p-hydroxyphenylacetic acid

Endpoint summary

Description of key information

Acute Oral Toxicity: 

In Acute oral toxicity,LD50 value was predicted based on OECD QSAR toolbox for target substance 4-Hydroxyphenylacetic Acid (156-38-7) was estimated to be 2021.14 mg/kg bw,and for different studies available on the structurally similar read across substance 4-Hydroxybenzoic Acid (99-96-7) was considered to be >10000 mg/kg bw and for Phenylacetic acid (103-82-2) was considered to be >5000 mg/kg bw.All these studies concluded that the LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 4-Hydroxyphenylacetic Acid (156-38-7) cannot be classified for acute oral toxicity.

Acute Inhalation Toxicity: 

4-Hydroxyphenylacetic Acid (156-38-7)has very low vapour pressure (0.0074 Pa=5.5504556613e-5 mm Hg).So the potential for the generation of inhalable vapours is very low. Also the normal conditions of use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be highly unlikely and therefore the acute inhalation toxicity end point was considered for waiver.

Acute Dermal Toxicity:

In Acute dermal toxicity, LD50 value was predicted based on OECD QSAR toolbox for target substance 4-Hydroxyphenylacetic Acid (156-38-7) was estimated to be 2378.83 mg/kg bw,and for different studies available on structurally similar read across substance Phenylacetic acid (103-82-2) was considered to be >5000 mg/kg bw and for 4-(2-methylhexyl)phenol; 4-heptylphenol (72624-02-3) was considered to be >2000 mg/kg bw.All these studies concluded that the LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 4-Hydroxyphenylacetic Acid (156-38-7) cannot be classified for acute dermal toxicity.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

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 predicted using OECD QSAR toolbox version 3.3 and QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

Prediction was done by using OECD QSAR toolbox v3.3,2018

GLP compliance:

not specified

Test type:

other: estimated data

Limit test:

no

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

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

No data available

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

No data available

Doses:

2021.14 mg/kg bw

No. of animals per sex per dose:

No data available

Control animals:

not specified

Details on study design:

No data available

Statistics:

No data available

Preliminary study:

No data available

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 021.14 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50% mortality was observed

Mortality:

No data available

Clinical signs:

other: No data available

Gross pathology:

No data available

Other findings:

No data available

The prediction was based on dataset comprised from the following descriptors: LD50
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" )  and ("s" and "t" )  )

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 Non-covalent interaction >> DNA intercalation >> Fused-Ring Primary Aromatic Amines 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 by ROS formation OR Radical >> Radical mechanism by ROS formation >> Polynitroarenes OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroaniline Derivatives 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) >> p-Aminobiphenyl Analogs OR Radical >> Radical mechanism via ROS formation (indirect) >> p-Substituted Mononitrobenzenes 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 >> Fused-Ring Primary Aromatic Amines OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> p-Aminobiphenyl Analogs 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 >> Nitroaniline Derivatives 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 >> Nitrobiphenyls and Bridged Nitrobiphenyls OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Polynitroarenes OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> p-Substituted Mononitrobenzenes OR SN2 OR SN2 >> Alkylation, direct acting epoxides and related OR SN2 >> Alkylation, direct acting epoxides and related >> Epoxides and Aziridines OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives OR SN2 >> DNA alkylation OR SN2 >> DNA alkylation >> Alkylphosphates, Alkylthiophosphates and Alkylphosphonates OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Haloalkanes Containing Heteroatom OR SN2 >> SN2 at an activated carbon atom OR SN2 >> SN2 at an activated carbon atom >> Quinoline Derivatives OR SN2 >> SN2 at sulfur atom OR SN2 >> SN2 at sulfur atom >> Sulfonyl Halides 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, NH2 group OR Moderate binder, OH grooup OR Non binder, impaired OH or NH2 group OR Non binder, MW>500 OR Non binder, non cyclic structure OR Non binder, without OH or NH2 group OR Strong binder, NH2 group OR Strong binder, OH group OR Very strong binder, OH group OR Weak binder, NH2 group by Estrogen Receptor Binding

