[No public or meaningful name is available]

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation, other

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Study period:

2021

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model, but not (completely) falling into its applicability domain, with adequate and reliable documentation / justification

Justification for type of information:

1. SOFTWARE
OECD QSAR Toolbox Version 4.5

2. MODEL
Automated Workflow for Skin Sensitization Defined Approached (DASS)

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
4 main components of the UVCB:

CC(=C)C(=O)OCCNC(=O)OCCOc1cccc(OCCOCC(COc2ccccc2)OC(=O)NCCOC(=O)C(=C)C)c1
CC(=C)C(=O)OCCNC(=O)OC(COCCOc1cccc(OCCOCC(COc2ccccc2)OC(=O)NCCOC(=O)C(=C)C)c1)COc3ccccc3
CC(=C)C(=O)OCCNC(=O)OC(COCCOc1cccc(OCCOCC(COc2ccccc2)OCC(COc3ccccc3)OC(=O)NCCOC(=O)C(=C)C)c1)COc4ccccc4
CC(=C)C(=O)OCCNC(=O)OC(COC(COCCOc1cccc(OCCOCC(COc2ccccc2)OCC(COc3ccccc3)OC(=O)NCCOC(=O)C(=C)C)c1)COc4ccccc4)COc5ccccc5

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
[[Explain how the model fulfils the OECD principles for (Q)SAR model validation. Consider attaching the QMRF and/or QPRF or providing a link]
- Defined endpoint: Human Health Hazards -> Sensitisation -> Skin -> in Vivo -> GPMT LLNA -> EC3 Skin sensitisation
- Unambiguous algorithm: takes the highest mode value from the 5 nearest neighbours
- Defined domain of applicability: 2/4 of the main components of the UVCB substance have log Kow values that fall within the applicability domain of all profiles of the skin sensitization category profiler. The log Kow values of the four main isomeric mixtures of ERGP-IEM were 2.9 for ER1GP-IEM, 4.3 for ER2GP-IEM, 5.6 for ER3GP-IEM and 6.9 for ER4GP-IEM. The active descriptor range of the category is 3.09-4.94. The automated workflow determined that all 4 of the main components of the UVCB were "in domain" of the overall workflow despite two components having log Kow values that were outside the category bound.
- Appropriate measures of goodness-of-fit and robustness and predictivity: Substances with structural alerts for protein binding have been shown to have skin sensitization potential. The components of the uvcb substance each have structural alerts for protein binding
- Mechanistic interpretation: The components of the UVCB substance each have structural alerts for protein binding. Structures containing methacrylate functional groups are well-documented skin sens itizers.
See attached documentation .pdf providing more detail around the automated workflow within OECD QSAR Toolbox version 4.5.

5. APPLICABILITY DOMAIN
- Descriptor domain: - Active descriptor(s) range:- log Kow: from 3.09 to 4.94
- Mechanistic domain: Methacrylate functional groups are identified as potential protein binders within the mechanistic framework of the automated workflow.
- Similarity with analogues in the training set: Other structures containing acrylate and methacrylate functional groups were present in the category assembles by the AW to determine the final prediction. Analogs had lower MWs and similar log Kow values indicating that the prediction is likely conservative as high molecular weight substances like the ERGP-IEM components generally have lower protein binding and skin sensitization potential when compared to lower molecular weight analogs.

6. ADEQUACY OF THE RESULT
The skin sensitization potential of this UVCB substance was evaluated with skin sensitization and protein binding structural alert profilers using OECD QSAR Toolbox version 4.5. Based on the structural alerts returned for this component of the UVCB and structural analogs with positive sensitization data, this component of the UVCB is predicted to be a GHS Category 1 skin sensitizer.

Data source

Reference

Reference Type:

other company data

Title:

Unnamed

Year:

2021

Report date:

2021

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

- Software tool(s) used including version: see field 'Justification for non-standard information'
- Model(s) used: see field 'Justification for non-standard information'
- Model description: see field 'Justification for non-standard information'
- Justification of QSAR prediction: see field 'Justification for type of information'

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Reaction products of 2,2'-(1,3-phenylenebis(oxy))diethanol with 2-(phenoxymethyl)oxirane and 2-isocyanatoethyl methacrylate

Cas Number:

1431303-59-1

Molecular formula:

Not assigned for UVCB substance.

IUPAC Name:

Reaction products of 2,2'-(1,3-phenylenebis(oxy))diethanol with 2-(phenoxymethyl)oxirane and 2-isocyanatoethyl methacrylate

Specific details on test material used for the study:

NA: Calculation method.

Results and discussion

In vivo (LLNA)

Results

Key result

Parameter:

other: See 'Remarks'

Remarks:

Computational Profiling

Remarks on result:

positive indication of skin sensitisation based on QSAR/QSPR prediction

Applicant's summary and conclusion

Interpretation of results:

Category 1 (skin sensitising) based on GHS criteria

Conclusions:

Based on the computational profiling conducted with the main components of the UVCB substance, ERGP-IEM is expected to be a GHS Category 1 sensitizer.

Executive summary:

The skin sensitization potential of this UVCB substance was evaluated with skin sensitization and protein binding structural alert profilers using OECD QSAR Toolbox version 4.5.  Based on the structural alerts returned for this component of the UVCB and structural analogs with positive sensitization data, this component of the UVCB is predicted to be a GHS Category 1 skin sensitizer.