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SECTION 1. CHEMICAL IDENTIFICATION

CHEMINFO Record Number: 81
CCOHS Chemical Name: Tetrachloroethylene

Synonyms:
Ethylene tetrachloride
PCE
Perc
Perchlor
Perchlorethylene
Perchloroethylene
Perk
Tetrachloroethene
Tetrachlorethylene
1,1,2,2-Tetrachloroethylene

Chemical Name French: Perchloroéthylène
Chemical Name Spanish: Percloroetileno

Trade Name(s):
Dowper
Perclene

CAS Registry Number: 127-18-4
UN/NA Number(s): 1897
RTECS Number(s): KX3850000
EU EINECS/ELINCS Number: 204-825-9
Chemical Family: Halogenated aliphatic hydrocarbon / unsaturated halogenated hydrocarbon / halogenated alkene / haloalkene / tetrahaloalkene / chloroalkene / tetrachloroalkene
Molecular Formula: C2-Cl4
Structural Formula: Cl2C=CCl2

SECTION 2. DESCRIPTION

Appearance and Odour:
Colourless liquid with mildly sweet odour, resembling diethyl ether or chloroform. The odour can be intense and unpleasant at high concentrations.(36)

Odour Threshold:
A wide range of values have been reported; 2 to 71 ppm. Reliable values are 47 ppm (detection) and 71 ppm (recognition).(37) Some people may not smell tetrachloroethylene at higher concentrations because they become accustomed to the odour.(36,38)

Warning Properties:
POOR - odour threshold is about the same magnitude as the TLV; eye irritation threshold (101-216 ppm) exceeds the TLV; causes olfactory fatigue.

Composition/Purity:
Tetrachloroethylene is available commercially in a number of grades, including a vapour degreasing grade, a dry-cleaning grade, an industrial grade for use in formulations, a high purity, low residue grade, a spectrophotometric grade and a grade specifically formulated for use as a transformer fluid. The various grades differ in the amount and type of added stabilizers.(10,39) It typically has a purity of 95% or more for dry-cleaning and industrial grades, 99% or more for more refined grades, and 99.995% for isomerization and fluorocarbon grades. Trichloroethylene may be present as an impurity.(10,36) Stabilizers are added to prevent decomposition by air, light, moisture and corrosion of aluminum, iron and zinc, and include amines, mixtures of epoxides and esters or phenols in various combinations at levels of 0.01 to 0.35%. Because of the high stability of tetrachloroethylene only minor amounts of stabilizers are required.(2,39)

Uses and Occurrences:
Tetrachloroethylene is used mainly as a chemical intermediate, in cold cleaning and vapour degreasing of metals, as a solvent for dry cleaning and for textile finishing and dyeing. It is also used as a transformer insulating fluid, for chemical maskant formulations, as a process solvent for desulfurizing coal, as a general industrial solvent, and to remove soot from industrial boilers.(2,39,40) It has historically been used in the treatment of hookworm and some nematode infestations, but has been replaced by drugs which are less toxic and easier to administer.(2)


SECTION 3. HAZARDS IDENTIFICATION

EMERGENCY OVERVIEW:
Colourless liquid with a mildly sweet odour, resembling diethyl ether or chloroform. The odour can be intense and unpleasant at high concentrations. Will not burn. Can decompose at high temperatures forming toxic gases such as hydrogen chloride, chlorine and phosgene. Closed containers may rupture and explode if heated releasing toxic gases or vapours. Can accumulate in low lying areas. TOXIC. Vapour causes irritation of the eyes, nose and throat. Central nervous system depressant. Vapour may cause headache, nausea, dizziness, drowsiness, incoordination, and confusion. High vapour concentrations may cause unconsciousness and death. SKIN IRRITANT. Causes severe skin irritation. Aspiration hazard. Swallowing or vomiting of the liquid may result in aspiration (breathing) into the lungs. SUSPECT CANCER HAZARD - may cause cancer, based on human information.



