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EC number: 200-115-8 | CAS number: 51-67-2
- 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
Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, repeated dose oral toxicity was predicted for the test compound 4-(2-aminoethyl)phenol ( 51-67-2). The study assumed the use of male and female Osborne-Mendel strain in chronic study of 17 weeks. No significant alterations were noted at the dose level of 712.75 mg/Kg bw/day. The predicted No Observed Adverse Effect Level (NOAEL) for compound 4-(2-aminoethyl)phenol is considered to be 712.75mg/Kg bw/day. Based on this value it can be concluded that the substance is considered to not toxic as per the criteria mentioned in CLP regulation.
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:
- Prediction is done using OECD QSAR Toolbox version 3.4 and the supporting QMRF report has been attached.
- Qualifier:
- according to guideline
- Guideline:
- other: As mention below
- Principles of method if other than guideline:
- Prediction is done using OECD QSAR Toolbox version 3.4, 2018.
- GLP compliance:
- not specified
- Limit test:
- no
- Specific details on test material used for the study:
- Name: 4-(2-Aminoethyl)phenol
SMILES:NCCc1ccc(O)cc1
InChI:1S/C8H11NO/c9-6-5-7-1-3-8(10)4-2-7/h1-4,10H,5-6,9H2
Mol. formula: C8H11NO
Molecular Weight: 137.1809 g/mole - Species:
- rat
- Strain:
- Osborne-Mendel
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Not specified
- Route of administration:
- oral: feed
- Details on route of administration:
- Not specified
- Vehicle:
- not specified
- Details on oral exposure:
- Not specified
- Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- Not specified
- Duration of treatment / exposure:
- 17 weeks
- Frequency of treatment:
- Not specified
- Remarks:
- Not specified
- No. of animals per sex per dose:
- Not specified
- Control animals:
- not specified
- Details on study design:
- Not specified
- Positive control:
- Not specified
- Observations and examinations performed and frequency:
- Not specified
- Sacrifice and pathology:
- Not specified
- Other examinations:
- Not specified
- Statistics:
- Not specified
- 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
- Dose descriptor:
- NOAEL
- Effect level:
- 712.75 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No significant effect were observed at this dose
- Remarks on result:
- other: No toxic effect were observed
- Critical effects observed:
- not specified
- Treatment related:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
- Conclusions:
- The predicted No Observed Adverse Effect Level (NOAEL) for 4-(2-aminoethyl)phenol ( 51-67-2) is considered to be 712.75 mg/Kg bw/day.
- Executive summary:
Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, repeated dose oral toxicity was predicted for the test compound 4-(2-aminoethyl)phenol ( 51-67-2). The study assumed the use of male and female Osborne-Mendel strain in chronic study of 17 weeks. No significant alterations were noted at the dose level of 712.75 mg/Kg bw/day. The predicted No Observed Adverse Effect Level (NOAEL) for compound 4-(2-aminoethyl)phenol is considered to be 712.75mg/Kg bw/day. Based on this value it can be concluded that the substance is considered to not toxic as per the criteria mentioned in CLP regulation.
