Carbon tetrachloride

Carbon tetrachloride is a colorless liquid with a sweetish odor

(NLM, 2003; Lewis, 1997). Synonyms include tetrachloromethane and
perchloromethane (NLM, 2003; ONeil and Smith, 2001).

Figure Carbon tetrachloride.

Physicochemical properties of carbon tetrachloride

1. Chemical Abstracts Service( CAS )number: 56-23-5 (Lide,
2.
3.
4.
5.
6.
7.
8.

2000)
Molecular weight (MW): 153.82 (ONeil and Smith, 2001)
Chemical formula: CCl4 (ONeil and Smith, 2001)
Boiling point: 76.8 C (NLM, 2003; Lide, 2000)
Melting point: 23 C (NLM, 2003; Lide, 2000)
Vapor pressure: 1.15 102 mm Hg at 25 C (NLM, 2003)
Density: 1.5940 g/mL at 20 C (NLM, 2003; Lide, 2000)
Vapor density (air=1): 5.32 (NLM, 2003); 5.41 (ONeil and

Smith, 2001)
9. Water solubility: 7.93 102 mg/L at 25 C (NLM, 2003;
Horvath, 1982).
10. Other solubility: Miscible with alcohol, benzene, chloroform,
ether, carbon disulfide, petroleum ether, oils (NLM, 2003; ONeil
and Smith, 2001)
11.Partition coefficient: log Kow = 2.83 (NLM, 2003; Hansch et
al., 1995)
12.Flash point: Not flammable (NLM, 2003)
13.Flammability limits: Not flammable(NIOSH, 1994).
14.Autoignition temperature: >1000 C (Holbrook, 1993) .
15.Latent heat of vaporization: 1.959 105 J/kg (U.S. Coast
Guard, 1999)
16.Heat of fusion: 5.09 cal/g (NLM, 2003; U.S. Coast Guard, 1999)

17.Critical temperature: 556.35 C (Daubert and Danner, 1995)

18.Critical pressure: 4.56 106 Pa (Daubert and Danner, 1995)
19.Viscosity: 0.922 cp at 24 C (U.S. Coast Guard, 1999)
20.Surface tension: 0.027 N/m at 20 C (U.S. Coast Guard, 1999)
21.Henrys law constant: 2.76 102 atm m3/mol at 25 C (NLM,
2003; Leighton
and Calo, 1981).
22. Bioconcentration factor: Log BCF = 1.24-1.48, not
significant(U.S. EPA, 1998)
23. Conversion factor: 1 ppm = 6.39 mg/m3(NIOSH, 1994).
24.
Uses
Carbon tetrachloride has been used as a dry-cleaning agent,
fabric-spotting fluid, solvent, reagent in chemical synthesis, fire
extinguisher fluid, and grain fumigant (NLM, 2003; Holbrook, 1993),
Carbon tetrachloride is used as a solvent for the recovery of tin in
tin-plating waste and in the manufacture of semiconductors. It is
used in petrol additives, refrigerants, metal degreasing, and as a
catalyst in the production of polymers. Carbon tetrachloride is also
used as a chemical intermediate in the production of fluorocarbons
and some pesticides (HSDB, 1995). In 1988, the U.S. production of
carbon tetrachloride was 761 million pounds. Its use has been
declining since 1974 at a rate of 7.9 percent per year (U.S. EPA
1998). However, since the Montreal Protocol on Substances that
Deplete the Ozone Layer(1987) and its amendments (1990 and
1992) established a timetable for the phase-out of the production
and consumption of carbon tetrachloride, manufacture has dropped
and will continue to drop (UNEP, 1996; IPCS, 1999). Currently,Carbon
tetrachloride is one of the most potent hepatotoxins (toxic to the
liver), and is widely used in scientific research to evaluate
hepatoprotective agents.[6][7] because damage by CCl4 is regarded as
the analogue of liver damage caused by a variety of hepatotoxins in
humans.
PHARMACOKINETICS

Carbon tetrachloride is well absorbed from the gastrointestinal and respiratory tracts
in animals and humans. Dermal absorption of liquid carbon tetrachloride is possible,
but dermal absorption of the vapour is slow. Distribution is throughout the whole
body, with highest concentrations in liver, brain, kidney, muscle, fat
and blood. Its tends to accumulate in fat (Sanzgiri et al., 1997; IPCS,
1999;Benson et al., 2001. It is generally accepted that the
hepatotoxicity of CCl4 results from the metabolism of CCl4 to the
trichloromethyl free radical (CCl 3) by the NADPHcytochrome P450
system, transferring an electron from NADPH to CCl 4 [1-2,9-12]. This
free

radical

is

oxidized

further,

forming

the

even

more

reactive

trichloromethylperoxyl radical (CCl3OO), which can react further to form phosgene.

Phosgene may be detoxified by reaction with water to produce carbon dioxide or with
glutathione or cysteine. Formation of chloroform and dichlorocarbene occurs
under anaerobic conditions (McGregor & Lang, 1996; IPCS, 1999).
The trichloromethyl free radical and related reactive species may
cause cellular damage by initiating lipid and protein peroxidation,
covalently binding to protein, causing a rise in intracellular Ca 2+,
depleting GSH, or releasing iron, ultimately leading to cell death [14]. The hepatotoxic action of CCl4 is known to be dependent on the
cosubstrate NADPH because the primary metabolism of CCl 4 to CCl3
was formed in conjunction with the NADPHcytochrome P450
electron-transport chain in the liver endoplasmic reticulum [1].
Cytochrome P450 transferred the electron from NADPH to CCl 4,
causing CCl4 to be reduced to CCl3 and Cl - [7]. Carbon tetrachloride and
its metabolites are excreted primarily in exhaled air and to a lesser extent in the urine
and faeces (IPCS, 1999).