POTENTIAL HEALTH EFFECTS

Effects of Short-Term (Acute) Exposure

Inhalation:
Short-term exposure can cause irritation of the nose and throat and central nervous system (CNS) depression with symptoms such as drowsiness, dizziness, giddiness, headache, nausea, loss of coordination, confusion and unconsciousness. Deaths have occurred following exposure to very high vapour concentrations.(1,2) Tetrachloroethylene is heavier than air and can accumulate in low lying areas.
Exposure to 100-200 ppm for 5-7 hours has produced headaches, drowsiness, dizziness and sleepiness. Nose and throat irritation have been reported at 200 ppm and above. Exposure to 280 ppm for 2 hours or 600 ppm for 10 minutes has produced incoordination. Intolerable irritation of the nose and throat has been observed at 1000 ppm and above. Faintness and dizziness were experienced during 2-hour exposures to 1000-1500 ppm. A 5-7 minute exposure to 2000 ppm caused volunteers to feel as though they were going to collapse.(1,2) A few deaths have been reported due to CNS depression and irregular heart beat. In one case, pulmonary edema (a potentially fatal accumulation of fluid in the lungs) was reported.(3) Liver and kidney injury has also been observed following exposure to very high concentrations which also caused significant CNS effects.(2)
Behaviourial effects (e.g. slow reaction time to visual stimuli and coordination) have been reported in volunteers exposed to concentrations as low as 50 ppm for 4 hours/day for 4 days or 100 ppm and above for several hours. Behaviourial effects were not observed in volunteers exposed to 25 or 100 ppm for 5.5 hours.(1,2)

Skin Contact:
Tetrachloroethylene is a severe skin irritant, based on human and animal evidence. Five volunteers placed their thumbs in beakers of tetrachloroethylene (99% pure) for 30 minutes. A mild burning sensation was noted within 5-10 minutes. The burning sensation reached its maximum intensity (mild-moderate burning) within 15-20 minutes. After exposure stopped, the burning sensation persisted for 1 hour. A marked erythema was present in all cases, subsiding in 1-2 hours after exposure stopped.(53) A case report describes a 68-year-old man who spilt a container of tetrachloroethylene on him, soaking his clothes. He became unconscious and was found 1/2 hour later. He was noted to have erythema and blistering covering 30% of his body. His burns were determined to be superficial. Five days later, the erythema had subsided and the blistering gone.(52) Another case report describes a 29-year-old man who came into direct contact with tetrachloroethylene for an unspecified period of time. He experienced extensive erythema a blistering involving 25-30% of his body. His burns gradually healed within 3 weeks.(51)
Animal and human information indicates that tetrachloroethylene absorption through the skin is minimal.(2) Harmful effects are not expected to occur by this route of exposure.

Eye Contact:
Liquid tetrachloroethylene is probably a mild eye irritant, based on animal information. Volunteers exposed to 101-216 ppm of tetrachloroethylene vapour have experienced mild eye irritation. A burning or stinging sensation was felt after exposure to 280 or 600 ppm and intense irritation occurred at 930 ppm.(1,2)

Ingestion:
Tetrachloroethylene has been used as a medicine and reported side-effects following administration of 4.2 to 6.0 gm include a feeling of drunkenness, vision disturbances and a feeling of exhilaration.(2) In one case, ingestion of 3 mL (approximately 4.9 gm) was reported to cause death. However, the patient had pre-existing medical disorders which likely played a role in his death.(2)
Tetrachloroethylene can probably be aspirated, based on its physical properties. Aspiration is the inhalation of the chemical into the lungs during ingestion or vomiting. Severe lung irritation, damage to the lung tissues and death may result. Ingestion is not a typical route of occupational exposure.

Effects of Long-Term (Chronic) Exposure

Nervous System:
Numerous studies have reported effects on the CNS following long-term occupational exposure to tetrachloroethylene and other solvents. Symptoms such as dizziness, forgetfulness, inability to concentrate, mood swings, nausea and fatigue and behaviourial effects such as reduced reaction time and incoordination have been described. This condition is sometimes generally referred to as "organic solvent syndrome". Many of the available studies are limited by factors such as exposure to other solvents at the same time, incomplete or no exposure information, and evaluation of only a small number of people.(2,4-9) Commonly, tetrachloroethylene exposures have occurred in the dry cleaning industry where there would normally be exposure to other solvents. Therefore, it is difficult to directly associate the observed effects to tetrachloroethylene exposure. In one controlled study using volunteers, exposure to 100 ppm for 11 weeks produced decreased coordination. Similar effects were not observed at 20 ppm.(2)

