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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
Key value for chemical safety assessment
Effects on fertility
Description of key information
Toxicity to reproduction
The reproductive toxicity study of 4-Hydroxyphenylacetic Acid (156-38-7) was estimated by SSS (2018) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and NOAEL was estimated to be 416.0mg/kg bw. When male and female Sprague-Dawley rats were exposed with4-Hydroxyphenylacetic Acid (156-38-7)orally.
Thus, based on the above predictions and experimental study of 4-Hydroxyphenylacetic Acid (156-38-7) and its structurally similar read across substance No Observed Adverse Effect Level (NOAEL) was considered to be 416.0mg/kg bw. Thus, comparing this value with the criteria of CLP regulation 4-Hydroxyphenylacetic Acid (156-38-7) cannot be classified as reproductive toxicant.
Link to relevant study records
- Endpoint:
- toxicity to reproduction
- 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 v3.3 and the QMRF report has been attached
- Qualifier:
- according to guideline
- Guideline:
- other: As mentioned below
- Principles of method if other than guideline:
- Prediction was done using OECD QSAR toolbox v3.3, 2018
- GLP compliance:
- not specified
- Limit test:
- no
- Justification for study design:
- No data available
- 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
- Details on species / strain selection:
- No data available
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- No data available
- Route of administration:
- oral: gavage
- Vehicle:
- not specified
- Details on exposure:
- No data available
- Details on mating procedure:
- No data available
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 10-13 weeks
- Frequency of treatment:
- Daily
- Details on study schedule:
- No data available
- Dose / conc.:
- 416 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- No data available
- Control animals:
- not specified
- Details on study design:
- No data available
- Positive control:
- No data available
- Parental animals: Observations and examinations:
- No data available
- Oestrous cyclicity (parental animals):
- No data available
- Sperm parameters (parental animals):
- No data available
- Litter observations:
- No data available
- Postmortem examinations (parental animals):
- No data available
- Postmortem examinations (offspring):
- No data available
- Statistics:
- No data available
- Reproductive indices:
- No data available
- Offspring viability indices:
- No data available
- Clinical signs:
- effects observed, treatment-related
- Dermal irritation (if dermal study):
- no effects observed
- Mortality:
- not specified
- Body weight and weight changes:
- not specified
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
- Reproductive function: oestrous cycle:
- not specified
- Reproductive function: sperm measures:
- not specified
- Reproductive performance:
- no effects observed
- Dose descriptor:
- NOAEL
- Effect level:
- 416 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- clinical signs
- reproductive performance
- Remarks on result:
- other: Generation not specified (migrated information)
- Critical effects observed:
- not specified
- System:
- other: not specified
- Organ:
- not specified
- Treatment related:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not specified
- Mortality / viability:
- not specified
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Sexual maturation:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- no effects observed
- Histopathological findings:
- not specified
- Other effects:
- not specified
- Behaviour (functional findings):
- not specified
- Developmental immunotoxicity:
- not specified
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- 416 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- not specified
- Basis for effect level:
- gross pathology
- Remarks on result:
- other: No toxic effects observed
- Critical effects observed:
- not specified
- System:
- other: not specified
- Organ:
- not specified
- Treatment related:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
- Reproductive effects observed:
- not specified
- Treatment related:
- not specified
- Relation to other toxic effects:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
- Conclusions:
- In reproductive toxicity study, NOAEL was estimated to be 416.0mg/kg bw. When male and female Sprague-Dawley rats were exposed with 4-Hydroxyphenylacetic Acid (156-38-7) orally.
- Executive summary:
The reproductive toxicity study of 4-Hydroxyphenylacetic Acid (156-38-7) was estimated by SSS (2018) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and NOAEL was estimated to be 416.0mg/kg bw. When male and female Sprague-Dawley rats were exposed with4-Hydroxyphenylacetic Acid (156-38-7)orally.
