4-(2-aminoethyl)phenol

Endpoint summary

Description of key information

Skin irritation

The dermal irritation potential of target chemical 4-(2-aminoethyl)phenol (CAS No: 51-67-2) was assessedin various experimental studies which were conducted on rabbits for target chemical4-(2-aminoethyl)phenol (CAS No: 51-67-2) and its structurally similar read across substancesPhenethyl phenyl acetate (CAS No. 102-20-5)andAnisic alcohol (CAS No: 105-13-5). The predicted data usingQSAR toolboxhas also been compared with the experimental data.Based on the available data for the target and read across substances and applying the weight of evidence approach, it can be concluded that chemical 4-(2-aminoethyl)phenol (CAS No: 51-67-2) is unable to cause skin irritation and thus considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

 

Eye irritation

An ocular irritation potential of target chemical 4-(2-aminoethyl)phenol (CAS No: 51-67-2) was assessedin various experimental studies which were conducted on rabbits for target chemical4-(2-aminoethyl)phenol (CAS No: 51-67-2) and its structurally similar read across substancesPhenethyl phenyl acetate (CAS No. 102-20-5) and Methylparaben (CAS No: 99-76-3). The predicted data usingQSAR toolboxhas also been compared with the experimental data.Based on the available data for the target and read across substances and applying the weight of evidence approach, it can be concluded that chemical 4-(2-aminoethyl)phenol (CAS No: 51-67-2) is unable to cause eye damage and thus can be considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

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 3.4 and QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: estimated data

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.4

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material: 4-(2-aminoethyl) phenol
- Common name: Tyramine
- Molecular formula: C8H11NO
- Molecular weight: 137.1809 g/mol
- Smiles notation: NCCc1ccc(O)cc1
- InChl: 1S/C8H11NO/c9-6-5-7-1-3-8(10)4-2-7/h1-4,10H,5-6,9H2
- Substance type: Organic
- Physical state: Solid

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

No data available

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

No data available

Duration of treatment / exposure:

24 hours

Observation period:

24 hours

Number of animals:

No data available

Details on study design:

No data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

24 h

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No skin irritation was observed in treated rabbits.

Estimation method: Takes mode value from the 6 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 ("k" and ( not "l") )  )  and ("m" and ( not "n") )  )  and ("o" and ( not "p") )  )  and ("q" and ( not "r") )  )  and ("s" and ( not "t") )  )  and ("u" and ( not "v") )  )  and ("w" and ( not "x") )  )  and ("y" and ( not "z") )  )  and ("aa" and ( not "ab") )  )  and ("ac" and ( not "ad") )  )  and ("ae" and ( not "af") )  )  and ("ag" and ( not "ah") )  )  and "ai" )  and ("aj" and ( not "ak") )  )  and ("al" and "am" )  )

