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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Key value for chemical safety assessment

Additional information

Genetic toxicity in in vitro microbiological systems:

In a study (Araki 2004), chosen as a key study, ambiguous results for genotoxicity were found in the strains TA98, E. coliWP2 uvr A pKM 101 and E. coli WP2 pKM 101 but only at very high concentrations (> 5'000 ppm) using a non-validated method (gas exposure method). Similar ambiguous results were obtained in other Ames test studies.


Genetic toxicity in in vitro mammalian cell systems:

Two summaries of many in vitro tests (microbial and mammalian cell lines, various strains, different technique) led to the same conclusions (ATSDR 2005, IUCLID entries 2009): some tests are positive, some are negative, and some are ambiguous. In most of the positive tests, the effects can be explained as most likely due to oxidative DNA damage, which occurs secondarily to cytotoxicity of CTC.


Genetic toxicity in in vivo cell systems:

Many tests have been carried out in different whole animal systems. Covalent adducts of CTC metabolites have been found in three studies but the amount of adducts is low as compared to the administered doses, and covalent adducts have no relevant significance if they are the only signs of genotoxicity. The key study (Suzuki 1997) as well as all other studies analysing genotoxic effects of CTC using established in vivo methods (Foureman 1994, Sawada 1991, Sasaki 1998, Barbin 1982, Bermudez 1982, Mirsalis 1982, Stewart, 1981 and Schwarz 1979), different species, strains and techniques gave negative results for the genotoxic potential of CTC in vivo. In oral gavage studies, there were no increase in the frequencies of chromosomal aberration, sister chromatid exchange, or micronucleus formation in the liver of rats or in the frequency of micronucleus formation in bone marrow of mice (Sawada et al. 1991; Suzuki et al. 1997). Therefore the in vivo genetic potential of CTC is considered to be negative in agreement with the judgment of Eastmond 2008 (as stated above).


In summary, carbon tetrachloride (CTC) is essentially negative in inducing gene mutations in Salmonella, but is consistently positive in inducing recombinations and aneuploidy in fungi. Negative or equivocal results were seen in most in vitro and in vivo studies in mammals, including mutation studies in transgenic mice. However, DNA adducts, primarily those derived from oxidation- and lipid-peroxidation-derived products as well as DNA double strand breaks, have been seen repeatedly in the liver of CTC-treated animals. On the basis of weight of evidence, CTC should not be considered a directly acting mutagenic agent. Mutagenic as well as other genotoxic effects, as they occur, will most likely be generated through indirect mechanisms resulting secondarily from oxidative and lipid peroxidative damage and/or damage occurring during necrosis or apoptosis.



Based on a weight of evidence approach allowed it is concluded that carbon tetrachloride is not genotoxic in vivo. This conclusion is supported by many scientific reviews. The ATSDR report concluded that carbon tetrachloride was not genotoxic and acted as carcinogenic by a threshold mode of action. The same conclusion was presented by other agencies, by OMS, and more recently, by the French Agency Afsset. A similar conclusion is supported by the SCOEL in their 2009 report on the OEL for carbon tetrachloride.

Short description of key information:

Many genetic toxicity (in vitro and in vivo) tests are available. All results were considered in a weight of evidence approach. The overall conclusion is that CTC is not genotoxic in vivo.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

The classification of the key parameter is based on a weight of evidence approach. The analysis of the literature data showed that mainly negative but also some positive and some ambiguous results were found in various in vitro test systems. Negative results were found for genetic toxicity in vivo for all reliable tests analysing genotoxic effects of CTC. Otherwise the substance is a recognized hepatic carcinogen, but the experimental data clearly showed that the carcinogenic response is not a linear dose-response. This last data supports the fact that carbon tetrachloride acts by a non-genotoxic mechanism in the liver.


Based on the results of the above mentioned studies, both in vitro and in vivo on the mutagenic potential of CTC via the oral and the inhalation route and based on considerations on the potential toxic mode of action of CTC, no classification concerning genetic toxicity is necessary for CTC according to EU directive 67/548/EEC and EU Regulation (EC) N0. 1272/2008 (CLP).