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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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

In vitro studies

Bacterial reverse mutation assay

In a bacterial reverse mutation assay (Shimizu et al., 1986), conducted similar to OECD Guideline 471 (Bacterial Reverse Mutation Assay but without a marker for cross-linking mutagenicity, e.g. E.coli), the test substance was analysed for mutagenicity by the detection of point mutations in bacteria (histidine-auxotrophic mutants of Salmonella typhimurium). Any mutagenic effects of the test substance is demonstrable on comparison of the number of bacteria in the treated and control cultures that have undergone back-mutation to histidine-prototrophism. To ensure that mutagenic effects of metabolites of the test substances formed in mammals would also be detected, experiments were also performed with the addition of an activation mixture (rat liver microsomes and co-factors). The strains TA 98, TA 100, TA 1535, TA 1537, and TA 1538 were treated with the test substance dissolved in DMSO in doses of 0.01, 0.05, 0.1, and 0.5 mg/plate (preincubation method). A vehicle control and appropriate positive control substances were also evaluated. At concentrations 0.1 mg/plate (TA 1537, without S9) and 0.5 mg/plate (all strains, with and without S9) cytotoxicity occurred. No dose-related biologically relevant increase or doubling in the number of his+ revertants was observed in any of the tested strains with or without metabolic activation. According to the results of the present study, the test substance is not mutagenic in the bacterial reverse mutation assay under the experimental conditions chosen. The positive controls yielded the expected results.


These findings are supported by several further studies conducted similar to OECD Guideline 471 (NTP No 306709; NTP No 743141). In these studies the mutagenic activity of the test substance was tested in the Salmonella typhimurium strains TA 98, TA 100, TA 1535, and TA 1537 with and without the addition of S9-mix for metabolic activation. Treatment with the test substance in doses of 3.3, 10, 33, 100, 333, 1000, and 3333 µg/plate (NTP No 306709), 3.3, 10, 33, 100, and 333 µg/plate (NTP No 743141), respectively, did not reveal any mutagenic effect. In addition, an e. coli reverse mutation assay (spot test) (ECB-IUCLID, 2000/ Szybalski 1958) did not reveal mutagenic properties of the test substance (no further details given, data is only available as secondary source).


In vitro mammalian chromosome aberration test

Data on test substance induced in vitro mammalian chromosome aberration is only available as secondary source (German Chemical Society (GDCh), GDCh-Advisory Committee on Existing Chemicals of Environmental Relevance (BUA), 1992):


Test substance induced chromosome aberration was assayed in vitro in chinese hamster cells by fluorimetric determination in a flow cytometer. The test was performed with and without metabolic activation. The results showed that the test substance induced chromosome aberration in the presence of a metabolic activation system. No genotoxicity was observed without metabolic activation. Nevertheless, the data has to be interpreted carefully, as the authors claimed that the determination of chromosome aberration by using a flow cytometer had not been validated so far.


In vivo studies

Drosophila SLRL test

In a Drosophila SLRL test (NTP No 891440), conducted similar to OECD Guideline 477 (Genetic Toxicology: Sex-linked Recessive Lethal Test in Drosophila melanogaster), the test substance was analysed for mutagenicity in vivo. The test substance was brought into a 5 % sucrose solution at doses of 400 and 500 ppm, respectively. Canton-S wild-type males were allowed to feed for 72 hours. Treated males were mated individually to three Basc females for 3 days and given fresh females at 2-day intervals to produce three matings of 3, 2, and 2 days (sperm from successive matings had been treated at successively earlier post-meiotic stages). F1 heterozygous females were mated with their siblings and then placed in individual vials. F1 daughters from the same parental male were kept together to identify clusters. (A cluster occurs when a number of mutants from a given male result from a single spontaneous premeiotic mutation event, and is identified when the number of mutants from that male significantly exceeds the number predicted by a Poisson distribution). If a cluster was identified, all data from the male in question were discarded. Presumptive lethal mutations were identified as vials containing fewer than 5% of the expected number of wild-type males after 17 days; these were retested to confirm the response.

Because no response was obtained the substance was tested by single injection in a following experiment. A solution of test chemical dissolved in saline or suspended in peanut oil was tested in doses of 2500 and 5000 ppm, respectively. To administer a chemical by injection, a glass Pasteur pipette is drawn out in a flame to a microfine filament and the tip is broken off to allow delivery of the test solution. Injection is performed either manually, by attaching a rubber bulb to the other end of the pipette and forcing through sufficient solution (0.2-0.3 µL) to slightly distend the abdomen of the fly, or by attaching the pipette to a microinjector that automatically delivers a calibrated volume. Flies are anaesthetized with ether and immobilized on a strip of tape. Injection into the thorax, under the wing, is performed with the aid of a dissecting microscope.

None of the experiments exhibited genotoxic potential of the test substance under the test conditions chosen.

Short description of key information:
In vitro studies:
Bacterial Reverse Mutation Assay (similar to OECD Guideline 471), Shimizu et al., 1986: negative
Bacterial Reverse Mutation Assay (similar to OECD Guideline 471), NTP, 306709: negative
Bacterial Reverse Mutation Assay (similar to OECD Guideline 471), NTP, 743141: negative
E. coli reverse mutation assay, ECB-IUCLID, 2000 / Szybalski 1958: negative
In vitro mammalian chromosome aberration test, ECB-IUCLID, 2000 / Koerdel et al., 1981: neagtive without metabolic activation, positive with metabolic activation

In vivo studies:
Drosophila SLRL test (similar to OECD Guideline 477), NTP No 891440: negative

Endpoint Conclusion:

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC) and Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008

Based on the available data, a gene mutating potential of the test substance is not assured. However, treatment of mammalian cells with the test substance in the presence of metabolic activation revealed a positive result and therefore, cytogenetic effects of the test substance can not be excluded. Hence, classification for genetic toxicity is inconclusive under Directive (67/548/EEC) and Regulation (EC) No. 1272/2008.