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 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: "g"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Acylation involving an activated (glucuronidated) carboxamide group OR Acylation >> Acylation involving an activated (glucuronidated) carboxamide group >> Carboxylic Acid Amides OR Acylation >> Acylation involving an activated (glucuronidated) ester group OR Acylation >> Acylation involving an activated (glucuronidated) ester group >> Arenecarboxylic Acid Esters OR Acylation >> Direct acylation involving a leaving group OR Acylation >> Direct acylation involving a leaving group >> Carboxylic Acid Amides OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR Acylation >> Ring opening acylation OR Acylation >> Ring opening acylation >> beta-Lactams  OR AN2 >> Michael addition to alpha, beta-unsaturated acids and esters OR AN2 >> Michael addition to alpha, beta-unsaturated acids and esters >> alpha,beta-Unsaturated Carboxylic Acids and Esters OR AN2 >> Michael-type addition to quinoid structures  >> Carboxylic Acid Amides OR AN2 >> Michael-type addition to quinoid structures  >> Hydroxylated Phenols OR AN2 >> Michael-type addition to quinoid structures  >> Substituted Anilines OR Michael addition OR Michael addition >> Michae addition on quinoide type compounds OR Michael addition >> Michae addition on quinoide type compounds >> Quinone methide(s)/imines; Quinoide oxime structure; Nitroquinones, Naphthoquinone(s)/imines  OR Michael addition >> Michael addition on conjugated systems with electron withdrawing group OR Michael addition >> Michael addition on conjugated systems with electron withdrawing group >> alpha,beta-Carbonyl compounds with polarized double bonds  OR No alert found OR Nucleophilic addition OR Nucleophilic addition >> Addition to carbon-hetero double bonds OR Nucleophilic addition >> Addition to carbon-hetero double bonds >> Ketones OR Radical reactions OR Radical reactions >> ROS Generation OR Radical reactions >> ROS Generation >> Sterically Hindered Piperidine Derivatives OR Schiff base formation OR Schiff base formation >> Direct acting Schiff base formers OR Schiff base formation >> Direct acting Schiff base formers >> 1,2-Dicarbonyls and 1,3-Dicarbonyls  OR Schiff base formation >> Schiff base formation with carbonyl compounds OR Schiff base formation >> Schiff base formation with carbonyl compounds >> Aldehydes OR Schiff base formation >> Schiff base formation with carbonyl compounds >> Aromatic carbonyl compounds OR SN2 OR SN2 >> Interchange reaction with sulphur containing compounds OR SN2 >> Interchange reaction with sulphur containing compounds >> Thiols and disulfide compounds  OR SN2 >> Nucleophilic substitution at sp3 carbon atom OR SN2 >> Nucleophilic substitution at sp3 carbon atom >> Alkyl halides  OR SN2 >> Nucleophilic substitution at sp3 carbon atom >> Phosphonates OR SN2 >> Nucleophilic substitution on benzilyc carbon atom OR SN2 >> Nucleophilic substitution on benzilyc carbon atom >> alpha-Activated benzyls  OR SN2 >> Protein and/or DNA alkylation OR SN2 >> Protein and/or DNA alkylation >> Dialkyl Alkylphosphonates OR SN2 >> Ring opening SN2 reaction OR SN2 >> Ring opening SN2 reaction >> Epoxides, Aziridines and Sulfuranes  OR SN2 >> SN2 Reaction at a sp3 carbon atom OR SN2 >> SN2 Reaction at a sp3 carbon atom >> Activated alkyl esters and thioesters  by Protein binding by OASIS v1.4

Domain logical expression index: "h"

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

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Direct Acylation Involving a Leaving group OR Acylation >> Direct Acylation Involving a Leaving group >> Acetates OR SN2 OR SN2 >> SN2 reaction at sp3 carbon atom OR SN2 >> SN2 reaction at sp3 carbon atom >> Allyl acetates and related chemicals by Protein binding by OECD

Domain logical expression index: "j"

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

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 16 - Oxygen O by Chemical elements

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Group 1 - Alkali Earth Li,Na,K,Rb,Cs,Fr by Chemical elements

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 16 - Oxygen O by Chemical elements

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Group 16 - Sulfur S OR Group 17 - Halogens Br by Chemical elements

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 16 - Oxygen O by Chemical elements

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Group 17 - Halogens I by Chemical elements

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 16 - Oxygen O by Chemical elements

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Group 17 - Halogens F by Chemical elements

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND (!Undefined)Group CN Lipid Solubility < 0.4 g/kg by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as (!Undefined)Group C Surface Tension > 62 mN/m by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND (!Undefined)Group CN Lipid Solubility < 0.4 g/kg by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as (N/A) by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND (!Undefined)Group CN Lipid Solubility < 0.4 g/kg by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as Group C Melting Point > 55 C by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "y"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND (!Undefined)Group CN Lipid Solubility < 0.4 g/kg by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "z"

Referential boundary: The target chemical should be classified as Group CHal Melting Point > 65 C by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "aa"

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

Domain logical expression index: "ab"

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

Domain logical expression index: "ac"

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: "ad"

Referential boundary: The target chemical should be classified as Alcohol by Organic Functional groups

Domain logical expression index: "ae"

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: "af"

Referential boundary: The target chemical should be classified as Aliphatic Amine, tertiary by Organic Functional groups

Domain logical expression index: "ag"

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: "ah"

Referential boundary: The target chemical should be classified as Alkoxy by Organic Functional groups

Domain logical expression index: "ai"

Similarity boundary:Target: NCCc1ccc(O)cc1
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "aj"

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

Domain logical expression index: "ak"

Referential boundary: The target chemical should be classified as Oxyphenistain (Hepatotoxicity) Alert by Repeated dose (HESS)

Domain logical expression index: "al"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.0571

Domain logical expression index: "am"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.94

Interpretation of results:

other: not irritating

Conclusions:

The chemical 4-(2-aminoethyl)phenol (CAS No: 51-67-2) was estimated to be not irritating to the skin of New Zealand White rabbits. Based on the estimated result 4-(2-aminoethyl)phenol (CAS No: 51-67-2) can be considered to be not irritating to skin.

