Registration Dossier

Toxicological information

Genetic toxicity: in vitro

Currently viewing:

Administrative data

Endpoint:
in vitro cytogenicity / chromosome aberration study in mammalian cells
Remarks:
Type of genotoxicity: other: "Chromosome Aberration"
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: OECD Toolbox 2.2, is a harmonized system for OSAR application, where the OECD principles are met.

Data source

Reference
Reference Type:
other: prediction by the QSAR OECD Toolbox
Title:
Unnamed
Year:
2011
Report Date:
2011

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
Principles of method if other than guideline:
No data
GLP compliance:
not specified
Type of assay:
in vitro mammalian chromosome aberration test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Type:
Constituent
Details on test material:
Target chemical:
- Name of test material (as cited in study report): 2,4-diisocyanato-1,3,5-tri(propan-2-yl)benzene;
- SMILES:c1(C(C)C)c(N=C=O)c(C(C)C)c(N=C=O)c(C(C)C)c1

Analogues:

- CAS: 91-93-0
- Name: 3,3'-dimethoxybenzidine-4,4'-diisocyanate

- CAS: 101-68-8
- Name: 1,1'-methylenebis[4-isocyanato]benzene

- CAS: 26471-62-5
- Name: tolylene diisocyanate

- CAS: 584-84-9
- Name: 2,4-diisocyanate-1-methylbenzene

Results and discussion

Test results
Genotoxicity:
negative
Remarks:
Read across prediction of "Chromosome Aberration", taking the highest mode from the nearest 5 neighbours, based on 7 data points from 4 neighbour chemicals

Any other information on results incl. tables






The prediction was based on dataset comprised from the following descriptors: "Chromosome aberration"
Estimation method: Taking highest mode value from the 5 nearest neighbours
Domain logical expression:Result: In Domain

("a" and ("b" and "c" ) )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Diisocyanates by US-EPA New Chemical Categories

Domain logical expression index: "b"

Parametric boundary:The target chemical should have a value of Molecular weight which is >= 174 Da

Domain logical expression index: "c"

Parametric boundary:The target chemical should have a value of Molecular weight which is <= 296 Da

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative

The target substance is predicted to be negative in in vitro Mammalian Chromosome Aberration Test.
Executive summary:

The chemical 2,4,6-triisopropyl-m-phenylene diisocyanate (CAS 2162 -73 -4) was evaluated by the QSAR OECD Toolbox software for its potential to induce chromosome aberrations in mammalian cells. The prediction was based on the measured values of chemicals assigned into the category.

The target chemical was classified as "Diisothiocyanates" by US EPA New Chemical Categories. Therefore, at first chemicals with the same classification were searched. 21 chemicals were assigned into the category. The prediction was performed based on the experimental data for in vitro Chromosome Aberration for 4 chemicals. Thereafter, the chemicals in the category were scanned for the differences to the target relevant for the genotoxicity endpoint. No further subcategorization was performed. All chemicals in the category possessed the same DNA binding mechanism and the same organic functional group (isocyanate) which can trigger genotoxicity events.