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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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: guideline study under GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1994
Report Date:
1994

Materials and methods

Test guideline
Qualifier:
according to
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
Details on test material:
lot no 280694
purity 99.8% (a/a)
appearance: white solid
storage conditions: dark at approximately 5°C
stability under test conditions: stable for 4 hours

Method

Target gene:
his
Species / strain
Species / strain / cell type:
S. typhimurium, other: TA98; TA 100; TA1535; TA1537
Additional strain / cell type characteristics:
other: all strains: rfa-cell wall deficiency; uvrB-deficient DNA excision-repair system. TA98 and TA 100 strains: presence of pKM101 plasmid (carying r-fctor) increased sensitivity to some mutagens
Metabolic activation:
with and without
Metabolic activation system:
S9-mix from livers of Arcolor 1254induced (500 mg/kg b.w.) male Sprague-Dawley rats
Test concentrations with justification for top dose:
0, 4, 20, 100, 500, 2500, 5000 µg/plate
Vehicle / solvent:
DMSO
Controls
Untreated negative controls:
yes
Remarks:
untreated
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
Positive controls:
yes
Positive control substance:
other: without S9: Sodium azide (TA 100, TA1535); 9-Aminoacridine (TA1537; 2-Nitrofluorene (TA98); with S9-mix: 2-Aminoanthracene
Details on test system and experimental conditions:
method of application: agar plate incorporation
duration: 48h,
temperature: 37°C,
other environmental conditions: in the dark

evaluation: visual thinning of the bacterial lawn and reduced rate of spontaneously occuring colonies determined through microscopical evalation

Evaluation criteria:
a) test produces at least 2-fold increase in the mean number of revertants per plate of at least one of the tester strains compared to the appropriate control
b) test induces a dose related increase in the mean number of revertants per plate of at least one of the tester strains compared to the appropirate control in at least 2 to 3 concentrations.

test results must be reproducible

Results and discussion

Test results
Species / strain:
S. typhimurium, other: TA98; TA 100; TA1535; TA1537
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
observed at 2500 and 5000 µg/plate with TA100
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'.

Any other information on results incl. tables

table presenting the aerage revertant counts for all tests is giving in attachments

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative with and without metabolic activation

Norbornene was not mutagenic in Salmonella typhimurium (TA98; TA 100; TA1535; TA1537) with and without metabolic activiation (Ames test OECD 471)
Executive summary:

Norbornene was tested in a reverse gene mutation assay (Ames test) in bacteria (S. typhimuriumTA98; TA 100; TA1535; TA1537) in concentrations ranging from 0 to 5000 µg/plate in the presence and absense of mammalian metabolic activation (S9 mix induced from rat liver). The study was performed according to OECD 471 under GLP.

there was no evidence of induced mutant colonies over background. Cytotoxicity was obsevered with TA 100 at the highest concentrations of 2500 and 5000 µg/plate.