Acetoacetamide

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: well performed GLP and OECD guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1997

Report date:

1997

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

no

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Acetoacetamide

EC Number:

227-774-4

EC Name:

Acetoacetamide

Cas Number:

5977-14-0

Molecular formula:

C4H7NO2

IUPAC Name:

acetoacetamide

Details on test material:

- Name of test material (as cited in study report): P0002 (deciphered as acetoacetamide by the study owner)

Method

Species / strain

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102

Metabolic activation:

with and without

Metabolic activation system:

phenobarbital and betanaphthoflavone induced rat liver S9 mix

Test concentrations with justification for top dose:

Toxicity test: 5000, 1580, 500, 158 and 50 µg/plate
Assay for reverse mutation: 5000, 2500, 1250, 625 and 313 µg/plate

Vehicle / solvent:

DMSO

Controls

Untreated negative controls:

yes

Remarks:

Untreated

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: sodium azide, 9-aminoacridine, 2-nitrofluorene, 2-aminoanthracene, cumene hydroperoxide

Evaluation criteria:

For the test substance to be considered mutagenic, two-fold or more increases in mean revertant numbers must be observed at two consecutive dose-levels or at the highest practicable dose-level only. In addition there must be evidence of a dose response relationship showing increasing numbers of mutant colonies with increasing dose-levels. The effect must be reproduced in an independent experiment.

Results and discussion

Test results

Species / strain:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

Slight toxicity in TA102 at the highest dose-level tested

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'.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative with and without metabolic activation

It can be concluded that the test item does not induce reverse mutation in Salmonella Typhimurium under the test conditions

Executive summary:

The test substance was examined for mutagenic activity by assaying for reverse mutation to histidine prototrophy in the prokaryotic Salmonella typhimurium.

The five tester strains TA1535, TA1537, TA98, TA100 and TA102 were used. Experiments were performed both in the absence and presence of metabolic activation, using liver S9 fraction from rats pre-treated with phenobarbitone and betanaphthoflavone. Test substance solutions were prepared using DMSO.

In the toxicity test, the test substance was assayed at a maximum dose-level of 5000 µg/plate and four lower dose-levels spaced at approximately half-log intervals.

Slight toxicity, as indicated by thinning of the background lawn, was observed with TA102 tester strain at the highest dose-level tested. The same maximum dose-level was selected for the principal assay.

Two independent experiments were performed, one using a plate incorporation method, the other using a pre-incubation method. The test substance was assayed at a maximum dose-level of 5000 µg/plate and four lower dose-levels, separated by two-fold dilutions: 2500, 1250, 625 and 313 µg/plate.

The test substance did not induce two-fold increases of the number of revertant colonies in the plate-incorporation or pre-incubation assay, at any dose-level, in any tester strain, in the absence and presence of S9 metabolism.