Sodium phenylacetate

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:

no

Specific details on test material used for the study:

- Name( IUPAC): sodium 2-phenylacetate
- Name of test material (as cited in study report): Sodium phenylacetate
- Molecular formula C8H8O2.Na
- Molecular weight: 158.1313 g/mol
- Smiles notation : c1(ccccc1)CC(=O)[O-].[Na+]
- InChl: 1S/C8H8O2.Na/c9-8(10)6-7-4-2-1-3-5-7;/h1-5H,6H2,(H,9,10);/q;+1/p-1
- Substance type: Organic
- Physical state: solid

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.:

274.09 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

mobility

Remarks on result:

other: not 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" or "d" )  and ("e" and ( not "f") )  )  and ("g" and ( not "h") )  )  and ("i" and ( not "j") )  )  and "k" )  and ("l" and ( not "m") )  )  and ("n" and ( not "o") )  )  and ("p" and "q" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Aryl OR Carboxylic acid by Organic Functional groups ONLY

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Aryl AND Carboxylic acid by Organic Functional groups (nested)

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aromatic Carbon [C] AND Carbonyl, aliphatic attach [-C(=O)-] AND Miscellaneous sulfide (=S) or oxide (=O) AND Olefinic carbon [=CH- or =C<] by Organic functional groups (US EPA)

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Anion AND Aromatic compound AND Carbonic acid derivative AND Carboxylic acid derivative AND Carboxylic acid salt AND Cation by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "e"

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

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Michael-type addition on alpha, beta-unsaturated carbonyl compounds OR AN2 >> Michael-type addition on alpha, beta-unsaturated carbonyl compounds >> Four- and Five-Membered Lactones OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation >> Geminal Polyhaloalkane Derivatives OR AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR AN2 >> Shiff base formation for aldehydes OR AN2 >> Shiff base formation for aldehydes >> Geminal Polyhaloalkane Derivatives OR 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 >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Geminal Polyhaloalkane Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroarenes with Other Active Groups 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 diazonium or carbenium ion formation OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation 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 >> Nitroarenes with Other Active Groups OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters OR SN2 >> Acylation involving a leaving group  OR SN2 >> Acylation involving a leaving group  >> Geminal Polyhaloalkane Derivatives OR SN2 >> Acylation involving a leaving group after metabolic activation OR SN2 >> Acylation involving a leaving group after metabolic activation >> Geminal Polyhaloalkane Derivatives OR SN2 >> Alkylation, direct acting epoxides and related OR SN2 >> Alkylation, direct acting epoxides and related >> Epoxides and Aziridines OR SN2 >> Alkylation, ring opening SN2 reaction OR SN2 >> Alkylation, ring opening SN2 reaction >> Four- and Five-Membered Lactones OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation >> Geminal Polyhaloalkane Derivatives OR SN2 >> SN2 at an activated carbon atom OR SN2 >> SN2 at an activated carbon atom >> Quinoline Derivatives OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 >> Nitroarenes with Other Active Groups by DNA binding by OASIS v.1.3

Domain logical expression index: "g"

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

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Acyl transfer via nucleophilic addition reaction OR Acylation >> Acyl transfer via nucleophilic addition reaction >> Isocyanates, Isothiocyanates  OR Acylation >> Direct acylation involving a leaving group OR Acylation >> Direct acylation involving a leaving group >> Azlactones and unsaturated lactone derivatives  OR Acylation >> Direct acylation involving a leaving group >> Carbamates  OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR Acylation >> Ester aminolysis or thiolysis OR Acylation >> Ester aminolysis or thiolysis >> Activated aryl esters  OR Acylation >> Ring opening acylation OR Acylation >> Ring opening acylation >> beta-Lactams  OR Ionic interaction OR Ionic interaction >> Substituted guanidines OR Ionic interaction >> Substituted guanidines >> Guanidines OR Michael Addition OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group >> Conjugated systems with electron withdrawing groups  OR Nucleophilic addition OR Nucleophilic addition >> Addition to carbon-hetero double bonds OR Nucleophilic addition >> Addition to carbon-hetero double bonds >> Ketones OR Schiff base formation OR Schiff base formation >> Direct acting Schiff base formers OR Schiff base formation >> Direct acting Schiff base formers >> 1,2-Dicarbonyls and 1,3-Dicarbonyls  OR Schiff base formation >> Pyrazolones and Pyrazolidinones derivatives OR Schiff base formation >> Pyrazolones and Pyrazolidinones derivatives >> Pyrazolones and Pyrazolidinones  OR Schiff base formation >> Schiff base formation with carbonyl compounds OR Schiff base formation >> Schiff base formation with carbonyl compounds >> Aldehydes OR SN2 OR SN2 >> Nucleophilic substitution at sp3 carbon atom OR SN2 >> Nucleophilic substitution at sp3 carbon atom >> Alkyl halides  OR SN2 >> Nucleophilic substitution at sp3 carbon atom >> alpha-Activated haloalkanes  OR SN2 >> Nucleophilic substitution on benzilyc carbon atom OR SN2 >> Nucleophilic substitution on benzilyc carbon atom >> alpha-Activated benzyls  OR SN2 >> SN2 Reaction at a sp3 carbon atom OR SN2 >> SN2 Reaction at a sp3 carbon atom >> Activated alkyl esters and thioesters  OR SNAr OR SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds OR SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds >> Activated aryl and heteroaryl compounds by Protein binding by OASIS v1.3

