p-hydroxyphenylacetic acid

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: 4-Hydroxyphenylacetic Acid
- IUPAC name: 4-Hydroxyphenylacetic Acid
- Molecular formula: C8H8O3
- Molecular weight: 152.148 g/mol
- Substance type: Organic
- Physical state: Solid

Analytical monitoring:

not specified

Vehicle:

not specified

Test organisms (species):

Desmodesmus subspicatus (previous name: Scenedesmus subspicatus)

Test type:

static

Water media type:

freshwater

Total exposure duration:

72 h

Key result

Duration:

72 h

Dose descriptor:

EC50

Effect conc.:

120.779 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

growth rate

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 ( not "l") )  )  and ("m" and ( not "n") )  )  and "o" )  and "p" )  and ("q" and "r" )  )

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 Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Class 2 (less inert compounds) by Acute aquatic toxicity classification by Verhaar (Modified)

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Acid moiety AND Phenols by Aquatic toxicity classification by ECOSAR

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 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) >> Nitroarenes with Other Active Groups OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR SN1 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 SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR SN2 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 Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Moderate binder, OH grooup by Estrogen Receptor Binding

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "j"

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

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Strong binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "n"

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

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Class 2 (less inert compounds) by Acute aquatic toxicity classification by Verhaar (Modified) ONLY

Domain logical expression index: "p"

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

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.229

Domain logical expression index: "r"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.49

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 to aquatic algae was predicted 4-Hydroxyphenylacetic Acid (CAS: 156-38-7). EC50 growth rate value was estimated to be 120.779 mg/l for Desmodesmus subspicatus for 72 hrs duration. It was concluded that 4-Hydroxyphenylacetic Acid (CAS: 156-38-7) was likely to be not toxic to aquatic algae.

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 to aquatic algae was predicted 4-Hydroxyphenylacetic Acid (CAS: 156-38-7). EC50 growth rate value was estimated to be 120.779 mg/l for Desmodesmus subspicatus for 72 hrs duration. It was concluded that 4-Hydroxyphenylacetic Acid (CAS: 156-38-7) was likely to be not toxic to aquatic algae.

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 to aquatic algae was predicted 4-Hydroxyphenylacetic Acid (CAS: 156-38-7). EC50 growth rate value was estimated to be 120.779 mg/l for Desmodesmus subspicatus for 72 hrs duration. It was concluded that 4-Hydroxyphenylacetic Acid (CAS: 156-38-7) was likely to be not toxic to aquatic algae.

Key value for chemical safety assessment

EC50 for freshwater algae:

120.779 mg/L

Additional information

Following studies of target chemical and structurally similar read across includes predicted data and experimental data to conclude the toxicity extent of 4-Hydroxyphenylacetic Acid (CAS: 156-38-7). 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 to aquatic algae was predicted 4-Hydroxyphenylacetic Acid (CAS: 156-38-7). EC50 growth rate value was estimated to be 120.779 mg/l for Desmodesmus subspicatus for 72 hrs duration. It was concluded that 4-Hydroxyphenylacetic Acid (CAS: 156-38-7) was likely to be not toxic to aquatic algae.

The above prediction for the target chemical The short-term toxicity of the 4-Hydroxyphenylacetic Acid (CAS: 156-38-7)to green algae is predicted using EPI Suite ECOSAR version 1.11. On the basis of effects observed in a static freshwater system during a 96 hr exposure, the effect concentration (EC50) for the substance is estimated to be 282.638 mg/L. Based on this value, it can be concluded that the test chemical4-Hydroxyphenylacetic Acid (CAS: 156-38-7) can be considered as non-toxic to green algae at environmentally relevant concentrations and can be considered "not-classified " as per the CLP classification criteria.

Similar estimation is done by Danish QSAR database Estimated 72 hrs EC50 value of4-Hydroxyphenylacetic Acid (CAS: 156-38-7)on Pseudokirchneriella subcapitata was determined by three different models i.e, Battery, Leadscope and SciQSAR used within Danish QSAR database. The average EC50 value was given by the third model i.e, Battery model. Based on inhibition in growth rate of test organism Pseudokirchneriella subcapitata in a static freshwater system, the estimated 72 hrs EC50 value was predicted to be 287.2258 mg/l. Thus, on the basis of EC50 value, it can be concluded that the4-Hydroxyphenylacetic Acid (CAS: 156-38-7) can be considered as "non-toxic" to green algae at environmentally relevant concentrations and can be considered "not-classified" as per the CLP classification criteria.

The above predicted data of target chemical is supported by the experimental study of structurally similar read across 4-methoxyphenylacetic acid (CAS No. 104-01-8) from the ABITEC Lab report 2017, suggests that the freshwater algal growth inhibition test was carried out on Desmodesmus subspicatus with the substance4-methoxyphenylacetic acid(CAS No.- 104 -01 -8) according to OECD Guideline 201.

The stock solution 150.0 mg/L was prepared by dissolving white powder in OECD growth medium. Test solutions of required concentrations were prepared by mixing the stock solution of the test sample with OECD growth medium and inoculum culture and tested at the concentrations 0, 0, 30.0, 45.0, 67.5, 100.0 and 150.0 mg/L.Effects on the growth rate of the organism were studied. The test was performed under static conditions in a static fresh water system at a temperature of 23± 2°C. Initial cell density of test organism used was 5x10(3) cells/ml. Determination of cell counting involve the use of microscope with counting chamber Cyrus I or electronic particle counter. ErC50 was calculated using non-linear regression by the software Prism 4.0.

The median effective concentration (ErC50) for the test substance,4-methoxyphenylacetic acid, in a freshwater algae Desmodesmus subspicatus was determined to be 106.9 mg/L on the basis of effects on growth rate in a 72 hour study with 95% Cl of 83.2 - 137.3 mg/L. Thus, based on this ErC50 value and according to CLP Criteria for aquatic classification of the substance, it is concluded that4-methoxyphenylacetic acid (CAS No.- 104 -01 -8) does not exhibits toxicity to aquatic algae (Desmodesmus subspicatus).

Another supporting experimental study for the structurally similar read across 4-Hydroxybenzoic acid (CAS: 99 -96 -7) from theJapan chemicals collaborative knowledge database (J-check), 2017, also suggests that the Short term toxicity study of 4-Hydroxybenzoic acid on the growth of freshwater green algae was carried out for 72 hrs. The effective concentration (EC50) value of 4-Hydroxybenzoic acid in aquatic green algae in a 72 hr study on the basis of growth rate effect and AUG was 110 mg/l and 69 mg/l. But the NOEC on the basis of AUG and growth rate was 32 mg/l and 51 mg/l. Based on the growth inhibition of green algae due to the 4-Hydroxybenzoic acid, the EC50 was 110 mg/l. Thus 4-Hydroxybenzoic acid was nontoxic and cannot be classified as toxic to aquatic algae as per the CLP classification criteria.

Thus based on the effect concentrations which is in the range 106.9 mg/L to 287.2258 mg/l give the conclusion that test substance 4-Hydroxyphenylacetic Acid (CAS: 156-38-7) is likely to be not toxic to aquatic environment at environmentally relevant concentrations and applying weight of evidence approach it can be considered to be “not classified” as per the CLP classification criteria.