3-phenylpropionic acid

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:

The supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.4 with log kow as the primary discriptors.

GLP compliance:

not specified

Specific details on test material used for the study:

- IUPAC name: 3-phenylpropanoic acid
- Molecular formula: C9 H10 O2
- Molecular weight: 150.176 g/mol
- Smiles: c1(CCC(O)=O)ccccc1
- InChI: 1S/C9H10O2/c10-9(11)7-6-8-4-2-1-3-5-8/h1-5H,6-7H2,(H,10,11)
- Substance type: Organic
- Physical state: solid

Test organisms (species):

Daphnia magna

Test type:

static

Water media type:

freshwater

Total exposure duration:

48 h

Test temperature:

20 degree C

pH:

8.0 ± 0.2

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

769.06 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

other: Intoxication

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 ( not "l") )  )  and "m" )  and "n" )  and ("o" and ( not "p") )  )  and ("q" and ( not "r") )  )  and ("s" and ( not "t") )  )  and ("u" and "v" )  )

Domain logical expression index: "a"

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

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 Acid, aliphatic attach [-COOH] AND Alcohol, olefinic attach [-OH] AND 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 Acid, aliphatic attach [-COOH] AND Alcohol, olefinic attach [-OH] AND 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: "e"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.4

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >>  Michael-type addition, quinoid structures OR AN2 >>  Michael-type addition, quinoid structures >> Quinones and Trihydroxybenzenes 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 Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide and Aminoalkylamine Side Chain OR Non-covalent interaction >> DNA intercalation >> Quinolone Derivatives OR Non-covalent interaction >> DNA intercalation >> Quinones and Trihydroxybenzenes OR Radical OR Radical >> Radical mechanism by ROS formation OR Radical >> Radical mechanism by ROS formation >> Five-Membered Aromatic Nitroheterocycles OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Conjugated Nitro Compounds OR Radical >> Radical mechanism via ROS formation (indirect) >> Geminal Polyhaloalkane Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitrobiphenyls and Bridged Nitrobiphenyls OR Radical >> Radical mechanism via ROS formation (indirect) >> Quinones and Trihydroxybenzenes 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 nitrenium ion formation OR SN1 >> Nucleophilic attack after 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 >> Conjugated Nitro Compounds OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitrobiphenyls and Bridged Nitrobiphenyls OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters 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 >> 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 by DNA binding by OASIS v.1.4

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Non binder, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Moderate binder, OH grooup OR Non binder, impaired OH or NH2 group OR Non binder, MW>500 OR Non binder, non cyclic structure OR Strong binder, OH group OR Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OASIS v1.4

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Acylation involving an activated (glucuronidated) carboxamide group OR Acylation >> Acylation involving an activated (glucuronidated) carboxamide group >> Carboxylic Acid Amides 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 >> Carboxylic Acid Amides OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR Acylation >> Ring opening acylation OR Acylation >> Ring opening acylation >> beta-Lactams  OR AN2 OR AN2 >> Michael-type addition to quinoid structures  OR AN2 >> Michael-type addition to quinoid structures  >> Carboxylic Acid Amides OR AN2 >> Michael-type addition to quinoid structures  >> N-Substituted Aromatic Amines 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 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 v1.4

Domain logical expression index: "k"

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

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as SNAr OR SNAr >> Nucleophilic aromatic substitution OR SNAr >> Nucleophilic aromatic substitution >> Activated halo-benzenes by Protein binding by OECD

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as No superfragment by Superfragments ONLY

Domain logical expression index: "n"

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

Domain logical expression index: "o"

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: "p"

Referential boundary: The target chemical should be classified as Acid moiety OR Halopyrdines OR Pyrazoles/Pyrroles OR Pyridine-alpha by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as No alert found by Carcinogenicity (genotox and nongenotox) alerts by ISS

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Halogenated benzene (Nongenotox) OR Phenoxy herbicides (Nongenotox) OR Structural alert for nongenotoxic carcinogenicity by Carcinogenicity (genotox and nongenotox) alerts by ISS

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Not known precedent reproductive and developmental toxic potential by DART scheme v.1.0

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Alpha aryloxy substituted acetic acid (9c) OR Aryl/heteroaryl substituted alkyl (C1-C3) acids (9b) OR Known precedent reproductive and developmental toxic potential OR Toluene and small alkyl toluene derivatives (8a) by DART scheme v.1.0

