p-hydroxyphenylacetic acid

Endpoint summary

Description of key information

Short-term toxicity to fish

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 fish was predicted 4-Hydroxyphenylacetic Acid (CAS: 156-38-7). LC50 mortality value was estimated to be 135.153 mg/l for Danio rerio for 96.0 hrs duration. It was concluded that 4-Hydroxyphenylacetic Acid (CAS: 156-38-7) was likely to be not toxic to aquatic fish.

Short-term toxicity to aquatic invertebrates

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 invertebrate was predicted 4-Hydroxyphenylacetic Acid (CAS: 156-38-7). EC50 Intoxication value was estimated to be 268.1873 mg/l for Daphnia magna for 48.0 hrs duration. It was concluded that 4-Hydroxyphenylacetic Acid (CAS: 156-38-7) was likely to be not toxic to aquatic invertebrate.

Toxicity to aquatic algae and cyanobacteria

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.

Toxicity to microorganisms

The toxicity values were from a population growth impairment test using the freshwater ciliate T. pyriformis (strain GL-C), performed.

Test conditions allow for 8–9 cell cycles in control cultures. Each definitive test replicate consisted of six to eight different concentrations with duplicate flasks of each concentration. Only replicates with control-absorbency values between 0.60 and 0.75 were used in the analyses.

The 50% growth inhibition concentration, IGC50, was determined for each compound using the Probit Analysis routine in the Statistical Analysis System (SAS) software.

The 50% growth inhibition concentration, IGC50 to Tetrahymena pyriformis when exposed to 4-Hydroxyphenylacetic Acid for 48 hr is 4810 mg/L.

Thus based on the results of effect concentrations obtained from the publications, experimental reports,authoratative database and predicted data for fish, aquatic invertebrate, aquatic algae and cyanobacteria and micro-organisms gives 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.

Additional information

Short-term toxicity to fish

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 fish 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 fish was predicted 4-Hydroxyphenylacetic Acid (CAS: 156-38-7). LC50 mortality value was estimated to be 135.153 mg/l for Danio rerio for 96.0 hrs duration. It was concluded that 4-Hydroxyphenylacetic Acid (CAS: 156-38-7) was likely to be not toxic to aquatic fish.

The above prediction for the target chemical done using the OECD QSAR toolbox version 3.3 suggests that Based on the prediction done by EPI suite, ECOSAR version 1.1, on the basis of similarity of structure to chemicals for which the aquatic toxicity has been previously measured by structure-activity relationships (SARs) program, the LC 50 value for short term toxicity to aquatic invertebrates was predicted.

On the basis of this program, the LC 50 value for short term toxicity to aquatic invertebrates was predicted to be 1100.263 mg/l for 4-Hydroxyphenylacetic Acid in 96 hrs.

Based on this value it can be concluded that the 4-Hydroxyphenylacetic Acid is considered to be not toxic to aquatic environment and can be "not classified " category as per the criteria mentioned in CLP regulation.

Similar Prediction done using average value of both models i.e Leadscope and SciMatics SciQSAR model and the result were predicted in Battery model. Based on the Danish (Q)SAR Database, the 96hours LC50 was estimated to be 286.0272 mg/L on Pimephales promelas for 4-Hydroxyphenylacetic Acid (CAS: 156-38-7) with mortality effects. Thus based on this value it can be concluded that the 4-Hydroxyphenylacetic Acid (CAS: 156-38-7) can be "not classified" per the criteria of CLP regulation.

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 UERL Lab report 2017, suggests that theFish Acute Toxicity test according to OECD Guideline 203 was conducted for 4-methoxyphenylacetic acid. The nominal concentration selected for the experiment were 100mg/L and test fish were exposed to these concentration for 96 hours. The median lethal concentration (LC50) for 4-methoxyphenylacetic acid on Danio rerio in a 96 hours study on the basis of mortality effect was found to be >100 mg/L. Thus, on the basis of this LC50 value and according to CLP criteria for aquatic classification of the substance, it is concluded that the substance, 4-methoxyphenylacetic acid (CAS No. 104-01-8) does not exhibit short term toxicity to fish.

LC0 (96 hours) (highest loading at which no mortality was observed) = 100 mg/L

LC50 (96 hours) Experimental = >100 mg/L

Thus based on the effect concentrations which is in the range >100 mg/L to1100.263 mg/lgive 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.