Reference
The
prediction was based on dataset comprised from the following
descriptors: NOAEL
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 (
not "i")
)
)
and ("j"
and (
not "k")
)
)
and ("l"
and (
not "m")
)
)
and ("n"
and (
not "o")
)
)
and "p" )
and "q" )
and ("r"
and "s" )
)
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 Radical OR Radical >> Radical
mechanism via ROS formation (indirect) OR Radical >> Radical mechanism
via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic
Amines OR SN1 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 SN2
OR SN2 >> DNA alkylation OR SN2 >> DNA alkylation >> Alkylphosphates,
Alkylthiophosphates and Alkylphosphonates 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 Weak binder, OH group by
Estrogen Receptor Binding
Domain
logical expression index: "i"
Referential
boundary: The
target chemical should be classified as Moderate binder, OH grooup by
Estrogen Receptor Binding
Domain
logical expression index: "j"
Referential
boundary: The
target chemical should be classified as Weak binder, OH group by
Estrogen Receptor Binding
Domain
logical expression index: "k"
Referential
boundary: The
target chemical should be classified as Non binder, non cyclic structure
by Estrogen Receptor Binding
Domain
logical expression index: "l"
Referential
boundary: The
target chemical should be classified as Weak binder, OH group by
Estrogen Receptor Binding
Domain
logical expression index: "m"
Referential
boundary: The
target chemical should be classified as Non binder, without OH or NH2
group OR Strong binder, NH2 group by Estrogen Receptor Binding
Domain
logical expression index: "n"
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: "o"
Referential
boundary: The
target chemical should be classified as Non-steroid nucleus derived
estrogen receptor (ER) and androgen receptor (AR) by DART scheme v.1.0
Domain
logical expression index: "p"
Referential
boundary: The
target chemical should be classified as Bioavailable by Lipinski Rule
Oasis ONLY
Domain
logical expression index: "q"
Referential
boundary: The
target chemical should be classified as Aromatic compound AND Carbonic
acid derivative AND Carboxylic acid AND Carboxylic acid derivative AND
Hydroxy compound AND Phenol by Organic functional groups, Norbert Haider
(checkmol) ONLY
Domain
logical expression index: "r"
Parametric
boundary:The
target chemical should have a value of log Kow which is >= 0.0859
Domain
logical expression index: "s"
Parametric
boundary:The
target chemical should have a value of log Kow which is <= 4.18
Effect on fertility: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 416 mg/kg bw/day
- Study duration:
- subchronic
- Species:
- rat
- Quality of whole database:
- Data is Klimicsh 2 and from QSAR Toolbox 3.3. (2018)
Effect on fertility: via inhalation route
- Endpoint conclusion:
- no study available
Effect on fertility: via dermal route
- Endpoint conclusion:
- no study available
Additional information
Reproductive toxicity
In different studies on 4-Hydroxyphenylacetic Acid (156-38-7) has been investigated for reproductive toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments and estimated data in rodents, i.e. most commonly in rats for 4-Hydroxyphenylacetic Acid (156-38-7).The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies performed on structurally similar read across substance.
The reproductive toxicity study of 4-Hydroxyphenylacetic Acid (156-38-7) was estimated by SSS (2018) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and NOAEL was estimated to be 416.0mg/kg bw. When male and female Sprague-Dawley rats were exposed with4-Hydroxyphenylacetic Acid (156-38-7) orally.
It is supported by experimental study conducted by Sustainability Support Services (Europe) AB (reort no. 15_49_124, 2016) on functionally and structurally similar read across substance Methyl Phenyl acetate (CAS No.: 101-41-7) Combined repeated dose repro-developmental toxicity study was to provide evaluations of general and reproduction/ developmental toxicity endpoints associated with administration of repeated doses of Methyl Phenyl acetate (CAS No.: 101-41-7) in Wistar rats according to OECD guideline 422. The animals were randomly allocated to the four main groups (13/sex/group) and two recovery groups (5/sex/group). The doses selected for main groups were; 0 (G1-control),308 mg/kg body weight (G2), 556 mg/kg body weight (G3) and 1000 mg/kg body weight (G4) daily for 64 days. The recovery groups G1-R and G4-R were dosed with similar doses of respective main groups.Vehicle corn oil to G1 and G1-R and test item to G2, G3, G4 and G4-R animals were administered by oral gavage route each day during the dosing period. No mortality and morbidity were observed any of the groups of animals throughout the study period. Animals of all dose groups were observed for Clinical signs/ symptoms daily once during the experimental period. No apparent treatment related clinical signs were observed in any of the animals throughout the treatment and recovery period. Detailed clinical examinations like Home cage observation, Handling observation and Open field observation of all animals were observed to be normal during study period. Number of rear, urine pools, fecal bolus in animals of all the test groups of both the sexes was comparable and did not show any treatment related significant difference as compared to the respective control groups. Body weight, per cent body weight changes and feed consumption in animals of all the test groups of both the sexes was comparable and did not show any treatment related significant difference as compared to the respective control groups. The sensory reactivity measurements were comparable and no statistically significant changes were revealed in animals of treatment groups in both the sexes. Foot splay and fore limb and hind limb grip strength parameters were comparable and no treatment related changes were revealed in any of the animals of all treated groups as compare to the respective control groups. Motor activity measurements were comparable and no changes were revealed in any of the animals of all treated groups of both the sexes as compared to control group. Estrous cycle was evaluated for checking the regularity during treatment period and in cohabitation for confirmation of pregnancy.