Executive summary:

The dermal irritation potential of 4-(2-aminoethyl)phenol (CAS No: 51-67-2) was estimated using OECD QSAR toolbox version 3.4 with logPow as the primary descriptor. The chemical 4-(2-aminoethyl)phenol (CAS No: 51-67-2) was estimated to be not irritating to the skin of New Zealand White rabbits. Based on the estimated result 4-(2-aminoethyl)phenol (CAS No: 51-67-2) can be considered to be not irritating to skin and can be classified under the category ˋ Not Classified’ as per CLP regulation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

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 3.4 and QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: estimated data

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.4

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material: 4-(2-aminoethyl) phenol
- Common name: Tyramine
- Molecular formula: C8H11NO
- Molecular weight: 137.1809 g/mol
- Smiles notation: NCCc1ccc(O)cc1
- InChl: 1S/C8H11NO/c9-6-5-7-1-3-8(10)4-2-7/h1-4,10H,5-6,9H2
- Substance type: Organic
- Physical state: Solid

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

No data available

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

0.1 mL

Duration of treatment / exposure:

single application

Observation period (in vivo):

48 hours

Number of animals or in vitro replicates:

No data available

Details on study design:

No data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

48 h

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No eye irritation was observed in treated rabbits.

Estimation method: Takes mode value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

((((((((((((((((((("a" or "b" or "c" or "d" or "e" )  and "f" )  and ("g" and ( not "h") )  )  and ("i" and ( not "j") )  )  and ("k" and ( not "l") )  )  and ("m" and ( not "n") )  )  and ("o" and ( not "p") )  )  and "q" )  and "r" )  and "s" )  and "t" )  and ("u" and ( not "v") )  )  and ("w" and ( not "x") )  )  and ("y" and ( not "z") )  )  and ("aa" and ( not "ab") )  )  and ("ac" and ( not "ad") )  )  and "ae" )  and "af" )  and ("ag" and "ah" )  )

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 Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Inclusion rules not met by Eye irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Derivatives of alpha amino benzene OR Organic sulphonic salts OR Substituted indoles by Eye irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as No alert found by Protein binding alerts for Chromosomal aberration by OASIS v.1.2

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Acylation involving an activated (glucuronidated) ester group OR Acylation >> Acylation involving an activated (glucuronidated) ester group >> Arenecarboxylic Acid Esters OR AN2 OR AN2 >> Michael addition to the quinoid type structures OR AN2 >> Michael addition to the quinoid type structures >> Hydroxylated Phenols OR AN2 >> Michael addition to the quinoid type structures >> Substituted Anilines OR AN2 >> Michael addition to the quinoid type structures >> Substituted Phenols OR Radical mechanism OR Radical mechanism >> ROS generation OR Radical mechanism >> ROS generation >> Sterically Hindered Piperidine Derivatives OR SN2 OR SN2 >> Protein and/or DNA alkylation OR SN2 >> Protein and/or DNA alkylation >> Dialkyl Alkylphosphonates by Protein binding alerts for Chromosomal aberration by OASIS v.1.2

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as No alert found by Protein binding alerts for skin sensitization by OASIS v1.4

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR Acylation >> Ring opening acylation OR Acylation >> Ring opening acylation >> beta-Lactams  OR Nucleophilic addition OR Nucleophilic addition >> Addition to carbon-hetero double bonds OR Nucleophilic addition >> Addition to carbon-hetero double bonds >> Ketones OR Schiff base formation OR Schiff base formation >> Direct acting Schiff base formers OR Schiff base formation >> Direct acting Schiff base formers >> 1,2-Dicarbonyls and 1,3-Dicarbonyls  OR Schiff base formation >> Schiff base formation with carbonyl compounds OR Schiff base formation >> Schiff base formation with carbonyl compounds >> Aromatic carbonyl compounds OR SN2 OR SN2 >> Interchange reaction with sulphur containing compounds OR SN2 >> Interchange reaction with sulphur containing compounds >> Thiols and disulfide compounds  OR SN2 >> Nucleophilic substitution on benzilyc carbon atom OR SN2 >> Nucleophilic substitution on benzilyc carbon atom >> alpha-Activated benzyls  by Protein binding alerts for skin sensitization by OASIS v1.4

