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Endpoint:
relative density
Type of information:
(Q)SAR
Adequacy of study:
key study
Study period:
2 December 2018 to 3 December 2018
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model, but not (completely) falling into its applicability domain, with adequate and reliable documentation / justification
Justification for type of information:
1. SOFTWARE
Chemistry Dashboard (ACD Labs)
Chemistry Dashboard (T.E.S.T. v4.2.1 US EPA)

2. MODEL (incl. version number)
ACD Labs
T.E.S.T. v4.2.1

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.109: “Density of Liquids and Solids”.

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.109: “Density of Liquids and Solids”.

6. ADEQUACY OF THE RESULT
Based on the QSAR used, the final Density for Tetrasodium 1,3,6,8-pyrenetetrasulfonate was predicted as 2105 mg/cm3.
The final Density was derived by applying a consensus method on the reliable results derived from the two methodologies. 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 109 (Density of Liquids and Solids)
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:
relative density
Density:
2.015 g/cm³
Remarks on result:
other: Consensus result derived from combining results from individual models.
Type:
relative density
Density:
2.15 g/cm³
Remarks on result:
other: US EPA TEST
Type:
relative density
Density:
2.06 g/cm³
Remarks on result:
other: ACD Labs
Conclusions:
The final Density predicted for Tetrasodium 1,3,6,8-pyrenetetrasulfonate assigned by the study investigator: 2105 mg/cm3 (Average of the final results from two different methods in the applied model).
Klimisch score assigned by the study investigator for the final prediction: K2
Executive summary:

Introduction. A Quantitative Structure Activity Relationship (QSAR) model were used to predict the Density of the test item Tetrasodium 1,3,6,8-pyrenetetrasulfonate. 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.109: “Density of Liquids and Solids”.

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

·       US EPA T.E.S.T v4.2.1 (via chemistry dashboard)

·       ACD/Labs (via chemistry dashboard)

 

 Results.

Based on the QSAR used, the final Density for Tetrasodium 1,3,6,8-pyrenetetrasulfonate was predicted as 2105 mg/cm3.

The final Density was derived by applying a consensus method on the reliable results derived from the two methodologies. The final QSAR result can be associated with a Klimisch score: K2

Endpoint:
relative density
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 to 3 December 2018
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model, but not (completely) falling into its applicability domain, with adequate and reliable documentation / justification
Justification for type of information:
QSAR information

1. SOFTWARE
Chemistry Dashboard (ACD Labs)
Chemistry Dashboard (T.E.S.T. v4.2.1 US EPA)

2. MODEL (incl. version number)
ACD Labs
T.E.S.T. v4.2.1

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.109: “Density of Liquids and Solids”.

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.109: “Density of Liquids and Solids”.

6. ADEQUACY OF THE RESULT
Based on the QSAR used, the final Density for trisodium 8-hydroxypyrene-1,3,6-trisulfonate was predicted as 2045 mg/cm3.
The final Density was derived by applying a consensus method on the reliable results derived from the two methodologies. The final QSAR result can be associated with a Klimisch score: K2

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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 (Experimental study, key value JS Member opt-out) suggest that there the selection of these QSAR models to predict the Relative Density 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 109 (Density of Liquids and Solids)
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:
relative density
Density:
2.045 g/cm³
Remarks on result:
other: Consensus result derived from combining results from individual models.
Type:
relative density
Density:
2.09 g/cm³
Remarks on result:
other: US EPA TEST
Type:
relative density
Density:
2 g/cm³
Remarks on result:
other: ACD Labs
Type:
relative density
Density:
1.857 g/cm³
Temp.:
20 °C
Remarks on result:
other: (key study, JS Member opt-out) Experimental data retrieved from the ECHA dossier https://echa.europa.eu/registration-dossier/-/registered-dossier/17360/4/4/?documentUUID=d2128fd4-aa13-4dbf-9e08-337c4b4b9297
Remarks:
In our understanding, the result of 1857 mg/cm3 appears to be more accurate.
Type:
relative density
Density:
0.715 g/cm³
Temp.:
20 °C
Remarks on result:
other: (key study) Experimental data retrieved from the ECHA dossier https://echa.europa.eu/registration-dossier/-/registered-dossier/17360/4/4/?documentUUID=d2128fd4-aa13-4dbf-9e08-337c4b4b9297
Remarks:
In our understanding, the result of 1857 mg/cm3 appears to be more accurate.
Conclusions:
The final Density predicted for trisodium 8-hydroxypyrene-1,3,6-trisulfonate assigned by the study investigator: 2045 mg/cm3 (Average of the final results from two different methods in the applied model).
Klimisch score assigned by the study investigator for the final prediction: K2

Description of key information

A Quantitative Structure Activity Relationship (QSAR) model were used to predict the Density of the test item Tetrasodium 1,3,6,8-pyrenetetrasulfonate.

Based on the QSAR used, the final Density for Tetrasodium 1,3,6,8-pyrenetetrasulfonate was predicted as 2105 mg/cm3.

The final Density was derived by applying a consensus method on the reliable results derived from the two methodologies. The final QSAR result can be associated with a Klimisch score: K2

The same method was used to predict the Density of the analogue test item trisodium 8-hydroxypyrene-1,3,6-trisulfonate. The final density predicted for trisodium 8-hydroxypyrene-1,3,6-trisulfonate assigned by the study investigator: 2045 mg/cm3. Klimisch score assigned by the study investigtor for the final prediction: K2

Test results published on the ECHA website provided a result of 1857 mg/cm3 for density for the analogue test item trisodium 8-hydroxypyrene-1,3,6-trisulfonate.

Although not completely within the compatability domain and taking into consideration the data available on the analogue substance, it can be concluded 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

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 (Experimental study, key value JS Member opt-out) suggest that the selection of these QSAR models to predict the Relative Density of the query and read-across substance was valid and reliable.