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Partition coefficient

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Endpoint:
partition coefficient
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
ACD/Labs Consensus
ACD/Labs
Chemistry Dashboard (OPERA v1.5)
Chemistry Dashboard (NICEATM)

2. MODEL (incl. version number)
ACD/Labs Consensus
ACD/Labs
OPERA v1.5
NICEATM

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. 107: Partition Coefficient (n-octanol/water): Shake Flask Method”.
Please see attached QMRF for further details.

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. 107: Partition Coefficient (n-octanol/water): Shake Flask Method”.

6. ADEQUACY OF THE RESULT
Based on multiple QSAR models applied, the final n-Octanol/water partition coefficient for Tetrasodium 1,3,6,8-pyrenetetrasulfonate was predicted as -0.37.
The final n-Octanol/water partition coefficient was derived by applying a consensus method on the reliable results derived for individual models. 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 107 (Partition Coefficient (n-octanol / water), Shake Flask Method)
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+]
Key result
Type:
log Pow
Partition coefficient:
-0.37
Remarks on result:
other: Average of the final results from the four models.
Type:
log Pow
Partition coefficient:
0.595
Remarks on result:
other: NICEATM
Type:
log Pow
Partition coefficient:
0.21
Remarks on result:
other: ACD/Labs Consensus
Type:
log Pow
Partition coefficient:
-3.17
Remarks on result:
other: ACD/Labs
Type:
log Pow
Partition coefficient:
0.899
Remarks on result:
other: OPERA v1.5
Conclusions:
The final n-Octanol/water partition coefficient predicted for Tetrasodium 1,3,6,8-pyrenetetrasulfonate assigned by the study investigator: -0.37 (Average of the final results from the four models).
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 log n-Octanol/ water partition coefficient 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. 107: Partition Coefficient (n-octanol/water): Shake Flask Method”.

Methods. The purpose of the in silico study was to predict the log n-Octanol/ water partition coefficient of the test item Tetrasodium 1,3,6,8-pyrenetetrasulfonate. This prediction was performed using the following QSAR models reported in the Chemistry Dashboard (https://comptox.epa.gov/dashboard)

·       ACD/Labs Consensus

·       ACD/Labs

·       OPERA v1.5 (via Chemistry Dashboard)

·       NICEATM (via Chemistry Dashboard)

 

Results.

Based on multiple QSAR models applied, the final n-Octanol/water partition coefficient for Tetrasodium 1,3,6,8-pyrenetetrasulfonate was predicted as-0.37.

The final n-Octanol/water partition coefficient was derived by applying a consensus method on the reliable results derived for individual models. The final QSAR result can be associated with a Klimisch score:K2

Endpoint:
partition coefficient
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:
QSAR information

1. SOFTWARE
ACD/Labs Consensus
ACD/Labs
Chemistry Dashboard (OPERA v1.5)
Chemistry Dashboard (NICEATM)

2. MODEL (incl. version number)
ACD/Labs Consensus
ACD/Labs
OPERA v1.5
NICEATM

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. 107: Partition Coefficient (n-octanol/water): Shake Flask Method”.
Please see attached QMRF for further details.

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. 107: Partition Coefficient (n-octanol/water): Shake Flask Method”.

6. ADEQUACY OF THE RESULT
Based on multiple QSAR models applied, the final n-Octanol/water partition coefficient for trisodium 8-hydroxypyrene-1,3,6-trisulfonate was predicted as -0.38.
The final n-Octanol/water partition coefficient was derived by applying a consensus method on the reliable results derived for individual models. 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 101) 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.

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 physico-chemical properties. Moreover, Read-Across substance being less hydrophilic than the query substance, it will be a worst-case (or conservative) prediction, for instance when estimating the accumulation potential of the substance.
Consequently, trisodium 8-hydroxypyrene-1,3,6-trisulfonate is judged to be a good Read-Across for tetrasodium 1,3,6,8-pyrenetetrasulfonate.
Conclusion: Strong similarity between the predicted and experimental values suggest that there the selection of QSAR models to predict the Log Kow of the query and read-across substance was valid and reliable.
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 107 (Partition Coefficient (n-octanol / water), Shake Flask Method)
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
Key result
Type:
log Pow
Partition coefficient:
-0.38
Remarks on result:
other: Average of the final results from the four models.
Type:
log Pow
Partition coefficient:
-0.68
Remarks on result:
other: Experimental data retrieved from the ECHA dossier https://echa.europa.eu/registration-dossier/-/registered-dossier/17360/4/8
Type:
log Pow
Partition coefficient:
0.215
Remarks on result:
other: NICEATM
Type:
log Pow
Partition coefficient:
-0.938
Remarks on result:
other: ACD/Labs Consensus
Type:
log Pow
Partition coefficient:
-2.04
Remarks on result:
other: ACD/Labs
Type:
log Pow
Partition coefficient:
1.25
Remarks on result:
other: OPERA v1.5
Conclusions:
The final n-Octanol/water partition coefficient predicted for trisodium 8-hydroxypyrene-1,3,6-trisulfonate assigned by the study investigator: -0.38 (Average of the final results from the four models).
Klimisch score assigned by the study investigator for the final prediction: K2

Description of key information

Multiple Quantitative Structure Activity Relationship (QSAR) models were used to predict the log n-Octanol/ water partition coefficient of the test item Tetrasodium 1,3,6,8-pyrenetetrasulfonate.

Based on multiple QSAR models applied, the final n-Octanol/water partition coefficient for Tetrasodium 1,3,6,8-pyrenetetrasulfonatewas predicted as -0.37.

The final n-Octanol/water partition coefficient was derived by applying a consensus method on the reliable results derived for individual models. The final QSAR result can be associated with a Klimisch score:K2

The same method was used to predict the log n-Octanol/water partition coefficient of the analogue test item trisodium 8-hydroxypyrene-1,3,6-trisulfonate. The final log n-Octanol/water partition/water coefficient predicted for trisodium 8-hydroxypyrene-1,3,6-trisulfonate assigned by the study investigator: -0.38. Klimisch score assigned by the study investigtor for the final prediction: K2

Test results published on the ECHA website provided a result of -0.68 for log n-Octanol/water partition coefficient for the analogue test item trisodium 8-hydroxypyrene-1,3,6-trisulfonate.

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 be expected to provide a result consistent with that generated using QSAR.

Key value for chemical safety assessment

Log Kow (Log Pow):
-0.37

Additional information

Both the structures are expected to have very similar physico-chemical properties. Moreover, Read-Across substance being less hydrophilic than the query substance, it will be a worst-case (or conservative) prediction, for instance when estimating the accumulation potential of the substance.

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

Conclusion: Strong similarity between the predicted and experimental values suggest that there the selection of QSAR models to predict the Log Kow of the query and read-across substance was valid and reliable.