Reaction products of tetrabromophthalic anhydride with 2,2'-oxydiethanol and methyloxirane

Endpoint summary

Description of key information

The skin sensitization potential was modeled in silico using OECD Toolbox version 4.2. Due to the complex nature of the UVCB substance the in silico approach seems a reasonable approach for a worst case assessment of the skin snsitizing potential. Specimen of all fractions of the UVCB, with one, two or 3 aromatic rings were modeled. although the low molecular weight components are viewed as a reasonable worst case as the higher molecular weight components are unlikely to penetrate sufficiently far to reach the living cell layers. All QSAR predictions for all components were consistently negative.

and predict that the respective component is not a skin sensitizer. In addition no protein binding was predicted by OASIS and no structural alert for skin sensitization was identified. The substances were all within the applicability domain of the model for all parameters. Based on this it can reasonably be concluded that the substance is not sensitizing to skin.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Reference 1

Endpoint:

skin sensitisation, other

Remarks:

QSAR

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

accepted calculation method

Justification for type of information:

1. SOFTWARE: OECD QSAR Toolbox

2. MODEL (incl. version number): 4.2

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
CAS: 20566-35-2, Smiles: CC(O)COC(=O)c1c(Br)c(Br)c(Br)c(Br)c1C(=O)OCCOCCO
4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL . QMRF attached.
- Defined endpoint: skin sensitization
- Unambiguous algorithm: Read across analysis takes highest value from nearest 5 neighbours
- Defined domain of applicability: within applicability domain for all criteria log Kow, Ester structural group, protein binding OASIS, chemical elelments analysis, structure similarity subcharacterization.
- Appropriate measures of goodness-of-fit and robustness and predictivity: yes see QMRF
- Mechanistic interpretation: no structural alert

5. APPLICABILITY DOMAIN
- Descriptor domain: log Kow in range of 3.04 to 4.61
- Structural and mechanistic domains: Ester structural group
- Similarity with analogues in the training set: 11 analogs of which 10 negative
- Other considerations (as appropriate): no structural alerts, no protein binding predicted

6. ADEQUACY OF THE RESULT
The result confirms an absence of groups that could react with proteins as the first step of a skin senstization AOP. This substance represents the lowest molecular weight components and thus a worst case assessment. Higher molecular weight components are unlikely to be absorbed through the skin and reach the target layer for skin sensitization.

Principles of method if other than guideline:

- Software tool(s) used including version:
- Model(s) used: OECD Toolbox version 4.2
- Model description: see field 'Justification for non-standard information', 'Attached justification'
- Justification of QSAR prediction: see field Justification for type of information', 'Attached justification'.

GLP compliance:

no

Justification for non-LLNA method:

In silico model preferred to animal testing

Specific details on test material used for the study:

OTHER SPECIFICS: lowest molecular weight structural component

Key result

Parameter:

other: protein binding and skin sensitization

Remarks on result:

no indication of skin sensitisation

Interpretation of results:

GHS criteria not met

Conclusions:

The QSAR prediction derived from 11 close analogs of which 10 were negative predicts that the chemical is not a skin sensitizer. In addition no protein bindign is predicted by OASIS and no structural alert for skin sensitization is identified. The substance is within the applicability domain of the model for all parameters. Based on this, it can reasonably be concluded that the substance, including higher molecular weight components that are less likely to pass the stratum corneum barrier, is not a skin sensitizer and additional testing is not considered necessary.

Executive summary:

The skin sensitization potential was modeled in silico using OECD Toolbox version 4.2. Due to the complex nature of the UVCB substance the in silico approach using the lower molecualr weight components of the substance seems a reasonable approach for a worst case assessment of the skin snsitizing potential.

The QSAR prediction derived from 11 close analogs of which 10 were negative predicts that the chemical is not a skin sensitizer. In addition no protein binding is predicted by OASIS and no structural alert for skin sensitization is identified. The substance is within the applicability domain of the model for all parameters. Based on this it can reasonably be concluded that the substance including higher molecular weight components that are less likely to pass the stratum corneum barrier is not a skin sensitizer and additional testing is not considered necessary.

