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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
Repeated dose toxicity: Oral
Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, repeated dose toxicity was predicted for 4-Hydroxyphenylacetic Acid. The study assumed the use of male and female F344 rats in a 13 weeks toxicity study. Since no significant treatment related effects were observed at the mentioned dose level, hence the No Observed Adverse Effect Level (NOAEL) for 4-Hydroxyphenylacetic Acid is predicted to be 879.677429199 mg/Kg bw/day.
Based on this value it can be concluded that the substance is considered to be not toxic as per the criteria mentioned in CLP regulation.
Repeated dose toxicity: Inhalation
4-Hydroxyphenylacetic Acid (CAS no. 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 end point for repeated dose toxicity by inhalation route is considered for waiver.
Repeated dose toxicity: Dermal
The acute dermal toxicity value for4-Hydroxyphenylacetic Acid (CAS No. – 156-38-7)(as provided in section 7.2.3) is >2000 mg/kg body weight. The substance was also found to be not irritating and not sensitizing to the skin. Based on these considerations, the end point for repeated dermal toxicity is considered as waiver.
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- repeated dose 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 from OECD QSAR Toolbox version 3.3 and the supporting QMRF report has been attached
- Qualifier:
- according to guideline
- Guideline:
- other: Refer below principle
- Principles of method if other than guideline:
- Final Report on the Safety Assessment of Sodium m-Nitrobenzenesulfonate
- GLP compliance:
- not specified
- Specific details on test material used for the study:
- - Name of test material: 4-Hydroxyphenylacetic Acid
- IUPAC name: 4-Hydroxyphenylacetic Acid
- Molecular formula: C8H8O3
- Molecular weight: 152.148 g/mol
- Substance type: Organic - Species:
- rat
- Strain:
- Fischer 344
- Details on species / strain selection:
- No data
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- No data
- Route of administration:
- oral: unspecified
- Details on route of administration:
- No data
- Vehicle:
- not specified
- Details on oral exposure:
- No data
- Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- No data
- Duration of treatment / exposure:
- 13 weeks
- Frequency of treatment:
- Daily
- Remarks:
- No data
- No. of animals per sex per dose:
- No data
- Control animals:
- not specified
- Details on study design:
- No data
- Positive control:
- No data
- Observations and examinations performed and frequency:
- No data
- Sacrifice and pathology:
- No data
- Other examinations:
- No data
- Statistics:
- No data
- Clinical signs:
- not specified
- 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
- Gross pathological findings:
- not specified
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
- Details on results:
- No data
- Dose descriptor:
- NOAEL
- Effect level:
- 879.677 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No significant effects were noted at the mentioned dose level
- Critical effects observed:
- not specified
- Conclusions:
- The No Observed Adverse Effect Level (NOAEL) for 4-Hydroxyphenylacetic Acid is predicted to be 879.677429199 mg/Kg bw/day.
- Executive summary:
Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, repeated dose toxicity was predicted for 4-Hydroxyphenylacetic Acid. The study assumed the use of male and female F344 rats in a 13 weeks toxicity study. Since no significant treatment related effects were observed at the mentioned dose level, hence the No Observed Adverse Effect Level (NOAEL) for 4-Hydroxyphenylacetic Acid is predicted to be 879.677429199 mg/Kg bw/day.
Based on this value it can be concluded that the substance is considered to be not toxic as per the criteria mentioned in CLP regulation.
Reference
The
prediction was based on dataset comprised from the following
descriptors: NOEL
Estimation method: Takes average value from the 6 nearest neighbours
Domain logical expression:Result: In Domain
(((((("a"
or "b" or "c" or "d" )
and "e" )
and ("f"
and (
not "g")
)
)
and ("h"
and (
not "i")
)
)
and ("j"
and (
not "k")
)
)
and ("l"
and "m" )
)
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
OECD ONLY
Domain
logical expression index: "f"
Referential
boundary: The
target chemical should be classified as Weak binder, OH group by
Estrogen Receptor Binding
Domain
logical expression index: "g"
Referential
boundary: The
target chemical should be classified as Non binder, impaired OH or NH2
group by Estrogen Receptor Binding
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 Non binder, without OH or NH2
group 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 Strong binder, OH group by
Estrogen Receptor Binding
Domain
logical expression index: "l"
Parametric
boundary:The
target chemical should have a value of log Kow which is >= 0.161
Domain
logical expression index: "m"
Parametric
boundary:The
target chemical should have a value of log Kow which is <= 4.01
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 879.7 mg/kg bw/day
- Study duration:
- chronic
- Species:
- rat
- Quality of whole database:
- Data is from K2 prediction database
Repeated dose toxicity: inhalation - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: inhalation - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Repeated dose toxicity: Oral
Prediction model based estimation for the target chemical and data from read across chemicals has been reviewed to determine the toxic nature of 4 - hydroxyphenylacetic acid upon repeated exposure by oral route. The studies are as mentioned below:
Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, repeated dose toxicity was predicted for 4-Hydroxyphenylacetic Acid. The study assumed the use of male and female F344 rats in a 13 weeks toxicity study. Since no significant treatment related effects were observed at the mentioned dose level, hence the No Observed Adverse Effect Level (NOAEL) for 4-Hydroxyphenylacetic Acid is predicted to be 879.677429199 mg/Kg bw/day.
