1,3-isobenzofurandione, reaction products with methylquinoline and quinoline

Genetic toxicity: in vitro

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

Test material information

Constituent 1

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:

2-(quinolin-2-yl)-2,3-dihydro-1H-indene-1,3-dione

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.