Reference 2

Endpoint:

skin sensitisation, other

Remarks:

QSAR

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

accepted calculation method

Justification for type of information:

1. SOFTWARE: OECD QSAR Toolbox

2. MODEL (incl. version number): 4.2

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
Smiles: CC(O)COC(C)COC(=O)c1c(Br)c(Br)c(Br)c(Br)c1C(=O)OCCOCCO
4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL . QMRF attached.
- Defined endpoint: skin sensitization
- Unambiguous algorithm: Read across analysis takes highest value from nearest 5 neighbours
- Defined domain of applicability: within applicability domain for all criteria log Kow, Ester structural group, protein binding OASIS, chemical elelments analysis, structure similarity subcharacterization.
- Appropriate measures of goodness-of-fit and robustness and predictivity: yes see QMRF
- Mechanistic interpretation: no structural alert

5. APPLICABILITY DOMAIN
- Descriptor domain: log Kow in range of 3.04 to 4.61
- Structural and mechanistic domains: Ester structural group
- Similarity with analogues in the training set: 11 analogs of which 10 negative
- Other considerations (as appropriate): no structural alerts, no protein binding predicted

6. ADEQUACY OF THE RESULT
The result confirms an absence of groups that could react with proteins as the first step of a skin senstization AOP. This substance represents the lowest molecular weight components and thus a worst case assessment. Higher molecular weight components are unlikely to be absorbed through the skin and reach the target layer for skin sensitization.

Principles of method if other than guideline:

- Software tool(s) used including version:
- Model(s) used: OECD Toolbox version 4.2
- Model description: see field 'Justification for non-standard information', 'Attached justification'
- Justification of QSAR prediction: see field Justification for type of information', 'Attached justification'.

GLP compliance:

no

Justification for non-LLNA method:

In silico model preferred to animal testing

Specific details on test material used for the study:

Component of one ring fraction with smiles CC(O)COC(C)COC(=O)c1 c(Br)c(Br)c(Br)c(Br) c1C(=O)OCCOCCO was modeled.

Key result

Parameter:

other: protein binding and skin sensitization

Remarks on result:

no indication of skin sensitisation

Interpretation of results:

GHS criteria not met

Conclusions:

The QSAR prediction derived from 11 close analogs of which 10 were negative predicts that the chemical is not a skin sensitizer. In addition no protein binding is predicted by OASIS and no structural alert for skin sensitization is identified. The substance is within the applicability domain of the model for all parameters. Based on this, it can reasonably be concluded that the substance, including higher molecular weight components that are less likely to pass the stratum corneum barrier, is not a skin sensitizer and additional testing is not considered necessary. The substance is part of the one ring fraction with one diethyleneglycol and two propyleneglycol residues.

Executive summary:

The skin sensitization potential was modeled in silico using OECD Toolbox version 4.2. Due to the complex nature of the UVCB substance the in silico approach using the lower molecualr weight components of the substance seems a reasonable approach for a worst case assessment of the skin snsitizing potential. The substance is part of the one ring fraction with one diethyleneglycol and two propyleneglycol residues.

The QSAR prediction derived from 11 close analogs of which 10 were negative predicts that the chemical is not a skin sensitizer. In addition no protein binding is predicted by OASIS and no structural alert for skin sensitization is identified. The substance is within the applicability domain of the model for all parameters. Based on this it can reasonably be concluded that the substance including higher molecular weight components that are less likely to pass the stratum corneum barrier is not a skin sensitizer and additional testing is not considered necessary.

Reference 3

Endpoint:

skin sensitisation, other

Remarks:

QSAR

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

accepted calculation method

Justification for type of information:

1. SOFTWARE: OECD QSAR Toolbox

2. MODEL (incl. version number): 4.2

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
Smiles: CC(O)COC(C)COC(C)COC(=O)c1c(Br)c(Br)c(Br)c(Br)c1C(=O)OCCOCCO
4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL . QMRF attached.
- Defined endpoint: skin sensitization
- Unambiguous algorithm: Read across analysis takes highest value from nearest 5 neighbours
- Defined domain of applicability: within applicability domain for all criteria log Kow, Ester structural group, protein binding OASIS, chemical elelments analysis, structure similarity subcharacterization.
- Appropriate measures of goodness-of-fit and robustness and predictivity: yes see QMRF
- Mechanistic interpretation: no structural alert

5. APPLICABILITY DOMAIN
- Descriptor domain: log Kow in range of 3.78 to 4.61
- Structural and mechanistic domains: Ester structural group
- Similarity with analogues in the training set: 9 analogs of which 8 negative
- Other considerations (as appropriate): no structural alerts, no protein binding predicted

6. ADEQUACY OF THE RESULT
The result confirms an absence of groups that could react with proteins as the first step of a skin senstization AOP. This substance represents the lowest molecular weight components and thus a worst case assessment. Higher molecular weight components are unlikely to be absorbed through the skin and reach the target layer for skin sensitization.

