N-methylacetamide

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:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Meets scientific standards (partly limited documentation, tested only without metabolic activation, extremely high dose levels).

Data source

Reference

Reference Type:

publication

Title:

XIII. Tests of Chemicals for Mutagenicity

Author:

Hemmerly J & Demerec M

Year:

1955

Bibliographic source:

Cancer Res 15: 69-75

Materials and methods

Principles of method if other than guideline:

Reverse mutation in E. coli WP-14 and SD-4

GLP compliance:

no

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

N-methylacetamide

EC Number:

201-182-6

EC Name:

N-methylacetamide

Cas Number:

79-16-3

Molecular formula:

C3H7NO

IUPAC Name:

N-methylacetamide

Details on test material:

no details

Method

Target gene:

Sd-4, a streptomycin-dependent mutant, gene: sd-4
WP-14, requires proline, gene: pro-1

Species / strain

Species / strain / cell type:

other: Escherichia coli Sd-4 and WP-14

Metabolic activation:

without

Test concentrations with justification for top dose:

10, 20 or 50 mg/ml in SD-4
20 or 50 mg/ml in WP-14

Vehicle / solvent:

distilled water or buffer

Controls

Negative solvent / vehicle controls:

yes

Positive controls:

other: no, but positive results in parallel trials with mutagenic substances

Details on test system and experimental conditions:

Escherichia coli reverse mutation assay, incubation with the test substance for 1-6 h; revertants corrected for spontaneous mutations.

Evaluation criteria:

not clearly stated

Statistics:

no

Results and discussion

Test results

Species / strain:

E. coli, other: Escherichia coli Sd-4

Metabolic activation:

without

Genotoxicity:

ambiguous

Cytotoxicity / choice of top concentrations:

other: no, but very high dose levels tested

Vehicle controls validity:

not specified

Positive controls validity:

other: positive results in parallel trials with mutagenic substances

Additional information on results:

Details are presented in the Table below. Mutagenic effects were clearly not dose dependent.
No data on osmolality and pH although very high doses were tested.

Any other information on results incl. tables

Mutagenic effects of N-methylacetamide in E. coli Sd-4 and WP-14

Strain	Dose in mg/ml	Exposure time in hours	Survival in % of control	Revertants in 10^8 surviving cells
Sd-4	10	1	56	15.4
Sd-4	20	3	85	None
Sd-4	50	1	67	37.5
Sd-4	50	1	100	None
WP-14	20	3	63	64
WP-14	20	3	93	212
WP-14	20	6	64	454
WP-14	50	3	72	167

 

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
ambiguous

In the Escherichia coli reverse mutation assay mutagenic activity was detected without a metabolic activation system only at very high dose levels >= 10 mg/ml without a dose dependency.

Executive summary:

Meets scientific standards (partly limited documentation, tested only without metabolic activation, extremely high dose levels).

In this assay reverse mutation in E. coli WP-14 and Sd-4 were studied. Bacteria were incubated for 1 -6 h without a metablic activation system to 10 -50 mg/ml. Increase in revertants was detected in comparison to vehicle control in WP-14 but effects were not dose dependent; contradictory results were found in Sd-4; no clear cytotoxic effects. No concurrent positive control was available, however, in parallel experiments with mutagenic substances clearly positive results were obtained at low dose levels.

Conclusion: In the Escherichia coli reverse mutation assay mutagenic activity was detected without a metabolic activation system only at high dose levels >=10 mg/ml without a dose dependency.