Skin:
Repeated or prolonged contact is expected to cause red, itchy, dry and cracked skin (dermatitis).(2)

Heart/Blood Vessels:
In a controlled study using volunteers, no harmful effects on the electrical activity of the heart were observed following exposure to up to 100 ppm tetrachloroethylene, over 11 weeks. In a single case report, an employee exposed to tetrachloroethylene for 7 months developed an irregular heartbeat, which returned to normal after exposure stopped.(2)

Kidneys/Urinary System:
The available studies of people with long-term occupational exposure are limited by the fact that exposure to other potentially harmful chemicals may have occurred at the same time and the number of people evaluated is relatively small. In a controlled study using volunteers, no signs of kidney injury were observed following exposure to up to 100 ppm over 11 weeks.(2) Kidney effects were also not observed in people with long-term occupational to approximately 20 ppm.(4,5) A few occupational studies have shown evidence of minor kidney effects following exposure to 10-20 ppm.(2,10,11)
In animal studies, kidney injury has been observed in rats and mice. Rats are most sensitive to the kidney effects of tetrachloroethylene, because there are important differences in the way that rats, especially male rats, metabolize tetrachloroethylene.(2)

Liver:
The available studies of people with long-term occupational exposure are limited by the fact that exposure to other potentially harmful chemicals may have occurred at the same time and the number of people evaluated is relatively small. In a controlled study using volunteers, no signs of liver injury were observed following exposure to up to 100 ppm over 11 weeks.(2) Liver effects were also not observed in people with long-term occupational to approximately 20 ppm.(4,5) A few occupational studies have shown evidence of minor liver effects following exposure to 10-20 ppm.(2,10,11) In another study, 3 of 7 workers exposed to 232-385 ppm tetrachloroethylene had signs of liver damage.(6)
In animal studies, long-term inhalation exposure has produced severe liver damage in mice exposed to 200 ppm and above. Mice are the species most sensitive to the liver effects of tetrachloroethylene, because of the way in which they metabolize tetrachloroethylene. The liver effects in mice are also thought to result from peroxisome proliferation, a response to chemical exposure that is minimal in humans.(2) Therefore, liver effects are not expected to occur in people exposed to tetrachloroethylene unless exposure levels are very high.

Carcinogenicity:

Several human population studies have shown more esophageal cancer, non-Hodgkin's lymphoma and cervical cancer in people occupationally exposed to tetrachloroethylene. The International Agency for Research on Cancer (IARC) has concluded that there is limited evidence for the carcinogenicity of tetrachloroethylene in humans. There is sufficient evidence for carcinogenicity in animals.(10)

The International Agency for Research on Cancer (IARC) has concluded that this chemical is probably carcinogenic to humans (Group 2A).

The American Conference of Governmental Industrial Hygienists (ACGIH) has designated this chemical as an animal carcinogen (A3).

The US National Toxicology Program (NTP) has listed this chemical as reasonably anticipated to be a human carcinogen.

Teratogenicity and Embryotoxicity:
A number of human population studies have evaluated the effects of exposure to chemicals in the laundry and dry cleaning industry on pregnancy. Exposure to tetrachloroethylene commonly occurs in this industry. None of the studies have shown an increase in birth defects or stillbirths or decreased weight of the newborn child. A few studies have shown an association with increased miscarriage rates, while others did not. It is not yet possible to draw firm conclusions from the available information because of limitations in the study design such exposure to other chemicals at the same time, lack of exposure information, self-reporting biases and the relatively small number of people studied.(2,3,13-15)
One case report describes jaundice and an enlarged liver in a 6-week old infant exposed to tetrachloroethylene in its mother's breast milk. The mother did experience other harmful effects (for example, dizziness) during exposure. The infant recovered once exposure stopped.(16)
Harmful effects have only been observed in the offspring of animals in the presence of significant harmful effects in the mothers.