Principles of method if other than guideline:

- Software tool(s) used including version:
- Model(s) used: OECD Toolbox version 4.2
- Model description: see field 'Justification for non-standard information', 'Attached justification'
- Justification of QSAR prediction: see field Justification for type of information', 'Attached justification'.

GLP compliance:

no

Justification for non-LLNA method:

In silico model preferred to animal testing

Specific details on test material used for the study:

Component of one rign fraction with smiles CC(O)COC(C)COC(C)COC(=O)c1c(Br)c(Br)c(Br)c(Br)c1C(=O)OCCOCCO was modeled.

Key result

Parameter:

other: protein binding and skin sensitization

Remarks on result:

no indication of skin sensitisation

Interpretation of results:

GHS criteria not met

Conclusions:

The QSAR prediction derived from 9 close analogs of which 8 were negative predicts that the chemical is not a skin sensitizer. In addition no protein binding is predicted by OASIS and no structural alert for skin sensitization is identified. The substance is within the applicability domain of the model for all parameters. Based on this, it can reasonably be concluded that the substance is not a skin sensitizer and additional testing is not considered necessary. The substance is part of the one ring fraction with one diethyleneglycol and three propyleneglycol residues.

Executive summary:

The skin sensitization potential was modeled in silico using OECD Toolbox version 4.2. Due to the complex nature of the UVCB substance the in silico approach using the lower molecualr weight components of the substance seems a reasonable approach for a worst case assessment of the skin snsitizing potential. The substance is part of the one ring fraction with one diethyleneglycol and three propyleneglycol residues.

The QSAR prediction derived from 11 close analogs of which 10 were negative predicts that the chemical is not a skin sensitizer. In addition no protein binding is predicted by OASIS and no structural alert for skin sensitization is identified. The substance is within the applicability domain of the model for all parameters. Based on this it can reasonably be concluded that the substance including higher molecular weight components that are less likely to pass the stratum corneum barrier is not a skin sensitizer and additional testing is not considered necessary.

Reference 4

Endpoint:

skin sensitisation, other

Remarks:

QSAR

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

accepted calculation method

Justification for type of information:

1. SOFTWARE: OECD QSAR Toolbox

2. MODEL (incl. version number): 4.2

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
Smiles: CC(O)COC(=O)c1c(Br)c(Br)c(Br)c(Br)c1C(=O)OCCOCCOC(=O)c1c(Br)c(Br)c(Br)c(Br)c1C(=O)OCC(C)O
4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL . QMRF attached.
- Defined endpoint: skin sensitization
- Unambiguous algorithm: Read across analysis takes highest value from nearest 6 neighbours
- Defined domain of applicability: within applicability domain for all criteria log Kow, Ester structural group, protein binding OASIS, chemical elelments analysis, structure similarity subcharacterization.
- Appropriate measures of goodness-of-fit and robustness and predictivity: yes see QMRF
- Mechanistic interpretation: no structural alert

5. APPLICABILITY DOMAIN
- Descriptor domain: log Kow in range of 8.39 to 10
- Structural and mechanistic domains: Ester structural group
- Similarity with analogues in the training set: 7 analogs of which 7 negative
- Other considerations (as appropriate): no structural alerts, no protein binding predicted

6. ADEQUACY OF THE RESULT
The result confirms an absence of groups that could react with proteins as the first step of a skin senstization AOP. This substance represents the two ring component. Higher molecular weight components like this one are unlikely to be absorbed through the skin and reach the target layer for skin sensitization.

Principles of method if other than guideline:

- Software tool(s) used including version:
- Model(s) used: OECD Toolbox version 4.2
- Model description: see field 'Justification for non-standard information', 'Attached justification'
- Justification of QSAR prediction: see field Justification for type of information', 'Attached justification'.

GLP compliance:

no

Justification for non-LLNA method:

In silico model preferred to animal testing

Specific details on test material used for the study:

Component of two ring fraction with smiles CC(O)COC(=O)c1c(Br)c(Br)c(Br)c(Br)c1C(=O)OCCOCCOC(=O)c1c(Br)c(Br )c(Br)c(Br)c1C(=O)OCC(C)O was modeled.

