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Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Short description of key information:
Genetic toxicity in vitro:
-Chromosome aberration assay: BASF SE 2010, according to OECD guideline 473, GLP study - not genotoxic, not mutagenic.
-Ames test: BASF SE 1995 & 2017, according to OECD guideline 471, GLP study - not genotoxic, not mutagenic.
-HPRT locus assay: BASF SE 2010, according to OECD guideline 476, GLP study - not genotoxic, not mutagenic.

Endpoint Conclusion: No adverse effect observed (negative)

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

Genetic toxicity in vivo

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Ames test

In a reverse gene mutation assay in bacteria (BASF SE 1995), TA 1535, TA 1537, TA 98 and TA 100 strains of Salmonella typhimurium were exposed to the test item at concentrations of 20, 100, 500, 2500 and 5000 µg/plate in the presence and absence of mammalian metabolic activation in a plate incorporation and a pre-incubation assay. The test item was tested up to limit concentration of 5000 µg/plate. However, precipitation was observed from about 500 µg/plate onward. The positive controls induced the appropriate responses in the corresponding strains.  There was no evidence of induced mutant colonies over background.

In an addtional Ames test (BASF SE, 2017), e. coli WP2 uvrA bacteria were exposed to the test item at concentrations of 33 - 5000 µg/plate in the presence and absence of mammalian metabolic activation in a plate incorporation and a pre-incubation assay. Precipitation of the test substance was found at a concentration of 500 µg/plate with and without S9 mix. A weak bacteriotoxic effect was only observed in the standard plate test with S9 mix at a concentration of 5000 µg/plate. A relevant increase in the number of trp+ revertants was not observed in the stadard plate test or in the preincubation test without S9 mix or after addition of a metabolizing system.

Chromosome aberration assay

In a mammalian chromosome aberration assay (BASF SE 2010/2011), V79 cell cultures were exposed to the test item dissolved in acetone at concentrations of 75, 150, 300, 2600, 3900 and 5200 µg/mL with and without metabolic activation. The test item was tested up to limit concentration of 5200 µg/mL. Positive controls induced the appropriate response. There was no concentration related positive response of chromosome aberrations induced over background in the presence and absence of metabolic activation.

 

Mammalian cell gene mutation assay

In a mammalian cell gene mutation assay [hprt locus] (BASF SE 2010), CHO cells cultured in vitro were exposed to the test item dissolved in acetone at concentrations of 0, 325, 650, 1300, 2600, 3900 and 5200 μg/mL in the first experiment and of 0, 162.5, 325, 650, 5200 μg/mL in the second experiment in the presence and absence of mammalian metabolic activation. The test item was tested up to limit concentration of 5200 µg/mL. The positive controls induce the appropriate response. There was no concentration related positive response of induced mutant colonies over background.

 

Conclusion

Both, the gene mutation assays and the cytogenetic assay did not indicate a genotoxic or mutagenic effect of the test substance under the test conditions chosen, according to the respective guidelines. Therefore the test substance is considered to be not mutagenic in vitro.

 

This assumption is supported by further in vitro assays (Ames test, MLA, CA) and two micronucleus assays in vivo with analogous substances. The test substance neither induced gene mutations nor chromosomal aberrations in vitro and no increase of the percentage of micronucleated polychromatophile erythrocytes was observed in vivo.

Justification for classification or non-classification

Due to the negative results obtained in all studies no classification according to GHS criteria is required.