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SECTION 1. CHEMICAL IDENTIFICATION

CHEMINFO Record Number: 117
CCOHS Chemical Name: Carbon tetrachloride

Synonyms:
Carbona
Carbon chloride
Carbon tet
Methane tetrachloride
Perchloromethane
Tetrachlorocarbon
Tetrachloromethane
Tetraform
Tetrachlorure de carbone

Chemical Name French: Tétrachlorure de carbone
Chemical Name Spanish: Tetracloruro de carbono
CAS Registry Number: 56-23-5
UN/NA Number(s): 1846
RTECS Number(s): FG4900000
EU EINECS/ELINCS Number: 200-262-8
Chemical Family: Halogenated aliphatic hydrocarbon / saturated halogenated hydrocarbon / halogenated alkane / haloalkane / tetrahaloalkane / chloroalkane / tetrachloroalkane / chlorinated methane
Molecular Formula: C-Cl4
Structural Formula: Cl(Cl)-C-(Cl)Cl

SECTION 2. DESCRIPTION

Appearance and Odour:
Colourless liquid with an sweet, chloroform-like odour.(48)

Odour Threshold:
A wide range of values have been reported; 1.6 to 706 ppm. The range of acceptable values is 140 to 584 ppm. Geometric mean air odour threshold: 252 ppm (detection); 250 ppm (recognition).(49)

Warning Properties:
POOR - odour threshold exceeds the TLV. Adaptation to the odour can occur.

Composition/Purity:
Commercial grades of carbon tetrachloride are available in high purity (greater than 99.9% wt%). The impurities present may include small amounts of hydrogen chloride, carbon disulfide, tetrachloroethylene, bromine, water and chloroform.(48,50,51) Carbon tetrachloride frequently contains stabilizers to prevent it from decomposing to corrosive hydrogen chloride upon reacting with water or heating in air. Effective stabilizers include alkyl cyanamides, such as diethyl cyanamide, diphenylamine (0.34- 1%), ethyl acetate, ethyl cyanide (up to 1%), fatty acid derivatives, hexamethylenetetramine, resins and amines, thiocarbamide and guanidine.(50) Carbon tetrachloride can be shipped in metal containers, or by tank truck, tank car, barge and ship.

Uses and Occurrences:
Carbon tetrachloride has a small use as a reaction medium solvent (e.g. for chlorine) or as a chemical intermediate. It was formerly used to make chlorofluorocarbons, as a metal degreasing agent, dry-cleaning fluid, fabric spotting fluid, fire extinguishing agent and agricultural fumigants. The use of carbon tetrachloride has declined significantly in recent years because of its toxicity and the effect of chlorofluorocarbons on the ozone layer.(50,51)
Carbon tetrachloride is included as a controlled substance in the Montreal Protocol on Substances that Deplete the Ozone Layer. Under these provisions, the product and imports of this substance should have been phased out by 1996, except under certain exemptions as provided for in the Protocol.


SECTION 3. HAZARDS IDENTIFICATION

EMERGENCY OVERVIEW:
Colourless liquid with an sweet, chloroform-like odour. Will not burn. Can decompose at high temperatures forming toxic and corrosive gases such as phosgene, hydrogen chloride and chlorine. Closed containers may rupture and explode if heated, releasing toxic gases or vapours. Forms impact sensitive compounds with alkali metals, such as potassium, sodium or sodium-potassium alloy and impact sensitive mixtures with aluminum, magnesium, decaborane and dinitrogen tetraoxide. VERY TOXIC. May be fatal if inhaled or swallowed. Central nervous system depressant. Vapour may cause headache, nausea, dizziness, drowsiness, incoordination, and confusion. May cause liver and kidney damage. Causes skin irritation. Aspiration hazard. Swallowing or vomiting of the liquid may result in aspiration (breathing) into the lungs. POSSIBLE CANCER HAZARD - may cause cancer.



POTENTIAL HEALTH EFFECTS

Effects of Short-Term (Acute) Exposure

Inhalation:
Carbon tetrachloride very readily forms high vapour concentrations at room temperature. It is very toxic and therefore poses a very high inhalation hazard. Carbon tetrachloride is a central nervous system (CNS) depressant causing symptoms such as headache, nausea, dizziness, vomiting, drunkenness and incoordination. It is can also cause kidney and liver damage following short-term exposure. Symptoms of liver injury may include pain and tenderness of the liver, and yellow skin and eyes (jaundice). Symptoms of kidney injury may include reduced or no urination and fluid accumulation in the body. There are many historical reports of death occurring following carbon tetrachloride exposure.(1,2)
There are numerous case reports of employees developing CNS depression following exposure to carbon tetrachloride. Unfortunately, information regarding exposure concentrations is often limited or unavailable. No symptoms were experienced by volunteers exposed to 50 ppm for 70 minutes or to 10 ppm for 3 hours.(3) Employees exposed to 45 to 100 ppm developed nausea, gastrointestinal upset and discomfort, headache, giddiness and depression toward the end of the work week. When exposures were lowered to less than 9 ppm, the symptoms resolved.(4) In another report, employees developed drowsiness, nausea, vomiting, and signs of drunkenness, as well as kidney and liver injury following brief exposure to 75-600 ppm (estimated average 210 ppm).(5) In another case, a 4-hour exposure to 250 ppm (estimated) caused mild headache and dizziness in two employees. Another employee, who was more sensitive to the effects of carbon tetrachloride because of alcohol abuse, died.(2) Kidney and liver injury as well as an accumulation of fluid in the lungs (pulmonary edema) is often observed in people who have died following exposure. The pulmonary edema is typically not seen until 8 days after exposure and is caused by kidney failure, rather than direct lung injury.(1)