NLM (National Library of Medicine). (2003) Carbon tetrachloride.

Hazardous Substances Data Bank (HSDB). National Institutes of
Health, U.S. Department of Health and Human Services, Bethesda,
MD. Available from: <http://toxnet.nlm.nih.gov>.
ONeil, MJ; Smith, A; eds. (2001) The Merck index: an encyclopedia
of chemicals, drugs, and biologicals. 13th edition. Whitehouse
Station, NJ: Merck and Co., Inc.; pp. 305-306.
Lewis, RJ, Sr; ed. (1997) Hawley's condensed chemical dictionary.
13th edition. New York, NY: John Wiley and Sons, Inc.; p. 213.
Lide, DR; ed. (2000) CRC handbook of chemistry and physics. 81st
Edition. Boca Raton, FL: CRC Press LLC, pp. 3-207.
Leighton, DT, Jr.; Calo, JM. (1981) Distribution coefficients of
chlorinated hydrocarbons in dilute air-water systems for
groundwater contamination applications. J Chem Eng 26:382-585.

Daubert, TE; Danner, RP. (1995) Physical and thermodynamic

properties of pure chemicals: data compilation. Supplement 5.
Washington, DC: Taylor and Francis.
Horvath, AL. (1982) Halogenated hydrocarbons: solubility-miscibility
with water. New York, NY: Marcel Dekker, Inc.; p. 889.
Hansch, C; Leo, A; Hoekman, D. (1995) Exploring QSAR:
Hydrophobic, electronic, and steric constants. ACSprofessional
reference book. Vol. 2. In: Heller, SR; ed. Washington, DC: American
Chemistry Society; p. 3.

Holbrook, MT. (1993) Carbon tetrachloride. In: Kroschwitz, JI; HoweGrant, M, eds. Kirk-Othmer encyclopedia of chemical technology. 4th
edition. Vol. 5. New York, NY: John Wiley and Sons; pp. 1062-1072.
U.S.Coast Guard. (1999) Carbon tetrachloride. Chemical Hazards
Response Information System (CHRIS) Hazardous Chemical Data.
Department of Transportation, Washington, DC; Available from:
<http://www.chrismanual.com/findform.htm>.

NIOSH (1994). Pocket Guide to Chemical Hazards. U.S. Dept. of

Health and Human Services, National Institute for Occupational
Safety and Health. NIOSH publication #94-116.
U.S.EPA (1998). Technical Fact Sheet on Carbon Tetrachloride.
National Primary Drinking Water Regulations.
www://epa.gov/OGWDW/dwh/t-voc/carbonte.html.
HSDB. 1995. Hazardous Substances Data Bank. National Library of
Medicine, Bethesda, MD (CD-ROM version). Denver, CO:
Micromedex, Inc. (edition expires 7/31/95).
UNEP (1996) The 1987 Montreal Protocol on Substances that
Deplete the Ozone Layer as adjusted and amended by the Second,
Fourth and Seventh Meetings of the Parties. In: Handbook for the
international treaties for the protection of the ozone layer, 4th ed.
Nairobi, United Nations Environment Programme, pp. 1839.
IPCS (1999) Carbon tetrachloride. Geneva, World Health
Organization, International Programme on Chemical Safety, pp. 1
177 (Environmental Health Criteria 208).
6. Use of Ozone Depleting Substances in Laboratories. TemaNord 516/2003.

7.^ Jump up to:a b Seifert WF, Bosma A, Brouwer A et al. (January 1994). "Vitamin A deficiency
potentiates carbon tetrachloride-induced liver fibrosis in rats". Hepatology 19 (1): 193201

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like lipid free radicals, nitric oxide, and enzymes NOS and NADPH in
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affinity and selectivity toward human CYP2 family enzymes. Arch
Biochem Biophys. 409: 32-44
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tetrachloride induce intrachromosomal recombination and oxidative
free radicals in Saccharomyces cerevisiae. Mut Res. 397:271-278
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Mechanisms of carbon tetrachloride toxicity. Pharmacol Ther.
43:139154
7) De Groot H, Halomethane TN. (1989) Hepatotoxicity: induction of
lipid peroxidation and inactivation of cytochrome P-450 in rat liver
microsomes under low oxygen partial pressures. Toxicol Appl
Pharmacol. 97: 530537
12) Tosmasi A, Albabo E, Banni S, Botti B, Corongiu F, Dessi MA,
Iannone A, Vannini V, Dianzani MU. (1987) Free-radical metabolism
of carbon tetrachloride in rat liver mitochondria. A study of the
mechanisms of activation. Biochem J. 246: 313317
Benson JM et al. (2001) Uptake, tissue distribution, and fate of
inhaled carbon tetrachloride: comparison of rat, mouse, and
hamster. Inhalation Toxicology, 13(3):207217.
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WHO (World Health Organization) (1999) Carbon Tetrachloride IPCS Environmental health
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Research, 366:181195.

The CCl3 radical can yield trichloromethanol, a precursor to

carbonyl chloride (phosgene), which is then hydrolyzed to form CO2

lipid peroxidation occur via reactive metabolic intermediates of carbon tetrachloride, in
particular the trichloromethylperoxyl radical (IPCS, 1999).