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" or "e" )
and ("f"
and (
not "g")
)
)
and ("h"
and (
not "i")
)
)
and ("j"
and (
not "k")
)
)
and ("l"
and (
not "m")
)
)
and ("n"
and (
not "o")
)
)
and ("p"
and (
not "q")
)
)
and "r" )
and ("s"
and (
not "t")
)
)
and "u" )
and "v" )
and ("w"
and "x" )
)
Domain
logical expression index: "a"
Referential
boundary: The
target chemical should be classified as Primary amines by OECD HPV
Chemical Categories
Domain
logical expression index: "b"
Referential
boundary: The
target chemical should be classified as Aliphatic Amines AND Phenols
(Acute toxicity) by US-EPA New Chemical Categories
Domain
logical expression index: "c"
Referential
boundary: The
target chemical should be classified as Michael addition AND Michael
addition >> P450 Mediated Activation to Quinones and Quinone-type
Chemicals AND Michael addition >> P450 Mediated Activation to Quinones
and Quinone-type Chemicals >> Alkyl phenols by DNA binding by OECD
Domain
logical expression index: "d"
Referential
boundary: The
target chemical should be classified as Weak binder, OH group by
Estrogen Receptor Binding
Domain
logical expression index: "e"
Referential
boundary: The
target chemical should be classified as AN2 AND AN2 >> Michael-type
addition to quinoid structures AND AN2 >> Michael-type addition to
quinoid structures >> Substituted Phenols by Protein binding by OASIS
v1.4
Domain
logical expression index: "f"
Referential
boundary: The
target chemical should be classified as No alert found by DNA binding by
OASIS v.1.4
Domain
logical expression index: "g"
Referential
boundary: The
target chemical should be classified as AN2 OR AN2 >> Michael-type
addition, quinoid structures OR AN2 >> Michael-type addition, quinoid
structures >> Quinoneimines OR AN2 >> Nucleophilic addition reaction
with cycloisomerization OR AN2 >> Nucleophilic addition reaction with
cycloisomerization >> Hydrazine Derivatives 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 via ROS formation
(indirect) OR Radical >> Radical mechanism via ROS formation (indirect)
>> Hydrazine Derivatives OR Radical >> Radical mechanism via ROS
formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines
OR Radical >> ROS formation after GSH depletion (indirect) OR Radical >>
ROS formation after GSH depletion (indirect) >> Quinoneimines OR SN1 OR
SN1 >> Nucleophilic attack after nitrenium ion formation OR SN1 >>
Nucleophilic attack after nitrenium ion formation >> Single-Ring
Substituted Primary Aromatic Amines OR SN2 OR SN2 >> Alkylation, direct
acting epoxides and related OR SN2 >> Alkylation, direct acting epoxides
and related >> Epoxides and Aziridines OR SN2 >> Alkylation,
nucleophilic substitution at sp3-carbon atom OR SN2 >> Alkylation,
nucleophilic substitution at sp3-carbon atom >> Haloalkanes Containing
Heteroatom OR SN2 >> Direct nucleophilic attack on diazonium cation OR
SN2 >> Direct nucleophilic attack on diazonium cation >> Hydrazine
Derivatives OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR
SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Haloalkanes
Containing Heteroatom by DNA binding by OASIS v.1.4
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 Strong binder, OH group OR Very
strong binder, OH 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 Non binder, without OH or NH2
group 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 Moderate binder, NH2 group OR
Moderate binder, OH grooup by Estrogen Receptor Binding
Domain
logical expression index: "n"
Referential
boundary: The
target chemical should be classified as Not possible to classify
according to these rules (GSH) by Protein binding potency
Domain
logical expression index: "o"
Referential
boundary: The
target chemical should be classified as Extremely reactive (GSH) OR
Extremely reactive (GSH) >> Phenyl acrylate (MA) by Protein binding
potency
Domain
logical expression index: "p"
Referential
boundary: The
target chemical should be classified as Non-Metals by Groups of elements
Domain
logical expression index: "q"
Referential
boundary: The
target chemical should be classified as Alkali Earth OR Halogens OR
Metalloids OR Transition Metals by Groups of elements
Domain
logical expression index: "r"
Referential
boundary: The
target chemical should be classified as Bioavailable by Lipinski Rule
Oasis ONLY
Domain
logical expression index: "s"
Referential
boundary: The
target chemical should be classified as Aliphatic Amine, primary AND
Aryl AND Phenol AND Precursors quinoid compounds by Organic Functional
groups
Domain
logical expression index: "t"
Referential
boundary: The
target chemical should be classified as Alcohol OR Aldehyde by Organic
Functional groups
Domain
logical expression index: "u"
Similarity
boundary:Target:
NCCc1ccc(O)cc1
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization
Domain
logical expression index: "v"
Similarity
boundary:Target:
NCCc1ccc(O)cc1
Threshold=80%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization
Domain
logical expression index: "w"
Parametric
boundary:The
target chemical should have a value of log Kow which is >= 0.289
Domain
logical expression index: "x"
Parametric
boundary:The
target chemical should have a value of log Kow which is <= 1.34
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 712.75 mg/kg bw/day
- Study duration:
- chronic
- Species:
- rat
- Quality of whole database:
- K2 data from prediction OECD QSAR 3.4
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: via oral route;
Prediction and experimental studies were reviewed to determine the toxic nature of target substance Tyramine, 4-(2-aminoethyl)phenol ( 51-67-2) upon repeated exposure by oral route. The studies are as mentioned below:
Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, repeated dose oral toxicity was predicted for the test compound 4-(2-aminoethyl)phenol ( 51-67-2). The study assumed the use of male and female Osborne-Mendel strain in chronic study of 17 weeks. No significant alterations were noted at the dose level of 712.75 mg/Kg bw/day. The predicted No Observed Adverse Effect Level (NOAEL) for compound 4-(2-aminoethyl)phenol is considered to be 712.75mg/Kg bw/day. Based on this value it can be concluded that the substance is considered to not toxic as per the criteria mentioned in CLP regulation.