Skin Contact:
Carbon tetrachloride is a mild to moderate skin irritant, based on animal and human information. Direct contact with undiluted carbon tetrachloride for 20 to 30 minutes has caused a mild burning sensation with mild redness that resolved within 1 to 2 hours.(6)
Carbon tetrachloride is absorbed through the skin and can cause harmful effects by this route of exposure.(6) In most cases, high inhalation exposures would also occur at the same time because carbon tetrachloride evaporates so quickly. Effects would be similar to those described for "Inhalation" above. There are historical case reports of deaths or near deaths following exposure to carbon tetrachloride in shampoo or as a solvent.(1)

Eye Contact:
Carbon tetrachloride is probably a mild eye irritant, based on animal information. There is no human information available.

Ingestion:
Carbon tetrachloride is toxic following ingestion. Two reviews indicate that ingestion of 14-20 mL or 50-150 mL could be fatal. Although, 1.5 mL has caused death in a few cases. History of alcohol abuse will increase the person's susceptibility to the toxic effects of carbon tetrachloride. Symptoms of central nervous system (CNS) depression, and liver and kidney damage (as described in "Inhalation" above), as well as stomach irritation have been reported.(1)
Based on its physical properties (viscosity and surface tension), it is possible that carbon tetrachloride can be aspirated (inhaled into the lungs) during ingestion or vomiting. Aspiration of even a small amount of liquid could result in a life threatening accumulation of fluid in the lungs. Severe lung damage (edema), respiratory failure, cardiac arrest and death may result. Ingestion is not a typical route of occupational exposure.

Effects of Long-Term (Chronic) Exposure

INHALATION EXPOSURE: Carbon tetrachloride is well known to be harmful to the liver. Early indications of liver injury were observed in employees exposed to 10-100 ppm for several months to many years and in employees repeatedly exposed to approximately 200 ppm (average).(5,7) Several cases of liver damage (hepatitis, cirrhosis), some of them fatal, have been reported in employees repeatedly exposed to carbon tetrachloride. Exposure information was not provided.(8,9) Signs and symptoms of liver injury include jaundice (yellow skin and eyes), liver tenderness and altered blood chemistry values.
Indications of kidney damage have also been observed in employees repeatedly exposed to unknown concentrations of carbon tetrachloride.(8,9) Signs and symptoms of kidney injury may include reduced urine output or lack of urination.
Historical reports describe workplaces where employees developed central nervous system (CNS) effects such as nausea, vomiting, loss of appetite, diarrhea, drowsiness, headache, dizziness and tiredness. Employees were repeatedly exposed to concentrations as low as 10 ppm, but in many cases exposures were much higher.(4,7,9-12)
There are several historical reports of visual disturbances occurring following the long-term inhalation of carbon tetrachloride. Although many of the studies have significant limitations, the evidence suggests that carbon tetrachloride may cause visual impairment.(8,9,13,14)

SKIN CONTACT: Carbon tetrachloride defats the skin and can cause red, dry, itch, scaly skin (dermatitis).(9)

Carcinogenicity:

Carbon tetrachloride is possibly carcinogenic to humans. There is very limited human information available. A few human population studies which have associated increased cancer deaths with possible occupational exposure to carbon tetrachloride. These studies had limitations such as exposure to other potentially harmful chemicals at the same time, other causal factors and/or a lack of specific carbon tetrachloride exposure information.(16) Carbon tetrachloride has produced liver tumours in animals following oral exposure.

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

The American Conference of Governmental Industrial Hygienists (ACGIH) has designated this chemical as a suspected human carcinogen (A2).

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

Teratogenicity and Embryotoxicity:
It is not possible to draw any conclusions from the limited human information available. Two related studies suggest that exposure to carbon tetrachloride in drinking water may be associated with certain developmental effects.(1) However, there could be many other explanations for the observed effects. Carbon tetrachloride has been observed in blood taken from the umbilical cord of newborns, indicating that it crosses the placenta.(19) Animal studies have only shown harmful effects in the offspring of rats exposed to doses which also produced significant maternal toxicity.

Reproductive Toxicity:
There is no human information available. There is insufficient animal information available to draw any conclusions about potential reproductive toxicity.

Mutagenicity:
One human population study has identified mutagenic effects in the white blood cells of 41 employees primarily exposed to hexachlorobenzene, carbon tetrachloride and perchloroethylene.(20) It is not possible to draw any conclusions about the potential mutagenicity of carbon tetrachloride from this report due to the small number of employees studied and their concurrent exposure to other potentially hazardous chemicals. No firm conclusions about the potential mutagenicity of carbon tetrachloride can be drawn based on the available animal information. Mutagenicity has been observed in the liver cells of live animals, but only at concentrations which would also have produced significant cell damage. Most tests using cultured mammalian cells or bacteria have produced negative results.

