Reaction mass of (((1,3-phenylenebis(oxy))bis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1-diyl) bis(2-methylacrylate) and (1,3-phenylenebis(oxy))bis(propane-3,1-diyl) bis(2-methylacrylate) and 3-(3-(2-(2-(methacryloyloxy)ethoxy)ethoxy)phenoxy)propyl methacrylaterate

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 4.4.1

2. MODEL: Automated workflow for Skin Sensitization Defined Approaches

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

CC(=C)C(=O)OCCCOc1cc(OCCCOC(=O)C(=C)C)c(Br)cc1Br.
CC(=C)C(=O)OCCCOc1cc(OCCOCCOC(=O)C(=C)C)c(Br)cc1Br.
CC(=C)C(=O)OCCOCCOc1cc(OCCOCCOC(=O)C(=C)C)c(Br)cc1Br.

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
- Defined endpoint: EC3, Skin sensitisation;
- Unambiguous algorithm: See attached documentation .pdf providing more detail around the automated workflow within OECD QSAR Toolbox version 4.4.1.
- Defined domain of applicability: 1/3 of the components of the UVCB substance have log Kow values that fall within the applicability
domain of the skin sensitization category profiler. The average log Kow was 5.22 for DiBrOE2MA, 5.36
for DiBrORMA, and 4.77 for DiBrE4RMA. The active descriptor range of the category is 3.09-4.94.
All the components fall within the applicability domain of the following profilers:
Protein binding alerts for skin sensitization by OASIS (Primary Grouping)
Protein binding alerts for skin sensitization by OASIS (Subcategorization)
- 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 sensitizers.

See attached documentation .pdf providing more detail around the automated workflow within OECD QSAR Toolbox version 4.4.1.

5. APPLICABILITY DOMAIN
[Explain how the substance falls within the applicability domain of the model]
- 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 similar MWs and log Kow values.

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 4.4.1 Additionally, the constituents and estimated metabolites were evaluated using a category approach to determine if
structural analogs of the constituents are dermal sensitizers. Based on the structural alerts for the constituents of the mixture and the structural analogs with positive sensitization data, the multiconstituent target 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: OECD QSAR Toolbox v. 4.4.1
- 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 mass of (((1,3-phenylenebis(oxy))bis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1-diyl) bis(2-methylacrylate) and (1,3-phenylenebis(oxy))bis(propane-3,1-diyl) bis(2-methylacrylate) and 3-(3-(2-(2-(methacryloyloxy)ethoxy)ethoxy)phenoxy)propyl methacrylaterate

EC Number:

944-271-1

Cas Number:

2305048-54-6

Molecular formula:

not applicable for multi-constituent.

IUPAC Name:

Reaction mass of (((1,3-phenylenebis(oxy))bis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1-diyl) bis(2-methylacrylate) and (1,3-phenylenebis(oxy))bis(propane-3,1-diyl) bis(2-methylacrylate) and 3-(3-(2-(2-(methacryloyloxy)ethoxy)ethoxy)phenoxy)propyl methacrylaterate

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, DiBrORMA is expected to be a GHS Category 1 skin 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 4.4.1 Additionally, the constituents and estimated metabolites were evaluated using a category approach to determine if structural analogs of the constituents are dermal sensitizers. Based on the structural alerts for the constituents of the mixture and the structural analogs with positive sensitization data, the UVCB target is predicted to be a GHS Category 1 skin sensitizer.