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Diss Factsheets

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: The accordance of the study with its protocol, the OECD Guideline and the Principles of Good Laboratory Practice (GLP) is guaranteed.
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001
Report date:
2001

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
no
Principles of method if other than guideline:
-
GLP compliance:
yes (incl. QA statement)
Type of assay:
bacterial reverse mutation assay

Test material

Constituent 1
Chemical structure
Reference substance name:
1,5-dihydro-3-isopropyl-8-methyl-[1,3]dioxepino[5,6-c]pyridin-9-yl acetate
EC Number:
296-417-2
EC Name:
1,5-dihydro-3-isopropyl-8-methyl-[1,3]dioxepino[5,6-c]pyridin-9-yl acetate
Cas Number:
92671-67-5
Molecular formula:
C14H19NO4
IUPAC Name:
8-methyl-3-(propan-2-yl)-1H,3H,5H-[1,3]dioxepino[5,6-c]pyridin-9-yl acetate

Method

Target gene:
TA97: hisD6610, TA 98: hisD3052 TA 100 und TA 1535 hisG46,
TA102: hisG428
Species / strain
Species / strain / cell type:
S. typhimurium, other: TA97, TA98, TA100, TA102, TA1535
Details on mammalian cell type (if applicable):
not applicable
Additional strain / cell type characteristics:
other: rfa, delta-uvrB, pKM101
Metabolic activation:
with and without
Metabolic activation system:
S9-mix
Test concentrations with justification for top dose:
5, 2.5, 1.25, 0.625, 0.3125 mg/l
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: DMSO
Controls
Untreated negative controls:
yes
Remarks:
with and without S9
Negative solvent / vehicle controls:
yes
Remarks:
with and without S9
True negative controls:
yes
Remarks:
with and without S9
Positive controls:
yes
Remarks:
see below
Positive control substance:
benzo(a)pyrene
Remarks:
Migrated to IUCLID6: + 4-Nitro-l,2-phenylendiamin, Natriumazid
Details on test system and experimental conditions:
METHOD OF APPLICATION: in medium; in agar (plate incorporation); preincubation; in suspension; as impregnation on paper disk


DURATION
- Preincubation period:
- Exposure duration:
- Expression time (cells in growth medium):
- Selection time (if incubation with a selection agent):
- Fixation time (start of exposure up to fixation or harvest of cells):


SELECTION AGENT (mutation assays):
SPINDLE INHIBITOR (cytogenetic assays):
STAIN (for cytogenetic assays):


NUMBER OF REPLICATIONS:


NUMBER OF CELLS EVALUATED:


DETERMINATION OF CYTOTOXICITY
- Method: mitotic index; cloning efficiency; relative total growth; other:


OTHER EXAMINATIONS:
- Determination of polyploidy:
- Determination of endoreplication:
- Other:


OTHER:
Evaluation criteria:
?
Statistics:
?

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:
not determined
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH:
- Effects of osmolality:
- Evaporation from medium:
- Water solubility:
- Precipitation:
- Other confounding effects:


RANGE-FINDING/SCREENING STUDIES:


COMPARISON WITH HISTORICAL CONTROL DATA:


ADDITIONAL INFORMATION ON CYTOTOXICITY:
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

no additional remarks

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative

Substance is not mutagenic
Executive summary:

Isobutyralacetate was evaluated for mutagenic activity in the Ames test. A standard plate incorporation and a preincubation modification assay in absence and in presence of an exogenous metabolic activation system (S9) were performed. Five Salmonella typhimurium

tester strains (TA1535, TA97, TA98, TA100, and TA102) were employed. The activity of the S9 -mix and the responsiveness of the tester strains were verified by including appropriate controls into each experiment. The substance was dissolved in dimethylsulfoxide (DMSO). Concentration ranges between 0.3125 to 5 mg/plate were chosen for the main experiments.

No significant increase in the number of revertant colonies was apparent in all five tester strains (TA1535, TA97, TA98, TA100, and TA102) using both methods, after treatment with Isobutyralacetate.

Based on these data Isobutyralacetate can be considered as not mutagenic in the Ames test under the described experimental conditions.