Toxicologically Synergistic Materials:
Drinking alcohol (ethanol) has repeatedly been associated with increased susceptibility to the effects of carbon tetrachloride-induced liver and kidney injury in humans. Other alcohols (e.g. isopropyl, methyl, decyl, t-butyl, pentyl, hexyl and octyl) have also caused increased carbon tetrachloride toxicity, as have some ketones (e.g. acetone, 2-butanone, kepone), phenobarbital, DDT, polybrominated biphenyls (PBBs), polychlorinated biphenyls (PCBs), chlordecone, mirex, Vitamin A, acetominophen and certain haloalkanes (e.g. trichloroethylene, 1,2-dichloroethane). In most cases, the combined exposure to any of these chemicals and carbon tetrachloride has increased the liver toxicity of carbon tetrachloride.(1,16,21-23)

Potential for Accumulation:
Carbon tetrachloride is readily absorbed following inhalation and ingestion, and more slowly through the skin. It is distributed to all the major organs, with the highest concentrations occurring in body fat. Placental transfer has been shown in animal studies. It is metabolized to a trichloromethyl intermediate, which depending on conditions, can form chloroform, hexachloroethane, phosgene, carbon monoxide and carbon dioxide, as well as bind directly to lipids, proteins and DNA. Animal studies indicate that absorbed carbon tetrachloride is excreted mainly in exhaled air (unchanged and as chloroform and carbon dioxide) (30-75%), and in the feces (unchanged and as undetermined nonvolatile metabolites) (30-60%), while only small amounts are excreted in the urine. Carbon tetrachloride may take weeks to be eliminated from the body fat, based on animal information.(1,8)


SECTION 4. FIRST AID MEASURES

Inhalation:
Take proper precautions to ensure your own safety before attempting rescue, e.g. wear appropriate protective equipment. Remove source of contamination or move victim to fresh air. Obtain medical attention immediately.

Skin Contact:
Avoid direct contact with this chemical. Wear chemical protective gloves, if necessary. Quickly and gently blot or brush away excess chemical. Wash gently and thoroughly with water and non-abrasive soap for 20 minutes or until chemical is removed. Under running water, remove contaminated clothing, shoes and leather goods (e.g. watchbands, belts). If irritation persists, repeat flushing. Obtain medical attention immediately. Discard contaminated clothing, shoes and leather goods.

Eye Contact:
Avoid direct contact. Wear chemical protective gloves, if necessary. Quickly and gently blot or brush away excess chemical on skin around the eye(s). Immediately flush the contaminated eye(s) with lukewarm, gently flowing water for 5 minutes or until chemical is removed, holding the eyelid(s) open. Obtain medical attention immediately.

Ingestion:
NEVER give anything by mouth if victim is rapidly losing consciousness or is unconscious or convulsing. DO NOT INDUCE VOMITING. Have victim drink 240 to 300 mL (8 to 10 ozs) of water to dilute material in stomach. If vomiting occurs naturally, have victim lean forward to reduce risk of aspiration. Repeat administration of water. Obtain medical attention immediately.

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

Note to Physicians:
NOTE: Carbon tetrachloride can produce liver and/or kidney injury, in the absence of other symptoms.



SECTION 5. FIRE FIGHTING MEASURES

Flash Point:
Not combustible (does not burn) (52)

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:
Carbon tetrachloride can accumulate static charge by flow, splashing or agitation due its very low electrical conductivity (4 X 10(-4) pS/m at 18 deg C).(53) Since it does not burn, it will not be ignited by a static discharge.

Combustion and Thermal Decomposition Products:
Hydrogen chloride, phosgene, chlorine, chlorine dioxide.(48,54,55)

Fire Hazard Summary:
Carbon tetrachloride does not burn. At high temperatures or in contact with hot metal, carbon tetrachloride decomposes forming toxic and/or corrosive hydrogen chloride, phosgene, chlorine, carbon monoxide and carbon dioxide. Closed containers may explode if exposed to excess heat for a sufficient period of time releasing large quantities of toxic gases or vapours. Carbon tetrachloride vapour affects the explosion limits of several gaseous mixtures, e.g. air-hydrogen and air-methane.(50)

Extinguishing Media:
Carbon tetrachloride is not combustible. Use extinguishing media suitable for surrounding fire.(52,54)

Fire Fighting Instructions:
If a fire occurs in the vicinity of containers of carbon tetrachloride, evacuate area and fight fire from a safe distance or a protected location. Approach fire from upwind to avoid toxic carbon tetrachloride or its 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 and evacuate the area.
Carbon tetrachloride is a suspected human carcinogen and its decomposition products are extremely toxic. 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: 3 - Short exposure could cause serious temporary or 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: 153.82

Conversion Factor:
1 ppm = 6.278 mg/m3; 1 mg/m3 = 0.159 ppm (calculated)

Physical State: Liquid
Melting Point: -23 deg C (-9.4 deg F) (1,53,54,56)
Boiling Point: 76.7 deg C (170.1 deg F) (50,51,53,57)
Relative Density (Specific Gravity): 1.595 at 20 deg C (50,51,58); 1.589 at 25 deg C (53) (water = 1)
Solubility in Water: Practically insoluble (80 mg/100 mL at 20 deg C) (1,48)
Solubility in Other Liquids: Soluble in all proportions with ethanol, benzene, chloroform, diethyl ether, carbon disulfide and petroleum ether (53,58); soluble in acetone.(56)
Coefficient of Oil/Water Distribution (Partition Coefficient): Log P(oct) = 2.64 (1,59); 2.83 (58)
pH Value: Not applicable
Vapour Density: 5.32 (air = 1) (50,58)
Vapour Pressure: 11.94 kPa (89.55 mm Hg) at 20 deg C (50,51); 15 kPa (112.5 mm Hg) at 25 deg C (57)
Saturation Vapour Concentration: 11.78% (117850 ppm) at 20 deg C; 14.8% (148050 ppm) at 25 deg C (calculated)
Evaporation Rate: 4.5 (n-butyl acetate = 1) (57)
Critical Temperature: 283.2 deg C (541.8 deg F)(50,56); 556.4 deg C (1033.5 deg F) (51,53)

