Registration Dossier

Administrative data

Description of key information

Multiple Quantitative Structure Activity Relationship (QSAR) models were used to predict the the Acute Demal Irritation/Corrosion and Acute Eye Irritation/Corrosion of the test item Tetrasodium 1,3,6,8-pyrenetetrasulfonate. The final acute dermal irritation/corrosion and acute eye irritation/corrosion were predicted by applying a consensus method on the reliable results derived for individual models.

The final Acute Dermal Irritation/Corrosion predicted for Tetrasodium 1,3,6,8-pyrenetetrasulfonate assigned by the study investigator: non irritant to skin. The final QSAR result can be associated with a Klimisch score:K2

The final Acute Eye Irritation/Corrosion predicted forTetrasodium 1,3,6,8-pyrenetetrasulfonate assigned by the study investigator: non irritant to the eye. The final QSAR result can be associated with a Klimisch score:K2

The same method was used to predict the Acute Dermal Irritation/Corrosion and Acute Eye Irritation/Corrosion of the analogue test item trisodium 8-hydroxypyrene-1,3,6-trisulfonate.

The final acute dermal irriation/corrosion predicted for trisodium 8-hydroxypyrene-1,3,6-trisulfonate assigned by the study investigator: non irritant to skin. Klimisch score assigned by the study investigtor for the final prediction: K2

The final acute eye irriation/corrosion predicted for trisodium 8-hydroxypyrene-1,3,6-trisulfonate assigned by the study investigator: non irritant to the eye. Klimisch score assigned by the study investigtor for the final prediction: K2

Test results published on the ECHA website provided a conclusion of non irritant to skin and eye for Acute Dermal Irritatin/Corrosion and Acute Eye Irritation/Corrosion for the analogue test item trisodium 8-hydroxypyrene-1,3,6-trisulfonate.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vitro / ex vivo
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 adequate and reliable documentation / justification
Justification for type of information:
1. SOFTWARE
Danish QSAR Database
OECD QSAR Toolbox v4.2 (profiling results)
Nexus DEREK v6.0.1

2. MODEL (incl. version number)
SciQSAR, Case Ultra, LeadScope
OECD QSAR Toolbox v4.2 (profiling results)
Nexus DEREK v6.0.1

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. 404: Acute Dermal Irritation/Corrosion.

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. 404: Acute Dermal Irritation/Corrosion.

6. ADEQUACY OF THE RESULT
Based on multiple QSAR models applied, Tetrasodium 1,3,6,8-pyrenetetrasulfonate was predicted as non-irritant 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 404 (Acute Dermal Irritation / Corrosion)
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+]
Irritation / corrosion parameter:
other: Danish QSAR Database, SciQSAR
Vehicle controls validity:
not applicable
Negative controls validity:
not applicable
Positive controls validity:
not applicable
Remarks on result:
no indication of irritation
Remarks:
In silico result (inside the applicability domain)
Irritation / corrosion parameter:
other: Danish QSAR Database, Leadscope
Vehicle controls validity:
not applicable
Negative controls validity:
not applicable
Positive controls validity:
not applicable
Remarks on result:
not determinable
Remarks:
In silico result
Irritation / corrosion parameter:
other: Danish QSAR Database, CASE Ultra
Vehicle controls validity:
not applicable
Negative controls validity:
not applicable
Positive controls validity:
not applicable
Remarks on result:
no indication of irritation
Remarks:
In silico result (inside the applicability domain)
Irritation / corrosion parameter:
other: OECD QSAR Toolbox v4.2
Run / experiment:
Skin irritation/corrosion Exclusion rules by BfR - Group All log Kow<-3.1
Vehicle controls validity:
not applicable
Negative controls validity:
not applicable
Positive controls validity:
not applicable
Remarks on result:
no indication of irritation
Remarks:
In silico result (Inclusion rules not met)
Irritation / corrosion 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 irritation
Remarks:
No structural alerts were triggered with this tool for skin irritation.

Results with Danish QSAR Database

Only the result based on SciQSAR is reliable as it is inside the applicability domain. Based on this model, the query substance will not be classified as irritant to the skin.

Results with OECD QSAR Toolbox v4.2

As per the profiling results, the query substance will not be classified as skin irritant.

 

Results with Nexus DEREK

No structural alerts were triggered with this tool for skin irritation.

