Bis(4-hydroxy-N-methylanilinium) sulphate

Toxicity to aquatic algae and cyanobacteria

Link to relevant study record(s)

Reference

Endpoint:

toxicity to aquatic algae and cyanobacteria

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):

Raphidocelis subcapitata (previous names: Pseudokirchneriella subcapitata, Selenastrum capricornutum)

Test type:

static

Water media type:

freshwater

Limit test:

no

Total exposure duration:

72 h

Key result

Duration:

72 h

Dose descriptor:

EC50

Effect conc.:

0.506 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

growth rate

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 ( not "g") )  )  and "h" )  and "i" )  and ("j" and ( not "k") )  )  and ("l" and ( not "m") )  )  and ("n" and ( not "o") )  )  and ("p" and ( not "q") )  )  and ("r" and "s" )  )

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 Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide Side Chain 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) >> Nitroaniline Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR SN1 OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroaniline Derivatives OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR SN2 OR SN2 >> Alkylation, direct acting epoxides and related OR SN2 >> Alkylation, direct acting epoxides and related >> Epoxides and Aziridines OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Haloalkanes Containing Heteroatom by DNA binding by OASIS v.1.3

Domain logical expression index: "f"

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

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Michael addition OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Alkyl phenols OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Hydroquinones OR SN1 OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine by DNA binding by OECD

Domain logical expression index: "h"

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: "i"

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: "j"

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

Domain logical expression index: "k"

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

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Aliphatic Amine, secondary AND Ammonium salt AND Aryl AND Phenol AND Precursors quinoid compounds by Organic Functional groups

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as tert-Butyl by Organic Functional groups

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Aliphatic Amine, secondary AND Ammonium salt AND Aryl AND Phenol AND Precursors quinoid compounds by Organic Functional groups

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Dihydroxyl group by Organic Functional groups

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Anion AND Aromatic compound AND Cation AND Hydroxy compound AND Phenol AND Primary aliphatic amine AND Primary amine AND Primary aromatic amine AND Sulfuric acid derivative by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Primary alcohol by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "r"

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

Domain logical expression index: "s"

Parametric boundary:The target chemical should have a value of log Kow which is <= 5.97

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 algae predicted for bis(4-hydroxy-N-methylanilinium) sulfate (CAS: 55-55-0). Effect concentration i.e EC50 value estimated to be 0.506 mg/l for Pseudokirchneriella subcapitata for 72 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 algae, 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 algae predicted for bis(4-hydroxy-N-methylanilinium) sulfate (CAS: 55-55-0). Effect concentration i.e EC50 value estimated to be 0.506 mg/l for Pseudokirchneriella subcapitata for 72 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 algae, 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 algae predicted for bis(4-hydroxy-N-methylanilinium) sulfate (CAS: 55-55-0). Effect concentration i.e EC50 value estimated to be 0.506 mg/l for Pseudokirchneriella subcapitata for 72 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 algae, 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

EC50 for freshwater algae:

0.506 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 algae 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 algae predicted for bis(4-hydroxy-N-methylanilinium) sulfate (CAS: 55-55-0). Effect concentration i.e EC50 value estimated to be 0.506 mg/l for Pseudokirchneriella subcapitata for 72 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 algae, hence it can be considered to be “Aquatic Acute 1" as per the CLP classification criteria for aquatic environment.

The above predicted data of the target chemical is assissted by the exeprimental study of structurally similar read across Oxybenzone (CAS:131-57-7) from Chemosphere 2014, indicates that the Aquatic algae and cyanobacteria test was carried for 72 Hour(s) under static condition to study the effects of Oxybenzone on aquatic algae. The test was carried out at temp: 20 C, pH:~ 8, salinity: 34 0/00, DISSOLVED OXYGEN: >= 8 mg/L, Population growth rate was measured during the test.

Lowest observable effect concentration (LOEC) to Isochrysis galbana 0.3 mg/L at 72 hrs. It can be concluded that Oxybenzone is toxic to the aquatic algae and can be considered as “aquatic acute 1” a per classification for aquatic environment.

Further it is supported by another exeprimental study ofstructurally similar read across 4-aminophenol (CAS:123-30 -8) from J-check database indicates that effective concentration EC50 to 50% ofPseudokirchnerella subcapitata in 72 hr is 0.67mg/L. Growth Inhibition was observed during the test. It can be concluded from the value that the 4-aminophenol is toxic to the aquatic algae 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 0.30 mg/l to 0.67 mg/l give the conclusion that test substance 4-aminophenol (CAS: 55-55-0) was likely to be toxic to aquatic algae 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 for aquatic environment.