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Description of key information

Multiple Quantitative Structure Activity Relationship (QSAR) models were used to predict the Skin Sensitization potential of the test item Tetrasodium 1,3,6,8-pyrenetetrasulfonate.

The final skin sensitization result was predicted by applying a consensus method on the reliable results derived for individual models.

The final Skin Sensitization result predicted for Tetrasodium 1,3,6,8-pyrenetetrasulfonate assigned by the study investigator: non sensitizing to the skin. The final QSAR result can be associated with a Klimisch score:K2

The same method was used to predict the Skin Sensitization potential of the analogue test item trisodium 8-hydroxypyrene-1,3,6-trisulfonate.

The final skin sensitization result predicted for trisodium 8-hydroxypyrene-1,3,6-trisulfonate assigned by the study investigator: non sensitizing to skin. Klimisch score assigned by the study investigtor for the final prediction: K2

Test results published on the ECHA website provided a conclusion of non sensitizing to skin for Skin Sensitization potential for the analogue test item trisodium 8-hydroxypyrene-1,3,6-trisulfonate.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in chemico
Type of information:
(Q)SAR
Adequacy of study:
key study
Study period:
2 December 2018 and 3 December 2018
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 limited documentation / justification
Justification for type of information:
1. SOFTWARE
Nexus DEREK v6.0.1
OECD QSAR Toolbox v4.2

2. MODEL (incl. version number)
Nexus DEREK v6.0.1
OECD QSAR Toolbox v4.2

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
Smiles: C1=CC2=C3C(=C(C=C2S(=O)(=O)[O-])S(=O)(=O)[O-])C=CC4=C(C=C(C1=C43)S(=O)(=O)[O-])S(=O)(=O)[O-].[Na+].[Na+].[Na+].[Na+]
Substance name: Tetrasodium 1,3,6,8-pyrenetetrasulfonate
CAS: 59572-10-0

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
KREATiS explanation for Klimisch 2: Final QSAR result is reliable and can reliably replace an experimental result with the OECD Guideline for Testing of Chemicals No. 429: Skin Sensitisation.

5. APPLICABILITY DOMAIN
This QSAR model has been designed to be used for regulatory purposes and based on the QSAR results, this report predicts the consensus endpoint value which would be expected when testing the substance under experimental conditions in a laboratory following the OECD Guideline for Testing of Chemicals No. 429: Skin Sensitisation.

6. ADEQUACY OF THE RESULT
Based on multiple QSAR models applied, Tetrasodium 1,3,6,8-pyrenetetrasulfonate was predicted as non-sensitising to the skin.
The final QSAR result can be associated with a Klimisch score: K2
Guideline:
other: REACH Guidance on QSARs R.6
Version / remarks:
OECD (2004) Principles for the validation, for regulatory purposes, of (Quantitative) Structure Activity-Relationship Models, http://www.oecd.org/env/ehs/risk-assessment/oecdquantitativestructureactivityrelationshipsprojectqsars.htm
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Version / remarks:
OECD (2004) Principles for the validation, for regulatory purposes, of (Quantitative) Structure Activity-Relationship Models, http://www.oecd.org/env/ehs/risk-assessment/oecdquantitativestructureactivityrelationshipsprojectqsars.htm
Specific details on test material used for the study:
C1=CC2=C3C(=C(C=C2S(=O)(=O)[O-])S(=O)(=O)[O-])C=CC4=C(C=C(C1=C43)S(=O)(=O)[O-])S(=O)(=O)[O-].[Na+].[Na+].[Na+].[Na+]
Details on the study design:
Following QSAR models were applied to predict the Skin Sensitisation potential for Tetrasodium 1,3,6,8-pyrenetetrasulfonate:

Nexus DEREK

DEREK predicts the skin sensitisation potential of a substance based on the triggered structural alerts for this endpoint. If the substance is a sensitiser, DEREK also provides the EC3 value. The report also provides detailed information about each triggered alert.