Domain logical expression index: "m"

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

Domain logical expression index: "n"

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

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 16 - Oxygen O by Chemical elements

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Group 15 - Phosphorus P OR Group 16 - Sulfur S by Chemical elements

Domain logical expression index: "q"

Similarity boundary:Target: NCCc1ccc(O)cc1
Threshold=10%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "r"

Similarity boundary:Target: NCCc1ccc(O)cc1
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "s"

Similarity boundary:Target: NCCc1ccc(O)cc1
Threshold=80%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "t"

Similarity boundary:Target: NCCc1ccc(O)cc1
Threshold=40%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Phenols by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as Primary and secondary aliphatic amines by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND (!Undefined)Group CN Lipid Solubility < 0.4 g/kg by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as (N/A) OR Exclusion rules not met by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "y"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND (!Undefined)Group CN Lipid Solubility < 0.4 g/kg by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "z"

Referential boundary: The target chemical should be classified as Group CN log Kow > 4.5 by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "aa"

Referential boundary: The target chemical should be classified as Primary amines by OECD HPV Chemical Categories

Domain logical expression index: "ab"

Referential boundary: The target chemical should be classified as Diethylene glycol ethers by OECD HPV Chemical Categories

Domain logical expression index: "ac"

Referential boundary: The target chemical should be classified as Primary amines by OECD HPV Chemical Categories

Domain logical expression index: "ad"

Referential boundary: The target chemical should be classified as Secondary amines by OECD HPV Chemical Categories

Domain logical expression index: "ae"

Referential boundary: The target chemical should be classified as Biodegrades Fast by Biodeg probability (Biowin 1) ONLY

Domain logical expression index: "af"

Referential boundary: The target chemical should be classified as Biodegrades Fast by Biodeg probability (Biowin 2) ONLY

Domain logical expression index: "ag"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.289

Domain logical expression index: "ah"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.63

Interpretation of results:

other: not irritating

Conclusions:

The chemical 4-(2-aminoethyl)phenol (CAS No: 51-67-2) was estimated to be not irritating into the eyes of New Zealand White rabbits. Based on the estimated result 4-(2-aminoethyl)phenol (CAS No: 51-67-2) can be considered to be not irritating to eye.

Executive summary:

The ocular irritation potential of 4-(2-aminoethyl)phenol (CAS No: 51-67-2) was estimated using OECD QSAR toolbox version 3.4 with logPow as the primary descriptor. The chemical 4-(2-aminoethyl)phenol (CAS No: 51-67-2) was estimated to be not irritating into the eyes of New Zealand White rabbits. Based on the estimated result 4-(2-aminoethyl)phenol (CAS No: 51-67-2) can be considered to be not irritating to eye and can be classified under the category ˋ Not Classified’ as per CLP regulation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation:

Various studieshas been investigated for the test chemical4-(2-aminoethyl)phenol (CAS No: 51-67-2) to observe the potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits and guinea pigs for target chemical4-(2-aminoethyl)phenol (CAS No: 51-67-2) and its structurally similar read across substancesPhenethyl phenyl acetate (CAS No. 102-20-5)andAnisic alcohol (CAS No: 105-13-5).The predicted data using the OECD QSAR toolbox has also been compared with the experimental data and summarized as below;

 

