Registration Dossier

Diss Factsheets

Toxicological information

Genetic toxicity: in vitro

Currently viewing:

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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study according OECD guideline, GLP, well documented

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1999
Report date:
1999

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Qualifier:
according to guideline
Guideline:
EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
GLP compliance:
yes (incl. QA statement)
Type of assay:
bacterial reverse mutation assay

Test material

Constituent 1
Chemical structure
Reference substance name:
N,N-dimethyldecan-1-amide
EC Number:
238-405-1
EC Name:
N,N-dimethyldecan-1-amide
Cas Number:
14433-76-2
Molecular formula:
C12H25NO
IUPAC Name:
N,N-dimethyldecanamide
Details on test material:
- Name of test material (as cited in study report): SAT 990 560
- Chemical name: N,N-Dimethyldecan-1-amide
- Physical state: liquid
- Purity: 100 % active substance
- Lot/batch No.: 10048316
- Expiration date of the lot/batch: November 2001
- Storage condition of test material: room temperature

Method

Target gene:
his operon
Species / strainopen allclose all
Species / strain / cell type:
S. typhimurium TA 102
Additional strain / cell type characteristics:
not applicable
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Additional strain / cell type characteristics:
not applicable
Metabolic activation:
with and without
Metabolic activation system:
S9 (Phenobarbital, ß-Napthoflavone)
Test concentrations with justification for top dose:
Experiment I (TA 98, TA 100): 3; 10; 33; 100 and 1000 µg/plate
Experiment I (TA 1535, TA 1537, TA102): 33; 66; 100; 333; 666 and 1000 µg/plate
Experiment II (all strains): 33; 66; 100; 333; 666 and 1000 µg/plate
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: chosen because of the test item solubility
Controls
Untreated negative controls:
yes
Remarks:
untreated controls
Negative solvent / vehicle controls:
yes
Remarks:
solvent controls
Positive controls:
yes
Positive control substance:
other: sodium azide, 4-nitro-o-phenylene-diamine, methyl methane sulfonate, 2-aminoanthracene
Details on test system and experimental conditions:
METHOD OF APPLICATION: pre mixed suspension (test solution, S9mix or buffer, bacteria suspension, overlay agar) were poured onto agar plates
Evaluation criteria:
according to guideline
Statistics:
no

Results and discussion

Test resultsopen allclose all
Species / strain:
S. typhimurium TA 102
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
in higher concentrations, tested up to cytotoxic concentration
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
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:
cytotoxicity
Remarks:
in higher concentrations, tested up to cytotoxic concentration
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
ADDITIONAL INFORMATION ON CYTOTOXICITY:
Cytotoxicity was checked for higher concentration in pre-experiment. The backround growth was reduced at 2500 µg/plate with and without S9 mix
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

The test item did not induce gene mutations under the experimental conditions with the tested strains
SAT 990560 is considered to be non-mutagenic in the salmonella typhimurium reverse mutation assay
Executive summary:

This study was performed to investigate the potential of SAT 990560 (N,N-Dimethyldecan-1 -amide) to induce gene muta­tions according to the plate incorporation test (experiment I) and the pre-incubation test (experiment II) using the Salmonella typhimurium strainsTA1535,TA1537,TA98,TA100,and TA102.

The assay was performed with and without liver microsomal activation. Due to technical reasons the results of experiment II had to be dismissed and an additional experiment was performed under identical conditions. The results of this additional experiment are included in this report as experiment II. Each concentration, including the controls, was tested in triplicate. The test item was tested at the following concentrations:

Experiment I(TA98,TA100): 3; 10; 33; 100; 333; and 1000 ug/plate

Experiment I(TA1535,TA1537,TA102): 33; 66; 100; 333; 666; and 1000 ug/plate Experiment II (all strains): 33; 66; 100; 333; 666; and 1000 ug/plate

Toxic effects, evident as a reduction in the number of revertants, occurred at the following concentrations:

Strain

Experiment I(µg/plate)

Experiment II (µg/plate)

 

withoutS9mix

with S9 mix

withoutS9mix

withS9mix

TA1535

333 - 1000

666 - 1000

333 - 1000

666 - 1000

TA1537

333 - 1000

666 - 1000

666 - 1000

666 - 1000

TA98

333 - 1000

/

666- 1000

1000

TA100

333 - 1000

1000

666- 1000

666 - 1000

TA102

666 - 1000

/

666 - 1000

/

/ no relevant toxic effects observed

In experiment I, the background growth was reduced at the higher concentrations with and without S9 mix in all strains.

No substantial increase in revertant colony numbers of any of the five tester strains was observed following treatment with SAT 990560 (N,N-Dimethyldecan-1 -amide) at any dose level, neither in the presence nor absence of metabolic activation (S9 mix). There was also no tendency of higher mutation rates with increasing concentrations in the range below the generally acknowledged border of biological relevance.

Appropriate reference mutagens were used as positive controls and showed a distinct in­crease of induced revertant colonies.

Conclusion

In conclusion, it can be stated that during the described mutagenicity test and under the experimental conditions reported, the test item did not induce gene mutations by base pair changes or frameshifts in the genome of the strains used.

Therefore, SAT 990560 (N,N-Dimethyldecan-1 -amide) is considered to be non-mutagenic in this Salmonella typhimurium reverse mutation assay.