Other Physical Properties:
DYNAMIC-VISCOSITY: 0.96 to 0.965 mPa.s (0.96 to 0.969 centipoise) at 20 deg C (50,53,57); 0.793 mPa.s (0.793 centipoise) at 25 deg C (53)
VISCOSITY-KINEMATIC: 0.602 to 0.605 mm2/s (0.602 to 0.605 centistokes) at 20 deg C; 0.499 mm2/s (0.499 centistokes) at 25 deg C (calculated)
SURFACE TENSION: 26.77 to 26.95 mN/m (26.77 to 26.95 dynes/cm) at 20 deg C (53,56); 26.43 mN/m (26.43 dynes/cm) at 25 deg C (calculated)(53)
CRITICAL PRESSURE: 4550 to 4600 kPa (44.9 to 45.4 atm) (50,51,56)
DIELECTRIC CONSTANT: 2.21 to 2.24 at 20 deg C (50,53); 2.23 at 25 deg C (53)


SECTION 10. STABILITY AND REACTIVITY

Stability:
Relatively stable, when dry, even in the presence of air and light. In the presence of moisture, it decomposes minimally at room temperature, but can decompose to phosgene when it is subjected to ultraviolet irradiation.(50,51) At 250 deg C, it decomposes to form hydrogen chloride and carbon dioxide, when mixed with excess water. When the amount of water is limited, it forms phosgene.(50)

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.


ALKALI METALS (e.g. lithium, potassium, sodium or sodium- potassium alloy) - form impact sensitive compounds, resulting in weak explosions with lithium, strong explosions with potassium and sodium, and violent explosions with sodium-potassium alloy.(60)
ALUMINUM, MAGNESIUM, or ZINC POWDER - mixtures are impact sensitive or can explode on contact.(52,60)
ETHYLENE - may explode violently under various conditions, including high pressures, temperatures and the presence of organic peroxides (e.g. dibenzoyl peroxide).(52,60)
ALLYL ALCOHOL - reaction produces an unstable and explosive mixture of halogenated epoxides.(52,60)
BARIUM or FLUORINE - react violently or explosively.(52,60)
DIMETHYLFORMAMIDE - reacts violently at temperatures above 65 deg C.(52,54)
BERYLLIUM POWDER - flashes or sparks on heavy impact.(52,60)
BORANES (e.g. diborane), CALCIUM DISILICIDE, CALCIUM HYPOCHLORITE, DISILANE, PLUTONIUM, URANIUM or ZIRCONIUM - can explode violently.(52,60)
DECABORANE, DINITROGEN TETRAOXIDE or CHLORINE TRIFLUORIDE - form impact sensitive mixtures.(60)
POTASSIUM TERT-BUTOXIDE - ignition occurs on contact.(52,60)
SILVER PERCHLORATE and HYDROCHLORIC ACID (small amount) - reaction forms trichloromethyl perchlorate which detonates at 40 deg C.(52)
ALUMINUM TRIETHYL SESQUICHLORIDES (e.g. triethyldialuminum trichloride) - mixture can explode when warmed to room temperature.(52,60)

Hazardous Decomposition Products:
Phosgene and hydrogen chloride.

Conditions to Avoid:
Excessive heat, open flames, hot surfaces, welding arc, electric arc, or other high temperature sources which may cause thermal decomposition.

Corrosivity to Metals:
Dry carbon tetrachloride is not corrosive to iron, steel, stainless steel (types 304/347, 316, 400, 904-L), copper and its alloys, nickel and its alloys, tantalum, titanium and zirconium.(61,62) Wet carbon tetrachloride corrodes iron and steel, especially at high temperatures.(48,61) Wet carbon tetrachloride may also attack copper and its alloys, and lead at high temperatures.(62)

Stability and Reactivity Comments:
Will attack some plastics (such as ABS, acrylics, some polyesters, polyethylene and polystyrene), elastomers (such as ethylene-propylene, neoprene, nitrile BUNA, polysulfides, polyurethane, SBR styrene and silicone rubbers), rubbers and coatings.(61)


SECTION 11. TOXICOLOGICAL INFORMATION

LC50 (rat): 8000 ppm (4-hour exposure) (24)

LD50 (oral, male rat): 2500 mg/kg (25)
LD50 (oral, rat): 2920 mg/kg (26)

LD50 (dermal, guinea pig): greater than 15000 mg/kg (cited as greater than 0.94 mL/kg) (27)
LD50 (dermal, rat): 5070 mg/kg (28, unconfirmed)

Eye Irritation:

Application of 0.1 mL produced mild irritation in rabbits (scored 5/110).(29)

Skin Irritation:

Mild to moderate irritation was observed following the application of 0.5 mL of undiluted carbon tetrachloride to the intact or abraded skin of rabbits or guinea pigs (scored 2.2-4.1).(27) Application of 0.5 mL, under cover, produced moderate irritation (scored 4.2/8).(29)

Effects of Short-Term (Acute) Exposure:

Carbon tetrachloride is harmful to the liver and a central nervous system (CNS) depressant following short-term inhalation, skin contact or ingestion. The liver effects have been observed at concentrations lower than those required to produce CNS effects.

Inhalation:
In one study, a 4-hour exposure to 4800 ppm (cited as 30 mg/L) caused liver necrosis within 24 hours. Continued biweekly exposure led to fibrosis and cirrhosis within 12 weeks.(31) Changes in serum enzyme levels indicative of liver damage were observed in male rats following a 4-hour exposure to 530 ppm and above.(32) Signs of central nervous system (CNS) depression, such as incoordination, laboured respiration and unconsciousness were observed in mice exposed to very high concentrations (7000 to 10500 ppm for 8 hours) during LC50 testing.(33) In another study, drowsiness or signs of drunkenness were observed in rats exposed to 4600 ppm or less, drunkenness and incoordination at 7300 ppm and unconsciousness at 12000 and 19000 ppm for 0.1 to 8 hours.(34)

Skin Contact:
Liver injury (isolated areas of tissue death) was observed in guinea pigs following covered dermal application of an unspecified amount of carbon tetrachloride.(37)

Ingestion:
Short-term oral exposure has commonly caused liver injury in experimental animals. A single oral dose of 80 mg/kg produced slight liver injury (increased serum enzyme levels and some cellular changes) in rats. Exposure to 40 and 80 mg/kg produced liver injury after 4 days.(35) Exposure of rats to 5-40 mg/kg/day for 10-11 days produced mild to moderate signs of liver injury (minimal to mild vacuolar degeneration, no to mild necrosis, increased liver weight and/or enzyme changes), while 80 mg/kg/day caused clear liver damage.(35,36)

Effects of Long-Term (Chronic) Exposure:

Long-term inhalation to concentrations above 10 ppm or ingestion of 10 mg/kg/day has caused liver injury in rats, guinea pigs, rabbits and monkeys. Deaths have been observed following inhalation of concentrations as low as 82 ppm for 6 weeks.

Inhalation:
Rats, rabbits, guinea pigs and monkeys were repeatedly exposed for 7-hour periods to various concentrations. Liver and/or kidney damage (degeneration and/or cirrhosis), as well as high mortality, were seen in rats and guinea pigs exposed to 100, 200 or 400 ppm. Liver damage was also observed in rats, guinea pigs, and rabbits exposed to 25 or 50 ppm. Very slight liver injury (fatty degeneration) was seen in rats and guinea pigs exposed to 10 ppm. No significant effects were seen in monkeys exposed to 25, 50 or 100 ppm, or in rats and guinea pigs exposed to 5 ppm.(34) Liver damage (mottling, fibrosis and/or degeneration) and lung injury (inflammation or pneumonitis) were seen in guinea pigs, rats, rabbits, and monkeys exposed for 30 8-hour periods over 6 weeks to about 82 ppm. A few deaths also occurred (1/3 monkeys and 3/15 guinea pigs). No heart, spleen or kidney injury was observed. Liver damage (degeneration and fibrosis) was seen in guinea pigs, rats, rabbits, and monkeys exposed continuously for 90 days to about 10 ppm. No such injury was seen in similarly exposed dogs. No harmful effects were seen following continuous exposure for 90 days to about 1 ppm.(38) Exposure of rats, monkeys and guinea pigs to 400 ppm over 10 months did not cause observable central nervous system (CNS) depression. However, there were degenerative changes in the optic and sciatic nerves in animals exposed to 200-400 ppm.(7)

Ingestion:
No signs of liver injury were observed in rats orally exposed to 1 mg/kg/day for 12 weeks. Mild changes (some enzyme changes and mild centrilobular vacuolization) were observed at 10 mg/kg/day. Marked changes (significant enzyme changes and extensive liver damage) were observed at 33 mg/kg/day.(35) Other studies support these observations.(1,16) Kidney injury has been observed in animals with long-term oral exposure. For example, slight indications of kidney injury were observed in mice exposed to 1200 mg/kg for 90 days.(39) The doses which produce kidney changes are much higher than those associated with liver damage.

Carcinogenicity:
The International Agency for Research on Cancer (IARC) has concluded that there is sufficient evidence for the carcinogenicity of carbon tetrachloride in experimental animals. Carbon tetrachloride is a liver carcinogen and has caused tumours in mice, rats and hamsters following oral exposure.(1,8,15) In general, the doses which have produced cancer have also produced significant liver damage and extensive regeneration.(1,8)

Teratogenicity, Embryotoxicity and/or Fetotoxicity:
Fetotoxicity and embryotoxicity has been observed in rats exposed by inhalation or ingestion to maternally toxic doses.
Slight fetotoxicity (reduced size) was seen in the offspring of rats exposed by inhalation to 330 or 1000 ppm on days 6-15 of pregnancy. Maternal toxicity (weight loss and liver toxicity) was also observed.(40) In another study, rats were exposed by inhalation to approximately 250 ppm on days 10-15 of pregnancy. Some fetal effects were observed, but only under conditions producing maternal toxicity (reduced body weight and liver effects).(1,8,16) Embryotoxicity (embryo deaths) has been observed in rats exposed to maternally toxic doses.(8,41,42,43) There is no evidence that carbon tetrachloride has developmental effects in animals in the absence of maternal toxicity.

