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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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1980
Report Date:
1980

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Principles of method if other than guideline:
The tests were carried out in accordance with the method described by AMES et al.:
-AMES, B.N., F.D. LEE, and W.E. DURSTON (1973), An Improved Bacterial Test System for the Detection and Classification of Mutagens and Carcinogens. Proc. Natl. Acad. Sci. USA 70, 782-786.
-AMES, B.N., W.E. DURSTON, E. YAMASAKI, and F.D. LEE (1973), Carcinogens are Mutagens: A Simple Test System Combining Liver Homogenates for Activation and Bacteria for Detection. Proc. Natl. Acad. Sci. USA 70, 2281-2285.
-AMES, B.N., J. McCANN, and E. YAMASAKI (1975), Methods for Detecting Carcinogens and Mutagens with the Salmonella/ Mammalian-Microsome Mutagenicity Test. Mutation Res. 31, 347-364.
GLP compliance:
no
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- lot/batch No.of test material: EN 25005

Method

Target gene:
histidine gene
Species / strain
Species / strain / cell type:
S. typhimurium, other: TA 98, TA 100, TA 1535, TA 1537 and TA 1538
Metabolic activation:
with and without
Metabolic activation system:
Aroclor 1254 induced rat liver S9 mix
Test concentrations with justification for top dose:
Experiments were performed on strains TA 98, TA 100, TA 1535, TA 1537 with concentrations of 25, 75, 225, 675 and 2025 µg/0.1 mL
Additional experiments were performed on Strains TA 98 and TA 1538 with concentrations of 1000, 2000, 4000 and 8000 µg/0.1 mL
Vehicle / solvent:
DMSO
Controlsopen allclose all
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
cyclophosphamide
Remarks:
Strain TA 1535 with metabolic activation
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
2-nitrofluorene
Remarks:
Strain TA 1538 without metabolic activation
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 9(5)aminoacridine hydrochloride monohydrate
Remarks:
Strain TA 1537 without metabolic activation
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: N-methyl-N'- nitro-N-nitrosoguanidine
Remarks:
Strain TA 1535 without metabolic activation
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
4-nitroquinoline-N-oxide
Remarks:
Strain TA 100 without metabolic activation
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: daunorubicin- HCl
Remarks:
Strain TA 98 without metabolic activation
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Incubation duration: about 48 hours
- Incubation temperature: 37°C in darkness

1 mL activation mixture contained: 0.3 mL S9 fraction of liver from rats induced with Aroclor 1254 and 0.7 mL of a solution of co-factors.
Evaluation criteria:
A test substance is generally considered to be nonmutagenic if the colony count in relation to the negative control is not doubled at any concentration.

Results and discussion

Test resultsopen allclose all
Key result
Species / strain:
bacteria, other: S. typhimurium TA 98, TA 100, TA 1535, TA 1537, TA 1538
Metabolic activation:
with
Genotoxicity:
positive
Remarks:
Strain TA 98 (2025 µg/0.1 mL) and TA 1538 (8000 µg/0.1 mL)
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Species / strain:
bacteria, other: S. typhimurium TA 98, TA 100, TA 1535, TA 1537, TA 1538
Metabolic activation:
without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid

Applicant's summary and conclusion