Reproductive Toxicity:
Tetrachloroethylene has not been shown to cause reproductive toxicity in men. One study reported subtle changes in sperm quality in employees exposed to elevated levels of tetrachloroethylene.(10,17) In other studies, partners of men occupationally exposed to tetrachloroethylene did not experience decreased fertility or an increase in miscarriages.(14,17)
One survey suggests that women exposed to tetrachloroethylene may have menstrual disorders.(18) This study is limited by factors such as a small sample size, possible multiple chemical exposures, no assessment of exposure and possible self-reporting bias. In another study, women with long-term exposure to tetrachloroethylene (average levels of 15 ppm) had increased levels of the hormone prolactin in the blood during part of the menstrual cycle. This effect is not likely biologically significant.(7)
The small number of animal studies available have not shown effects on fertility.

Mutagenicity:
No conclusions can be drawn from studies involving people occupationally exposed to tetrachloroethylene. Employees with long-term exposure to average concentrations of 10-220 ppm did not have an increase in structural chromosomal abnormalities or sister chromatid exchanges in their white blood cells, but there was a small increase in chromosomal abnormalities. No information was provided on the smoking habits of the people tested. In another study, limitations with the study design (that is, a possible effect from smoking, and multiple chemical exposures) prevent interpretation of the results.(10) Results from studies using live animals are negative.

Toxicologically Synergistic Materials:
Interactive effects, such as synergism, with other chemicals have been examined in a small number of studies. In behaviourial tests with volunteers, no interactive effects were observed when people were exposed to tetrachloroethylene and ethanol, or tetrachloroethylene and the prescription drug, diazepam.(19) In rats, short-term inhalation or oral exposure to tetrachloroethylene, in combination with two other solvents (acetone and ethylene dichloride) did not indicate chemical interactions.(20) In another study with rats, short-term oral exposure to tetrachloroethylene in combination with other chemicals (polyethylene glycol, butyl ether dioxane or acetophenone) indicated that chemical interactions were occurring.(21)

Potential for Accumulation:
Tetrachloroethylene is rapidly absorbed following inhalation and ingestion. A small amount is absorbed through the skin. It is rapidly distributed throughout the body. Most tetrachloroethylene (80-100% in humans) is eliminated unchanged in exhaled breath. Some is broken down in the body to other chemicals including trichloroacetic acid and trichloroethanol. Most of the metabolites (1-3%) are excreted in the urine in a few days. Some of the absorbed tetrachloroethylene is stored in body fat and may remain for several days or weeks before it is eliminated.(1,2)


SECTION 4. FIRST AID MEASURES

Inhalation:
This chemical is toxic and a suspect cancer hazard. Take proper precautions to ensure your own safety before attempting rescue (e.g. wear appropriate protective equipment, use the buddy system). Remove source of contamination or move victim to fresh air. If breathing has stopped, trained personnel should begin artificial respiration (AR) or, if the heart has stopped, cardiopulmonary resuscitation (CPR) or automated external defibrillation (AED) immediately. Quickly transport victim to an emergency care facility.

Skin Contact:
Avoid direct contact. Wear chemical protective clothing, if necessary. As quickly as possible, remove contaminated clothing, shoes and leather goods (e.g. watchbands, belts). Immediately flush with lukewarm, gently flowing water for 15-20 minutes. Immediately obtain medical attention. Double bag, seal, label and leave contaminated clothing, shoes and leather goods at the scene for safe disposal.

Eye Contact:
Avoid direct contact. Wear chemical protective gloves, if necessary. Quickly and gently blot or brush chemical off the face. Immediately flush the contaminated eye(s) with lukewarm, gently flowing water for 5 minutes, while holding the eyelid(s) open. Obtain medical advice.

Ingestion:
NEVER give anything by mouth if victim is rapidly losing consciousness, is unconscious or convulsing. Have victim rinse mouth thoroughly with water. DO NOT INDUCE VOMITING. If vomiting occurs naturally, have victim lean forward to reduce risk of aspiration. Have victim rinse mouth with water again. Immediately obtain medical attention.

First Aid Comments:
Provide general supportive measures (comfort, warmth, rest).
Consult a doctor and/or the nearest Poison Control Centre for all exposures except minor instances of inhalation or skin contact.
Some first aid procedures recommended above require advanced first aid training. Protocols for undertaking advanced procedures must be developed in consultation with a doctor and routinely reviewed.