OECD QSAR Toolbox v4.2

The latest version of the OECD QSAR Toolbox facilitates the profiling of a query substane based on the following skin sensitisation relevant profilers incorporated into its interface:

Profilers
General Mechanistic
Protein binding potency GSH
Protein binding potency Cys (DPRA 13%)
Protein binding by OASIS
Protein binding by OECD
Protein binding potency Lys (DPRA 13%)
Endpoint Specific
Protein Binding Potency h-CLAT
Protein binding alerts for skin sensitization by OASIS
Protein binding alerts for skin sensitization according to GHS
Key result
Parameter:
other: The final consensus result
Vehicle controls validity:
not applicable
Negative controls validity:
not applicable
Positive controls validity:
not applicable
Remarks on result:
no indication of skin sensitisation
Remarks:
The final consensus result based on result from all models.
Run / experiment:
other: Protein binding potency GSH
Parameter:
other: OECD QSAR Toolbox v4.2 Profilers for Skin Sensitisation
Remarks:
General Mechanistic
Vehicle controls validity:
not applicable
Negative controls validity:
not applicable
Positive controls validity:
not applicable
Remarks on result:
not determinable
Remarks:
Not possible to classify according to these rules (GSH)
Run / experiment:
other: Protein binding potency Cys (DPRA 13%)
Parameter:
other: OECD QSAR Toolbox v4.2 Profilers for Skin Sensitisation
Remarks:
General Mechanistic
Vehicle controls validity:
not applicable
Negative controls validity:
not applicable
Positive controls validity:
not applicable
Remarks on result:
no indication of skin sensitisation
Remarks:
DPRA less than 9% (DPRA 13%) >> No protein binding alert
Run / experiment:
other: Protein binding by OASIS
Parameter:
other: OECD QSAR Toolbox v4.2 Profilers for Skin Sensitisation
Remarks:
General Mechanistic
Vehicle controls validity:
not applicable
Negative controls validity:
not applicable
Positive controls validity:
not applicable
Remarks on result:
no indication of skin sensitisation
Remarks:
No alert found
Run / experiment:
other: Protein binding by OECD
Parameter:
other: OECD QSAR Toolbox v4.2 Profilers for Skin Sensitisation
Remarks:
General Mechanistic
Vehicle controls validity:
not applicable
Negative controls validity:
not applicable
Positive controls validity:
not applicable
Remarks on result:
no indication of skin sensitisation
Remarks:
No alert found
Run / experiment:
other: Protein binding potency Lys (DPRA 13%)
Parameter:
other: OECD QSAR Toolbox v4.2 Profilers for Skin Sensitisation
Remarks:
General Mechanistic
Vehicle controls validity:
not applicable
Negative controls validity:
not applicable
Positive controls validity:
not applicable
Remarks on result:
no indication of skin sensitisation
Remarks:
DPRA less than 9% (DPRA 13%) >> No protein binding alert
Run / experiment:
other: Keratinocyte gene expression
Parameter:
other: OECD QSAR Toolbox v4.2 Profilers for Skin Sensitisation
Remarks:
Endpoint Specific
Vehicle controls validity:
not applicable
Negative controls validity:
not applicable
Positive controls validity:
not applicable
Remarks on result:
not determinable
Remarks:
Not possible to classify according to these rules
Run / experiment:
other: Protein binding alerts for skin sensitization by OASIS
Parameter:
other: OECD QSAR Toolbox v4.2 Profilers for Skin Sensitisation
Remarks:
Endpoint Specific
Vehicle controls validity:
not applicable
Negative controls validity:
not applicable
Positive controls validity:
not applicable
Remarks on result:
no indication of skin sensitisation
Remarks:
No alert found
Run / experiment:
other: Protein binding alerts for skin sensitization according to GHS
Parameter:
other: OECD QSAR Toolbox v4.2 Profilers for Skin Sensitisation
Remarks:
Endpoint Specific
Vehicle controls validity:
not applicable
Negative controls validity:
not applicable
Positive controls validity:
not applicable
Remarks on result:
no indication of skin sensitisation
Remarks:
No alert found
Run / experiment:
other: Respiratory sensitisation
Parameter:
other: OECD QSAR Toolbox v4.2 Profilers for Skin Sensitisation
Remarks:
Endpoint Specific
Vehicle controls validity:
not applicable
Negative controls validity:
not applicable
Positive controls validity:
not applicable
Remarks on result:
no indication of skin sensitisation
Remarks:
No alert found
Run / experiment:
other: Protein Binding Potency h-CLAT
Parameter:
other: OECD QSAR Toolbox v4.2 Profilers for Skin Sensitisation
Remarks:
Endpoint Specific
Vehicle controls validity:
not applicable
Negative controls validity:
not applicable
Positive controls validity:
not applicable
Remarks on result:
no indication of skin sensitisation
Remarks:
No alert found
Parameter:
other: Nexus DEREK
Vehicle controls validity:
not applicable
Negative controls validity:
not applicable
Positive controls validity:
not applicable
Remarks on result:
no indication of skin sensitisation
Remarks:
No structural alerts were triggered for skin sensitisation
Other effects / acceptance of results:
Results with OECD QSAR Toolbox v4.2
As per the profiling results, the query substance will be predicted as non-sensitising to the skin.