Key result

Parameter:

other: protein binding and skin sensitization

Remarks on result:

no indication of skin sensitisation

Interpretation of results:

GHS criteria not met

Conclusions:

The QSAR prediction derived from 7 close analogs of which all were negative predicts that the chemical is not a skin sensitizer. In addition no protein binding is predicted by OASIS and no structural alert for skin sensitization is identified. The substance is within the applicability domain of the model for all parameters. Based on this, it can reasonably be concluded that the substance is not a skin sensitizer and additional testing is not considered necessary. The substance is part of the two ring fraction with one diethyleneglycol bridge and two propyleneglycol residues. It has a relatively high molecular weight and is unlikely to penetrate the skin.

Executive summary:

The skin sensitization potential was modeled in silico using OECD Toolbox version 4.2. Due to the complex nature of the UVCB substance the in silico approach seems a reasonable approach for an assessment of the skin snsitizing potential. The substance is part of the two ring fraction with one diethyleneglycol bridge and two propyleneglycol residues.

The QSAR prediction derived from 7 close analogs of which 7 were negative predicts that the chemical is not a skin sensitizer. In addition no protein binding is predicted by OASIS and no structural alert for skin sensitization is identified. The substance is within the applicability domain of the model for all parameters. The substance is part of the two ring fraction with one diethyleneglycol bridge and two propyleneglycol residues. It has a relatively high molecular weight and is unlikely to penetrate the skin.

Reference 5

Endpoint:

skin sensitisation, other

Remarks:

QSAR

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

accepted calculation method

Justification for type of information:

1. SOFTWARE: OECD QSAR Toolbox

2. MODEL (incl. version number): 4.2

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
Smiles: CC(O)COC(C)COC(=O)c1c(Br)c(Br)c(Br)c(Br)c1C(=O)OCCOCCOC(=O)c1c(Br)c(Br)c(Br)c(Br)c1C(=O)OCC(C)O
4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL . QMRF attached.
- Defined endpoint: skin sensitization
- Unambiguous algorithm: Read across analysis takes highest value from nearest 6 neighbours
- Defined domain of applicability: within applicability domain for all criteria log Kow, Ester structural group, protein binding OASIS, chemical elelments analysis, structure similarity subcharacterization.
- Appropriate measures of goodness-of-fit and robustness and predictivity: yes see QMRF
- Mechanistic interpretation: no structural alert

5. APPLICABILITY DOMAIN
- Descriptor domain: log Kow in range of 8.39 to 10.1
- Structural and mechanistic domains: Ester structural group
- Similarity with analogues in the training set: 11 analogs of which 10 negative
- Other considerations (as appropriate): no structural alerts, no protein binding predicted

6. ADEQUACY OF THE RESULT
The result confirms an absence of groups that could react with proteins as the first step of a skin senstization AOP. This substance represents the two ring component. Higher molecular weight components like this one are unlikely to be absorbed through the skin and reach the target layer for skin sensitization.

Principles of method if other than guideline:

- Software tool(s) used including version:
- Model(s) used: OECD Toolbox version 4.2
- Model description: see field 'Justification for non-standard information', 'Attached justification'
- Justification of QSAR prediction: see field Justification for type of information', 'Attached justification'.

GLP compliance:

no

Justification for non-LLNA method:

In silico model preferred to animal testing

Specific details on test material used for the study:

Component of two ring fraction with smiles CC(O)COC(C)COC(=O)c1c(Br)c(Br)c(Br)c(Br)c1C(=O)OCCOCCOC(=O)c1c(Br)c(Br)c(Br)c(Br)c1C(=O)OCC(C)O was modeled.

Key result

Parameter:

other: protein binding and skin sensitization

Remarks on result:

no indication of skin sensitisation

Interpretation of results:

GHS criteria not met

Conclusions:

The QSAR prediction derived from 9 close analogs of which 8 were negative predicts that the chemical is not a skin sensitizer. In addition no protein binding is predicted by OASIS and no structural alert for skin sensitization is identified. The substance is within the applicability domain of the model for all parameters. Based on this, it can reasonably be concluded that the substance is not a skin sensitizer and additional testing is not considered necessary. The substance is part of the two ring fraction with a bridge consisting of two diethyleneglycol units and three propyleneglycol residues.It has a relatively high molecular weight and is unlikely to penetrate the skin.

