Bis(4-hydroxy-N-methylanilinium) sulphate

Short-term toxicity to aquatic invertebrates

Link to relevant study record(s)

Reference

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

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 limited documentation / justification

Justification for type of information:

Data is from OECD QSAR toolbox version.3.3 and QMRF report has been attached.

Qualifier:

according to guideline

Guideline:

other: Predicted data

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3 with log kow as the primary discriptors.

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material: p-Methylaminophenol sulfate- IUPAC name: Bis(4-hydroxy-N-methylanilinium) sulphate- Molecular formula: C14H20N2O6S- Molecular weight: 344.386 g/mole- Smiles:CNc1ccc(cc1)O.CNc1ccc(cc1)O.OS(=O)(=O)O- Inchl: 1S/2C7H9NO.H2O4S/c2*1-8-6-2-4-7(9)5-3-6;1-5(2,3)4/h2*2-5,8-9H,1H3;(H2,1,2,3,4)- Substance type: Organic- Physical state: Solid crystalline (off white - white)

Analytical monitoring:

not specified

Vehicle:

not specified

Test organisms (species):

Daphnia magna

Test type:

static

Water media type:

freshwater

Limit test:

no

Total exposure duration:

48 h

Key result

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

0.724 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

mobility

Remarks on result:

other: toxic

The prediction was based on dataset comprised from the following descriptors: EC50
Estimation method: Takes average value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

((((((((((("a" or "b" or "c" )  and ("d" and ( not "e") )  )  and "f" )  and "g" )  and "h" )  and "i" )  and "j" )  and "k" )  and ("l" and ( not "m") )  )  and "n" )  and ("o" and "p" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Phenols (Acute toxicity) by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Strong binder, NH2 group OR Very strong binder, OH group by Estrogen Receptor Binding ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Phenols, Poly by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.3

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide Side Chain OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Primary Aromatic Amines OR Radical OR Radical >> Generation of ROS by glutathione depletion (indirect) OR Radical >> Generation of ROS by glutathione depletion (indirect) >> Haloalkanes Containing Heteroatom OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitro Azoarenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR SN1 OR SN1 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Fused-Ring Primary Aromatic Amines OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitro Azoarenes OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters OR SN2 >> Alkylation, direct acting epoxides and related OR SN2 >> Alkylation, direct acting epoxides and related >> Epoxides and Aziridines OR SN2 >> DNA alkylation OR SN2 >> DNA alkylation >> Alkylphosphates, Alkylthiophosphates and Alkylphosphonates OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Haloalkanes Containing Heteroatom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters by DNA binding by OASIS v.1.3

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Strong binder, NH2 group AND Very strong binder, OH group by Estrogen Receptor Binding ONLY

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Not calculated by Hydrolysis half-life (Kb, pH 7)(Hydrowin) ONLY

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OECD ONLY

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OASIS v1.3 ONLY

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Class 3 (unspecific reactivity) by Acute aquatic toxicity classification by Verhaar (Modified) ONLY

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Reactive unspecified by Acute aquatic toxicity MOA by OASIS ONLY

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Non-Metals by Groups of elements

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Alkali Earth by Groups of elements

Domain logical expression index: "n"

Similarity boundary:Target: CN{+}(c1ccc(O)cc1).O{-}S(=O)(=O)O{-}.N{+}(C)c1ccc(O)cc1
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is >= 2.52

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is <= 6.1

Conclusions:

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the closest read across substances, the toxicity on aquatic invertebrate predicted for bis(4-hydroxy-N-methylanilinium) sulfate (CAS: 55-55-0). Effect concentration i.e EC50 value estimated to be 0.724 mg/l for Daphnia magna for 48 hrs duration. It can be concluded that the bis(4-hydroxy-N-methylanilinium) sulfate (CAS: 55-55-0) is likely to be toxic to aquatic invertebrate, hence it can be considered to be “Aquatic Acute 1” as per the CLP classification criteria for aquatic environment.

Executive summary:

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the closest read across substances, the toxicity on aquatic invertebrate predicted for bis(4-hydroxy-N-methylanilinium) sulfate (CAS: 55-55-0). Effect concentration i.e EC50 value estimated to be 0.724 mg/l for Daphnia magna for 48 hrs duration. It can be concluded that the bis(4-hydroxy-N-methylanilinium) sulfate (CAS: 55-55-0) is likely to be toxic to aquatic invertebrate, hence it can be considered to be “Aquatic Acute 1” as per the CLP classification criteria for aquatic environment.

Description of key information

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the closest read across substances, the toxicity on aquatic invertebrate predicted for bis(4-hydroxy-N-methylanilinium) sulfate (CAS: 55-55-0). Effect concentration i.e EC50 value estimated to be 0.724 mg/l for Daphnia magna for 48 hrs duration. It can be concluded that the bis(4-hydroxy-N-methylanilinium) sulfate (CAS: 55-55-0) is likely to be toxic to aquatic invertebrate, hence it can be considered to be “Aquatic Acute 1” as per the CLP classification criteria for aquatic environment.

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Effect concentration:

0.724 mg/L

Additional information

Following studies include the predicted data and experimental study for the target chemical and structurally similar read across to conclude the toxicity extent of 4-aminophenol (CAS: 55-55-0) towards aquatic invertebrate is summarized as follows:

 

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the closest read across substances, the toxicity on aquatic invertebrate predicted for bis(4-hydroxy-N-methylanilinium) sulfate (CAS: 55-55-0). Effect concentration i.e EC50 value estimated to be 0.724 mg/l for Daphnia magna for 48 hrs duration. It can be concluded that the bis(4-hydroxy-N-methylanilinium) sulfate (CAS: 55-55-0) is likely to be toxic to aquatic invertebrate, hence it can be considered to be“Aquatic Acute 1”as per the CLP classification criteria for aquatic environment.

 

Further it is supported by the experimental study of structurally similar read across 4-aminophenol (CAS: 123-30-8) from the publication Water Research 1989 suggests that the Short-term toxicity to aquatic invertebrates test was carried out for 48 hr to study the effects of 4-aminophenol. The effective concentration to 50% of Daphnia magna at 48 hrs is 0.24 mg/L. The number of animals in the control and test solutions that could still swim were counted. It can be concluded form the value that the 4-aminophenol is toxic to the aquatic environment.

 

Another experimental study of structurally similar read across 4-aminophenol (CAS: 123-30-8) from the

J-check 2010, indicates that the Short-term toxicity to aquatic invertebrates test was carried according to the OECD Guideline 202 (Daphnia sp. Acute Immobilisation Test). Immobilizationwas observed during the test. The effective concentrationEC50 to 50% of Daphnia magnain 48 hr is 0.315 mg/L. It can be concluded from the value that the 4-aminophenol is toxic to the aquatic environment and can be considered as“Aquatic Acute 1”as per the classification for aquatic environment.

 

Thus based on the effect concentrations which is in the range 0.019 mg/l to 0.724 mg/l give the conclusion that test substance 4-aminophenol (CAS: 55-55-0) was likely to be toxic to aquatic invertebrate at environmentally relevant concentrations and applying weight of evidence approach it can be considered to be“Aquatic Acute 1”as per the CLP classification criteria.