Results with Nexus DEREK
No structural alerts were triggered for skin sensitisation.
Interpretation of results:
GHS criteria not met
Conclusions:
The final consensus result predicted assigned based on the above results:
Tetrasodium 1,3,6,8-pyrenetetrasulfonate is predicted as a non-sensitising to the skin.
Klimisch score assigned by the study investigator for the final prediction: K2
Executive summary:

Introduction. Multiple Quantitative Structure Activity Relationship (QSAR) models were used to predict the Skin Sensitisation potential of the test item Tetrasodium 1,3,6,8-pyrenetetrasulfonate. These QSAR models has been designed to be used for regulatory purposes and based on the QSAR results, this report predicts the consensus endpoint value which would be expected when testing the substance under experimental conditions in a laboratory following the OECD Guideline for Testing of Chemicals No. 429: Skin Sensitisation.

Methods. The purpose of the in silico study was to predict the Skin Sensitisation potential of the test item Tetrasodium 1,3,6,8-pyrenetetrasulfonate. This prediction was performed using the following QSAR models:

·        Nexus DEREK v6.0.1

·        OECD QSAR Toolbox v4.2

 

The final Skin Sensitisation potential was derived by applying a consensus method on the reliable results derived for individual models.

 

Results.

Based on multiple QSAR models applied, Tetrasodium 1,3,6,8-pyrenetetrasulfonate was predicted as non-sensitising to the skin.

The final QSAR result can be associated with a Klimisch score: K2

Endpoint:
skin sensitisation: in chemico
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Remarks:
Using QSAR
Adequacy of study:
supporting study
Study period:
2 December 2018 and 3 December 2018
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
Nexus DEREK v6.0.1
OECD QSAR Toolbox v4.2

2. MODEL (incl. version number)
Nexus DEREK v6.0.1
OECD QSAR Toolbox v4.2

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
Smiles: [Na+].[Na+].[Na+].OC1=C2C=CC3=C(C=C(C4=CC=C(C(=C1)S([O-])(=O)=O)C2=C34)S([O-])(=O)=O)S([O-])(=O)=O
Substance name: trisodium 8-hydroxypyrene-1,3,6-trisulfonate
CAS: 6358-69-6

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
KREATiS explanation for Klimisch 2: Final QSAR result is reliable and can reliably replace an experimental result with the OECD Guideline for Testing of Chemicals No. 429: Skin Sensitisation.

5. APPLICABILITY DOMAIN
This QSAR model has been designed to be used for regulatory purposes and based on the QSAR results, this report predicts the consensus endpoint value which would be expected when testing the substance under experimental conditions in a laboratory following the OECD Guideline for Testing of Chemicals No. 429: Skin Sensitisation.

6. ADEQUACY OF THE RESULT
Based on multiple QSAR models applied, trisodium 8-hydroxypyrene-1,3,6-trisulfonate was predicted as non-sensitising to the skin.
The final QSAR result can be associated with a Klimisch score: K2

-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

Read-across information

REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
STRUCTURAL SIMILARITY
Both the substances share the same carbon skeleton, which is pyrene. The query substance holds four sulfonates groups while the proposed analogue has one hydroxy group replacing a sulfonate. Both sulfonate and hydroxy groups are hydrophilic in nature. However, the hydroxy group is only ionised at high pHs (pKa of phenol is around 10) while the sulfonate group would remain ionised over the whole range of aqueous pHs. Therefore, Read-Across substance is expected to be slightly less hydrophilic and more volatile than the query substance, which is confirmed by the log KOW and vapour pressure studies.
Both the substances are expected to be stable in pure form or in water, and they are expected to be not volatile (high boiling point, low vapour pressure), highly hydrophilic (low log KOW, high water solubility) due to the presence of four strongly hydrophilic groups.
 
MECHANISMS OF ACTION PREDICTION
The mechanisms of action of both substances are predicted as follows:

Substance MechoA MechoA detail
Query 1.1 non-polar narcosis for all species
Read-Across 1.2 polar narcosis for all species

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
See Test material sections of the source and target records for details.

