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Toxicological information

Genetic toxicity: in vitro

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Administrative data

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

Data source

Reference
Reference Type:
publication
Title:
Mutagenic Screening of Marker Grenade Dyes by the Salmonella Reversion Assay, L5178Y/TK+/- Mouse Lymphoma Assay, and In Vivo Sister Chromatid Exchange Analysis in Mice
Author:
Martha M. Moore, James W. Allen, Larry Claxton, Carolyn Doerr, Carolyn Gwaltney, John S. Dutcher, Michael Kohan, B. Kay Lawrence, Ruth Templeton, and Barbara Westbrook-Collins
Year:
1988
Bibliographic source:
Environmental and Molecular Mutagenesis 12:219-233 (1988)

Materials and methods

Test guideline
Qualifier:
according to guideline
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

Test material

Constituent 1
Chemical structure
Reference substance name:
1,3-isobenzofurandione, reaction products with methylquinoline and quinoline
EC Number:
232-318-2
EC Name:
1,3-isobenzofurandione, reaction products with methylquinoline and quinoline
Cas Number:
8003-22-3
Molecular formula:
C18H11NO2
IUPAC Name:
1,3-isobenzofurandione, reaction products with methylquinoline and quinoline
Test material form:
other: Solid
Details on test material:
- Name of test material (as cited in study report): Solvent Yellow 33; 2-(2-Quinolyl)-1,3-indandione
- Molecular formula (if other than submission substance): C18H11NO2
- Molecular weight (if other than submission substance): 273.29
- Substance type: Organic
- Physical state: Solid
Purity :99.9% (for the purified dye); Not mentioned (Impure dye)
- Impurities (identity and concentrations): No data available

Method

Target gene:
TK+/- locus
Species / strain
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
Controls
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

Results and discussion

Test results
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

Applicant's summary and conclusion

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.