The above mentioned predicted data is further supported by the data from read across chemicals as mentioned below:
In a combined repeated dose- reproductive developmental toxicity study (Sustainability Support Services (Europe) AB, 2015), Wistar male and female rats were treated with functionally similar read across chemical Methyl Phenyl acetate (RA CAS no 101 -41 -7) in the concentration of 0, 308, 556 and 1000 mg/kg bw orally by gavage in Corn oil for 63 days. No mortality or morbidity and apparent treatment related clinical signs were observed any of the groups of animals throughout the study 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, percent 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, Foot splay, fore limb and hind limb grip strength parameters and Motor activity were comparable and no treatment related changes were revealed in any of the animals of all treated groups as compare to the repective control groups. Similarly,No treatment related changes were observed inhematological and clinical chemistry parameters of treated male and female rats as compared to control.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.In addition, no significant change in organ weight,External and visceral examination of treated and recovery groups as compared to control.Focal to multifocal minimal lymphocytic infiltration of male and female and focal minimal necrosis in male in liver, focal minimal lymphocytic infiltration of male and female and focal mild mineralization in female in kidney, multifocal minimal lymphocytic infiltration in male and female andfocal minimal histiocyte infiltration in female lungs, focal minimal lymphocytic infiltration in heart of male, focal minimal aneurysm in aorta of male, focal moderate cystic dilationof cortex of Mandibular Lymph Node in female,focal mildsquamous epitheliumhyperplasia stomach of female, focal moderate cystic dilation of cortex in Mesenteric lymph node, focalto diffuse minimal to mild extramedullary hematopoesis in spleen and mild to moderate atrophy in Thymus of female, focal to multifocal minimal to moderate Neutrophilic/lymphocytic infiltration of Trachea of male and female, unilateral accessory adrenocortical tissue of Adrenals and focal to multifocal minimal to mildretention of mature sperm,focal minimal to milddegeneration of seminiferous tubules,focal to multifocal minimalsloughing of Pachytene Spermatocyte,focal minimalsloughing of round spermatid andfocal mildinfiltration of multinucleated giant cells of Testes,multifocal mildneutrophilic/lymphocytic infiltration of Seminal Vesicles and focal moderate necrotic debris in lumen of Prostate observed in male rats, multifocal to diffuse mild reduction of stromal cells, focal moderate necrosis, multifocal mild to moderate nodular hyperplasia of Uterus and focal minimal lymphocytic infiltration of Cervix in female rats were observed. 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 Therefore, No Observed Adverse Effect Level (NOAEL) is considered to be 1000 mg Methyl Phenyl acetate (CAS No.: 101-41-7) / kg body weight when Wistar male and female rats were orally treated with Methyl Phenyl acetate (CAS No.: 101-41-7).
Combined repeated dose repro-devp. screen was performed (J-check, 2018; OECD SIDS 1999) to evaluate the oral toxic nature of 70 -60% structurally siilar read across chemical 4-Hydroxybenzoic acid (RA CAS no 99 -96 -7) using rats. The chemical was given at dose levels of 0, 40, 200 or 1000 mg/Kg to 13 male and 13 female Sprague Dawley rats (Crj: CD, SPF) per group. Males were treated once daily for 42 days and females were treated with the chemical before mating period (2 weeks), during mating period (2 weeks) and in mating females throughout the pregnancy period 3 days after delivery. Male and females animals were note only observed for general condition, mortality, hematology, clinical chemistry, gross pathology and histopathology parameters but also for reproductive parameters and developmental parameters in the developing fetuses. No mortality was observed in any of the dose groups and also in the control animals. Abnormal respiratory sounds or transient salivation after administration were observed intermittently throughout the administration period in both males and females in 200 mg/Kg group. In males, suppression of body weight gain was observed with a dose of 1000 mg / kg. Based on the results of hematology and blood biochemical tests conducted in males, the reduction of lymphocyte ratio and glucose with a dose of 200 mg/kg or more, the decrease of total protein due to the dose of 1000 mg/kg and the A / G ratio An increase in GPT and GOT levels were observed. There was no effect on body weight of female, feeding amount of male and female, organ weight, autopsy and histopathological findings. These changes were significant, but not considered adverse effects. Based on these considerations, the repeated dose No observed Adverse Effect level (NOAEL) for 4-Hydroxybenzoic acid in rats is 1000 mg/Kg/day.
Repeated dose toxicity: Inhalation
4-Hydroxyphenylacetic Acid (CAS no. 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 end point for repeated dose toxicity by inhalation route is considered for waiver.
Repeated dose toxicity: Dermal
The acute dermal toxicity value for4-Hydroxyphenylacetic Acid (CAS No. – 156-38-7)(as provided in section 7.2.3) is >2000 mg/kg body weight. The substance was also found to be not irritating and not sensitizing to the skin. Based on these considerations, the end point for repeated dermal toxicity is considered as waiver.
Based on the data available for the target chemical and its read across, 4- hydroxyphenylacetic acid is not likely to be toxic upon repeated exposure by oral route as per the criteria mentioned in CLP regulation.
Justification for classification or non-classification
Based on the data available for the target chemical and its read across, 4- hydroxyphenylacetic acid (CAS no 156 -38 -7) is not likely to be toxic upon repeated exposure by oral route as per the criteria mentioned in CLP regulation.
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