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EC number: 205-851-3 | CAS number: 156-38-7
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
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
- 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
- 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.
Reference
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
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
- Endpoint:
- acute toxicity: inhalation
- Data waiving:
- other justification
- Justification for data waiving:
- other:
Reference
Endpoint conclusion
- Quality of whole database:
- Waiver
Acute toxicity: via dermal route
Link to relevant study records
- 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
- 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.
Reference
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
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.
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