Acute Dermal Irritation/corrosion Study of read across chemical Phenethyl phenyl acetate (CAS No. 102-20-5) in Rabbits, was performed in an OECD GLP laboratory (Sustainability Support Services (Europe) AB has the letter of access,2014) as per OECD guideline No. 404. Three healthy young adult female rabbits were used for conducting acute dermal irritation/corrosion study. Initially, the test item was applied to the clipped area of skin of one rabbit. The test site was covered with gauze patch. After 4 hours of exposure in animal no.1, no erythema and edema was observed at 1 hour of observation. At 24, 48 and 72 hours observation no erythema and no edema was observed. Hence the confirmatory test was conducted on additional two rabbits (No. 2 and 3) to confirm the non-irritant nature of the test item. The patch was removed after 4 hours and rabbits were observed for erythema and edema at 1, 24, 48 and 72 hours after patch removal, evaluated and graded as per Draize method. In animal no. 2, at 1 hour observation post patch removal, revealed very slight erythema (barely perceptible) and no edema whereas animal no. 3 showed no erythema and edema. At 24, 48 and 72 hours, animal nos. 2 and 3 showed no erythema and no edema. The other untreated side revealed no erythema and no edema and was found to be normal throughout the experimental period. The individual mean score at 24, 48 and 72 hours for treated site for animal nos. 1, 2 and 3 were 0.00, 0.00, 0.00 and 0.00, 0.00, 0.00, for erythema and edema formation, respectively. No erythema and no edema (skin irritation) were found at the end of 72 hour observation period after patch removal. Hence, it was concluded that Phenethyl phenyl acetate (CAS No. – 102 -20-5) was Non-Irritating to the skin of Female New Zealand White rabbits under the experimental conditions tested and is Classified as “Category- Not Classified as Skin Irritant” as per CLP criteria for Classification.

 

In another Guideline study conducted for same read across substance Phenethyl phenyl acetate (CAS No. 102-20-5) at Sustainability Support Services sponsored lab.(report number 20167, 2012) 3 female New Zealand White rabbits were used. The rabbits were prepared 24 hours prior to application of test product. The furs from the dorsal area of trunk of animals were removed with electric clippers exposing an area measuring approximately 6 cm2 of body surface area of animal. The care was taken such that abrasion penetrated the Stratum corneum only and not dermis. 0.5 gm of the test compound was applied on a small area 6 square cms of the intact test site. Each site of application was covered with an impervious dressing which was secured with an adhesive tape. The animals were housed individually and restrained by the use of plastic collars. After patch removal [4 hours later] the unabsorbed test chemical was removed and the test site was washed with lukewarm water. The intact skin site of application was observed for erythema and edema at 1, 24, 48 and 72 hours till 14 days after application and scored according to Draize method. Phenethyl phenylacetate did not produce erythema or edema throughout the observation period of 14 days. The dermal irritation index was calculated to be 0.00. Phenethyl phenylacetate did not produce any clinical signs of toxicity throughout the study. Based on the score and observations, Phenethyl phenylacetate can be considered not irritating to skin.

 

The above results were further supported by thePreliminary irritation testcarried out byD.W. SHARP {Toxicology, 9 (1978) 261-271} forread across substanceAnisic alcohol (CAS No: 105-13-5)in guinea pigs to determine the concentration suitableforthe sensitization study[injection challenge concentration (ICC) and application challenge concentration(ACC)].In the preliminary test, the guinea pigs were treated intradermally and dermally. 4 guinea pigs were (same sex) were injected intradermally in the clipped and shaved flanks with 0.1ml aliquots of a range of concentration of test substance in physiological saline. 24 hours later, the skin was examined for erythema and edema.The concentration giving slight but perceptible irritation with no oedema was selected as the injection challenge concentration (ICC).Aliquots of 0.1ml using a range of concentration of the test substance in distilled water were applied in small circular areas to the shaved flanks of 4 previously untreated guinea pigs.24 hours later, the skin was examined for erythema and the highest concentration which caused no irritation was selected as the application challenge concentration (ACC).As a result of preliminary studies, the concentrations of Anisic alcohol at which no irritation was observed were 0.25% for the ICC and 10% for ACC.Since the test chemical did not induce any cutaneous effects at these concentrations, the Anisic alcohol (CAS No: 105-13-5) was considered to be not irritating to the skin of guinea pigs.

 

 

Thus based on the available data for the target and read across substances and applying the weight of evidence approach, it can be concluded that chemical 4-(2-aminoethyl)phenol (CAS No: 51-67-2) is unable to cause skin irritation and considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

 

 

Eye irritation:

In different studies,the test chemical4-(2-aminoethyl)phenol (CAS No: 51-67-2) has been investigated for potential for ocular irritationto a greater or lesser extent. The studies are based on in vivo experiments in rabbits for target chemical4-(2-aminoethyl)phenol (CAS No: 51-67-2) andits structurally similar read across substancessubstancePhenethyl phenyl acetate (CAS No. 102-20-5) and Methylparaben (CAS No: 99-76-3).The predicted data using the OECD QSAR toolbox has also been compared with the experimental data and summarized as below;

 

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the eye irritation potential was estimated for test chemical4-(2-aminoethyl)phenol (CAS No: 51-67-2) .The chemical 4-(2-aminoethyl)phenol (CAS No: 51-67-2) is estimated to be not irritating to eye of New Zealand White rabbits.

