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Key value for chemical safety assessment

Additional information

- Genetic toxicity in vitro:

The classification of 1,2,3-trichloropropane as positive for genetic toxicity in vitro is based on the summary of results from 21 different studies as summarized in the “Summary entry on all other available in vitro test on genetic toxicity” in chapter 7.6.1. In this summary article the results from 20 different tests on the genetic toxicity of 1,2,3-trichloropropane and its metabolites 1,3-Dichloro-2-propanol and 1,3-Dichloroacetone are combined. For 1,2,3-trichloropropane mainly positive but also negative results depending on test system and conducting laboratory were found. Positive results occurred in most cases only with activation (including the bacterial reverse mutation assay (Ames Test, positive), in-vitro cytogenetic assays in mammalian cell lines (positive), a chromosome aberrations assay (negative but tested only without activation), a non-standardin vitromicronucleus assay (positive, with inherent activation), UDS assays in mammalian cell lines (negative), sister chromatid exchange assays in mammalian cells (positive, with activation) and DNA binding studies (positive)). In the Ames Test, genotoxicity occurred at relatively low levels after activation (0.02 mg/plate, Monsanto 1982).
The two metabolites 1,3-dichloro-2-propanol and 1,3-dichloroacetone were positive in bacterial mutation assays as well as in sister chromatid exchange assays (in V79 cells) with and without activation.
It can therefore be concluded that 1,2,3-trichloropropane and its metabolites 1,3-dichloro-2-propanol and 1,3-dichloroacetone are positive for in vitro genotoxicity.
This assumption is in-line with the assessments of IARC ( IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Volume 63, Dry Cleaning, Some Chlorinated Solvents and Other Industrial Chemicals, 1995, IARC Lyon, France, p. 223 -242; http://monographs.iarc.fr/ENG/Monographs/PDFs/index.php) and SCOEL (Recommendation from the Scientific Committee on Occupational Exposure Limits for 1,2,3-trichloropropane, SCOEL/SUM/170, November 2009, For public consultation).

- Genetic toxicity in vivo:

Diverging results have been obtained with test for in vivo genetic toxicity of 1,2,3-trichloropropane. La 1995 (rat and mouse, single gavage of 3 and 30 and 6 and 60 mg/Kg respectively) as well as Weber & Sipes 1990B (single ip injection in male F344 rats at 30, 100 and 300 mg/Kg bw) describe the formation of DNA adducts, namely S-[1-(hydroxymethyl)-2-(N 7-guanyl)ethyl]glutathion. Nevertheless both describe also cytotoxicity at this doses and it remains unclear whether this is the cause of DNA damage or the result of it. A slightly different scenario is seen in Tafazoli (1996). This is an in vitro test, but as human primary blood were tested it might have a special significance for human in vivo. Cells analysed with single cell electrophoresis showed strong DNA damage without S9 activation and even higher with activation but also in the latter case high cytotoxicity (exposure: 3 h at 2 and 4 mM in culture medium, with and without ). Interestingly at the same culture conditions with S9 and at even longer incubation times without S9 activation (24 h) no effect was seen in a micronucleus assay.
Other in vivo tests like a rodent dominant lethal assay (Saito-Suzuki 1982, rat 5 successive applications (gavage) at 80 mg/Kg bw), mouse bone marrow micronucleus test (Douglas et al., 1985 in IPCS CICADS 56 - 1,2,3-trichloropropane ) and unscheduled DNA synthesis in rat hepatocytes in vivo (Mirsalis et al., 1983 in IPCS CICADS 56 - 1,2,3-trichloropropane) gave negative results, but are either not available or only as abstracts and can therefore not be assessed for their reliability.
This is also true for an abstract to a poster presentation by Ito (1996) where some evidence was presented that induction of lipid peroxidation might have an influence on the genotoxicity of 1,2,3-trichloropropane.
Based on the above stated data an unambiguous conclusion on in vivo genotoxicity 1,2,3-trichloropropene is not possible.

This assumption is in-line with the assessments of IARC ( IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Volume 63, Dry Cleaning, Some Chlorinated Solvents and Other Industrial Chemicals, 1995, IARC Lyon, France, p. 223 -242; http://monographs.iarc.fr/ENG/Monographs/PDFs/index.php) and SCOEL (Recommendation from the Scientific Committee on Occupational Exposure Limits for 1,2,3-trichloropropane, SCOEL/SUM/170, November 2009, For public consultation).


Short description of key information:
- Genetic toxicity in vitro: positive, (bacterial reverse mutation assay/Ames test): S. typhimuriurn TA TA 98, TA 100 and TA 1535, study Monsanto (1982) (OECD TG 471)
- Genetic toxicity in vivo: ambiguous, (weight of evidence approach covering all available studies)

Endpoint Conclusion: Adverse effect observed (positive)

Justification for classification or non-classification

As a conclusion to the above discussed data 1,2,3-trichloropropane is deemed genotoxic in vitro and of unclear genotoxicity in vivo. Therefore it is to be classified as Category 2 (H341: Suspected of causing genetic defects) concerning mutagenicity according to CLP (REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL) as implementation of UN-GHS in the EU.

This classification is in-line with the assessments of IARC ( IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Volume 63, Dry Cleaning, Some Chlorinated Solvents and Other Industrial Chemicals, 1995, IARC Lyon, France, p. 223 -242; http://monographs.iarc.fr/ENG/Monographs/PDFs/index.php) and SCOEL (Recommendation from the Scientific Committee on Occupational Exposure Limits for 1,2,3-trichloropropane, SCOEL/SUM/170, November 2009, For public consultation).