2,4,6-triisopropyl-m-phenylene diisocyanate

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Remarks:

Allergic Contact Dermatitis Guinea pig and human

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Study period:

22 June 2020

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification

Justification for type of information:

1. SOFTWARE
Danish QSAR database, OECD QSAR Toolbox v4.4

2. MODEL (incl. version number)
SciQSAR v3.1.00
CASEUltra v1.4.6.6
Leadscope v3.1.1‐10

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
CC(C)c1cc(C(C)C)c(N=C=O)c(C(C)C)c1N=C=O

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
please refer to attached QMRFs

5. APPLICABILITY DOMAIN
Please refer to attached QPRF

Data source

Reference

Reference 1

Reference Type:

other: QSAR

Title:

MultiCASE CASE Ultra commercial model A33 for allergic contact dermatitis (ACD) in guinea pig and human, Danish QSAR Group at DTU Food.

Author:

MultiCASE Inc.; 23811 Chagrin Blvd Ste 305, Beachwood, OH, 44122, USA;

Year:

2014

Bibliographic source:

A categorical (Q)SAR model based on structural fragments and calculated molecular descriptors

Reference 2

Reference Type:

other: QSAR

Title:

Leadscope Enterprise version of commercial CASE Ultra model A33 for allergic contact dermatitis (ACD) in guinea pig and human, Danish QSAR Group at DTU Food.

Author:

MultiCASE Inc.; 23811 Chagrin Blvd Ste 305, Beachwood, OH, 44122, USA;

Year:

2014

Bibliographic source:

A categorical (Q)SAR model based on structural features and numeric molecular descriptors.

Reference 3

Reference Type:

other: QSAR tool

Title:

SciMatics SciQSAR version of commercial CASE Ultra model A33 for allergic contact dermatitis (ACD) in guinea pig and human, Danish QSAR Group at DTU Food.

Author:

MultiCASE Inc.23811 Chagrin Blvd Ste 305, Beachwood, OH, 44122, USA

Year:

2014

Bibliographic source:

This is a categorical (Q)SAR model based on calculated molecular descriptors, and if available the modeller’s own or third party descriptors or measured endpoints can be imported and used as descriptors.

Reference 4

Reference Type:

other: QSAR software

Title:

Unnamed

Year:

2020

Materials and methods

Test guideline

Guideline:

other: REACH Guidance on QSARs R.6

Principles of method if other than guideline:

- Software tool(s) used including version: Danish QSAR database, OECD QSAR Toolbox v4.4
- Model(s) used: SciQSAR, Leadscope, CaseUltra
- Model description: see field 'Justification for non-standard information', 'Attached justification'
- Justification of QSAR prediction: see field 'Justification for type of information', 'Attached justification'

Justification for non-LLNA method:

Data for these models include results from human epidemiological studies on ACD and results from the Guinea Pig Maximization Test (GPMT). The experimental protocol for GPMT is described in OECD guideline 406.

Test material

Test material information

Constituent 1

Reference substance name:

2,4,6-triisopropyl-m-phenylene diisocyanate

EC Number:

218-485-4

EC Name:

2,4,6-triisopropyl-m-phenylene diisocyanate

Cas Number:

2162-73-4

Molecular formula:

C17H22N2O2

IUPAC Name:

2,4-diisocyanato-1,3,5-tris(propan-2-yl)benzene

Test material form:

liquid

Specific details on test material used for the study:

CC(C)c1cc(C(C)C)c(N=C=O)c(C(C)C)c1N=C=O

Results and discussion

In vivo (non-LLNA)

Results

Results 1

Remarks on result:

positive indication of skin sensitisation

Remarks:

Leadscope model (in applicability domain)

Results 2

Remarks on result:

positive indication of skin sensitisation

Remarks:

SciQSAR model (in applicability domain)

Results 3

Remarks on result:

not determinable

Remarks:

CASEUltra model

Results 4

Key result

Remarks on result:

positive indication of skin sensitisation

Remarks:

battery approach (2 out of three models give positive prediction in applicability domain)

Any other information on results incl. tables

The substance was predicted positive by the models SciQSAR and Leadscope. These predictions were in the applicability domain of these models. The model CaseUltra could not make a prediction. Overall, applying the battery approach, the substance is predicted to be a skin sensitiser (2 out of 3 models make positive predictions within the applicability domain).

Applicant's summary and conclusion

Interpretation of results:

Category 1 (skin sensitising) based on GHS criteria

Conclusions:

The substance was predicted positive by the models SciQSAR and Leadscope. These predictions were in the applicability domain of these models. The model CaseUltra could not make a prediction. Overall, applying the battery approach, the substance is predicted to be a skin sensitiser (2 out of 3 models make positive predictions within the applicability domain).

Executive summary:

Skin sensitisation was predicted by the statistical QSAR models SciQSAR, Leadscope and CaseUltra implemented in the Danish QSAR database. The substance was predicted positive by the models SciQSAR and Leadscope. These predictions were in the applicability domain of these models. The model CaseUltra could not make a prediction. Overall, applying the battery approach, the substance is predicted to be a skin sensitiser (2 out of 3 models make positive predictions within the applicability domain). Thus, the prediction is considered to be reliable.