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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:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Read-across from GLP-compliant guideline study performed with similar substance.

Data source

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

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Version / remarks:
of 1997
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
Version / remarks:
of 2008
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder

Method

Species / strain
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2
Details on mammalian cell lines (if applicable):
E. coli WP2 uvr A pKM101
Additional strain characteristics:
other: essential amino acid requiring strains
Metabolic activation:
with and without
Metabolic activation system:
liver S9 mix from male Sprague Dawley rats treated with phenobarbital and 5,6-benzoflavone for enzyme induction.
Test concentrations with justification for top dose:
Experiment 1: 0; 5; 15; 50; 150; 500; 1500 and 5000 μg/plate
Experiment 2: 0; 50; 150; 500; 1500 and 5000 μg/plate
Vehicle:
Acetone
Justification for choice of solvent/vehicle:
A suspension in acetone was prepared suitable for exposure to the test substance up to the maximum guideline recommended test substance concentration of 5000 μg/plate.
Controlsopen allclose all
Negative controls:
other: Sterility controls were included, i.e. tester strain free plates with soft agar, S9 mix, buffer, vehicle and/or test substance.
Solvent controls:
yes
Remarks:
without and with S9 mix
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: Sodium azide; 9-aminoacridine; 2-nitrofluorene; 4-nitroquinoline-1-oxide.
Remarks:
Positive control substances for tests without metabolic activation (S9 mix).
Negative controls:
other: Sterility controls were included, i.e. tester strain free plates with soft agar, S9 mix, buffer, vehicle and/or test substance.
Solvent controls:
yes
Remarks:
without and with S9 mix
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 2-aminoanthracene; Benzo[a]pyrene
Remarks:
Positive control substances for tests with metabolic activation (S9 mix).
Details on test system and conditions:
Standard Plate Incorporation Tests were performed in both experiments (Experiments 1 and 2) and both experiments were conducted without and with metabolic activation (S9 mix). Test procedures varied in that the proportion of S9 fraction in the S9 mix was 10% v/v in Experiment 1 whereas 20% v/v in Experiment 2.


Evaluation criteria:
The test substance is considered to exhibit mutagenic activity in this assay if the following criteria are met:
A reproducible increase in revertant colony number, (i.e. at least twice for strains TA 100, TA 98 and WP2 uvrA and at least three times for strains TA 1535 and TA 1537 the concurrent vehicle controls), with some evidence of a positive dose-response relationship. Such positive response in at least one tester strain without or with metabolic activation (S9 mix.) is sufficient for concluding mutagenic activity.

A test substance is considered non-mutagenic in this test if:
Exposure to a test substance does not produce a reproducible increase in revertant colony numbers.
Statistics:
The data were not statistically analysed. The study result was unequivocal.

Results and discussion

Test results
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity:
no
Remarks:
tested up to the recommended maximum concentration of 5000 µg/plate
Vehicle controls valid:
yes
Negative controls valid:
not applicable
Positive controls valid:
yes
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.
Additional information on results:
All sterility control plates were colony free. Hence the absence of microbial contamination of the S9 mix, buffer and test substance formulation was confirmed. Viability counts were satisfactory meeting the acceptance criteria.

Any other information on results incl. tables

As outlined in the „Validity Assessment Report“ for the read-across approach (see IUCLID Section 13) read-across from testing data obtained with the UVCB substance WS405777 is considered appropriate for the safety evaluation as well as classification and labelling of the mono-constituent substance WS406663 based on the close chemical similarity between the two substances.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative with and without metabolic activation (S9 mix)
Executive summary:

As outlined in the „Validity Assessment Report“ for the read-across approach (see IUCLID Section 13) read-across from testing data obtained with the UVCB substance WS405777 is considered appropriate for the safety evaluation as well as classification and labelling of the mono-constituent substance WS406663 based on the close chemical similarity between the two substances.

Like the read-across source substance WS405777 the read-across target substance WS406663 is considered non-mutagenic in the Ames test.