1,3,6,8-Pyrenetetrasulfonic acid, sodium salt

Endpoint summary

Description of key information

Multiple Quantitative Structure Activity Relationship (QSAR) models were used to predict the the Acute Oral Toxicity of the test item Tetrasodium 1,3,6,8-pyrenetetrasulfonate. The final acute oral toxicity was predicted by applying a consensus method on the reliable results derived for individual models.The final Ready Biodegradability predicted for

Tetrasodium 1,3,6,8-pyrenetetrasulfonateassigned by the study investigator: non readily biodegradable. Based on multiple QSAR models applied, the final Acute Oral Toxicity for Tetrasodium 1,3,6,8-pyrenetetrasulfonate was predicted as 170000 mg/kg/d (Oral Rat LD₅₀). The final QSAR result can be associated with a Klimisch score: K2

The same method was used to predict the Acute Oral Toxicity of the analogue test item trisodium 8-hydroxypyrene-1,3,6-trisulfonate. The final acute oral toxicity predicted for trisodium 8-hydroxypyrene-1,3,6-trisulfonate assigned by the study investigator: LD₅₀ 58000 mg/kg/bw. Klimisch score assigned by the study investigtor for the final prediction: K2

Test results published on the ECHA website provided a LD₅₀ of 15000 mg/kg/bw for Acute Oral Toxicity for the analogue test item trisodium 8-hydroxypyrene-1,3,6-trisulfonate.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

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

2. MODEL (incl. version number)
ACDLabs model for Acute Oral toxicity in Rats

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. 401: Acute Oral Toxicity”. .

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. 401: Acute Oral Toxicity”.

6. ADEQUACY OF THE RESULT
Based on multiple QSAR models applied, the final Acute Oral Toxicity for Tetrasodium 1,3,6,8-pyrenetetrasulfonate was predicted as 170000 mg/kg/d (Oral Rat LD50).
The final acute oral toxicity was predicted 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 401 (Acute Oral Toxicity)

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

Dose descriptor:

LD50

Effect level:

170 000 mg/kg bw

Remarks on result:

other: ACDLabs model for Acute Oral toxicity in Rats

Interpretation of results:

GHS criteria not met

Conclusions:

The final Acute Oral Toxicity (Oral Rat LD50) predicted for Tetrasodium 1,3,6,8-pyrenetetrasulfonate assigned by the study investigator: 170000 mg/kg.
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 Oral Toxicity 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. 401: Acute Oral Toxicity”.

 

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

·       Danish QSAR Database

 

 Results.

Based on multiple QSAR models applied, the final Acute Oral Toxicity for Tetrasodium 1,3,6,8-pyrenetetrasulfonate was predicted as 170000 mg/kg/d (Oral Rat LD₅₀).

The final acute oral toxicity was predicted 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

Reference 2

Endpoint:

acute toxicity: oral

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:

test procedure in accordance with national standard methods with acceptable restrictions

Justification for type of information:

1. SOFTWARE
Danish QSAR Database

2. MODEL (incl. version number)
ACDLabs model for Acute Oral toxicity in Rats

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. 401: Acute Oral Toxicity”. .

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. 401: Acute Oral Toxicity”.

6. ADEQUACY OF THE RESULT
Based on multiple QSAR models applied, the final Acute Oral Toxicity for trisodium 8-hydroxypyrene-1,3,6-trisulfonate was predicted as 58000 mg/kg/d (Oral Rat LD50).
The final acute oral toxicity was predicted 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 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 401 (Acute Oral Toxicity)

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

Dose descriptor:

LD50

Remarks:

Rat

Effect level:

58 000 mg/kg bw

Remarks on result:

other: Danish QSAR Database

Dose descriptor:

LD50

Effect level:

> 15 000 mg/kg bw

Remarks on result:

other: Experimental data from the ECHA dossier for Acute oral toxicity (Rat LD50): https://echa.europa.eu/registration-dossier/-/registered-dossier/17360/7/3/2

Dose descriptor:

LD50

Remarks:

Mouse

Effect level:

7 100 mg/kg bw

Remarks on result:

other: Danish QSAR Database

Interpretation of results:

other: GHS criteria not met for structural analogue.

Conclusions:

The final Acute Oral Toxicity (Oral Rat LD50) predicted for trisodium 8-hydroxypyrene-1,3,6-trisulfonate assigned by the study investigator: 58000 mg/kg.
Klimisch score assigned by the study investigator for the final prediction: K2

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

170 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

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 toxicity.

Justification for classification or non-classification

Multiple Quantitative Structure Activity Relationship (QSAR) models were used to predict the Acute Oral Toxicity 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. 401: Acute Oral Toxicity”.

Based on multiple QSAR models applied, the final Acute Oral Toxicity for Tetrasodium 1,3,6,8-pyrenetetrasulfonate was predicted as 170000 mg/kg/d (Oral Rat LD₅₀).

The final acute oral toxicity was predicted 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

Based on the result of 170000 mg/kg/d the substance can be considered to be not classified for acute oral toxicity.