Interpretation of results:
GHS criteria not met
Conclusions:
The final consensus result assigned based on the above results:
Tetrasodium 1,3,6,8-pyrenetetrasulfonate is predicted as non-irritant 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 Acute Skin Irritation/Corrosion potential of the test item Tetrasodium 1,3,6,8-pyrenetetrasulfonate. These QSAR models have 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. 404: Acute Dermal Irritation/Corrosion.

Methods.The purpose of the in silico study was to predict the Acute Dermal Irritation/Corrosion of the test item Tetrasodium 1,3,6,8-pyrenetetrasulfonate. This prediction was performed using the following QSAR models:

·       Danish QSAR Database

·       OECD QSAR Toolbox v4.2 (profiling results)

·       Nexus DEREK v6.0.1

 

The final consensus result for acute skin irritation/corrosion 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-irritant to the skin.

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

Endpoint:
skin irritation: in vitro / ex vivo
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
Danish QSAR Database
OECD QSAR Toolbox v4.2 (profiling results)
Nexus DEREK v6.0.1

2. MODEL (incl. version number)
SciQSAR, Case Ultra, LeadScope
OECD QSAR Toolbox v4.2 (profiling results)
Nexus DEREK v6.0.1

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. 404: Acute Dermal Irritation/Corrosion.

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. 404: Acute Dermal Irritation/Corrosion.

6. ADEQUACY OF THE RESULT
Based on multiple QSAR models applied, trisodium 8-hydroxypyrene-1,3,6-trisulfonate was predicted as non-irritant 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 404 (Acute Dermal Irritation / Corrosion)
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
Irritation / corrosion parameter:
other: OECD QSAR Toolbox v4.2
Run / experiment:
Skin irritation/corrosion Exclusion rules by BfR - Group All log Kow<-3.1
Vehicle controls validity:
not applicable
Negative controls validity:
not applicable
Positive controls validity:
not applicable
Remarks on result:
no indication of irritation
Remarks:
In silico result (Inclusion rules not met)
Irritation / corrosion parameter:
other: Experimental data from the ECHA dossier: Non-irritant Reference: https://echa.europa.eu/registration-dossier/-/registered-dossier/17360/7/4/1
Remarks on result:
no indication of irritation
Irritation / corrosion parameter:
other: Danish QSAR Database, CASE Ultra
Vehicle controls validity:
not applicable
Negative controls validity:
not applicable
Positive controls validity:
not applicable
Remarks on result:
no indication of irritation
Remarks:
In silico result (inside the applicability domain)
Irritation / corrosion parameter:
other: Danish QSAR Database, SciQSAR
Vehicle controls validity:
not applicable
Negative controls validity:
not applicable
Positive controls validity:
not applicable
Remarks on result:
no indication of irritation
Remarks:
In silico result (inside the applicability domain)
Irritation / corrosion parameter:
other: Danish QSAR Database, Leadscope
Vehicle controls validity:
not applicable
Negative controls validity:
not applicable
Positive controls validity:
not applicable
Remarks on result:
positive indication of irritation
Remarks:
In silico result (inside applicability domain)
Irritation / corrosion parameter:
other: Danish QSAR Database
Run / experiment:
Battery
Vehicle controls validity:
not applicable
Negative controls validity:
not applicable
Positive controls validity:
not applicable
Remarks on result:
not determinable
Remarks:
In silico - inconclusive

Final KREATiS Prediction: Non-irritant

Experimental data from the ECHA dossier: Non-irritant

 

Reference: https://echa.europa.eu/registration-dossier/-/registered-dossier/17360/7/4/1

Interpretation of results:
other: GHS criteria not met for structural analogue
Conclusions:
The final consensus result assigned based on the above results:
trisodium 8-hydroxypyrene-1,3,6-trisulfonate is predicted as non-irritant to the skin.
Klimisch score assigned by the study investigator for the final prediction: K2
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vitro / ex vivo
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:
accepted calculation method
Justification for type of information:
1. SOFTWARE
Nexus
OECD QSAR Toolbox v4.2 (profiling results)

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

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. 405: Acute Eye Irritation/Corrosion.

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. 405: Acute Eye Irritation/Corrosion.