Domain logical expression index: "i"

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: "j"

Referential boundary: The target chemical should be classified as Known precedent reproductive and developmental toxic potential OR Non-steroid nucleus derived estrogen receptor (ER) and androgen receptor (AR) OR Non-steroid nucleus derived estrogen receptor (ER) and androgen receptor (AR) >> 4-alkylphenol-like derivatives (2b-3) OR Piperazine-, dioxane-, morpholine-, tetrahydrothiopyran-like derivatives and cyclohexanamine (17c) OR Polyhalogenated benzene derivatives (8c) OR Toluene and small alkyl toluene derivatives (8a) by DART scheme v.1.0

Domain logical expression index: "k"

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

Domain logical expression index: "l"

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

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Not categorized by Repeated dose (HESS)

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as 3-Methylcholantrene (Hepatotoxicity) Alert OR Chlorphentermine (Hepatotoxicity) Alert OR Hydroquinones (Hepatotoxicity) Rank B OR Methyldopa (Hepatotoxicity) Alert OR Oxyphenistain (Hepatotoxicity) Alert OR Phenols (Mucous membrane irritation) Rank C by Repeated dose (HESS)

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Aryl AND Carboxylic acid AND Phenol AND Precursors quinoid compounds by Organic Functional groups ONLY

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Carboxylic acid AND Overlapping groups AND Precursors quinoid compounds by Organic Functional groups (nested) ONLY

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Aryl AND Carboxylic acid AND Phenol AND Precursors quinoid compounds by Organic Functional groups ONLY

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Aryl AND Carboxylic acid AND Phenol AND Precursors quinoid compounds by Organic Functional groups ONLY

Domain logical expression index: "s"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.269

Domain logical expression index: "t"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.59

Interpretation of results:

other: not classified

Conclusions:

The LD50 value was estimated to be 2021.14 mg/kg bw,when male and female Sprague-Dawley rats were orally exposed with 4-Hydroxyphenylacetic Acid (156-38-7) via gavage.

Executive summary:

In a prediction done by SSS (2018) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for 4-Hydroxyphenylacetic Acid (156-38-7).The LD50 was estimated to be 2021.14 mg/kg bw,when male and female Sprague-Dawley rats were orally exposed with 4-Hydroxyphenylacetic Acid (156-38-7) via gavage.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 021.14 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from QSAR toolbox 3.3

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

other justification

Justification for data waiving:

other:

Endpoint conclusion

Quality of whole database:

Waiver

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

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 predicted using OECD QSAR toolbox version 3.3 and QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

Prediction was done by using OECD QSAR toolbox v3.3,2018

GLP compliance:

not specified

Test type:

other: estimated data

Limit test:

no

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

Species:

rabbit

Strain:

New Zealand White

Sex:

not specified

Details on test animals or test system and environmental conditions:

No data available

Type of coverage:

occlusive

Vehicle:

not specified

Details on dermal exposure:

No data available

Duration of exposure:

24 hours

Doses:

2378.83 mg/kg bw

No. of animals per sex per dose:

No data available

Control animals:

not specified

Details on study design:

No data available

Statistics:

No data available

Preliminary study:

No data available

Sex:

not specified

Dose descriptor:

LD50

Effect level:

2 378.83 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50% mortality was observed

Mortality:

No data available

Clinical signs:

other: No data available

Gross pathology:

No data available

Other findings:

No data available

The prediction was based on dataset comprised from the following descriptors: LD50
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 "h" )  and "i" )  and "j" )  and ("k" and ( not "l") )  )  and "m" )  and ("n" and "o" )  )

