitoring Parameters Levels

Radiographic Studies

Methods

Life Support

Patient Disposition

Monitoring

Oral Exposure

Inhalation Exposure

Eye Exposure

Dermal Exposure

Case Reports

Summary

Therapeutic Dose

Minimum Lethal Exposure

Maximum Tolerated Exposure

Serum Plasma Blood Concentrations

Workplace Standards

Toxicity Information

Pharmacologic Mechanism

Toxicologic Mechanism

Physical Characteristics

Molecular Weight

General Bibliography