3. ANALOGUE APPROACH JUSTIFICATION
DISCUSSION AND CONCLUSION
Therefore, both the structures are expected to have very similar (eco)toxicological profile. Moreover, Read-Across substance being less hydrophilic than the query substance and having a more toxic MechoA, the prediction of (eco)toxicological endpoints will be a worst-case scenario, because the less hydrophilic a substance is, the more toxic it is.
Consequently, trisodium 8-hydroxypyrene-1,3,6-trisulfonate is judged to be a good Read-Across for tetrasodium 1,3,6,8-pyrenetetrasulfonate.
Guideline:
other: REACH Guidance on QSARs R.6
Version / remarks:
OECD (2004) Principles for the validation, for regulatory purposes, of (Quantitative) Structure Activity-Relationship Models, http://www.oecd.org/env/ehs/risk-assessment/oecdquantitativestructureactivityrelationshipsprojectqsars.htm
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Version / remarks:
OECD (2004) Principles for the validation, for regulatory purposes, of (Quantitative) Structure Activity-Relationship Models, http://www.oecd.org/env/ehs/risk-assessment/oecdquantitativestructureactivityrelationshipsprojectqsars.htm
Specific details on test material used for the study:
[Na+].[Na+].[Na+].OC1=C2C=CC3=C(C=C(C4=CC=C(C(=C1)S([O-])(=O)=O)C2=C34)S([O-])(=O)=O)S([O-])(=O)=O
Details on the study design:
Following QSAR models were applied to predict the Skin Sensitisation potential for trisodium 8-hydroxypyrene-1,3,6-trisulfonate:

Nexus DEREK

DEREK predicts the skin sensitisation potential of a substance based on the triggered structural alerts for this endpoint. If the substance is a sensitiser, DEREK also provides the EC3 value. The report also provides detailed information about each triggered alert.

OECD QSAR Toolbox v4.2

The latest version of the OECD QSAR Toolbox facilitates the profiling of a query substane based on the following skin sensitisation relevant profilers incorporated into its interface:

Profilers
General Mechanistic
Protein binding potency GSH
Protein binding potency Cys (DPRA 13%)
Protein binding by OASIS
Protein binding by OECD
Protein binding potency Lys (DPRA 13%)
Endpoint Specific
Protein Binding Potency h-CLAT
Protein binding alerts for skin sensitization by OASIS
Protein binding alerts for skin sensitization according to GHS
Key result
Parameter:
other: The final consensus result
Vehicle controls validity:
not applicable
Negative controls validity:
not applicable
Positive controls validity:
not applicable
Remarks on result:
no indication of skin sensitisation
Remarks:
The final consensus result based on result from all models.
Parameter:
other: Experimental data from the ECHA dossier: https://echa.europa.eu/registration-dossier/-/registered-dossier/17360/7/5/1
Remarks on result:
no indication of skin sensitisation
Run / experiment:
other: Protein binding potency GSH
Parameter:
other: OECD QSAR Toolbox v4.2 Profilers for Skin Sensitisation
Remarks:
General Mechanistic
Vehicle controls validity:
not applicable
Negative controls validity:
not applicable
Positive controls validity:
not applicable
Remarks on result:
not determinable
Remarks:
Not possible to classify according to these rules (GSH)
Run / experiment:
other: Protein binding potency Cys (DPRA 13%)
Parameter:
other: OECD QSAR Toolbox v4.2 Profilers for Skin Sensitisation
Remarks:
General Mechanistic
Vehicle controls validity:
not applicable
Negative controls validity:
not applicable
Positive controls validity:
not applicable
Remarks on result:
no indication of skin sensitisation
Remarks:
DPRA less than 9% (DPRA 13%) >> No protein binding alert
Run / experiment:
other: Protein binding by OASIS
Parameter:
other: OECD QSAR Toolbox v4.2 Profilers for Skin Sensitisation
Remarks:
General Mechanistic
Vehicle controls validity:
not applicable
Negative controls validity:
not applicable
Positive controls validity:
not applicable
Remarks on result:
no indication of skin sensitisation
Remarks:
No alert found
Run / experiment:
other: Protein binding by OECD
Parameter:
other: OECD QSAR Toolbox v4.2 Profilers for Skin Sensitisation
Remarks:
General Mechanistic
Vehicle controls validity:
not applicable
Negative controls validity:
not applicable
Positive controls validity:
not applicable
Remarks on result:
no indication of skin sensitisation
Remarks:
No alert found
Run / experiment:
other: Protein binding potency Lys (DPRA 13%)
Parameter:
other: OECD QSAR Toolbox v4.2 Profilers for Skin Sensitisation
Remarks:
General Mechanistic
Vehicle controls validity:
not applicable
Negative controls validity:
not applicable
Positive controls validity:
not applicable
Remarks on result:
no indication of skin sensitisation
Remarks:
DPRA less than 9% (DPRA 13%) >> No protein binding alert
Run / experiment:
other: Keratinocyte gene expression
Parameter:
other: OECD QSAR Toolbox v4.2 Profilers for Skin Sensitisation
Remarks:
Endpoint Specific
Vehicle controls validity:
not applicable
Negative controls validity:
not applicable
Positive controls validity:
not applicable
Remarks on result:
not determinable
Remarks:
Not possible to classify according to these rules
Run / experiment:
other: Protein binding alerts for skin sensitization by OASIS
Parameter:
other: OECD QSAR Toolbox v4.2 Profilers for Skin Sensitisation
Remarks:
Endpoint Specific
Vehicle controls validity:
not applicable
Negative controls validity:
not applicable
Positive controls validity:
not applicable
Remarks on result:
no indication of skin sensitisation
Remarks:
No alert found
Run / experiment:
other: Protein binding alerts for skin sensitization according to GHS
Parameter:
other: OECD QSAR Toolbox v4.2 Profilers for Skin Sensitisation
Remarks:
Endpoint Specific
Vehicle controls validity:
not applicable
Negative controls validity:
not applicable
Positive controls validity:
not applicable
Remarks on result:
no indication of skin sensitisation
Remarks:
No alert found
Run / experiment:
other: Respiratory sensitisation
Parameter:
other: OECD QSAR Toolbox v4.2 Profilers for Skin Sensitisation
Remarks:
Endpoint Specific
Vehicle controls validity:
not applicable
Negative controls validity:
not applicable
Positive controls validity:
not applicable
Remarks on result:
no indication of skin sensitisation
Remarks:
No alert found
Run / experiment:
other: Protein Binding Potency h-CLAT
Parameter:
other: OECD QSAR Toolbox v4.2 Profilers for Skin Sensitisation
Remarks:
Endpoint Specific
Vehicle controls validity:
not applicable
Negative controls validity:
not applicable
Positive controls validity:
not applicable
Remarks on result:
no indication of skin sensitisation
Remarks:
No alert found
Parameter:
other: Nexus DEREK
Vehicle controls validity:
not applicable
Negative controls validity:
not applicable
Positive controls validity:
not applicable
Remarks on result:
no indication of skin sensitisation
Remarks:
No structural alerts were triggered for skin sensitisation
Other effects / acceptance of results:
Results with OECD QSAR Toolbox v4.2
As per the profiling results, the query substance will be predicted as non-sensitising to the skin.

