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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:
key study
Study period:
2003-07-23 to 2003-07-26
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Only three strains are tested. However, an expert statement is added in the field "any other remarks" to justify the fact that no further testing is necessary.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2004
Report Date:
2004

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
: Only three strains of bacteria were tested.
GLP compliance:
no
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): T002325
Specific details on test material used for the study:
Description: Pale yellow powder
Date received: 2003-04-24
Storage conditions : Room temperature in the dark

Method

Target gene:
Histidine locus
Species / strain
Species / strain:
other: TA98, TA100 and TA102
Additional strain characteristics:
not specified
Metabolic activation:
with and without
Metabolic activation system:
S9 rat liver homogenate (10% liver S9 in standard co-factors)
Test concentrations with justification for top dose:
0, 0.5, 1.5, 5, 15, 50, 150, 500, 1500 and 5000 µg/plate
Vehicle:
- Vehicle(s)/solvent(s) used: sterile distilled water
- Justification for choice of solvent/vehicle: no data
Controlsopen allclose all
Negative controls:
yes
Solvent controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
N-ethyl-N-nitro-N-nitrosoguanidine
Remarks:
without metabolic activation; for TA100 at 3 µg/plate
Negative controls:
yes
Solvent controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
mitomycin C
Remarks:
without metabolic activation; TA102 at 0.5 µg/plate
Negative controls:
yes
Solvent controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 4-nitroquinoline-N-oxide
Remarks:
with metabolic activation; TA98 at 0.2 µg/plate
Details on test system and conditions:
METHOD OF APPLICATION: In agar (plate incorporation)

DURATION:
Exposure duration: 3 days

SELECTION AGENT (mutation assays): histidine

NUMBER OF REPLICATIONS: 3

DETERMINATION OF CYTOTOXICITY
- Method: reduction in the growth of the bacterial background lawn
Rationale for test conditions:
no data
Evaluation criteria:
no data
Statistics:
no data

Results and discussion

Test results
Species / strain:
other: TA98, TA100 and TA102
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity:
no
Vehicle controls valid:
yes
Negative controls valid:
yes
Positive controls valid:
yes
Remarks on result:
other: all strains/cell types tested
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS
- Water solubility: no data
- Precipitation: no test substance precipitate was observed on the plates at any of the doses tested in either the presence or absence of S9-mix

RANGE-FINDING/SCREENING STUDIES: no data

COMPARISON WITH HISTORICAL CONTROL DATA:
The vehicle (sterile distilled water) control plates gave counts of revertant colonies within the normal range. All of the positive control chemicals used in the test induced marked increases in the frequency of revertant colonies, both with and without metabolic activation. Thus, the sensitivity of the assay and the efficacy of the S9-mix were validated.

ADDITIONAL INFORMATION ON CYTOTOXICITY: The test substance caused no visible reduction in the growth of the bacterial background lawn at any dose level. The test substance was, therefore, tested up to the maximum recommended dose level of 5000 μg/plate.

Applicant's summary and conclusion

Conclusions:
Intepretation of results:
negative with and without metabolic activation

The test substance was evaluated for mutagenic potential in the Ames assay using S. typhimurium strains TA98, TA100 and TA102 in the absence and presence of metabolic activation. T002325 was considered to be non-mutagenic under the conditions of this test in all strains.