Registration Dossier

Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
key study
Study period:
September 25th, 2003 to October 27th, 2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2003
Report Date:
2003

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
GLP compliance:
yes
Type of assay:
bacterial forward mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Specific details on test material used for the study:
Test material name (as stated in the report): Cetonal
Batch No.: 9000503780
Expiry date: February 09, 2015

Method

Species / strain
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102
Metabolic activation:
with and without
Metabolic activation system:
S9 mix
Test concentrations with justification for top dose:
See below the "Any other informtaion on materials and methods " boxe
Vehicle:
Distilled water and DMSO
Controlsopen allclose all
Negative controls:
yes
Solvent controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
sodium azide
Negative controls:
yes
Solvent controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
9,10-dimethylbenzanthracene
Negative controls:
yes
Solvent controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
2-nitrofluorene
Negative controls:
yes
Solvent controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 2-Aminoanthracene
Negative controls:
yes
Solvent controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
cumene hydroperoxide

Results and discussion

Test results
Key result
Species / strain:
other: S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity:
yes
Vehicle controls valid:
yes
Negative controls valid:
yes
Positive controls valid:
yes

Any other information on results incl. tables

In the toxicity test, the test item was assayed at a maximum dose level of 5000 microf/plate and at four does levels spaced at approximately half - log intervals: 1580, 500, 158 and 50 microg/plate. Toxicity as indicated by the thinning of the background lawn and/or reduction in revertant numbers was observed with TA1537 and TA100 both in the absence and presence of S9 metabolic avctivation and with TA102 in its absence. With TA100 tester strain the toxic effects were not dose related but evident at all dose levels.

Dose levels used with all tester strains were selected on the basis of the results obtained in an additional experiment where the dose range assayed proved to be too toxic. Toxicity as indicated by thinning of the background law and reduction in revertant numbers was observed at higher dose levels with all tester strains both in the absence and presence of S9 metabolic activation. No increase in revertant numbers were observed at any concentrations assays.

Applicant's summary and conclusion

Conclusions:
It is concluded that the test item CETONAL does not induce reverse mutation in Salmonella Typhimurium under the reported experimental conditions.