Registration Dossier

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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
Well performed GLP and OECD guideline study. But according to a previous guideline a different combination of tester strains was used (i.e. without E. coli WP2 uvrA or TA 102)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report Date:
1991

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Version / remarks:
Adopted: 26 May 83,
Deviations:
yes
Remarks:
yes: related to the current guideline version / no: related to the guideline version referenced
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Barbituric acid

Method

Species / strain
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Metabolic activation system:
Aroclor 1254(R) induced rat liver S9-mix
Test concentrations with justification for top dose:
0, 8, 40, 200, 1000, 5000 µg/plate with and without metabolic activation
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: deionized water for test item, DMSO for positive controls
Controlsopen allclose all
Untreated negative controls:
yes
Remarks:
No "untreated" negative control was set up
Negative solvent / vehicle controls:
no
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: sodium azide, nitrofurantoin, 4-nitro-1,2-phenylene diamine
Remarks:
without metabolic activation
Untreated negative controls:
yes
Remarks:
No "untreated" negative control was set up
Negative solvent / vehicle controls:
no
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 2-aminoanthracene
Remarks:
with metabolic activation
Details on test system and experimental conditions:
METHOD OF APPLICATION:
in agar (plate incorporation)

DURATION
- Exposure duration: incubation for 48 hours

NUMBER OF REPLICATIONS: 4 plates per strain and dose level, including controls, two independent experiments

Evaluation criteria:
A reproducible and dose-related increase in mutant counts of at least one strain is considered to be a positive result. For TA 1535, TA 100 and TA 98 this increase should be about twice the amount of negative controls, whereas for TA 1537, at least a threefold increase should be reached. Otherwise, the result is evaluated as negative.
Statistics:
Arithmetic means of the counted colonies were calculated.

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:
cytotoxicity
Remarks:
weak effect > 200 µg/plate
Vehicle controls validity:
not examined
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 item did not exert mutagenic activity in the Salmonella typhimurium reverse mutation assay (plate incorporation test) with and without metabolic activation.
Executive summary:

Mutagenic activity of the test item was investigated in Salmonella typhymurium strains 1535, 1537, 98 and100 with and without metabolic activation (induced rat liver S9-mix) at concentrations of 0, 8, 40, 200, 1000 and 5000 µg/plate according to OECD guideline 471. Under the conditions tested the test compound did not cause a significant increase in the number of revertant colonies and no dose dependent effect was observed.

Therefore the test item is not considered mutagenic under the conditions in this bacterial reverse mutation assay.