Domain logical expression index: "i"

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

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Direct Acylation Involving a Leaving group OR Acylation >> Direct Acylation Involving a Leaving group >> Acetates OR Acylation >> Direct Acylation Involving a Leaving group >> Azlactone by Protein binding by OECD

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Class 5 (Not possible to classify according to these rules) by Acute aquatic toxicity classification by Verhaar (Modified) ONLY

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Not Related to an Existing ECOSAR Class by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Acid moiety OR Aliphatic Amines OR Amides OR Anilines (Hindered) OR Benzyl Alcohols OR Esters OR Inorganic Compound OR Ketone alcohols OR Melamines OR Neutral Organics OR Nicotinoids OR Not classified OR Phenol Amines OR Phenols OR Phenols, Poly OR Pyrazoles/Pyrroles OR Salt OR SHOULD NOT BE PROFILED OR Substituted Ureas OR Surfactants-Anionic OR Surfactants-Cationic OR Triazines, Aromatic by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Group 1 - Alkali Earth Li,Na,K,Rb,Cs,Fr AND Group 14 - Carbon C AND Group 16 - Oxygen O by Chemical elements

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Group 15 - Nitrogen N OR Group 16 - Sulfur S OR Group 17 - Halogens Cl OR Group 17 - Halogens F,Cl,Br,I,At by Chemical elements

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is >= -4.27

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is <= -0.746

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 invertebrate was predicted sodium 2-phenylacetate (CAS: 114-70-5). Effect concentration i.e EC50 value was estimated to be 274.09 mg/l for Daphnia magna for 48 hrs duration. It was concluded that the sodium 2-phenylacetate (CAS: 114-70-5) was likely to be not toxic to aquatic invertebrate, hence it can be considered to be “not Classified” 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 invertebrate was predicted sodium 2-phenylacetate (CAS: 114-70-5). Effect concentration i.e EC50 value was estimated to be 274.09 mg/l for Daphnia magna for 48 hrs duration. It was concluded that the sodium 2-phenylacetate (CAS: 114-70-5) was likely to be not toxic to aquatic invertebrate, hence it can be considered to be “not Classified” 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 invertebrate was predicted sodium 2-phenylacetate (CAS: 114-70-5). Effect concentration i.e EC50 value was estimated to be 274.09 mg/l for Daphnia magna for 48 hrs duration. It was concluded that the sodium 2-phenylacetate (CAS: 114-70-5) was likely to be not toxic to aquatic invertebrate, hence it can be considered to be “not Classified” as per the CLP classification criteria for aquatic environment.

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Effect concentration:

274.09 mg/L

Additional information

Following studies includes the predicted data and experimental data of target chemical and stucturally similar read across chemical to conclude the sodium 2-phenylacetate (CAS: 114-70-5) toxicity towards the 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 invertebrate was predicted sodium 2-phenylacetate (CAS: 114-70-5). Effect concentration i.e EC50 value was estimated to be 274.09 mg/l for Daphnia magna for 48 hrs duration. It was concluded that the sodium 2-phenylacetate (CAS: 114-70-5) was likely to be not toxic to aquatic invertebrate, hence it can be considered to be “not Classified” as per the CLP classification criteria for aquatic environment.

The above predicted data of target chemical is supported by the stucturally similar read across chemical phenylacetic acid (CAS: 103-82-2) from Chemosphere 2003, suggests that the short term toxicity of read across phenylacetic acid to Daphnia magna was assessed during a 24-hour static test. The carrier of fluoranthene and its metabolites was recommended standard fresh water, composed for the test as follows (mg/l): NaHCO3 ¼ 48; CaSO4 2H2O ¼ 30; MgSO4 7H2O ¼ 30 and KCl ¼ 2. The pH was adjusted to 7.40.2 and the solution was aerated until the dissolved oxygen concentration has reached saturation. Thus, he Effective concentration (EC50) value of phenylacetic acid in aquatic invertebrate (Thamnocephalus platyurus) in a 24 hr study on immobility effect was found to be 236 mg/L.Thus,considering the CLP Criteria for aquatic classification of the substance , it is concluded that phenylacetic acid does not exhibit short term toxicity to aquatic invertebrate (Thamnocephalus platyurus).

Similar study for another structurally similar read across Succinic acid(CAS: 110-15-6) from Journal - Water Pollution Control Federation, 1980 inidicates that the Short-term toxicity to aquatic invertebrates test was carried out for 48 hr under static condition to study the effects of Succinic acid on aquatic environment.Immobility Intoxication effect of Daphnia magna was measured during the test.

The Effective concentration EC50 to 50% of 5Daphnia magna at 48 h is 374 mg/l. It can be concluded from the value that the Succinic acid is not toxic to the aquatic environment.

Thus based on the effect concentrations which is in the range 236 mg/l to374 mg/lgive the conclusion that test substancesodium 2-phenylacetate (CAS: 114-70-5)is likely to be non-toxic to aquatic invertebrate at environmentally relevant concentrations and applying weight of evidence approach it can be considered to be “not classified” as per the CLP classification criteria.