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Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Gene mutation in bacteria / Ames: negative (Ciba Geigy Ltd. 1986 and 1978; BASF AG 1982); Gene mutation in mammalian cells: TK-Assay: negative at non-precipitating concentrations (Harrington-Brock 1991); Cytogenicity in mammalian cells: chromosomal aberration test: negative (US NTP 1990); sister chromatid exchange assay: positive (US NTP 1990)

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Additional information from genetic toxicity in vitro:

Gene mutation in bacteria:

In a reverse gene mutation assay in bacteria conducted according to OECD 471 (Ciba Geigy Ltd. 1986; reliability score 2), strains [TA 1535, TA 1537, TA 98 and TA 100] of S. typhimurium were exposed to the test substance (no data on purity) dissolved in DMSO at concentrations of 20, 78, 313, 1250 and 5000 µg/0.1 mL in the absence and presence of Aroclor 1254-induced rat liver S9 mix (in both experiments, the plate incorporation test was used).  No cytotoxicity was observed, but the test substance was tested up to precipitating concentrations (precipitation of the test item in soft agar was observed at concentrations of 313 µg/0.1 mL and above). No significant increase in mutant frequency was observed, either with or without metabolic activation.The positive controls induced the appropriate responses in the corresponding strains.

Additionally, there are two other Ames tests (Ciba Geigy Ltd. 1978, BASF AG 1982; both: reliability score 2) which were conducted similar or according to OECD 471.

In the first assay (Ciba Geigy Ltd. 1978), strains [TA 1535, TA 1537, TA 98 and TA 100] of S. typhimurium were exposed to the test substance (no data on purity) dissolved in DMSO at concentrations of 5, 15, 45, 135, and 405 µg/0.1 mL in the absence and presence of induced rat liver S9 fraction mixed with a series of cofactors (plate incorporation test was used).  No data on cytotoxicity was given and no significant increase in mutant frequency was observed, either with or without metabolic activation.The positive controls induced the appropriate responses in the corresponding strains.

In the second Ames test (BASF 1982), strains [TA 1535, TA 1537, TA 98, TA 100 and TA 1538] of S. typhimurium were exposed to the test substance (purity: 99.5%) dissolved in DMSO at concentrations of 4, 20, 100, 500, 2500 µg/0.1 mL in the absence and presence of Aroclor 1254 induced rat liver S9 fraction mixed with a series of cofactors (plate incorporation test was used). No cytotoxicity was observed, but the test substance was tested up to precipitating concentrations (precipitation of the test item was observed at 2500 µg/plate). Also in this assay no significant increase in mutant frequency was observed, either with or without metabolic activation.The positive controls induced the appropriate responses in the corresponding strains.

Gene mutation in mammalian cells:

A formulation containing 48% of the test substance was examined in a TK-assay similar to OECD 476 with mouse lymphoma L5178Y cells (with and without Aroclor-induced rat liver activation). The highest testable dose (due to solubility problems) was 30 µg/mL without and 20 µg/mL with metabolic activation. The exposure duration was 4 h, expression time 48 h and selection time with 5-trifluoromethyl-thymidine 9 - 11 days. No mutagenic potential was observed at non-precipitating concentrations. The test substance formulation could not be further evaluated due to its limited solubility in DMSO and its lack of cytotoxicity at its maximum solubility. However, the TK-test was conducted to the solubility limit of the test substance under the test conditions and therefore the study is regarded as reliable (Harrington-Brock 1991, reliability score 2).

Cytogenicity in mammalian cells:

A chromosomal aberration test according to US NTP standard protocol (similar to OECD 473) in Chinese hamster ovary cells with and without metabolic activation was performed with the test substance (purity unknown). The test concentrations were 0.016, 0.03 and 0.05 mg/mL (vehicle DMSO). Harvest time was 12 h at the first and 13 h at the second experiment, respectively. No data on cytotoxicity was given and the result was negative (US NTP 1990, reliability score 2).

Additionally, a sister chromatid exchange assay in Chinese hamster ovary cells with and without metabolic activation was performed with the test substance (purity unknown). The test concentrations were 1.6, 5, 16 and 50 mg/L (vehicle DMSO). No data on cytotoxicity was given. The substance increased the occurence of sister chromatide exchanges (US NTP 1990, reliability score 2). The biological relevance of sister chromatide assays is not clear, it does not contribute to the hazard assessment.

Taken together, the test substance was not mutagenic in bacteria and in mammalian cells in vitro.

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC):

The available studies are considered reliable and suitable for classification purposes under 67/548/EEC. As a result the substance is not considered to be classified for genotoxicity under Directive 67/548/EEC.

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008:

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for genotoxicity under Regulation (EC) No. 1272/2008.