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Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information
The substance is considered to be not mutagenic based on the GLP compliant, OECD 471 guideline study.
Link to relevant study records
Reference
Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP compliant guideline study, available as unpublished report, no restrictions, fully adequate for assessment
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Qualifier:
according to
Guideline:
EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
Qualifier:
according to
Guideline:
EPA OPPTS 870.5100 - Bacterial Reverse Mutation Test (August 1998)
GLP compliance:
yes (incl. certificate)
Remarks:
BASF SE, Experimental Toxicology and Ecology, 67056 Ludwigshafen, Germany
Type of assay:
bacterial reverse mutation assay
Test material information:
Composition 1
Target gene:
- His-locus
- Trp-locus
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Metabolic activation system:
Liver S9 fraction of phenobarbital and β-naphthoflavone-induced rats
Species / strain:
E. coli WP2 uvr A
Metabolic activation:
with and without
Metabolic activation system:
Liver S9 fraction of phenobarbital and β-naphthoflavone-induced rats
Test concentrations with justification for top dose:
0, 33, 100, 333, 1000, 2500, 5000 µg/plate
Vehicle:
- Vehicle(s)/solvent(s) used: ultrapure water
- Justification for choice of solvent/vehicle: due to the good solubility of the test substance in ultrapure water, this was used as vehicle.
Negative controls:
yes
Solvent controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 2-aminoanthracene
Remarks:
all strains with metabolic activation
Negative controls:
yes
Solvent controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: N-methyl-N'-nitro-N-nitrosoguanidine
Remarks:
TA 1535, TA 100; without metabolic activation
Negative controls:
yes
Solvent controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 4-nitro-o-pheylenediamine
Remarks:
TA 98; without metabolic activation
Negative controls:
yes
Solvent controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
9-aminoacridine
Remarks:
TA 1537; without metabolic activation
Negative controls:
yes
Solvent controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
4-nitroquinoline-N-oxide
Remarks:
E.coli WP2 uvrA; without metabolic activation
Details on test system and conditions:
Plate incorporation
- Exposure duration: 48 – 72 hours
- 3 plates per dose or control
- Determination of cytotoxicity: decreased in the number of revertants, clearing or diminution of the background lawn, and/or reduction in the titer.

Preincubation experiment
- Preincubation period: 20 min
- Exposure duration: 48 – 72 hours
- 3 plates per dose or control
- Determination of cytotoxicity: decreased in the number of revertants, clearing or diminution of the background lawn, and/or reduction in the titer.
Evaluation criteria:
- The test substance is considered positive in this assay if the following criteria are met: A dose-related and reproducible increase in the number of revertant colonies, i.e. about doubling of the spontaneous mutation rate in at least one tester strain either without S9 mix or after adding a metabolizing system.
- A test substance is generally considered non-mutagenic in this test if the number of revertants for all tester strains were within the historical negative control range under all experimental conditions in at least two experiments carried out independently of each other.
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity:
no
Vehicle controls valid:
yes
Negative controls valid:
yes
Positive controls valid:
yes
Species / strain:
E. coli WP2 uvr A
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity:
no
Vehicle controls valid:
yes
Negative controls valid:
yes
Positive controls valid:
yes
Additional information on results:
- Precipitation: No test substance precipitation was found with and without S9 mix.
Conclusions:
Interpretation of results (migrated information):
negative
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vitro:

In a GLP compliant mutagenicity test, performed according to OECD guideline 471, several of strains of Salmonella typhimurium (TA 1535, TA 1537, TA 98, TA 100) and one E.coli strain (WP2 uvrA) were used to test the mutagenic potential of 2,5-dihydrofuran both with and without metabolic activation (BASF 2013). Two experiments were performed. In the first experiment: a standard plate test, strains were exposed to 0, 33, 100, 333, 1000, 2500, 5000 µg/plate. The second experiment was a preincubation test using the same test concentrations as in the standard plate test. No precipitation of the test substance was found. No bacteriotoxic effect was observed. An increased number of hits+ or trp+ revertants was not observed in the standard plate test or in the preincubation test either without S9 mix or after the addition of a metabolizing system. It was therefore concluded that the test substance is not mutagenic under these experimental conditions.


Justification for selection of genetic toxicity endpoint
One genetic toxicity in vitro study is available. This study is adequate for covering this endpoint.

Justification for classification or non-classification

Because no mutagenic effects were observed, classification genetic toxicity is not warranted in accordance with EU Directive 67/548 (DSD) and EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation No. 1272/2008.