Reproductive Toxicity:
There is insufficient information available to draw conclusions about the potential reproductive toxicity of carbon tetrachloride.
Testicular atrophy was seen in rats exposed repeatedly to 200 ppm. Similar effects were not observed in other species, nor in rats exposed to higher or lower concentrations.(34) In a limited study, the fertility of rats exposed to 200 or 400 ppm for 10.5 months (approximately 2 generations) was decreased.(7) This study would not meet current standards for reproductive toxicity testing. In addition, exposures were so high enough to produce significant other toxicity. In another study, no reproductive effects were observed in rats fed a diet containing 8.0 ppm (about 6 mg/kg/day) or 200 ppm (about 15 mg/kg/day) for 5-6 weeks.(44)

Mutagenicity:
No firm conclusions can be drawn regarding the mutagenicity of carbon tetrachloride.
In general, negative results have been obtained in tests using live animals exposed orally.(1,8) Unscheduled DNA synthesis and replicative DNA synthesis have been observed in rats exposed to high doses which caused cell damage or would be expected to cause significant cell damage.(8,45,46,47) No conclusions can be drawn from a poorly reported study which observed chromosomal aberrations in the bone marrow of rats treated orally with 1492 mg/kg.(8)
Overall the evidence indicates that carbon tetrachloride is not mutagenic in well-validated assays for reverse mutation in bacteria and chromosome damage and unscheduled DNA synthesis in cultured mammalian cells.(1,8,15)
Negative results were obtain in a Drosophila sex-linked recessive lethal test.(8)


