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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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: According to or similar to study guidelines OECD 471: GLP

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)
Version / remarks:
and Method B14 (92/69/EEC Directive)
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report):MCP992
- Physical state: amber liquid
- Storage condition of test material: room temperature

Method

Target gene:
Not applicable
Species / strain
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Metabolic activation system:
S9 liver microsomal fraction from Arochlor 1254 induced male SD rats
Test concentrations with justification for top dose:
10ul/50ul, 3.1ul/50ul, 0.97/50ul, 0.3ul/50ul, and 0.094ul/50ul
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: acetone
Controls
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
9-aminoacridine
Remarks:
Vehicle is acetone

Migrated to IUCLID6: 2-aminoanthracene, 2-nitrofluorene, N-methyl-N-nitro-N-nitrosoguanidine
Details on test system and experimental conditions:
Serial dilutions were prepared in acetone to deliver 10, 3.1, 0.97, 0.3, and 0.094ul of test material in plates with and without metabolic activation in 50ul aliquots per bacterial plate. Five concentrations of the test material were assayed in triplicate against each tester strain, using the direct plate incorporation method. Measured aliquots of one of the bacterial cultures were dispensed into sets of test tubes followed by 2.0ml of molten, trace histidine supplemented , top agar, 0.1ml of the test material formulation, vehicle or positive control and either 0.5ml S9-mix or phosphate buffer. The contents of each test tube were mixed and equally distributed onto the surface of agar plates. This procedure was repeated, in triplicate, for each bacterial strain and for each concentration of test material both with and without S9-mix.

Results and discussion

Test results
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:
no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
Remarks:
No toxicity at 5000 ug/plate
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
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 bacterial reverse mutation test to assess the genotoxicity of the test material was negative. This finding does not warrant classification of the test material as a mutagen under the new Regulation (EC) 1272/2008 on classification, labeling, and packaging of substances and mixtures (CLP) or under the Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.
Executive summary:

The test material was studied in the Ames assay using Salmonella typhimurium test strains TA98, TA100, TA102, TA1535, and TA1537 in the absence and presence of a liver S9 fraction for metabolic activation. Two tests were performed using five dose levels. The test material did not induce any significant changes in the number of revertant colonies with or without metabolic activation and was not cytotoxic and any dose level. All of the positive control chemicals used in the test induced marked increases in the frequency of revertant colonies. It is concluded that in this study, the test material is not a mutagenic agent. This finding does not warrant classification of the test material as a genotoxin under the new Regulation (EC) 1272/2008 on classification, labeling, and packaging of substances and mixtures (CLP) or under the Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.