3,3'-dimethylbiphenyl-4,4'-diyl diisocyanate

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro cytogenicity / chromosome aberration study in mammalian cells

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1996

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:

publication

Title:

Mutagenicity Test Data of Existing Chemical Substances

Author:

anonymous

Year:

1996

Bibliographic source:

Japan Chemical Industry Ecology Toxicology & Information Center, Japan (JETOC)

Report date:

1996

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method B.10 (Mutagenicity - In Vitro Mammalian Chromosome Aberration Test)

GLP compliance:

not specified

Type of assay:

in vitro mammalian chromosome aberration test

Test material

Test material information

Constituent 1

Reference substance name:

3,3'-dimethylbiphenyl-4,4'-diyl diisocyanate

EC Number:

202-112-7

EC Name:

3,3'-dimethylbiphenyl-4,4'-diyl diisocyanate

Cas Number:

91-97-4

Molecular formula:

C16H12N2O2

IUPAC Name:

3,3'-dimethylbiphenyl-4,4'-diyl diisocyanate

Test material form:

solid

Method

Target gene:

Chromosome of CHL cells.

Species / strain

Species / strain / cell type:

other: CHL cell

Details on mammalian cell type (if applicable):

CHL cells were received from the lung of a newborn Chinese hamster.

Additional strain / cell type characteristics:

not specified

Metabolic activation:

with and without

Metabolic activation system:

S9 Mix

Test concentrations with justification for top dose:

Without activation (24h, 48h): 0.1, 0.2, 0.3, 0.4, 0.5 mg/mL
With and without activation (6h): 0.2, 0.3, 0.4, 0.5, 0.6 mg/mL

Controls

Controls 1

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

yes

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

mitomycin C

Remarks:

without metabolic activation

Controls 2

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

yes

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

other: methyl chloride

Remarks:

without metabolic activation

Controls 3

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

yes

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

benzo(a)pyrene

Remarks:

with metabolic activation

Controls 4

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

yes

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

cyclophosphamide

Remarks:

with metabolic activation

Controls 5

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

yes

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

other: vinyl chloride

Remarks:

with metabolic activation

Details on test system and experimental conditions:

METHOD OF APPLICATION: in medium
- Cell density at seeding: 2*10E4 cells

DURATION
- Exposure duration: 24 and 48 hours (- S9 mix); 6 hours (+/- S9 mix)

Evaluation criteria:

The number of cells with chromosomal aberrations from and the incidence of polyploid of 100 metaphases were counted per each culture bottle.
For the evaluation of the frequency of structural aberrations and polyploidy, the following criteria were used:
negative: less than 5%
equivocal: from 5% to less than 10%
positive: 10% or more
The total frequencies of structural aberrations include the frequencies of aberrant cells which have only gaps.

Quantitative evaluation:
When the test was positive, the D20 value was calculated from the result. The D20 value is the concentration (mg/mL) required to induce any aberration in 20% of metaphases. Thus, a low D20 value indicates that the agent induces chromosomal aberrations at relatively low dose levels.

Results and discussion

Test results

Key result

Species / strain:

other: CHL cell

Metabolic activation:

with and without

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Applicant's summary and conclusion

Conclusions:

The Chromosome Abberation Test in CHL cells shows, that after metabolic activation, the test item induced chromosomal aberrations at 0.6 mg TODI/mL. The D20 value was calculated to be 0.79 (structural chromosomal aberrations). Therefore, TODI is considered mutagenic in this Chromosome Abberation Test.

Executive summary:

A Chromosome Aberration Test in CHL cells was performed to assess the mutagenicity potency of TODI. The method followed OECD Guideline 473 (In vitro Mammalian Chromosome Aberration Test) and EU Method B.10 (Mutagenicity - In Vitro Mammalian Chromosome Aberration Test) of Commission Directive 92/69/EEC (which constitues Annex V of Council Directive 67/548/EEC). The test substance was examined with and without metabolic activation up to 0.6 mg/mL. The reported data of this Chromosome Aberration Test shows, that under the experimental conditions described, the test item induced chromosome aberration after metabolic activation at 0.6 mg/mL. The D20 value was calculated to be 0.79 (structural chromosomal aberrations).Therefore, TODI was considered mutagenic in this Chromosome Aberration Test in the presence of S9 mix.