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 >> Generation of ROS by glutathione depletion (indirect) OR Radical >> Generation of ROS by glutathione depletion (indirect) >> Haloalkanes Containing Heteroatom OR Radical >> Radical mechanism by ROS formation OR Radical >> Radical mechanism by ROS formation >> Polynitroarenes 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 >> Nitrobiphenyls and Bridged Nitrobiphenyls OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Polynitroarenes 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 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 DNA binding by OECD ONLY

Domain logical expression index: "h"

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

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Aryl AND Carboxylic acid AND Phenol AND Precursors quinoid compounds by Organic Functional groups ONLY

Domain logical expression index: "k"

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

Domain logical expression index: "l"

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

Domain logical expression index: "m"

Similarity boundary:Target: OC(=O)Cc1ccc(O)cc1
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.799

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.06

Interpretation of results:

other: not classified

Conclusions:

The LD50 value was estimated to be 2378.83 mg/kg bw,when new Zealand white rabbits were occlusively exposed with 4-Hydroxyphenylacetic Acid (156-38-7) by dermal application for 24 hours.

Executive summary:

In a prediction done by SSS (2018) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute dermal toxicity was estimated for 4-Hydroxyphenylacetic Acid (156-38-7).The LD50 was estimated to be 2378.83 mg/kg bw,when new Zealand white rabbits were occlusively exposed with 4-Hydroxyphenylacetic Acid (156-38-7) by dermal application for 24 hours. 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 378.83 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from QSAR toolbox 3.3

Additional information

Acute Oral Toxicity: 

In different studies, 4-Hydroxyphenylacetic Acid (156-38-7) has been investigated for acute oral toxicity to a greater or lesser extent. Often the studies are based on in vivo experiments and estimated data in rodents, i.e. most commonly in rats for 4-Hydroxyphenylacetic Acid (156-38-7) along with the study available on the structurally similar read across substance 4-Hydroxybenzoic Acid (99-96-7) and Phenylacetic acid (103-82-2). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies. The studies are summarized as below –

In a prediction done by SSS (2018) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for 4-Hydroxyphenylacetic Acid (156-38-7).The LD50 was estimated to be 2021.14 mg/kg bw,when male and female Sprague-Dawley rats were orally exposed with 4-Hydroxyphenylacetic Acid (156-38-7) via gavage.

The above study was further supported by U.S. National Library of Medicine (Chemidplus Database,U.S. National Library of Medicine,2017) and IFA GESTIS (Gestis Substance Database ,2018) for the structurally similar read across substance 4-Hydroxybenzoic Acid (99-96-7). Acute oral toxicity study was performed in rats using test material 4-Hydroxybenzoic Acid(99-96-7).No mortality was observed at dose 10000 mg/kg bw.Clinical signs like dyspnea and muscle weakness were observed.Hence,LD50 value was considered to be >10000 mg/kg bw,when rats were treated with 4-Hydroxybenzoic Acid(99-96-7)orally.

This is further supported by D.L.J. Opdyke (Food and Cosmetics Toxicology Volume 13, Issue 6, 1975, Pages 901-902) for the structurally similar read across substance Phenylacetic acid (103-82-2). Acute oral toxicity study was done in rat using test material Phenylacetic acid(103-82-2). No mortality was observed at dose 5000mg/kg bw. Hence LD50 was considered to be >5000 mg/kg body weight. When rats were treated with Phenylacetic acid(103-82-2) orally.

Thus, based on the above studies on 4-Hydroxyphenylacetic Acid (156-38-7) and it’s structurally similar read across substances 4-Hydroxybenzoic Acid (99-96-7) and for Phenylacetic acid (103-82-2), it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 4-Hydroxyphenylacetic Acid (156-38-7) cannot be classified for acute oral toxicity.

Acute Inhalation Toxicity: 

4-Hydroxyphenylacetic Acid (156-38-7)has very low vapour pressure (0.0074 Pa=5.5504556613e-5 mm Hg).So the potential for the generation of inhalable vapours is very low. Also the normal conditions of use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be highly unlikely and therefore the acute inhalation toxicity end point was considered for waiver.

