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

Toxicity to aquatic algae and cyanobacteria

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

toxicity to aquatic algae and cyanobacteria

Data waiving:

study technically not feasible

Justification for data waiving:

other:

Justification for type of information:

A review of the toxicity of fluorescent water tracers carried out by H. Behrens et al in 2001 concluded that due to interferences caused by the fluorescence of most tracers, the algae test required as a base-set test for the ecotoxicological assessment of chemicals under the German Chemicals Act (1994) provided no conclusive results and therefore could not be used for ecotoxicological assessments.

Reference 2

Endpoint:

toxicity to aquatic algae and cyanobacteria

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:

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
Battery of SciQSAR and Leadscope models incorporated into Danish QSAR Database
EPIsuite

2. MODEL (incl. version number)
Battery of SciQSAR and Leadscope models
ECOSAR

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. 201, "Freshwater Alga and Cyanobacteria, Growth Inhibition Test".

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. 201, "Freshwater Alga and Cyanobacteria, Growth Inhibition Test".

6. ADEQUACY OF THE RESULT
Based on multiple QSAR models applied, the final Acute Aquatic Toxicity to Algae (72h ErC50) for Tetrasodium 1,3,6,8-pyrenetetrasulfonate was predicted as 84687.83 mg/L.
The final Acute Aquatic Toxicity to Algae (72h ErC50) 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 201 (Freshwater Alga and Cyanobacteria, Growth Inhibition Test)

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

Effect conc.:

84 687.83 mg/L

Remarks on result:

other: geometric mean

Effect conc.:

14 500.01 mg/L

Remarks on result:

other: Leadscope (via Danish QSAR Database)

Remarks:

inside applicability domain

Effect conc.:

173 811.2 mg/L

Remarks on result:

other: SciQSAR (via Danish QSAR Database)

Remarks:

inside applicablity domain

Effect conc.:

241 000 mg/L

Remarks on result:

other: ECOSAR (via EPISuite)

Remarks:

neutral organics - Acid

Conclusions:

Based on the methodology discussed in section 2 of this report and combining the results derived from individual models discussed earlier in this section:
The final Acute Aquatic Toxicity to Algae (72h ErC50) predicted for Tetrasodium 1,3,6,8-pyrenetetrasulfonate assigned by the study investigator: 84687.83 mg/L
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 Aquatic Toxicity to Algae (72h ErC50) 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. 201, "Freshwater Alga and Cyanobacteria, Growth Inhibition Test"

 

Methods. The purpose of the in silico study was to predict the Acute Aquatic Toxicity to Algae (72h ErC50) of the test item Tetrasodium 1,3,6,8-pyrenetetrasulfonate. This prediction was performed using the following QSAR models.

·       Battery of SciQSAR and Leadscope models incorporated into Danish QSAR Database

 

·       ECOSAR (via EPIsuite) 

 

Results.

Based on multiple QSAR models applied, the final Acute Aquatic Toxicity to Algae (72h ErC50) for Tetrasodium 1,3,6,8-pyrenetetrasulfonate was predicted as 84687.83 mg/L.

The final Acute Aquatic Toxicity to Algae (72h ErC50) 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 3

Endpoint:

toxicity to aquatic algae and cyanobacteria

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
Battery of SciQSAR and Leadscope models incorporated into Danish QSAR Database
EPIsuite

2. MODEL (incl. version number)
Battery of SciQSAR and Leadscope models
ECOSAR

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. 201, "Freshwater Alga and Cyanobacteria, Growth Inhibition Test".

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. 201, "Freshwater Alga and Cyanobacteria, Growth Inhibition Test".

6. ADEQUACY OF THE RESULT
Based on multiple QSAR models applied, the final Acute Aquatic Toxicity to Algae (72h ErC50) for trisodium 8-hydroxypyrene-1,3,6-trisulfonate was predicted as 12075.55 mg/L.
The final Acute Aquatic Toxicity to Algae (72h ErC50) 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 201 (Freshwater Alga and Cyanobacteria, Growth Inhibition Test)

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

Effect conc.:

12 075.55 mg/L

Remarks on result:

other: geometric mean

Effect conc.:

200 mg/L

Remarks on result:

other: Experimental data from the ECHA dossier: https://echa.europa.eu/registration-dossier/-/registered-dossier/17360/6/2/6/?documentUUID=2352f92d-08d2-486d-9062-4b3acac1c66e

Effect conc.:

9 980.52 mg/L

Remarks on result:

other: Leadscope (via Danish QSAR Database)

Remarks:

inside applicability domain

Effect conc.:

17 566 mg/L

Remarks on result:

other: SciQSAR (via Danish QSAR Database)

Remarks:

inside applicablity domain

Effect conc.:

10 043.72 mg/L

Remarks on result:

other: ECOSAR (via EPISuite)

Remarks:

neutral organics - SAR

Conclusions:

The final Acute Aquatic Toxicity to Algae (72h ErC50) predicted for trisodium 8-hydroxypyrene-1,3,6-trisulfonate assigned by the study investigator: 12075.55 mg/L
Klimisch score assigned by the study investigator for the final prediction: K2

Description of key information

It was not considered to be feasible to conduct a study to assess the acute aquatic toxicity to algae due to interferences caused by the fluorescence of most tracers.

Multiple Quantitative Structure Activity Relationship (QSAR) models were used to predict the Acute Aquatic Toxicity to Algae (72h ErC50) f the test item Tetrasodium 1,3,6,8-pyrenetetrasulfonate.The final Acute Aquatic Toxicity to Algae (72h ErC50)

predicted for Tetrasodium 1,3,6,8-pyrenetetrasulfonate assigned by the study investigator: 84687.83 mg/L. Klimisch score assigned by the study investigator for the final prediction: K2

The same method was used to predict the Acute Aquatic Toxicity to Algae (72h ErC50) of the analogue test itemtrisodium 8-hydroxypyrene-1,3,6-trisulfonate.The final Acute Aquatic Toxicity to Algae (72h ErC50) predicted for trisodium 8-hydroxypyrene-1,3,6-trisulfonateassigned by the study investigator: 12075.55 mg/L. Klimisch score assigned by the study investigtor for the final prediction: K2

Test results published on the ECHA website provided a conclusion of 200 mg/L for Acute Aquatic Toxicity to Algae (72h ErC50) for the analogue test item trisodium 8-hydroxypyrene-1,3,6-trisulfonate

Key value for chemical safety assessment

EC50 for freshwater algae:

100 mg/L

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.

Although not completely within the applicability domain, comparison with the QSAR results for the analogue substance, together with the available data on the analogue substance indicate that testing (should conditions be feasible) using 8-hydroxypyrene-1,3,6-trisulfonate would not be expected to show evidence of toxicity.

Conclusion: Using Multiple Quantitative Structure Activity Relationship (QSAR) models to predict the Acute Aquatic Toxicity to Algae (72h ErC50) of the test item Tetrasodium 1,3,6,8-pyrenetetrasulfonate, the final Acute Aquatic Toxicity to Algae (72h ErC50) predicted for Tetrasodium 1,3,6,8-pyrenetetrasulfonate was 84687.83 mg/L. Although not completely within the compatability domain and taking into consideration the data available on the analogue substance, it can be concluded that under test conditions (should conditions be feasible) a 72h ErC50 of > 100 mg/L can be expected. Based on this, the test material Tetrasodium 1,3,6,8-pyrenetetra sulfonate is not considered to be toxic to Algae at < 100 mg/L.