All first aid procedures should be periodically reviewed by a doctor familiar with the material and its condition of use in the workplace.



SECTION 5. FIRE FIGHTING MEASURES

Flash Point:
None measured by conventional test methods. Not combustible (does not burn).(41)

Lower Flammable (Explosive) Limit (LFL/LEL):
Not applicable

Upper Flammable (Explosive) Limit (UFL/UEL):
Not applicable

Autoignition (Ignition) Temperature:
Not applicable

Sensitivity to Mechanical Impact:
Not sensitive. Stable material.

Sensitivity to Static Charge:
Will not accumulate static charge by flow or agitation. The electrical conductivity of tetrachloroethylene is very high (5.6 X 10(10) pS/m).(42) Tetrachloroethylene will not be ignited by a static discharge because it does not burn.

Combustion and Thermal Decomposition Products:
Chlorine, phosgene, hydrogen chloride gas and other toxic and irritating compounds.(36,43)

Fire Hazard Summary:
Tetrachloroethylene is not combustible. Closed containers may explode if exposed to excess heat for a sufficient period of time releasing large quantities of toxic gases or vapours (e.g. hydrogen chloride, phosgene and/or chlorine).

Extinguishing Media:
Tetrachloroethylene is not combustible. Use extinguishing media suitable for surrounding fire.(36,43)

Fire Fighting Instructions:
If a fire occurs in the vicinity of containers of tetrachloroethylene, evacuate area and fight fire from a safe distance or a protected location. Approach fire from upwind to avoid toxic decomposition products.
If possible, isolate materials not yet involved in the fire, move containers from the fire area if this can be done without risk, and protect personnel. Otherwise, fire-exposed containers or tanks should be cooled by application of water spray. Application should begin as soon as possible and should concentrate on any unwetted portions of the container. Apply water from the side and from a safe distance until well after the fire is out.
Stay away from the ends of tanks involved in the fire, but be aware that flying material from ruptured tanks may travel in any direction. Withdraw immediately in case of rising sound from venting safety device or any discolouration of tank due to fire.
For a massive fire, it may be prudent to use unmanned hose holder or monitor nozzles.
Tetrachloroethylene is a possible cancer hazard. Do not enter without wearing specialized protective equipment suitable for the situation. Firefighter's normal protective clothing (Bunker Gear) will not provide adequate protection. A full-body encapsulating chemical resistant suit with positive pressure self-contained breathing apparatus (MSHA/NIOSH approved or equivalent) may be necessary.



NATIONAL FIRE PROTECTION ASSOCIATION (NFPA) HAZARD IDENTIFICATION

NFPA - Health: 2 - Intense or continued (but not chronic) exposure could cause temporary incapacitation or possible residual injury.
NFPA - Flammability: 0 - Will not burn under typical fire conditions.
NFPA - Instability: 0 - Normally stable, even under fire conditions, and not reactive with water.

SECTION 9. PHYSICAL AND CHEMICAL PROPERTIES

Molecular Weight: 165.83

Conversion Factor:
1 ppm = 7.4 mg/m3; 1 mg/m3 = 0.135 ppm (calculated)

Physical State: Liquid
Melting Point: -22.5 deg C (-8.5 deg F) (36,39,44); -19 deg C (-2.2 deg F) (2,38)
Boiling Point: 121 deg C (250 deg F) (42,44,45)
Relative Density (Specific Gravity): 1.623 at 20 deg C (water = 1) (39,40,44)
Solubility in Water: Practically insoluble (15 mg/100 mL at 25 deg C) (36,39,40)
Solubility in Other Liquids: Soluble in all proportions in ethanol, diethyl ether, chlorinated organic solvents, such as chloroform and carbon tetrachloride, acetone, benzene, hexane and oils.(38,39,44)
Coefficient of Oil/Water Distribution (Partition Coefficient): Log P(oct) = 3.40 (2,10,38)
pH Value: Not applicable
Vapour Density: 5.83 (air = 1) (43,45)
Vapour Pressure: 1.9 kPa (14.25 mm Hg) at 20 deg C (40,42); 2.5 kPa (18.5 mm Hg) at 25 deg C (38,45)
Saturation Vapour Concentration: 18800 ppm (1.88%) at 20 deg C; 24300 ppm (2.43%) at 25 deg C (calculated)
Evaporation Rate: 1.5 (n-butyl acetate = 1) (45); 2.59 (n-butyl acetate = 1) (42); 6.0 (diethyl ether = 1) (42)
Critical Temperature: 347 deg C (657 deg F) (39,40,44)