6. ADEQUACY OF THE RESULT
Based on multiple QSAR models applied, Tetrasodium 1,3,6,8-pyrenetetrasulfonate was predicted as Non-irritant to Eye.
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 405 (Acute Eye Irritation / Corrosion)
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+]
Irritation parameter:
other: OECD QSAR Toolbox v4.2
Run / experiment:
Eye irritation/corrosion Inclusion rules by BfR
Vehicle controls validity:
not applicable
Negative controls validity:
not applicable
Positive controls validity:
not applicable
Remarks on result:
no indication of irritation
Remarks:
In silico result (inclusion rules not met)
Irritation parameter:
other: OECD QSAR Toolbox v4.2
Run / experiment:
Eye irritation/corrosion Exclusion rules by BfR
Vehicle controls validity:
not applicable
Negative controls validity:
not applicable
Positive controls validity:
not applicable
Remarks on result:
no indication of irritation
Remarks:
In silico results (Group All log Kow<-3.1,)
Irritation 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 irritation
Remarks:
In silico result - No structural alerts for eye irritation were triggered.

Results with OECD QSAR Toolbox v4.2

As per the profiling results, the query substance will not be classified as eye irritant. 

 

Results with Nexus DEREK 

No structural alerts for eye irritation were triggered.

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 non-irritant to the eye.
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 Acute Eye Irritation/Corrosion 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. 405: Acute Eye Irritation/Corrosion.

Methods.The purpose of the in silico study was to predict the Acute Eye Irritation/Corrosion 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 (profiling results)

 

The final consensus result for Acute Eye Irritation/Corrosion 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-irritant to Eye.

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

Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
(Q)SAR
Adequacy of study:
supporting study
Study period:
2 December 2018 and 3 December 2018
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
accepted calculation method
Justification for type of information:
1. SOFTWARE
Nexus
OECD QSAR Toolbox v4.2 (profiling results)

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

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. 405: Acute Eye Irritation/Corrosion.

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. 405: Acute Eye Irritation/Corrosion.

6. ADEQUACY OF THE RESULT
Based on multiple QSAR models applied, trisodium 8-hydroxypyrene-1,3,6-trisulfonate was predicted as Non-irritant to Eye.
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 405 (Acute Eye Irritation / Corrosion)
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
Irritation parameter:
other: OECD QSAR Toolbox v4.2
Run / experiment:
Eye irritation/corrosion Inclusion rules by BfR
Vehicle controls validity:
not applicable
Negative controls validity:
not applicable
Positive controls validity:
not applicable
Remarks on result:
no indication of irritation
Remarks:
In silico result (inclusion rules not met)
Irritation parameter:
other: OECD QSAR Toolbox v4.2
Run / experiment:
Eye irritation/corrosion Exclusion rules by BfR
Vehicle controls validity:
not applicable
Negative controls validity:
not applicable
Positive controls validity:
not applicable
Remarks on result:
no indication of irritation
Remarks:
In silico results (Group All log Kow<-3.1,)
Irritation parameter:
other: Experimental data from the ECHA dossier: https://echa.europa.eu/registration-dossier/-/registered-dossier/17360/7/4/1
Vehicle controls validity:
not applicable
Negative controls validity:
not applicable
Positive controls validity:
not applicable
Remarks on result:
no indication of irritation

Final KREATiS Prediction: Non-irritant

Experimental data from the ECHA dossier: Non-irritant

 

Reference: https://echa.europa.eu/registration-dossier/-/registered-dossier/17360/7/4/1

Interpretation of results:
other: GHS criteria not met for structural analogue
Conclusions:
The final consensus result predicted assigned based on the above results:
trisodium 8-hydroxypyrene-1,3,6-trisulfonate is predicted as non-irritant to the eye.
Klimisch score assigned by the study investigator for the final prediction: K2
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Both structures for the substances Tetrasodium 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 irritation/corrosion.

Skin irritation

Conclusion: Strong similarity between the predicted and experimental values suggest that the selection of the QSAR models to predict the skin irritation/corrosion of the query and read-across substance was valid and reliable.

Eye irritation

Conclusion: Strong similarity between the predicted and experimental values suggest that the selection of this QSAR models to predict the eye irritation/corrosion of the query and read-across substance was valid and reliable.

Justification for classification or non-classification

Multiple Quantitative Structure Activity Relationship (QSAR) models were used to predict the Acute dermal irritation/corrosion potential and the Acute Eye Irritation/Corrosion 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. 404: Acute Dermal Irritation/Corrosion and OECD Guideline for Testing of Chemicals No. 405: Acute Eye Irritation/Corrosion.

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

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