Results with Nexus DEREK
No structural alerts were triggered for skin sensitisation.
Interpretation of results:
other: GHS criteria not met by structural analogue
Conclusions:
The final consensus result predicted assigned based on the above results:
trisodium 8-hydroxypyrene-1,3,6-trisulfonate is predicted as a non-sensitising to the skin.
Conclusions from published data: Non-sensitiser to the skin
Klimisch score assigned by the study investigator for the final prediction: K2
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Both structures for the substancesTetrasodium 1,3,6,8-pyrenetetrasulfonate and 8-hydroxypyrene-1,3,6-trisulfonate are expected to have very similar (eco)toxicological profiles. Moreover, the Read-Across substance being less hydrophilic than the query substance and having a more toxic MechoA, the prediction of (eco)toxicological endpoints will be a worst-case scenario, because the less hydrophilic a substance is, the more toxic it is.

Consequently, trisodium 8-hydroxypyrene-1,3,6-trisulfonate is judged to be a good Read-Across for tetrasodium 1,3,6,8-pyrenetetrasulfonate.

Comparison with the QSAR results for the analogue substance, together with the available data on the analogue substance indicate that testing using 8-hydroxypyrene-1,3,6-trisulfonate would not be expected to show evidence of sensitization.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Multiple Quantitative Structure Activity Relationship (QSAR) models were used to predict the Skin Sensitisation potential of the test item Tetrasodium 1,3,6,8-pyrenetetrasulfonate. These QSAR models has been designed to be used for regulatory purposes and based on the QSAR results, the report predicts the consensus endpoint value which would be expected when testing the substance under experimental conditions in a laboratory following the OECD Guideline for Testing of Chemicals No. 429: Skin Sensitisation.

Based on multiple QSAR models applied, Tetrasodium 1,3,6,8-pyrenetetrasulfonate was predicted as non-sensitising to the skin and as such does not meet the criteria for classification.

The final QSAR result can be associated with a Klimisch score: K2