Other Physical Properties:
VISCOSITY-DYNAMIC: 0.88 mPa.s (0.88 centipoise) at 20 deg C (40,42,45)
VISCOSITY-KINEMATIC: 0.54 m2/s (0.54 centistokes) at 20 deg C (calculated)
SURFACE TENSION: 32.3 mN/m (32.3 dynes/cm) at 20 deg C (45)
CRITICAL PRESSURE: 4489 kPa (44.3 atm) (44); 9740 kPa (96.1 atm) (39,42)


SECTION 10. STABILITY AND REACTIVITY

Stability:
Decomposes slowly in the presence of light (especially ultraviolet light) and air to form trichloroacetyl chloride and phosgene, if unstabilized.(39,40) The unstabilized compound also hydrolyzes very slowly in the presence of water to form corrosive trichloroacetic acid and hydrochloric acid.(39)

Hazardous Polymerization:
Does not occur

Incompatibility - Materials to Avoid:

NOTE: Chemical reactions that could result in a hazardous situation (e.g. generation of flammable or toxic chemicals, fire or detonation) are listed here. Many of these reactions can be done safely if specific control measures (e.g. cooling of the reaction) are in place. Although not intended to be complete, an overview of important reactions involving common chemicals is provided to assist in the development of safe work practices.


STRONG ACIDS (e.g. sulfuric acid or hydrochloric acid) - may react violently with risk of fire and explosion.(36)
STRONG OXIDIZING AGENTS (e.g. dinitrogen tetroxide, nitric acid, perchloric acid, oxygen, or peroxides) - may react violently with risk of fire and explosion.(36,46)
STRONG BASES (e.g. sodium hydroxide, potassium hydroxide) - produces spontaneously explosive and flammable dichloroacetylene gas when trichloroethylene is present as an impurity.(36,46)
COPPER - can react with any dichloroethylenes present as an impurity, to form explosive acetylides.(40)
ALUMINUM POWDER - may react violently or explosively, especially in the presence of water, aluminum chloride and/or cutting oils.(46)
CHEMICALLY ACTIVE METALS (e.g. granular barium, lithium shavings, beryllium powder, magnesium powder, potassium, sodium or zinc powder) - can ignite or explode violently.(36,39,41,46)
BUTYLLITHIUM - an explosive reaction occurs with butyllithium in petroleum ether solution.(39)

Hazardous Decomposition Products:
Hydrogen chloride gas, hydrochloric acid, phosgene.

Conditions to Avoid:
Excessive heat, open flames, electrical arcs, welding arcs, hot surfaces or other high temperature sources, sunlight, moisture, depletion of stabilizers.

Corrosivity to Metals:
Pure, stabilized tetrachloroethylene is not corrosive to any of the common construction materials, such as steel, cast iron, stainless steels, or nickel and its alloys at temperatures up to about 140 deg C.(39) The unstabilized material is corrosive to aluminum, iron and zinc in the presence of water.(36)

Stability and Reactivity Comments:
Tetrachloroethylene will attack some forms of plastics, rubber and coatings.(36)


SECTION 11. TOXICOLOGICAL INFORMATION

LC5O (rat): Approximately 3786 ppm (4-hour exposure) (22); approximately 4000 ppm (4-hour exposure) (23)
LC50 (mouse): 5200 ppm (4-hour exposure) (24)

LD5O (oral, rat): Approximately 2600 mg/kg (cited as 1.6 mL/kg) (20)
LD50 (oral, male rat): 3835 mg/kg (25)
LD50 (oral, female rat): 3005 mg/kg (25)

LD50 (dermal, rabbit): Greater than 3245 mg/kg (0/5 animals died) (2)

Eye Irritation:

The available information suggests that tetrachloroethylene is a slight to mild eye irritant.