Another chronic toxicity study for Read across was performed by E. C. Hagan et al.( Food and cosmetics toxicology,1967) to determine the oral toxic nature of Phenethyl phenyl acetate; IUPAC name ; 2-phenylethyl phenylacetate (102-20-5). The read across substances share high similarity in structure and log kow .Therefore, it is acceptable to derive information on toxicity from the analogue substance. Repeated dose oral study for Phenethyl phenylacetate was assessed for its possible toxic potential. For this purpose Subchronic study for 17 weeks was conducted on Osborne-Mendel male and female rats. The test material was exposed at the concentration of 0, 50, 250 and 500 mg/kg bw (1000.2500 and 10000ppm)by oral feed. The animal’s weight, food intake and general condition were recorded every week. Haematological examinations were made at termination of the subacute studies. These examinations included white cell counts, red cell counts, haemoglobins and haematocrits. At the termination of the experiments the rats were sacrificed and exsanguinated. The tissues of all the rats were examined macroscopically at the time of sacrifice. The viscera were removed and the liver, kidneys, spleen, heart, and testes were weighed. These organs, the remaining abdominal and thoracic viscera, and one hind leg, for bone, bone marrow, and muscle, were preserved in 10 ~o buffered formalin-saline solution for histopathological examination. For routine histopathology, sections were embedded in paraffin wax and stained with haematoxylin and eosin. No mortality observed. No significant effect were observed at doses 0, 50, 250 or 500 mg/kg bw in treated group compare to control in clinical sign, Body weight, Food intake , Haematology, organ weight ,gross and histopathology . Hence the NOAEL was considered to be 500 mg/kg bw for Phenethyl phenylacetate in male and female rats by oral feed for 17 weeks study.
Repeated inhalation study:
According to Annex IX of the REACH regulation, testing by the inhalation route is appropriate only if exposure of humans via inhalation is likely. Taking into account the low vapour pressure of the substance 4-(2-aminoethyl)phenol ( 51-67-2) ,which is reported as 0.0031697607mmHg at 25 C. Also considering the particle size distribution of the substance the majority of the particles was found to be in the size of 150 micron to 53 micron which is much larger size range compared to the inhalable particulate matter. Thus, exposure to inhalable dust, mist and vapour of the chemical 4-(2-aminoethyl)phenol is highly unlikely. Therefore this study is considered for waiver.
Repeated dermal study;
The acute toxicity value for 4-(2-aminoethyl)phenol ( 51-67-2) (as provided in section 7.2.3) is 3044 mg/kg body weight. Also, given the use of the chemical; repeated exposure by the dermal route is unlikely since the use of gloves is common practice in industries. Thus, it is expected that 4-(2-aminoethyl) phenol shall not exhibit 28 day repeated dose toxicity by the dermal route. In addition, there is no data available that suggests that 4-(2-aminoethyl) phenol exhibit repeated dose toxicity by the dermal route. Hence this end point was considered for waiver.
Based on the data available for the target chemical and its prediction, Tyramine, 4-(2-aminoethyl)phenol does not exhibit toxic nature upon repeated exposure by oral, inhalation and dermal route of exposure and hence is not likely to classify as per the criteria mentioned in CLP regulation.
Justification for classification or non-classification
Based on the data available for the target chemical Tyramine, 4-(2-aminoethyl)phenol does not exhibit toxic nature upon repeated exposure by oral, inhalation and dermal route of exposure and hence is not likely to classify as per the criteria mentioned in CLP regulation.
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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