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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:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study (OECD 471 and 472), GLP compliant.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995
Report date:
1996

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Qualifier:
according to guideline
Guideline:
OECD Guideline 472 (Genetic Toxicology: Escherichia coli, Reverse Mutation Assay)
Qualifier:
according to guideline
Guideline:
EPA OPP 84-2
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay

Test material

Constituent 1
Chemical structure
Reference substance name:
4,4'-dithiobis(5-amino-1-(2,6-dichloro-4-(trifluoromethyl)phenyl)-1H-pyrazole-3-carbonitrile)
EC Number:
603-434-4
Cas Number:
130755-46-3
Molecular formula:
C22 H8 Cl4 F6 N8 S2
IUPAC Name:
4,4'-dithiobis(5-amino-1-(2,6-dichloro-4-(trifluoromethyl)phenyl)-1H-pyrazole-3-carbonitrile)
Details on test material:
- Name of test material (as cited in study report): Disulfide / MB 46307 / RPA 098028.
- Physical state: yellow powder.
- Analytical purity: 97.2%.
- Lot/batch No.: 95-4023.
- Storage condition of test material: in an air-tight, light resistant container at room temperature.

Method

Target gene:
his
Species / strain
Species / strain / cell type:
S. typhimurium, other: TA100, TA1535, TA102, TA98 and TA1537
Metabolic activation:
with and without
Metabolic activation system:
S-9 mix from Aroclor 1254 induced rat liver homogenate
Test concentrations with justification for top dose:
1) SPT: 10, 25, 50, 100, 250 and 500 µg/plate
2) PIT: in the absence of S9 mix: 5, 10, 25, 50, 100, 250 and 500 µg/plate.
Retry with TA100 and TA1535 in the absence of S9 mix: 1, 2.5, 5, 10, 25, 50, 100, 250 and 500 µg/plate. In the presence of S9 mix: 10, 25, 50, 100, 250, 500 and 1000 µg/plate.
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: DMSO
Controls
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
yes
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
other: In the absence of S9 mix: Sodium azide for TA100 and TA1535, 2-nitrofluorene for TA98, Cumene hydroperoxyde for TA102, 9-aminoacridine for TA1537. In the presence of S9 mix for all strains: 2-aminoanthracene.
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Exposure duration: 72 h

NUMBER OF REPLICATIONS:3



METHOD OF APPLICATION: preincubation

DURATION
- Preincubation period: 60 min
- Exposure duration: 72 h

NUMBER OF REPLICATIONS: 3

Results and discussion

Test results
Species / strain:
S. typhimurium, other: TA100, TA1535, TA102, TA98 and TA1537
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
other: In the absence of S9 mix, cytotoxic effects were observed in strain TA1537 at test substance concentrations from 100 µg/plate on and in strains TA100 and TA1535 at test substance concentrations of 250 µg/plate and above.
Vehicle controls validity:
valid
Untreated negative controls validity:
not specified
Positive controls validity:
valid
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: dependend on strain and test condition from 250 µg/plate onwards
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

In the mutagenicity tests, MB 46307 did not induce any concentration-dependent significant increase in the numbers of revertants of any strain at any of the test substance concentrations studied. The numbers of revertant colonies observed on solvent (dimethylsulfoxide) and standard positive control plates were considered to be acceptable and in concordance with values previously observed in this laboratory.

MB 46307 was considered to be non-mutagenic under the conditions of this assay.

Applicant's summary and conclusion