Domain logical expression index: "u"

Parametric boundary:The target chemical should have a value of log Kow which is >= 1.39

Domain logical expression index: "v"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.6

Validity criteria fulfilled:

not specified

Conclusions:

The short term toxicity on aquatic invertebrates was predicted for3-phenylpropanoic acid(CAS: 501-52-0). EC50 value was estimated to be 769.06 mg/l for Daphnia magna for 48 hrs duration

Executive summary:

Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, the short term toxicity on aquatic invertebrates was predicted for 3-phenylpropanoic acid(CAS: 501-52-0). EC50 value was estimated to be 769.06 mg/l for Daphnia magna for 48 hrs duration.Based on the value, 3-phenylpropanoic acid(CAS: 501-52-0) was considered to be non-toxic to aquatic invertebrates and can be considered to be not classified as per the CLP regulations.

Description of key information

Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, the short term toxicity on aquatic invertebrates was predicted for3-phenylpropanoic acid(CAS: 501-52-0). EC50 value was estimated to be 769.06 mg/l for Daphnia magna for 48 hrs duration.

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Effect concentration:

769.06 mg/L

Additional information

Short term toxicity to aquatic invertebrates for3-phenylpropanoic acid(CAS: 501-52-0)was summaries with two predicted data and two experimental studies with two read across substances are as follows:

Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, the short term toxicity on aquatic invertebrates was predicted for3-phenylpropanoic acid(CAS: 501-52-0). EC50 value was estimated to be 769.06 mg/l for Daphnia magna for 48 hrs duration.

Another study for 3-phenylpropanoic acid(CAS: 501-52-0)was predicted using EPI suite, ECOSAR version 1.1, based on the effects observed in a static freshwater system during a 48 hr exposure. The lethal concentration (LC50) for the substance is estimated to be 398.36mg/L.

Study was performed in Daphnia magna in read across benzyl butyrate (103-37-7) from Abitec laboratory (Report no: 490/16), 2016 following the OECD guideline 202. The test was performed for 48 hrs at different concentrations as control, 0, 2.5, 5.0, 10.0, 20.0; 40.0 mg/l at 95 % confidence limit of 14.7 -18.7mg/l. Reference substance used was K2Cr207. 5 daphnids after breeding were used in 4 numbers of replicates of chemical. The test was performed in temperature 20°C±1°C with taking 25ml per replicate in 50ml glass vessel for 48 hrs. Calculations of EC50 was calculated using nonlinear regression by the software Prism4.0 (GraphPadSoftware,Inc.,SanDiegoCA). After experiment the EC50 value for short term toxicity to aquatic invertebrates using OECD guideline 202 was determined to be 16.6 mg/l. Based on the value the benzyl butyrate was toxic to aquatic invertebrates but as the chemical was readily biodegradable, so it can be considered that benzyl butyrate was not hazardous to aquatic invertebrates and can be considered not classified as per the CLP regulations.

Another study was performed in read across Benzoic acid (65-85-0) which was 60-70 % structurally similar by Yasushi Kamaya et.al ,Chemosphere 59 (2005) 255–261 using Daphnia magna for 48 hrs. The young daphnids were obtained from continuous cultures in 1 liter glass beakers at 21 ± 0.3 degree C, in dechlorinated and conditioned tap water, the medium was renewed in three weeks and daphnids were fed daily with the green alga Selenastrum capricornutum. The pH of test solution was adjusted to 7.45 ± 0.05 with HCL and NaOH. The concentrations of the resultant solutions were checked before and after (48 h) exposure using a UV–visible spectrophotometer. As the experiment starts neonate were placed in 50 ml of beaker with 40 ml of test solution. All experiment was made in four replicates and performed at 21 ± 0.3 degree C under 16 h light: 8 h dark photoperiod. Immobility was observed after 24 and 48 hrs and EC 50 value was calculated. After the experiment the EC 50 value of Benzoic acid (65-85-0) for Daphnia magna was determined to be 860 mg/l in 48 hrs.

Based on the above predicted data and studies of read across chemicals it can be considered that all the above studies supported the target classification, so based on the results it was considered that all weight of evidences supported the classifications and3-phenylpropanoic acid(CAS: 501-52-0)was not hazardous to aquatic invertebrates and can be considered to be not classified as per the CLP regulations.