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:
other information
Study period:
Mar 1999
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: well reported GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1999
Report Date:
1999

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
no bacteria strain included to detect cross-linking mutagens
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): ZK 34517
- Batch No.: 27002001, 27002002, 27002003, 27002004, 27002005, 27002005, 27002006, and 27002007

Method

Target gene:
Histidine gene locus
Species / strain
Species / strain / cell type:
other: S. typhimurium TA 1535, TA 100, TA 1537, TA 1538, TA 98
Metabolic activation:
with and without
Metabolic activation system:
liver S9-mix from Aroclor 1254 -treated rats
Test concentrations with justification for top dose:
Dimethylenketon: six concentrations from 0.1 to 5.0 mg/plate
Sodium azide: 5 µg/plate (TA 1535 and TA 100 without S9)
2-Nitrofluorene: 10 µg/plate (TA 1538 and TA 98 without S9)
4-Nitro-o-phenylenediamine: 10 µg/plate (TA 1537 without S9)
Benzo[a]pyrene: 2.5 µg/plate (TA 100 and TA 98 with S9)
Cyclophosphamide: 400 µg/plate (TA 1535 with S9)
2-Aminoanthracene: 5 µg/plate (with S9)
Controls
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
Positive controls:
yes
Positive control substance:
other: Sodium azide (TA 1535 and TA 100, -S9), 2-Nitrofluorene (TA 1538 and TA 98, -S9), 4-Nitro-o-phenylenediamine (TA 1537, -S9), Benzo[a]pyrene (TA 100 and TA 98, +S9), Cyclophosphamide (TA 1535, +S9), 2-Aminoanthracene (+S9)

Results and discussion

Test results
Species / strain:
other: Salmonella typhimurium strains TA 1535, TA 100, TA 1537, TA 1538, TA 98
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'.

Any other information on results incl. tables

Precipitates in the agar were found at the highest dose of 5.0 mg/plate.

Applicant's summary and conclusion

Executive summary:

Dimethylenketon was tested in the Salmonella/microsome test for point-mutagenic effects in doses up to 5000 µg/plate on the five histidine-auxotrophic Salmonella typhimurium LT2 strains TA 1535, TA 100, TA 1537, TA 1538 and TA 98.

No cytotoxic effect was seen. Precipitates in the agar were found at the highest dose of 5.0 mg/plate.

There was no evidence for a mutagenic activity of Dimethylenketon, when tested up to the highest recommended dose level of 5.0 mg/plate in the absence and presence of S9 mix.