SECTION 16. OTHER INFORMATION

Selected Bibliography:
(1) Agency for Toxic Substances and Disease Registry. Toxicological profile for carbon tetrachloride (Update). TP- 93/02. Public Health Service, US Department of Health and Human Services, May, 1994
(2) Norwood, W.D., et al. Carbon tetrachloride poisoning: more regulation, more education needed. Archives of Industrial Hygiene and Occupational Medicine. Vol. 1 (1950). p. 90-100
(3) Stewart, R.D., et al. Human exposure to carbon tetrachloride vapour: relationship of expired air concentration to exposure and toxicity. Journal of Occupational Medicine. Vol. 3, no. 12 (Dec. 1961). p. 586-590
(4) Kazantzis, G., et al. Dyspepsia due to inhalation of carbon tetrachloride vapour. The Lancet. Vol. 1 (Feb. 13, 1960). p. 360-362
(5) Barnes, R., et al. Carbon tetrachloride poisoning. American Industrial Hygiene Association Journal. Vol. 28 (Nov.-Dec. 1967). p. 557-560
(6) Stewart, R.D., et al. Absorption of carbon tetrachloride, trichloroethylene, tetrachloroethylene, methylene chloride, and 1,1,1-trichloroethane through the human skin. Industrial Hygiene Journal. Vol. 25 (Sept.-Oct. 1964). p. 439-446
(7) Smyth, H.F., et al. The chronic toxicity of carbon tetrachloride: animal exposures and field studies. Journal of Industrial Hygiene and Toxicology. Vol. 18, no. 5 (May 1936). p. 277-298
(8) Standring, P., et al. Part one. Carbon tetrachloride. Toxicity review 23. Health and Safety Executive, 1992
(9) National Institute for Occupational Safety and Health. Criteria for a recommended standard: occupational exposure to carbon tetrachloride. Public Health Service, US Department of Health, Education and Welfare, 1975
(10) Heimann, H, et al. Low concentrations of carbon tetrachloride capable of causing mild narcosis. Industrial Bulletin. Vol. 2, no. 7-8 (July-Aug. 1941). 3 pages
(11) Elkins, H.B. Maximal allowable concentrations. I. Carbon tetrachloride. Journal of Industrial Hygiene and Toxicology. Vol. 24, no. 8 (Oct. 1942). p. 233-235
(12) Stewart, A., et al. Chronic carbon tetrachloride poisoning. British Journal of Industrial Medicine. Vol. 1 (1944). p. 11-19 (Reprinted in: British Journal of Industrial Medicine. Vol. 50 no.1 (Jan 1993). p. 7-16
(13) Grant, W.M., et al. Toxicology of the Eye. 4th ed. Charles C. Thomas, 1993. p. 328-330
(14) Smith, A.R. Optic atrophy following exposure to carbon tetrachloride. Archives of Industrial Hygiene and Occupational Medicine. Vol. 1 (1950). p. 37-39
(15) International Agency for Research on Cancer. Carbon tetrachloride. In: IARC monographs on the evaluation of the carcinogenic risk of chemicals to humans. Vol. 20. Some halogenated hydrocarbons. World Health Organization, 1979. p. 371-399
(16) Carbon tetrachloride. In: Documentation of threshold limit values and biological exposure indices. 6th ed. Suppl. American Conference of Governmental Industrial Hygienists, 1996. p. 1-12
(17) 1998 TLVs(R) and BEIs(R). Threshold limit values for chemical substances and physical agents; biological exposure indices. American Conference of Governmental Hygienists, 1998
(18) Report on Carcinogens. 11th ed. US Department of Health and Human Services, Public Health Service, National Toxicology Program
(19) Dowty, B.J., et al. The transplacental migration and accumulation in blood of volatile organic constituents. Pediatric Research. Vol. 20 (1976). p. 696-701
(20) da Silva Augusto, L.G., et al. Micronucleus monitoring to assess human occupational exposure to organochlorides. Environmental and Molecular Mutagenesis. Vol. 29, no. 1 (1997). p. 46-52
(21) El Sisi, A.E.D., et al. Characterization of Vitamin A potentiation of carbon tetrachloride-induced liver injury. Toxicology and Applied Pharmacology. Vol. 119, no.2 (Apr. 1993). p. 280-288
(22) El-Masri, H.A., et al. Physiologically based pharmokinetic/pharmodynamic modeling of the toxicologic interaction between carbon tetrachloride and Kepone. Archives of Toxicology. Vol. 70, no. 11 (1996). p. 704-713
(23) Wright, P.B., et al. Potentiation of the toxicity of model hepatotoxicants by acetaminophen. Toxicology and Applied Pharmacology. Vol. 109, no. 2 (June 15, 1991). p. 327-335
(24) Siegel, J., et al. Effects on experimental animals of acute, repeated and continuous inhalation exposures to dichloroacetylene mixtures. Toxicology and Applied Pharmacology. Vol. 18, no. 1 (Jan. 1971). p. 168-174
(25) Lorke, D. A new approach to practical acute toxicity testing. Archives of Toxicology. Vol. 54, no. 4 (Dec. 1983). p. 275-287
(26) McCollister, D.D., et al. Comparative inhalation toxicity of fumigant mixtures: individual and joint effects of ethylene dichloride, carbon tetrachloride, and ethylene dibromide. A.M.A. Archives of Industrial Health. Vol. 13 (1956). p. 1-7
(27) Roudabush, R.L., et al. Comparative acute effects of some chemicals on the skin of rabbits and guinea pigs. Toxicology and Applied Pharmacology. Vol. 7 (July 1965). p. 559-565
(28) Kenaga, E.E., et al. Commercial and experimental organic insecticides (1978 revision). Special Publication 78-1. Entomological Society of American, May 1978. p. 16
(29) Duprat, P., et al. Pouvoir irritant des principaux solvents chlores aliphatiques sur la peau et les muqueuses oculaires du lapin. European Journal of Toxicology - Journal Europeen De Toxicologie. Vol. 9, no. 3 (June 1976). p. 171-177
(30) Emergency response planning guidelines for carbon tetrachloride. American Industrial Hygiene Association, 1996
(31) Belyaev, N.D., et al. Liver plasma membrane-associated fibroblast growth: stimulatory and inhibitory activities during experimental cirrhosis. Hepatology. Vol. 15, no. 3 (1992). p. 525-531
(32) Brondeau, M.T., et al. Short-term inhalation test for evaluating industrial hepatotoxicants in rats. Toxicology Letters. Vol. 19, no. 1 (Oct. 1983). p. 139-146
(33) Svirbely, J.L., et al. The toxicity and narcotic action of mono-chloro-bromo-methane with special reference to inorganic and volatile bromide in blood, urine and brain. Journal of Industrial Hygiene and Toxicology. Vol. 29 (Nov. 1947). p. 382-389
(34) Adams, E.M., et al. Vapor toxicity of carbon tetrachloride determined by experiments on laboratory animals. A.M.A. Archives of Industrial Hygiene and Occupational Medicine. Vol. 6 (1952). p. 50-66
(35) Bruckner, J.V., et al. Oral toxicity of carbon tetrachloride: acute, subacute, and subchronic studies in rats. Fundamental and Applied Toxicology. Vol. 6, no. 1 (Jan. 1986). p. 16-34