In one study, undiluted tetrachloroethylene caused slight to mild irritation in rabbits.(26) In another study which does not conform to standard testing protocols, tetrachloroethylene was sprayed into the eyes using a pressurized container. Pain and some corneal damage was observed in rabbits, with recovery in two days.(27)

Skin Irritation:

Tetrachloroethylene is a severe skin irritant.

In an OECD compliant test, application of 0.5 mL of undiluted tetrachloroethylene for 4 hours produced severe irritation (primary irritation index: 5.67/8; maximum average score: erythema: 4/4; edema: 2.3/4).(50) In a Draize test, application of 0.5 mL of undiluted tetrachloroethylene for 24 hours caused severe irritation in female rabbits (primary irritation index: 6.1/8).(26)

Effects of Short-Term (Acute) Exposure:

Short-term inhalation and ingestion has caused liver injury and central nervous system (CNS) depression in animals.(1,2)

Inhalation:
Inhalation of 200 ppm for 4 days has caused minor behaviourial effects in rats. Brief exposures to concentrations of 1000 ppm and above have caused signs and symptoms of central nervous system depression such as dizziness, lethargy and unconsciousness in rats and mice. Similar effects have been observed in rats following the ingestion of 1000 mg/kg/day. Deaths have resulted from respiratory failure or cardiac arrest.(1,2) Inhalation of concentrations as low as 200 ppm for 4 hours has produced fatty degeneration of the liver in mice, which appear to be the most susceptible species. Liver changes have also been observed in mice exposed to concentrations as low as 9 ppm for 30 days.(1,2) Minor liver effects have been observed in mice following ingestion of 100 mg/kg/day for 6 weeks or greater or 250 mg/kg/day for 11 days. Liver damage has been observed in mice following ingestion of 500 mg/kg/day for 6 weeks.(1,2)

Ingestion:
Kidney injury has been observed in male rats following ingestion of doses of 1000 mg/kg/day for 10 days. Kidney injury was not observed in rats following inhalation of 400 ppm for 28 days.(1,2) The kidney lesions observed are specific to male rats and are probably not relevant to other species.

Effects of Long-Term (Chronic) Exposure:

Long-term exposure has produced severe liver damage in mice exposed by inhalation to 200 ppm and above. Kidney injury has been observed in rats exposed by inhalation to 200 ppm and above and mice exposed to 100 ppm and above. Kidney injury has also been observed in mice and rats exposed by ingestion to approximately 400 mg/kg/day and above.

Inhalation:
Rats exposed by inhalation to 200 or 400 ppm for 2 years developed changes in their kidney cells (karyomegaly). Decreased survival was observed in males at the high dose.(22) Mice exposed to 100 or 200 ppm for 2 years showed similar kidney cell changes. Kidney damage was observed in females. Signs of kidney dysfunction (casts in the urine) were observed in males at both dose levels, and females at the high dose. Severe liver damage (cellular degeneration and necrosis) was observed in males at both exposure levels, and in females at 200 ppm. Lung congestion was also observed. Survival was reduced in males at both concentrations, and in females at 200 ppm.(22)

Ingestion:
Rats exposed to 14, 400 or 1400 mg/kg/day tetrachloroethylene in the drinking water for 90 days had decreased body weight and increased kidney weights at the two high doses. Increased liver weights were observed at the high dose.(28) Kidney injury was observed in mice exposed to 386 mg/kg/day and above and in rats exposed to 471 mg/kg/day and above (time-weighted averages) for 78 weeks.(2)

Carcinogenicity:
The International Agency for Research on Cancer (IARC) has determined that there is sufficient evidence for the carcinogenicity of tetrachloroethylene in experimental animals.
In one feeding study with mice, an increase in liver tumours was observed in both sexes. In inhalation studies with mice and rats, liver tumours were increased in mice, and leukemia was increased in rats. Other studies were negative or conclusions could not be drawn because of limitations in study design.(10)