No test item related changes in estrous cyclicity and precoital interval were observed. There was statistically significant decrease in G3 (556 mg/kg body weight) as compared to control G1 (0 mg/kg body weight). This is not dose dependent hence not considered as treatment related. There was no statistically significant difference between the control and treatment groups in the maternal and pups parameters, except markedly decreased pregnancy index / fertility index in G4 (1000 mg/kg body weight), which was considered to be treatment related. All haematological and clinical chemistry parameters in animals of different treated groups of both the sexes were comparable to their respective control groups. No treatment related changes were observed in any of the treatment groups. At the end of treatment and recovery period, absolute and relative weight of organs of treated group rats of either sex did not differ significantly when compared to the respective control group rats. External and visceral examination of all male and female rats of control and all treated groups including recovery groups did not reveal any abnormality of pathological significance. Terminally sacrificed pups of all treated groups did not reveal any lesion of pathological significance in any of the group when compared with control group. Pups that died among the control and treated groups during the course of study, revealed various lesions when examined externally and internally but the observations were not considered treatment related. From the patho-morphological results presented, it is concluded that, the treatment of Methyl Phenyl acetate at 308, 556 and 1000 mg/kg body weight in male and female rats did not affect adversely and no alteration of pathological significance was observed in any of the organs including reproductive organs. Lesions observed in liver, kidneys, lungs, heart, aorta, stomach, lymph nodes, spleen, thymus, trachea, adrenal gland and reproductive organs of high dose treated group rats are well comparable with respective control group rats and exhibited no dose relationship. Further these observed lesions are common in occurrence in rodents during toxicological studies. Hence, occurrence of these lesions could be considered as spontaneous or incidental in nature and not to be attributed to the administration of the Test Item.Based on the findings of Repeated Dose Oral Toxicity Study in combination with Reproduction/ Developmental Toxicity of Methyl Phenyl acetate (CAS No.: 101-41-7) in Wistar Rats with 14 days recovery, where in 0, 308, 556 and 1000 mg/kg body weight, doses were tested; No Observed Adverse Effect Level (NOAEL) is considered to be 556 mg/kg bw. When male and female wistar rats were treated with Methyl Phenyl acetate (CAS No.: 101-41-7) orally.
It is supported by experimental study conducted by Dr. Paul Kotin and Dr. Hans Falk, NIH, Dr. A. J. Pallotta and Dr. E. Ross Hart, BRL (National Cancer Institute Division of Cancer Cause &Prevention Carcinogenesis Program Bethesda,Maryland,1968) on structurally similar read across substance (4-methoxyphenyl) acetic acid (CAS No.: 104-01-8). In a reproductive toxicity study, B6AKF1 female mice were treated with (4-methoxyphenyl) acetic acid in the concentration of 0 and 215 mg/kg bw/day in 0.5% gelatin for 7 to 28 day and after dose is administered through diet at 560 ppm for 18 months. Body weight gain was observed with the increase in duration of treatment. No gross pathological changes were observed in treated female mice. In addition, no fibroadenoma and carcinoma mammary gland were observed in treated female mice as compared to control. Therefore, NOAEL was considered to be > 215 mg/kg bw when B6AKF1 female mice by using (4-methoxyphenyl) acetic acid for 18 months.
Thus, based on the above predictions and experimental study of 4-Hydroxyphenylacetic Acid (156-38-7) and its structurally similar read across substance No Observed Adverse Effect Level (NOAEL) was considered to be 416.0mg/kg bw. Thus, comparing this value with the criteria of CLP regulation 4-Hydroxyphenylacetic Acid (156-38-7) cannot be classified as reproductive toxicant.
Effects on developmental toxicity
Effect on developmental toxicity: via oral route
- Endpoint conclusion:
- no study available
Effect on developmental toxicity: via inhalation route
- Endpoint conclusion:
- no study available
Effect on developmental toxicity: via dermal route
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
Thus, comparing this value with the criteria of CLP regulation 4-Hydroxyphenylacetic Acid (156-38-7) cannot be classified as reproductive toxicant.
Additional information
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
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