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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
significant methodological deficiencies
Remarks:
Comutagenic effect with norharman studied, only 2 strains tested.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1982
Report date:
1982

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
Comutagenic effect with norharman tested; only 2 strains.
Principles of method if other than guideline:
Comutagenic effect of the test item with norharman (9H-pyrido[3,4-b]indole).
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay

Test material

Constituent 1
Chemical structure
Reference substance name:
2-pyridylamine
EC Number:
207-988-4
EC Name:
2-pyridylamine
Cas Number:
504-29-0
Molecular formula:
C5H6N2
IUPAC Name:
pyridin-2-amine
Specific details on test material used for the study:
- Source: purchased from Tokyo Kasei Kogyo Co., Ltd., Tokyo.

Method

Species / strainopen allclose all
Species / strain / cell type:
S. typhimurium TA 98
Additional strain / cell type characteristics:
not specified
Species / strain / cell type:
S. typhimurium TA 100
Additional strain / cell type characteristics:
not specified
Metabolic activation:
with and without
Metabolic activation system:
S9-mix.
Test concentrations with justification for top dose:
200 µg per plate, 2 mg per plate.
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle:
Details on test system and experimental conditions:
METHOD OF APPLICATION: preincubation method.
- Aminopyridine derivatives and norharman were dissolved together in 0.1 ml DMSO and mixed with 0.5 ml of S9 mix or 0.5ml of 100 mM sodium phosphate buffer (pH 7.4) and 0.1 ml of bacterial culture. The mixture was preincubated at 37°C for 20 min, and revertants were counted after incubation for 2 days. Aminopyridine derivatives were tested at amounts up to 2 mg per plate and norharman was added at 200 µg per plate.

DURATION
- Preincubation period: 20 min
- Exposure duration: 2 days
- Expression time (cells in growth medium): 2 days

SELECTION AGENT (mutation assays):

NUMBER OF REPLICATIONS:

METHODS OF SLIDE PREPARATION AND STAINING TECHNIQUE USED:

NUMBER OF CELLS EVALUATED:

NUMBER OF METAPHASE SPREADS ANALYSED PER DOSE (if in vitro cytogenicity study in mammalian cells):

CRITERIA FOR MICRONUCLEUS IDENTIFICATION:

DETERMINATION OF CYTOTOXICITY
- Method: mitotic index; cloning efficiency; relative total growth; other:
- Any supplementary information relevant to cytotoxicity:

OTHER EXAMINATIONS:
- Determination of polyploidy:
- Determination of endoreplication:
- Methods, such as kinetochore antibody binding, to characterize whether micronuclei contain whole or fragmented chromosomes (if applicable):

- OTHER:

Results and discussion

Test resultsopen allclose all
Key result
Species / strain:
S. typhimurium TA 98
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Remarks on result:
other: Combined with norharman.

Applicant's summary and conclusion

Conclusions:
The test item combined with norharman (9H-pyrido[3,4-b]indole) was non-mutagenic. This can be regarded as indication of the non-mutagenicity of the test item.
Executive summary:

The mutagenicity of the test item was studied with norharman (9H-pyrido[3,4-b]indole) in the bacterial reverse mutation assay, with and without metabolic activation by S9 mix. The strains tested were Salmonella typhimurium TA 98 and TA 100. The test item combined with norharman (9H-pyrido[3,4-b]indole) was non-mutagenic. This can be regarded as indication of the non-mutagenicity of the test item.

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