alkyl 2-alkyl-1,2,3,4,4a,5,8,8a-octahydro-1,4:5,8-dimethanonaphthalene-2-carboxylate

Genetic toxicity: in vitro

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study was performed according to the recommended guidelines and GLP. There were minor deviations from the protocol which did not adversely affect the study integrity.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)

Deviations:

yes

Remarks:

Minor deviation which did not adversely affect the study integrity.

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Reference

Name:

Unnamed

Type:

Constituent

Method

Target gene:

Salmonella typhimurium: histidine gene
Escherichia coli: tryptophan gene

Species / strain

Species / strain 1

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Additional strain / cell type characteristics:

not specified

Species / strain 2

Species / strain / cell type:

E. coli WP2 uvr A

Additional strain / cell type characteristics:

not specified

Metabolic activation:

with and without

Metabolic activation system:

S9-mix induced by a combination of phenobarbital and B-naphthoflavone

Test concentrations with justification for top dose:

1 to 3330 µg/plate in the absence and presence of 5% (v/v) S9-mix
10 to 3330 µg/plate in the absence and presence of 10% (v/v) S9-mix

Vehicle / solvent:

DMSO

Controls

Controls 1

Untreated negative controls:

yes

Remarks:

DMSO

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

Controls 2

Positive controls:

yes

Positive control substance:

sodium azide

Remarks:

5 µg/plate in saline

Migrated to IUCLID6: for TA1535 without metabolic activation

Controls 3

Positive controls:

yes

Positive control substance:

9-aminoacridine

Remarks:

60 µg/plate in milli-Q water

Migrated to IUCLID6: for TA1537 without metabolic activation

Controls 4

Positive controls:

yes

Positive control substance:

2-nitrofluorene

Remarks:

10 µg/plate in DMSO

Migrated to IUCLID6: for TA98 without metabolic activation

Controls 5

Positive controls:

yes

Positive control substance:

methylmethanesulfonate

Remarks:

650 µg/plate in DMSO

Migrated to IUCLID6: for TA100 without metabolic activation

Controls 6

Positive controls:

yes

Positive control substance:

4-nitroquinoline-N-oxide

Remarks:

10 µg/plate in DMSO

Migrated to IUCLID6: for WP2uvrA without metabolic activation

Controls 7

Positive controls:

yes

Positive control substance:

other: 2 -aminoanthracene for all tester strains with metabolic activation

Evaluation criteria:

A test substance is considered negative (not mutagenic) in the test if:
a. The total number of revertants in tester strain TA100 is not greater than two times the concurrent control, and the total number of revertants in tester strains TA1535, TA1537, TA98 or WP2uvrA is not greater than three times the concurrent control.

A test substance is considered positive (mutagenic) in the test if:
a. The total number of revertants in tester strain TA100 is greater than two times the concurrent control, or the total number of revertants in tester strains TA1535, TA1537, TA98 or WP2uvrA is greater than three times the concurrent control.
b. In case a positive response will be repeated, the positive response should be reproducible in at least one independently repeated experiment.

Results and discussion

Test results

Test results 1

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:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 2

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

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 (migrated information):
negative with metabolic activation
negative without metabolic activation

All bacterial strains showed negative responses over the entire dose range, i.e. no significant dose-related increase in the number of revertants in independently repeated experiments.

The negative and strain-specific positive control values were within the laboratory historical control data ranges indicating that the test conditions were adequate and that the metabolic activation system functioned properly.

There were minor deviations from the protocol which did not adversely affect the study integrity; validity criteria have been fulfilled.

Based on the results of this study it is concluded that the test substance is not mutagenic in the Salmonella typhimurium reverse mutation assay and in the Escherichia coli reverse mutation assay.