MMCT

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Study period:

28 Apr - 02 Jun 2006

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Version / remarks:

adopted in 1997

Deviations:

yes

Remarks:

2-Aminoanthracene was used as sole positive control with S9 mix.

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)

Version / remarks:

adopted in 2000

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.5100 - Bacterial Reverse Mutation Test (August 1998)

Version / remarks:

adopted in 1998

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Reference

Name:

Unnamed

Type:

Constituent

Test material form:

liquid

Method

Target gene:

His operon

Species / strain

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102

Metabolic activation:

with and without

Metabolic activation system:

Cofactor supplemented post-mitochondrial fraction (S9 mix), prepared from the livers of rats treated with Aroclor 1254.

Test concentrations with justification for top dose:

First experiment: 16, 50, 158, 500, 1581 and 5000 µg/plate ± S9
Second experiment: 0.16, 0.5, 1.6, 5, 16, 50 and 158 µg/plate ± S9

Vehicle / solvent:

- Vehicle/solvent used: DMSO

Controls

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

no

Positive controls:

yes

Positive control substance:

sodium azide

cumene hydroperoxide

mitomycin C

other: 2-aminoanthracene (2-AA), 3 µg/plate in DMSO (+S9) for all strains; nitrofurantoin (NF), 0.2 µg/plate in DMSO (-S9) for TA 100; 4-nitro-1,2-phenylene diamine (4-NPDA), 10 µg/plate in DMSO (-S9) for TA 1537 and 0.5 µg/plate in DMSO for TA98

Results and discussion

Test results

Key result

Species / strain:

S. typhimurium, other: TA 98, TA 100, TA 102, TA 1535 and TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

at 158 µg/plate ±S9 mix for all strains

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

True negative controls validity:

not applicable

Positive controls validity:

valid

Applicant's summary and conclusion

Conclusions:

Under the conditions of the test, the test compound was not mutagenic in any of the five tested S. typhimurium strains (TA 98, TA 100, TA 102, TA 1535 and TA1537) with and without metabolic activation.
Interpretation of results: negative