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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:
25 March 1987 to 11 April 1987
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1987
Report Date:
1987

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
no strain to detect cross linking included
Principles of method if other than guideline:
Gene mutation toxicity study of the test chemical
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Details on test material:
white powder
stored at ambient temperature

Method

Target gene:
histidine
Species / strainopen allclose all
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Species / strain / cell type:
S. typhimurium TA 1538
Metabolic activation:
with and without
Metabolic activation system:
S-9 from aroclor 1254 induced rat livers
Test concentrations with justification for top dose:
dose range finding: 5, 50, 500 and 5000 ug/plate
main assay (with independent repeat): 15, 50, 150, 500 and 1500 ug/plate
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: no data
Controls
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
Positive controls:
yes
Positive control substance:
9-aminoacridine
2-nitrofluorene
N-ethyl-N-nitro-N-nitrosoguanidine
other: aminoanthrocene
Details on test system and experimental conditions:
METHOD OF APPLICATION: in medium; in agar (plate incorporation)
- Cell density at seeding (if applicable):ca 1E07/mL

DURATION
- Preincubation period: NA
- Exposure duration: 72 hours at 37 °C

NUMBER OF REPLICATIONS: 3/concentration (2 independent assays)

DETERMINATION OF CYTOTOXICITY
- Method:reduced bacterial back ground lawn and precipitate.
Evaluation criteria:
A test item is considered as mutagenic if:
- a significant and dose-related increase in the number of revertants occurs with sufficient reproducibility
- the number of revertant colonies is at least twice as high
Statistics:
NA

Results and discussion

Test resultsopen allclose all
Key result
Species / strain:
S. typhimurium TA 1535
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
at and above 5000 ug/plate
Vehicle controls validity:
valid
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 1537
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
at and above 5000 ug/plate
Vehicle controls validity:
valid
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 98
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
at and above 5000 ug/plate
Vehicle controls validity:
valid
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
at and above 5000 ug/plate
Vehicle controls validity:
valid
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 1538
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
at and above 5000 ug/plate
Vehicle controls validity:
valid
Positive controls validity:
valid

Applicant's summary and conclusion

Conclusions:
Test chemical failed to induce gene mutation in the S. typhimurium TA1535, TA1537, TA98, TA100 and TA1538 and hence is negative for mutation in vitro.
Executive summary:

Gene mutation assay was performed to evaluate the mutagenic nature of the test compound. Plate incorporation assay was performed using S. typhimurium TA1535, TA1537, TA98, TA100 and TA1538 in the presence and absence of S9 metabolic activation system. Positive control mutagens were run concurrently for each strain in each test. When S9 was used, aminoanthrocene was used as a positive control for S9 activity with all strains.In those cases where positive mutagen or S9 controls did not give the expected results, the data from that particular experiment were disregarded. The plates were observed for a dose dependent increase in the number of revertants/plate. Test chemical failed to induce gene mutation in the S. typhimurium TA1535, TA1537, TA98, TA100 and TA1538 and hence is negative for mutation in vitro.