 

Acute Eye Irritation/Corrosion Study of read across substance Phenethyl phenyl acetate (CAS No. 102-20-5) in Rabbits, was performed in an OECD GLP laboratory (Sustainability Support Services (Europe) AB has the letter of access) as per OECD guideline no. 405. Rabbits free from injury of eye were selected for the study. The eyes of all the rabbits were examined 24 hours prior to treatment. One eye of each rabbit served as control and other as treated. Control eye was left untreated whereas; 0.1 ml of test item (as such)was instilled in the other (treated) eye of rabbits. The eye was observed at 1, 24, 48, 72 hours after test item instillation. Ophthalmoscope was used for scoring of eye lesions. In the initial test,0.1 ml of as such test item was instilled into the conjunctival sac of the right eye of animal no.1 whereas the left eye of the rabbit served as the control. As animal no. 1 showed no severe ocular lesions hence a confirmatory test was conducted on additional two rabbits (animal no. 2 and 3);0.1 ml of as such test item was instilled into the conjunctival sac of right eye of both the rabbits and left eye served as the control. Untreated eye of all the three rabbits was normal throughout the experimental period of 72 hours. The following grading scores were observed in treated eye of tested rabbits. The individual mean score for animal nos. 1, 2 and 3 at 24, 48, 72 hours (at treated site) for corneal opacity, iris, conjunctiva and chemosis were found 0.00, 0.00, 0.33, 0.00; 0.00, 0.00, 0.33, 0.00 and 0.00, 0.00, 0.33, 0.00 respectively. Under the experimental conditions tested, Phenethyl phenyl acetate (CAS No. 102-20-5) is found to be Non Irritant to New Zealand White male rabbit eyes and is thus Classified as “Category- Not Classified as Eye Irritant” as per CLP criteria for Classification.

 

In another Guideline study conducted for same read across chemical Phenethyl phenyl acetate (CAS No. 102-20-5) at Sustainability Support Services sponsored lab.(report number 20167, 2012) 3 female New Zealand White rabbits were used. 0.1 ml of the test chemical was moistened with water was instilled in the conjunctival sac of rabbits after gently pulling the lower lid away from the eyeball. The other eye which remained untreated served as a control. The ocular lesions were evaluated at 1, 24, 48 and 72 hours after the treatment. The grades of ocular reactions (conjunctiva, cornea and iris) were recorded at each observation. To determine the reversibility of the effect the animals were observed normally for 21 days. Any other lesions in the eye viz pannus, staining were observed and scored accordingly. Examination of reactions was facilitated by use of biomicroscope and hand slit lamp. Individual animal weights before and during the study was observed. The overall irritation index of Phenethyl phenyl acetate was 0.0 after 72 hours. Also Phenethyl phenyl acetate did not produce any clinical signs of toxicity throughout the examination period of 21 days. Hence, under the test conditions, Phenethyl phenyl acetate can be concluded to be not irritating to New Zealand White rabbit eyes.

 

The Cosmetic Ingredients Review Expert Panel (CIR, 1984) conducted an eye irritation studyfor structurally similar read across substanceMethylparaben (CAS No: 99-76-3) on rabbits to determine the degree of eye irritancy.During the test, 0.1-02 % ofMethylparaben was instilled into the eye of each rabbit and later observed for ocular lesions. The chemical did not induce any ocular lesions at test concentration.Hence the chemicalMethylparaben (CAS No: 99-76-3)was considered to be not irritating to the rabbits’ eye.

 

 

Thus based on the available data for the target and read across substances and applying the weight of evidence approach, it can be concluded that chemical 4-(2-aminoethyl)phenol (CAS No: 51-67-2) is unable to cause eye irritation and considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Justification for classification or non-classification

The skin and eye irritation potential of test chemical 4-(2-aminoethyl)phenol (CAS No: 51-67-2) and its structurally similar read across substanceswere observed in various studies. The results obtained from these studies indicate that the chemical 4-aminobenzene-1,2-dicarbonitrile is unlikely to cause skin and eye irritation. Hence 4-(2-aminoethyl)phenol (CAS No: 51-67-2) can be classified under the category “Not Classified” for skin and eye as per CLP.