[No public or meaningful name is available]

Endpoint summary

Description of key information

Computational profiling was conducted on a representative structure of each of the four main isomeric mixture costituents of ERGP-IEM. All components were expected to have dermal sensitization potential based on the results of the profiling workflow.

Additionally, literature sources indicate that high molecular weight methacrylates are most often weak dermal sensitizers (Kimber et al., 2019).

Against this background and in conformity with ECHA's principle of avoiding unnecessary animal testing, it is considered unnecessary to perform an in vivo skin sensitization study and it is appropriate to conservatively classify ERGP-IEM as a GHS Category 1B skin sensitizer.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Reference 1

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.

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

Specific details on test material used for the study:

NA: Calculation method.

Key result

Parameter:

other: See 'Remarks'

Remarks:

Computational Profiling

Remarks on result:

positive indication of skin sensitisation based on QSAR/QSPR prediction

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.

Reference 2

Endpoint:

skin sensitisation, other

Type of information:

other: See 'Remarks'

Remarks:

Review article from a literature source.

Adequacy of study:

weight of evidence

Study period:

2019

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

ERGP-IEM is a UVCB substance that contains four main components with methacrylate functional groups.  Since the DPRA, h-CLAT and Keratinosens assays have not been validated for use with UVCB substances, alternative data sources were compiled to determine the skin sensitization potential of UVCB while avoiding unnecessary animal testing.  Methacrylates are generally well-documented to have skin sensitization potential.

ERGP-IEM is UVCB substance with four main isomeric mixtures of the same molecular mass (ER1GP-IEM, ER2GP-IEM, ER3GP-IEM, ER4GP-IEM).  Each of the isomers contains two terminal methacrylate functional groups.  While methacrylates are sensitizers, they are not usually considered potent skin sensitizers (Kimber et al., 2019).  In addition, some high molecular weight methacrylates (i.e., isodecyl methacrylate and dodecyl methacrylate) are not skin sensitizers in the local lymph node assay.  The molecular weight  of ERGP-IEM ranges from 658 to 1108 g/mol, which is higher than the molecular weights of the compounds evaluated by Kimber et al., (226 and 254 g/mol, respectively).  Since ERGP-IEM contains functional groups with sensitization potential but has a relatively high molecular weight, the weight of evidence suggests that a GHS Category 1B skin sensitization classification would be most appropriate.

Qualifier:

no guideline available

Principles of method if other than guideline:

Review article published in Regulatory Toxicology and Pharmacology.

Type of study:

other: Review article

Key result

Remarks on result:

other: See 'Remarks'

Remarks:

Positive indication of weak dermal sensitization potential for high molecular weight methacrylates.

Interpretation of results:

Category 1B (indication of skin sensitising potential) based on GHS criteria

Conclusions:

ERGP-IEM contains methacrylate functional groups with sensitization potential but has a relatively high molecular weight range. The weight of evidence suggests that a GHS Category 1B skin sensitization classification is most appropriate.

Executive summary:

ERGP-IEM is a UVCB substance that contains four main components with methacrylate functional groups.  Since the DPRA, h-CLAT and Keratinosens assays have not been validated for use with UVCB substances, alternative data sources were compiled to determine the skin sensitization potential of UVCB while avoiding unnecessary animal testing.  Methacrylates are generally well-documented to have skin sensitization potential.

ERGP-IEM is UVCB substance with four main isomeric mixtures of the same molecular mass (ER1GP-IEM, ER2GP-IEM, ER3GP-IEM, ER4GP-IEM).  Each of the isomers contains two terminal methacrylate functional groups.  While methacrylates are sensitizers, they are not usually considered potent skin sensitizers (Kimber et al., 2019).  In addition, some high molecular weight methacrylates (i.e., isodecyl methacrylate and dodecyl methacrylate) are not skin sensitizers in the local lymph node assay.  The molecular weight  of ERGP-IEM ranges from 658 to 1108 g/mol, which is higher than the molecular weights of the compounds evaluated by Kimber et al., (226 and 254 g/mol, respectively).  Since ERGP-IEM contains functional groups with sensitization potential but has a relatively high molecular weight, the weight of evidence suggests that a GHS Category 1B skin sensitization classification would be most appropriate.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Justification for classification or non-classification

ERGP-IEM contains methacrylate functional groups with sensitization potential but has a relatively high molecular weight range. The Weight of Evidence (WoE) suggests that a GHS Category 1B skin sensitization classification is most appropriate.