Short-term toxicity to aquatic invertebrates

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 inverbrate 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 invertebrate was predicted 4-Hydroxyphenylacetic Acid (CAS: 156-38-7). EC50 Intoxication value was estimated to be 268.1873 mg/l for Daphnia magna for 48.0 hrs duration. It was concluded that 4-Hydroxyphenylacetic Acid (CAS: 156-38-7) was likely to be not toxic to aquatic invertebrate.

The above prediction for the target chemicalBased on the prediction done by EPI suite, ECOSAR version 1.1, on the basis of similarity of structure to chemicals for which the aquatic toxicity has been previously measured by structure-activity relationships (SARs) program, the LC 50 value for short term toxicity to aquatic invertebrates was predicted.

On the basis of this program, the LC 50 value for short term toxicity to aquatic invertebrates was predicted to be566.917mg/l for4-Hydroxyphenylacetic Acid (CAS: 156-38-7)in 48 hrs. Based on this value it can be concluded that the substance is considered to be not toxic to aquatic environment and can be "not classified" category as per the criteria mentioned in CLP regulation.

Similar estimationBased on the average value of both models ( Leadscope Enterprise model and SciMatics SciQSAR model), the result were predicted in Battery model. Based on the Danish (Q)SAR Database, the 48 hours EC50 was estimated to be57.43105 mg/Lon Daphnia Magna for4-Hydroxyphenylacetic Acid (CAS: 156-38-7)with immobilization effects. Thus based on this value it can be concluded that the substance can be classified as"not classified"as per the criteria of CLP regulation.

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 theDetermination of the inhibition of the mobility of the crustacean Thamnocephalus platyurus was carried out for 24 h under static condition.

Immobilization effect was maesured duroing the test . The Effective concentration (EC50) value of phenylacetic acid in aquatic invetebrate (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).

Another supporting experimental study for the structurally similar read across phenylacetic acid (CAS: 103-82-2) from the publication Chemosphere 2003, also suggests that theDetermination of the inhibition of the mobility of Daphnids was carried out with the substance4-methoxyphenylacetic acidaccording to OECD Guideline 202.

The stock solution 150.0 mg/L was prepared by dissolving white powder in reconstituted water. The solution was kept in ultrasonic bath for 20 min. The test solutions of required concentrations were prpared by mixing the stock solution of the test sample in reconstituted water.The test substance was tested at the concentrations 0, 30.0, 45.0, 67.5, 100.0 and 150.0 mg/L.The test was performed under static conditions in a fresh water system at a temperature of 20°C. EC50 was calculated using non linear regression by the software Prism 4.0.

The median effective concentration (EC50) for the test substance,4-methoxyphenylacetic acid, in Daphnia magna was determined to be 100.8 mg/L for immobilisation effects with 95% CI of 94.7 to 107.4 mg/L. Thus, based on this EC50 value and after comparing with CLP criteria for aquatic classification of the substance it is concluded that the substance,4-methoxyphenylacetic aciddoes not exhibit short term toxicity to aquatic invertebrate (Daphnia Magna).

Thus based on the effect concentrations which is in the range 57.43105 mg/L to566.917 mg/lgive 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.

Toxicity to aquatic algae and cyanobacteria

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 chemicalThe 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 be282.638mg/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 be287.2258mg/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 thefreshwater 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 to287.2258 mg/lgive 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.

Toxicity to microorganisms

The toxicity values were from a population growth impairment test using the freshwater ciliate T. pyriformis (strain GL-C), performed.

Test conditions allow for 8–9 cell cycles in control cultures. Each definitive test replicate consisted of six to eight different concentrations with duplicate flasks of each concentration. Only replicates with control-absorbency values between 0.60 and 0.75 were used in the analyses.

The 50% growth inhibition concentration, IGC50, was determined for each compound using the Probit Analysis routine in the Statistical Analysis System (SAS) software.

The 50% growth inhibition concentration, IGC50 to Tetrahymena pyriformis when exposed to 4-Hydroxyphenylacetic Acid for 48 hr is 4810 mg/L.

Thus based on the results of effect concentrations obtained from the publications, experimental reports,authoratative database and predicted data for fish, aquatic invertebrate, aquatic algae and cyanobacteria and micro-organisms gives 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.