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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:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP guideline study with acceptable restrictions. Incomplete strain selection, but adequate at the time of testing.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report Date:
1989

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
Incomplete strain selection: TA-102 or equivalent is missing
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Crodamide SR (Stearamide), alternative name: Octadecanamide
- Molecular formula (if other than submission substance): C18H37NO
- Molecular weight (if other than submission substance): 283.496
- Physical state: Solid, white powder
- Analytical purity: 97 %

Method

Target gene:
His operon
Species / strain
Species / strain / cell type:
S. typhimurium, other: TA 1535, TA 1537, TA 1538, TA 98 and TA 100
Metabolic activation:
with and without
Metabolic activation system:
S9-mix prepared from Aroclor 1254 rats
Test concentrations with justification for top dose:
Dose range finding test: 5000, 500, 50, 5 µg/plate
Mutation tests: 5000, 1500, 500, 150, 50 µg/plate
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: Ethanol
Controlsopen allclose all
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
Remarks:
Ethanol
True negative controls:
no
Positive controls:
yes
Positive control substance:
2-nitrofluorene
Remarks:
without S9-mix

Migrated to IUCLID6: 1 µg/plate with TA-98, 2 µg/plate with TA-1538
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
Remarks:
Ethanol
True negative controls:
no
Positive controls:
yes
Positive control substance:
N-ethyl-N-nitro-N-nitrosoguanidine
Remarks:
without S9-mix

Migrated to IUCLID6: 3 µg/plate with TA-100, 5 µg/plate with TA-1535
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
Remarks:
Ethanol
True negative controls:
no
Positive controls:
yes
Positive control substance:
9-aminoacridine
Remarks:
without S9-mix

Migrated to IUCLID6: 80 µg/plate with TA-1537
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
Remarks:
Ethanol
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 2-Aminoanthracene, 0.5 µg/plate with TA 1538 and TA 98, 1 µg/plate with TA 100, 2 µg/plate with TA 1535 and TA 1537
Remarks:
with S9-mix
Details on test system and experimental conditions:
METHOD OF APPLICATION:
- In agar (plate incorporation)

DURATION
- Exposure duration: 3 days

NUMBER OF REPLICATIONS: 3, the procedures were repeated in a second mutation assay at a later date using the same dose levels

DETERMINATION OF CYTOTOXICITY
- Method: Relative total growth: Colonies were counted using a Biotran Automatic Colony Counter, and the mean number of revertant colonies per treatment group assessed


Evaluation criteria:
- If treatment with a test material produces an increase in revertant colony numbers of at least twice the concurrent solvent controls, with some evidence of a positive dose-relationship, in two separate experiments, with any bacterial strain either in the presence or absence of S9-mix, it will be considered to show evidence of mutagenic activity in this test system.
- If treatment with a test material does not produce reproducible increases of at least 1.5 times the concurrent solvent controls, at any dose level with any bacterial strain, it will be considered to show no evidence of mutagenic activity in this test system
Statistics:
No statistical analysis performed

Results and discussion

Test results
Species / strain:
S. typhimurium, other: TA-1535, TA-1537, TA-1538, TA-98, TA-100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Remarks:
maximum guideline concentration of 5 mg/plate tested
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Additional information on results:
RANGE-FINDING/SCREENING STUDIES:
The revertant colony counts for Stearamide obtained in the preliminary toxicity test revealed that Stearamide was not toxic towards the tester strains. Therefore 5000 µg/plate was chosen as the top dose level in the mutation tests.


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

Any other information on results incl. tables

No substantial increases in revertant colony numbers of any of the tester strains were observed following treatment with Stearamide at any dose level, either in the presence or absence of S9-mix. It is concluded that Stearamide shows no evidence of mutagenic activity when tested in this bacterial system.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative