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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
April to June 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of assay:
bacterial reverse mutation assay

Test material

Constituent 1
Test material form:
solid

Method

Species / strainopen allclose all
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Details on mammalian cell type (if applicable):
Not applicable
Species / strain / cell type:
E. coli WP2 uvr A
Details on mammalian cell type (if applicable):
Not applicable
Metabolic activation:
with and without
Metabolic activation system:
S-9
Test concentrations with justification for top dose:
Experiment 1: 1.5, 5, 15, 50, 150, 500, 1500 and 5000 µg/plate.
Experiment 2: 50, 150, 500, 1500 and 5000 µg/plate.
Vehicle / solvent:
Vehicle(s)/solvent(s) used: Acetone
Justification for choice of solvent/vehicle: The test material was initially noted to be insoluble in sterile distilled water, dimethyl sulphoxide, dimethyl formamide and acetonitrile at 50 mg/mL and acetone at 100 mg/mL but was fully soluble in tetrahydrofuran at 200 mg/mL. However, the test material in tetrahydrofuran could not be adequately dosed because the formulation immediately solidified during the pipetting stage. Therefore, the most suitable suspension was selected. The test material formed the best doseable suspension in acetone, therefore, this solvent was selected as the vehicle.
Controls
Untreated negative controls:
yes
Remarks:
ENNG: 2µg/plate for WP2uvrA, 3µg/plate for TA100, 5µg/plate for TA1535; 9AA: 80µg/plate for TA1537; 4NQO: 0.2µg/plate for TA98.
Negative solvent / vehicle controls:
yes
Remarks:
Acetone
True negative controls:
not specified
Positive controls:
yes
Remarks:
2AA: 1µg/plate for TA100, 2µg/plate for TA1535 and TA1537, 10µg/plate for WP2uvrA; BP: 5µg/plate for TA98.
Positive control substance:
benzo(a)pyrene
other: 2-Aminoanthracene (2AA)
Details on test system and experimental conditions:
METHOD OF APPLICATION:
Acetone is toxic to the bacterial cells at 100µl after employing the pre-incubation modification, therefore all of the formulation for Experiment 2 were prepared at concentrations two times greater than required on Vogel-Bonner agar plates. To compensate, each formulation was dosed using 0.05 mL (50µL) aliquots.

Results and discussion

Test results
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not determined
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:
Interpretation of results:
negative

The test material was considered to be non-mutagenic under the conditions of the study.
Executive summary:

In an OECD 471 study, conducted according to GLP, the test material is non-mutagenic (negative) to Salmonella typhimurium and Escherichia coli bacterial strains.