1,5-dihydro-3-isopropyl-8-methyl-[1,3]dioxepino[5,6-c]pyridin-9-yl acetate

Genetic toxicity: in vitro

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-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

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

Test material information

Constituent 1

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.