Teratogenicity, Embryotoxicity and/or Fetotoxicity:
Studies have not shown harmful effects in the offspring of rats, rabbits or mice in the absence of toxicity in the mothers.
In one study, rats and mice were exposed to 300 ppm tetrachloroethylene on days 6-15 of pregnancy. Maternal toxicity was observed in both the rats (decreased maternal weight) and the mice (increased liver weight). Fetotoxicity (e.g. decreased body weights and delayed bone formation) was observed in the offspring of mice. Embryotoxicity (resorptions) was observed in rats.(29) Two studies showed no harmful effects in the mothers or offspring following inhalation exposure of rats and rabbits to up to 500 ppm throughout pregnancy, or 3 weeks prior to mating and then throughout pregnancy.(30,31) Other studies have shown harmful effects in the offspring of rats following inhalation of up to 1000 ppm or ingestion of 900 mg/kg/day. Maternal toxicity was observed in all cases.(1,2,10)

Reproductive Toxicity:
The available studies have not shown harmful effects on fertility.
In a multi-generation study, no effects on reproductive outcome were observed in rats exposed to 300 ppm. Some effects (e.g. reduced pup survival) were observed in the 1000 ppm exposure group, in the presence of significant toxicity in the adult animals.(2) In another study which does not meet current study design standards, no adverse effects on fertility were observed in rats exposed to up to 470 ppm vapour for 27 weeks.(32) An increase in abnormally shaped sperm was observed in mice, but not rats, exposed to 500 ppm vapour for 5 days. No harmful effects were seen in a dominant lethal assay (which measures viability of embryos) when males were exposed by inhalation during a 7 week mating period.(31)

Mutagenicity:
Tetrachloroethylene produced negative results in a number of tests using live animals. No conclusions can be drawn from a small number of studies which have shown an effect on DNA (reversible single strand breaks and DNA binding) in live animals. These limited studies did not use validated methods for detecting DNA damage and the results can be explained by reasons other than mutagenicity.
In bacteria and in cultured mammalian cells, results are typically negative, but positive effects have been observed in some systems.(2,10,28,31,33-35)
Commercial tetrachloroethylene may contain mutagenic additives.(2,10)


SECTION 16. OTHER INFORMATION

Selected Bibliography:
(1) Perchloroethylene. In: Documentation of the threshold limit values and biological exposures indices. Supplements to the 6th ed. American Conference of Governmental Industrial Hygienists, 1996
(2) Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological profile for tetrachloroethylene (update). US Department of Health & Human Services, Sept. 1997
(3) Patel, R., et al. Pulmonary edema due to tetrachloroethylene. Environmental Health Perspectives. Vol. 21 (Dec. 1977). p. 247-249
(4) Cai, S., et al. Subjective symptom increase among dry-cleaning workers exposed to tetrachloroethylene vapor. Industrial Health. Vol. 29, no. 3 (1991). p. 111-121
(5) Lauwerys, R., et al. Health surveillance of workers exposed to tetrachloroethylene in dry-cleaning shops. International Archives of Occupational and Environmental Health. Vol. 52, no. 1 (1983). p. 69-77
(6) Coler, H.R., et al. Tetrachlorethylene exposure in a small industry. American Medical Association Archives of Industrial Hygiene and Occupational Medicine. Vol. 8 (1953) p. 227-233
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Information on chemicals reviewed in the CHEMINFO database is drawn from a number of publicly available sources. A list of general references used to compile CHEMINFO records is available in the database Help.


Review/Preparation Date: 1998-03-26

Revision Indicators:
TLV comments 1998-08-01
EU Classification 1998-11-01
EU Risk 1998-11-01
EU Safety 1998-11-01
ERPG 2001-03-01
Carcinogenicity 2002-12-19
Toxicological info 2003-09-19
Short-term skin contact 2003-09-19
WHMIS classification comments 2003-09-19
PEL transitional comments 2003-12-19
PEL-TWA transitional 2003-12-19
PEL-C transitional 2003-12-19
PEL-TWA final 2003-12-19
TLV basis 2004-01-04
Resistance of materials for PPE 2004-04-06
Bibliography 2005-04-11
Passive Sampling Devices 2005-04-11
Sampling/analysis 2005-04-11
Long-term exposure 2005-09-23
WHMIS detailed classification 2005-09-23
WHMIS health effects 2005-09-23
Emergency overview 2005-09-23
First aid inhalation 2005-09-23
First aid ingestion 2005-09-23
Note to physicians 2005-09-23
Handling 2005-09-27
First aid ingestion 2005-11-09



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