Acute Dermal Toxicity:

In different studies,4-Hydroxyphenylacetic Acid (156-38-7)has been investigated for acute dermal toxicity to a greater or lesser extent. Often the studies are based on in vivo experiments and estimated data in rodents, i.e. most commonly in rabbits for4-Hydroxyphenylacetic Acid (156-38-7)along with the study available on structurally similar read across substance Phenylacetic acid (103-82-2) and 4-(2-methylhexyl)phenol; 4-heptylphenol (72624-02-3).The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies. The studies are summarized as below –

In a prediction done by SSS (2018) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute dermal toxicity was estimated for 4-Hydroxyphenylacetic Acid (156-38-7).The LD50 was estimated to be 2378.83 mg/kg bw,when new Zealand white rabbits were occlusively exposed with 4-Hydroxyphenylacetic Acid (156-38-7) by dermal application for 24 hours. 

The above study was further supported by D.L.J. Opdyke (Food and Cosmetics Toxicology Volume 13, Issue 6, 1975, Pages 901-902) for the structurally similar read across substance Phenylacetic acid (103-82-2). Acute dermal toxicity study was done in rat using test material Phenylacetic acid(103-82-2). No mortality was observed at dose 5000 mg/kg bw. HenceLD50 was considered to be >5000mg/kg body weight,when rats were treated with Phenylacetic acid(103-82-2)by dermal application.

Also these results are further supported by U.S. Environmental Protection Agency  (Robust Summaries & Test Plans: Phenol, Heptyl Derivatives, U.S. Environmental Protection Agency,201-14888B,December 2003) for thestructurally similar read across substance 4-(2-methylhexyl)phenol; 4-heptylphenol (72624-02-3). In acute dermal toxicity study, male and female New Zealand White rabbits were occlusively treated with 4-(2-methylhexyl)phenol; 4-heptylphenol(72624-02-3)in the concentration of 2000 mg/kg bw by dermal application. No male mortality was observed.One female animal was found dead on day 12. One female which died showed clinical symptoms like diarrhea, signs of dehydration and a lack of formed fecal material in the lower gastrointestinal tract at necropsy. The female which died exhibited a body weight loss at day 7. In the males signs of necrosis and severe edema were observed in 5 of 5 animals after unwrapping at 24 hours. Eschar was noted at 48 hours (3/5) and 72 hours (2/5). The eschar began to peel at 7 days. One male exhibited a loss of body weight at 7 and 14 days.In the females signs of necrosis and severe edema were observed in 5 of 5 animals after unwrapping at 24 hours. Eschar was noted at 48 hours (5/5). The eschar began to peel at 8 days. No gross necropsy findings were evident in the males or females that were sacrificed on day 14.Therefore, LD50 value was considered to be >2000 mg/kg bw,when rabbits were treated with 4-(2-methylhexyl)phenol; 4-heptylphenol(72624-02-3)by dermal application following 14 days of observation period according to OECD Guideline 402 (Acute Dermal Toxicity).

Thus, based on the above studies on 4-Hydroxyphenylacetic Acid (156-38-7)and it’s structurally similar read across substances Phenylacetic acid (103-82-2) and 4-(2-methylhexyl)phenol; 4-heptylphenol (72624-02-3), it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation,4-Hydroxyphenylacetic Acid (156-38-7)cannot be classified for acute dermal toxicity.

 

Justification for classification or non-classification

Based on the above experimental studies and prediction on 4-Hydroxyphenylacetic Acid (156-38-7)and it’s structurally similar read across substances 4-Hydroxybenzoic Acid (99-96-7);Phenylacetic acid (103-82-2) and 4-(2-methylhexyl)phenol; 4-heptylphenol (72624-02-3), it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation,4-Hydroxyphenylacetic Acid (156-38-7)cannot be classified for acute oral and dermal toxicity. For Acute inhalation toxicity wavier was added so, not possible to classify.