(36) Smialowicz, R.J., et al. Immunotoxicological assessment of subacute exposure of rats to carbon tetrachloride with comparison to hepatotoxicity and nephrotoxicity. Fundamental and Applied Toxicology. Vol. 17, no. 1 (July 1991). p. 186-196
(37) Kronevi, T., et al. Histopathology of skin, liver and kidney after epicutaneous administration of five industrial solvents to guinea pigs. Environmental Research. Vol. 19, no. 1 (1979). p. 56-69
(38) Prendergast, J.A., et al. Effects on experimental animals of long-term inhalation of trichloroethylene, carbon tetrachloride, 1,1,1-trichloroethane, dichlorodifluoromethane, and 1,1-dichloroethylene. Toxicology and Applied Pharmacology. Vol. 10 (1967). p. 270-289
(39) Hayes, J.R., et al. Acute, 14-day repeated dosing, and 90- day subchronic toxicity studies of carbon tetrachloride in CD-1 mice. Fundamental and Applied Toxicology. Vol. 7, no. 3 (Oct. 1986). p. 454-463
(40) Schwetz, B.A., et al. Embryo- and fetotoxicity of inhaled carbon tetrachloride, 1,1-dichloroethane and methyl ethyl ketone in rats. Toxicology and Applied Pharmacology. Vol. 28 (1974). p. 452-464
(41) Wilson, J.G. Influence on the offspring of altered physiologic states during pregnancy in the rat. Annals of the New York Academy of Sciences. Vol. 57 (1954). p. 517-525
(42) Narotsky, M.G., et al. Effect of dosing vehicle on the developmental toxicity of bromodichloromethane and carbon tetrachloride in rats. Fundamental and Applied Toxicology. Vol. 40 no. 1 (Nov. 1997). p. 30-36
(43) Narotsky, M.G., et al. Critical period of carbon tetrachloride-induced pregnancy loss in Fischer-344 rats, with insights into the detection of resorption sites by ammonium sulfide staining. Teratology. Vol. 56, no. 4 (Oct. 1997). p. 252-261
(44) Alumot, E., et al. Tolerance and acceptable daily intake of chlorinated fumigants in the rat diet. Food and Cosmetics Toxicology. Vol. 14 (1976). p. 105-110
(45) Uno, Y., et al. An in vivo-in vitro replicative DNA synthesis (RDS) test using rat hepatocytes as an early prediction assay for nongenotoxic hepatocarcinogens screening of 22 known positives and 25 noncarcinogens. Mutation Research. Vol. 320, no. 3 (Feb. 1994). p. 189-205
(46) Gans, J.H., et al. Liver nuclear DNA synthesis in mice following carbon tetrachloride administration or partial hepatectomy. Proceedings of the Society for Experimental Biology and Medicine. Vol. 175, no. 2 (Feb. 1984). p. 237-242
(47) Sawada, S., et al. Comparison of autoradiography, liquid scintillation counting and immunoenzymatic staining of 5-bromo-2'- deoxyuridine for measurement of unscheduled DNA synthesis and replicative DNA synthesis in rat liver. Mutation Research. Vol. 344, No. 3-4 (1995). p. 109-116
(48) Emergency action guide for carbon tetrachloride. Association of American Railroads, Mar.1995
(49) Odor thresholds for chemicals with established occupational health standards. American Industrial Hygiene Association, 1989. p. 14, 50
(50) Holbrook, M.T. Chlorocarbons and chlorohydrocarbons: carbon tetrachloride. In: Kirk-Othmer encyclopedia of chemical technology. 4th ed. Vol. 5. John Wiley and Sons, 1993. p. 1062-1072
(51) Rossberg, M., et al. Chlorinated hydrocarbons: chloromethanes. In: Ullmann's encyclopedia of industrial chemistry. 5th completely revised ed. Vol. A 6. VCH Verlagsgesellschaft, 1986. p. 233-256
(52) Fire protection guide to hazardous materials. 13th ed. Edited by A.B. Spencer, et al. National Fire Protection Association, 2002. NFPA 49; NFPA 491
(53) Dean, J.A. Lange's handbook of chemistry. 14th ed. McGraw-Hill, Inc., 1992. p. 1.130, 5.97, 6.135, 8.162
(54) The Sigma-Aldrich library of chemical safety data. Ed II. Vol. 1. Sigma-Aldrich Corporation, 1988. p. 686B
(55) Peterson, J.E. Toxic pyrolysis products of solvents, paints, and polymer films. In: Occupational Medicine: State of the Art Reviews. Vol. 8, no. 3. De novo toxicants: combustion toxicology, mixing incompatibilties and environmental activation of toxic agents. Edited by D.J. Shusterman, et al. Hanley and Belfus, Inc., July-Sept. 1993. p. 533-547
(56) Weast, R.C., ed. Handbook of chemistry and physics. 66th ed. CRC Press, 1985-1986. p. C-350, D-196, F-33, F-39, F- 63
(57) Sullivan, D.A. Solvents, industrial. In: Kirk-Othmer encyclopedia of chemical technology. 4th ed. Vol. 22. John Wiley and Sons, 1997. p. 538-539, 550, 563
(58) HSDB database record for carbon tetrachloride. Last revision date: 98/06/02
(59) Leo, A., et al. Partition coefficients and their uses. Chemical Reviews. Vol. 17, no. 6 (Dec. 1971). p. 555
(60) Urben, P.G., ed. Bretherick's handbook of reactive chemical hazards. 5th ed. Vol. 1. Butterworth-Heinemann Ltd., 1995. p. 135-137
(61) Schweitzer, P.A. Corrosion resistance tables: metals, nonmetals, coatings, mortars, plastics, elastomers and linings, and fabrics. 4th ed. Part A, A-D. Marcel Dekker, Inc., 1995. p. 693-696
(62) Corrosion data survey: metals section. 6th ed. National Association of Corrosion Engineers, 1985. p. 32-11 to 33-11
(63) NIOSH pocket guide to chemical hazards. National Institute for Occupational Safety and Health, June 1997
(64) Forsberg, K., et al. Quick selection guide to chemical protective clothing. 4th ed. Van Nostrand Reinhold, 2002
(65) European Communities (EC). Commission Directive 2004/73/EC. Apr. 29, 2004
(66) Occupational Safety and Health Administration (OSHA). Organic Vapors. In: OSHA Analytical Methods Manual. Revision Date: Oct. 31, 2001. Available at: <www.osha-slc.gov/dts/sltc/methods/toc.html>
(67) National Institute for Occupational Safety and Health (NIOSH). Hydrocarbons, Halogenated. In: NIOSH Manual of Analytical Methods (NMAM(R)). 4th ed. Edited by M.E. Cassinelli, et al. DHHS (NIOSH) Publication 94-113. Aug. 1994. Available at: <www.cdc.gov/niosh/nmam/nmammenu.html>

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: 2000-01-04

Revision Indicators:
TDG 2002-05-29
PEL transitional comments 2004-01-08
PEL-C transitional 2004-01-08
PEL-TWA transitional 2004-01-08
PEL-TWA final 2004-01-08
Resistance of materials for PPE 2004-04-08
EU classification 2004-12-28
EU risks 2004-12-28
EU comments 2004-12-28
Bibliography 2005-02-02
Bibliography 2005-03-31
Passive Sampling Devices 2005-03-31
Sampling/analysis 2005-03-31



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