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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation
Remarks:
in vivo
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
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:
other: other guideline: OECD Guideline 406 (Skin sensitisation);EU Method B.6 (Skin sensitisation)
Deviations:
no
GLP compliance:
not specified
Type of study:
other: the prediction is based on 11 data points from 5 chemicals

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: 4098-71-9
- Name: 3-isocyanatomethyl-3,5,5-trimethylcyclohexyl isocyanate

- CAS: 5124-30-1
- Name: 1,1'-methylenebis(4-isocyanatocyclohexane)

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

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

- CAS: 822-06-0
- Name: heymethylene diisocyanate

In vivo test system

Test animals

Species:
other: Mouse; guinea pig

Results and discussion

Any other information on results incl. tables






The prediction was based on dataset comprised from the following descriptors: "Skin sensitisation"
Estimation method: Taking highest mode value from the 5 nearest neighbours
Domain logical expression:Result: Out of Domain

("a" and ("b" and "c" and "d" and "e" ) )

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 log Kow which is >= 3.19

Domain logical expression index: "c"

Parametric boundary:The target chemical should have a value of log Kow which is <= 6.12

Domain logical expression index: "d"

Parametric boundary:The target chemical should have a value of Similarity which is >= 0.413

Domain logical expression index: "e"

Parametric boundary:The target chemical should have a value of Similarity which is <= 0.703

Applicant's summary and conclusion

Interpretation of results:
other: Positive
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The substance is predicted to be sensitising.
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 skin sensitisation potential. The prediction was based on the measured values of chemicals assigned into the category.

The target chemical was classified as "Diisocyanates" by "US EPA New Chemical Categories". Therefore primarily analogues chemicals were searched by this profiling method. 21 chemicals were assigned into the category. The target chemical was predicted "positive" based on the experimental data of the nearest neighbours. Thereafter, the chemicals in the category were scanned for the differences relevant for the investigated endpoint. All chemicals in the category exhibited the same mechanism of binding to proteins by "Iso(thyo)cyanateprotein acyltransfer" mechanism, therefore the chemicals were not subcategorized according to this property. The chemicals in the category possess different organic functional groups but this subcategorization method destroys the category. Some of category members showed a quite high level of structural similarity. Taking only maximal values of skin sensitisation potential from available data points the chemical 1,1 methylenebis (4-isocyanatocyclohexane) (CAS 5124-30-1) appeared different by test conditions. This chemical was negative in the Guinea Pig Maximization Test while in the Buehler test it was positive. It was the only difference of this chemical to the others and by the reason that the guinea pig maximization test was the single test among 11 available tests on 5 category members the chemical was removed as an outlier.

The target chemical falls out of applicability domain because of logKow. However, the similarity of category members regarding protein binding mechanism because of the isocyanate functional group is crucial for exerting their sensitization activity and considered to be meaningful to accept prediction.