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Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

L5178Y TK+/- mouse lymphoma assay was performed to evaluate the mutagenic potential of the test compound C.I. Solvent Yellow No. 33. In addition, a > 99.9% pure sample of the yellow dye [2-(2‘-quinolyl)-l,3-indandione] with and without exogenous activation was also tested.

The impure dye was tested at concentrations of 0.0 (100µL DMSO), 0.0 (200µL DMSO), 2.0, 6.0, 12.0, 16.0, 20.0, 40 µg/ml and the purified dye at concentrations of 0.0, 0.1, 0.5, 1.0, 2.5, 5.0, 10.0, 20.0, 30.0, 40.0, 50.0 µg/ml

C.I. Solvent Yellow No. 33 induced mutation at the thymidine kinase locus in mouse lymphoma cells, produced both large- and small-colony trifluorothymidine-resistant mutants, and was clastogenic.

According to the publication, the test material is positive for mutation.

Link to relevant study records
Reference
Endpoint:
in vitro cytogenicity / chromosome aberration study in mammalian cells
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Data is from peer reviewed journal
Qualifier:
according to
Guideline:
other: Data is from Journal with permission
Principles of method if other than guideline:
Mouse lymphoma assay was performed to evaluate the mutagenic potential for the test compound C.I. Solvent Yellow No. 33
GLP compliance:
not specified
Type of assay:
mammalian cell gene mutation assay
Target gene:
TK+/- locus
Species / strain / cell type:
mouse lymphoma L5178Y cells
Details on mammalian cell type (if applicable):
- Type and identity of media: Fischer’s Medium for Leukemic Cells of Mice supplemented with sodium pyruvate, pluronic, penicillin, streptomycin, and horse serum was used.
- Properly maintained: yes
Additional strain / cell type characteristics:
not specified
Metabolic activation:
not specified
Test concentrations with justification for top dose:
Impure dye: 0.0 (100µL DMSO), 0.0 (200µL DMSO), 2.0, 6.0, 12.0, 16.0, 20.0, 40 µg/ml

Purified dye: 0.0, 0.1, 0.5, 1.0, 2.5, 5.0, 10.0, 20.0, 30.0, 40.0, 50.0 µg/ml
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: No data available
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
yes
True negative controls:
not specified
Positive controls:
not specified
Positive control substance:
not specified
Details on test system and experimental conditions:
METHOD OF APPLICATION: in medium
DURATION
- Preincubation period:
- Exposure duration: 4 hrs
- Expression time (cells in growth medium): 2 days
- Selection time (if incubation with a selection agent): after 2 days
- Fixation time (start of exposure up to fixation or harvest of cells):

SELECTION AGENT (mutation assays): TFT (1 µg/mL)
SPINDLE INHIBITOR (cytogenetic assays):
STAIN (for cytogenetic assays): Giemsa stain

NUMBER OF REPLICATIONS: Twice

NUMBER OF CELLS EVALUATED: 100 metaphase spreads

DETERMINATION OF CYTOTOXICITY
- Method: mitotic index; cloning efficiency; relative total growth; other: No data available

OTHER EXAMINATIONS:
- Determination of polyploidy:
- Determination of endoreplication:
OTHER: chromatid breakage and rearrangement; After 9-11 days of incubation at 37"C, colonies were counted on an Artek model 880 automatic colony counter with settings that optimize colony counts, compared with hand counts, without producing a spurious background
Statistics:
Survival was calculated according to the method of Clive and Spector
Species / strain:
mouse lymphoma L5178Y cells
Metabolic activation:
with and without
Genotoxicity:
positive
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not specified
Positive controls validity:
not specified
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'. Remarks: Cell line used
Conclusions:
Interpretation of results (migrated information):
other: Positive (With and without metabolic activation system)

The test material C.I. Solvent Yellow No. 33 is positive to induce mutations in the L5178Y TK+/- mouse lymphoma assay.
Executive summary:

L5178Y TK+/- mouse lymphoma assay was performed to evaluate the mutagenic potential of the test compound C.I. Solvent Yellow No. 33. In addition, a > 99.9% pure sample of the yellow dye [2-(2‘-quinolyl)-l,3-indandione] with and without exogenous activation was also tested.

The impure dye was tested at concentrations of 0.0 (100µL DMSO), 0.0 (200µL DMSO), 2.0, 6.0, 12.0, 16.0, 20.0, 40 µg/ml and the purified dye at concentrations of 0.0, 0.1, 0.5, 1.0, 2.5, 5.0, 10.0, 20.0, 30.0, 40.0, 50.0 µg/ml

C.I. Solvent Yellow No. 33 induced mutation at the thymidine kinase locus in mouse lymphoma cells, produced both large- and small-colony trifluorothymidine-resistant mutants, and was clastogenic.

According to the publication, the test material is positive for mutation.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (positive)

Additional information

Additional information from genetic toxicity in vitro:

Weight of evidence studies reviewed for Genetic toxicity from reliable sources having Klimish rating 2 

 

The summary of the results are presented below

 

Sr. No

Endpoint

Interpretation of results

Strain/Species

Sources

1

Gene mutation

positive without metabolic activation

mouse lymphoma L5178Y cells

Data from Publication

2

Gene mutation

Positive with and without activation

Salmonella typhimuriumTA98, TA100, TA102, TA104, TA1535, TA1537, and TA1538-For plate incorporation assays. TAl00 for preincubation assay

Data from Publication

3

Gene mutation

(In Vivo)

positive

Marrow cells, second division metaphase cells

Data from Publication

4

Gene mutation

(In Vivo)

Negative

Salmonella-microsome mutagenicity test

Data from study report

 

By applying weight of evidence approach, it was concluded that the test substance 1,3-isobenzofurandione, reaction products with methylquinoline and quinoline exhibit positive gene mutation effect.

 

Justification for selection of genetic toxicity endpoint

data from K2 publication.

Justification for classification or non-classification

The studies available for genetic toxicity potential of C.I. Solvent Yellow No. 33 indicate genetically toxic. Thus it was concluded that the test substance C.I. Solvent Yellow No. 33 exhibit positive gene mutation.