Executive summary:

The skin sensitization potential was modeled in silico using OECD Toolbox version 4.2. Due to the complex nature of the UVCB substance the in silico approach seems a reasonable approach for an assessment of the skin sensitizing potential. The substance is part of the two ring fraction with a bridge consisting of two diethyleneglycol units and three propyleneglycol residues.

The QSAR prediction derived from 11 close analogs of which 10 were negative predicts that the chemical is not a skin sensitizer. In addition no protein binding is predicted by OASIS and no structural alert for skin sensitization is identified. The substance is within the applicability domain of the model for all parameters.

The substance is part of the two ring fraction with a bridge consisting of two diethyleneglycol units and three propyleneglycol residues.

It has a relatively high molecular weight and is unlikely to penetrate the skin.

Reference 6

Endpoint:

skin sensitisation, other

Remarks:

QSAR

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

accepted calculation method

Justification for type of information:

1. SOFTWARE: OECD QSAR Toolbox

2. MODEL (incl. version number): 4.2

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
Smiles: CC(O)COC(=O)c1c(Br)c(Br)c(Br)c(Br)c1C(=O)OCCOCCOC(=O)c1c(Br)c(Br)c(Br)c(Br)c1C(=O)OCCOCCOC(=O)c1c(Br)c(Br)c(Br)c(Br)c1C(=O)OCC(C)
4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL . QMRF attached.
- Defined endpoint: skin sensitization
- Unambiguous algorithm: Read across analysis takes highest value from nearest 6 neighbours
- Defined domain of applicability: within applicability domain for all criteria log Kow, Ester structural group, protein binding OASIS, chemical elelments analysis, structure similarity subcharacterization.
- Appropriate measures of goodness-of-fit and robustness and predictivity: yes see QMRF
- Mechanistic interpretation: no structural alert

5. APPLICABILITY DOMAIN
- Descriptor domain: log Kow in range of 11.8 to 14.2
- Structural and mechanistic domains: Ester structural group
- Similarity with analogues in the training set: 7 analogs of which 7 negative
- Other considerations (as appropriate): no structural alerts, no protein binding predicted

6. ADEQUACY OF THE RESULT
The result confirms an absence of groups that could react with proteins as the first step of a skin senstization AOP. This substance represents the two ring component. Higher molecular weight components like this one are unlikely to be absorbed through the skin and reach the target layer for skin sensitization.

Principles of method if other than guideline:

- Software tool(s) used including version:
- Model(s) used: OECD Toolbox version 4.2
- Model description: see field 'Justification for non-standard information', 'Attached justification'
- Justification of QSAR prediction: see field Justification for type of information', 'Attached justification'.

GLP compliance:

no

Justification for non-LLNA method:

In silico model preferred to animal testing

Specific details on test material used for the study:

Component of 3-ring fraction with smiles CC(O)COC(=O)c1c(Br)c(Br)c(Br)c(Br)c1C(=O)OCCOCCOC(=O)c1c(Br)c(Br)c(Br)c(Br)c1C(=O)OCCOCCOC(=O)c1c(Br)c(Br)c(Br)c(Br)c1C(=O)OCC(C) was modeled

Key result

Parameter:

other: protein binding and skin sensitization

Remarks on result:

no indication of skin sensitisation

Interpretation of results:

GHS criteria not met

Conclusions:

The QSAR prediction derived from 7 close analogs of which 7 were negative predicts that the chemical is not a skin sensitizer. In addition no protein binding is predicted by OASIS and no structural alert for skin sensitization is identified. The substance is within the applicability domain of the model for all parameters. Based on this, it can reasonably be concluded that the substance is not a skin sensitizer and additional testing is not considered necessary. The substance is part of the three ring fraction with two diethyleneglycol bridges consisting of two units and two propyleneglycol residues.It has a relatively high molecular weight and is unlikely to penetrate the skin.

Executive summary:

The skin sensitization potential was modeled in silico using OECD Toolbox version 4.2. Due to the complex nature of the UVCB substance the in silico approach seems a reasonable approach for an assessment of the skin sensitizing potential. The substance is part of the three ring fraction with two diethyleneglycol  bridges consisting of two units and two propyleneglycol residues.It has a relatively high molecular weight and is unlikely to penetrate the skin.

The QSAR prediction derived from 7 close analogs of which 7 were negative predicts that the chemical is not a skin sensitizer. In addition no protein binding is predicted by OASIS and no structural alert for skin sensitization is identified. The substance is within the applicability domain of the model for all parameters.

