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Toxicological information

Genetic toxicity: in vitro

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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

Reference
Name:
Unnamed
Type:
Constituent
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 108 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.