The substance is part of the three ring fraction with two diethyleneglycol  bridges consisting of two units and two propyleneglycol residues.It has a relatively high molecular weight and is unlikely to penetrate the skin.

Reference 7

Endpoint:

skin sensitisation, other

Remarks:

QSAR

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

accepted calculation method

Justification for type of information:

1. SOFTWARE: OECD QSAR Toolbox

2. MODEL (incl. version number): 4.2

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
Smiles: CC(O)COC(C)COC(=O)c1c(Br)c(Br)c(Br)c(Br)c1C(=O)OCCOCCOC(=O)c1c(Br)c(Br)c(Br)c(Br)c1C(=O)OCCOCCOC(=O)c1c(Br)c(Br)c(Br)c(Br)c1C(=O)OCC(C)O
4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL . QMRF attached.
- Defined endpoint: skin sensitization
- Unambiguous algorithm: Read across analysis takes highest value from nearest 5 neighbours
- Defined domain of applicability: within applicability domain for all criteria log Kow, Ester structural group, protein binding OASIS, chemical elelments analysis, structure similarity subcharacterization.
- Appropriate measures of goodness-of-fit and robustness and predictivity: yes see QMRF
- Mechanistic interpretation: no structural alert

5. APPLICABILITY DOMAIN
- Descriptor domain: log Kow in range of 11.8 to 14.2
- Structural and mechanistic domains: Ester structural group
- Similarity with analogues in the training set: 7 analogs of which 7 negative
- Other considerations (as appropriate): no structural alerts, no protein binding predicted

6. ADEQUACY OF THE RESULT
The result confirms an absence of groups that could react with proteins as the first step of a skin senstization AOP. This substance represents the two ring component. Higher molecular weight components like this one are unlikely to be absorbed through the skin and reach the target layer for skin sensitization.

Principles of method if other than guideline:

- Software tool(s) used including version:
- Model(s) used: OECD Toolbox version 4.2
- Model description: see field 'Justification for non-standard information', 'Attached justification'
- Justification of QSAR prediction: see field Justification for type of information', 'Attached justification'.

GLP compliance:

no

Justification for non-LLNA method:

In silico model preferred to animal testing

Specific details on test material used for the study:

Component of 3-ring fraction with smiles CC(O)COC(C)COC(=O)c1c(Br)c(Br)c(Br)c(Br)c1C(=O)OCCOCCOC(=O)c1c(Br)c(Br)c(Br)c(Br)c1C(=O)OCCOCCOC(=O)c1c(Br)c(Br)c(Br)c(Br)c1C(=O)OCC(C)O was modeled.

Key result

Parameter:

other: protein binding and skin sensitization

Remarks on result:

no indication of skin sensitisation

Interpretation of results:

GHS criteria not met

Conclusions:

The QSAR prediction derived from 7 close analogs of which 7 were negative predicts that the chemical is not a skin sensitizer. In addition no protein binding is predicted by OASIS and no structural alert for skin sensitization is identified. The substance is within the applicability domain of the model for all parameters. Based on this, it can reasonably be concluded that the substance is not a skin sensitizer and additional testing is not considered necessary. The substance is part of the three ring fraction with two diethyleneglycol bridges consisting of two units and three propyleneglycol residues.It has a relatively high molecular weight and is unlikely to penetrate the skin.

Executive summary:

The skin sensitization potential was modeled in silico using OECD Toolbox version 4.2. Due to the complex nature of the UVCB substance the in silico approach seems a reasonable approach for an assessment of the skin sensitizing potential. The substance is part of the three ring fraction with two diethyleneglycol  bridges consisting and three propyleneglycol residues.It has a relatively high molecular weight and is unlikely to penetrate the skin.

The QSAR prediction derived from 7 close analogs of which 7 were negative predicts that the chemical is not a skin sensitizer. In addition no protein binding is predicted by OASIS and no structural alert for skin sensitization is identified. The substance is within the applicability domain of the model for all parameters.

The substance is part of the three ring fraction with two diethyleneglycol  bridges consisting of two units and two propyleneglycol residues.It has a relatively high molecular weight and is unlikely to penetrate the skin.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Justification for classification or non-classification

The model predictions for one, two and three-ring components were consistently negative for all structures modeled. Therfore it can reasonably be concluded that the substance is unlikely to be a skin sensitizer and no classification for skin sensitization is warranted.