4-(2-aminoethyl)phenol

Endpoint summary

Description of key information

The skin sensitization potential of target chemical 4-(2-aminoethyl)phenol (CAS No: 51-67-2) was assessedin various experimental studies which were conducted on guinea for target chemical4-(2-aminoethyl)phenol (CAS No: 51-67-2) and its structurally similar read across substancesMethylparaben (CAS No: 99-76-3) and Anisic 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 sensitization and thus can be considered as not sensitizing. 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 sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

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

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

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:

guinea pig

Strain:

other: Pirbright White

Sex:

not specified

Details on test animals and environmental conditions:

No data available

Route:

intradermal and epicutaneous

Vehicle:

not specified

Concentration / amount:

No data available

Adequacy of induction:

not specified

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

not specified

Concentration / amount:

No data available

Day(s)/duration:

48 hours

Adequacy of challenge:

not specified

No. of animals per dose:

20

Details on study design:

No data available

Challenge controls:

No data available

Reading:

1st reading

Hours after challenge:

48

Group:

test chemical

Dose level:

No data available

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

No skin sensitization was observed in treated guinea pigs.

Cellular proliferation data / Observations:

No skin sensitization was observed in treated guinea pigs.

The prediction was based on dataset comprised from the following descriptors: "Skin Sensitisation"
Estimation method: Takes highest 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 ( not "g") )  )  and ("h" and ( not "i") )  )  and ("j" and ( not "k") )  )  and ("l" and ( not "m") )  )  and "n" )  and "o" )  and ("p" and "q" )  )

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 Protein binding by OECD

Domain logical expression index: "g"

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 Acylation >> Ring Opening Acylation OR Acylation >> Ring Opening Acylation >> alpha-Lactams OR Michael addition OR Michael addition >> Quinones and Quinone-type Chemicals OR Michael addition >> Quinones and Quinone-type Chemicals >> Quinone-diimine OR Schiff Base Formers OR Schiff Base Formers >> Direct Acting Schiff Base Formers OR Schiff Base Formers >> Direct Acting Schiff Base Formers >> 1-3-Dicarbonyls OR SN2 OR SN2 >> Epoxides and Related Chemicals OR SN2 >> Epoxides and Related Chemicals >> Epoxides OR SN2 >> SN2 reaction at sp3 carbon atom OR SN2 >> SN2 reaction at sp3 carbon atom >> Alkyl halides OR SN2 >> SN2 reaction at sp3 carbon atom >> Allyl acetates and related chemicals OR SN2 >> SN2 reaction at sp3 carbon atom >> Phosphonates by Protein binding by OECD

Domain logical expression index: "h"

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: "i"

Referential boundary: The target chemical should be classified as (!Undefined)Group C Surface Tension > 62 mN/m OR (!Undefined)Group CNS Surface Tension > 62 mN/m OR (N/A) OR Exclusion rules not met OR Group All log Kow < -3.1 OR Group All log Kow > 9 OR Group All Melting Point > 200 C OR Group C Aqueous Solubility < 0.0001 g/L OR Group C Melting Point > 55 C OR Group C Molecular Weight > 350 g/mol OR Group C Vapour Pressure < 0.0001 Pa OR Group CHal Melting Point > 65 C OR Group CHal Molecular Weight > 280 g/mol OR Group CN Aqueous Solubility < 0.0001 g/L OR Group CN Aqueous Solubility < 0.1 g/L OR Group CN log Kow > 4.5 OR Group CN log Kow > 5.5 OR Group CN Melting Point > 180 C OR Group CN Molecular Weight > 290 g/mol OR Group CN Molecular Weight > 540 g/mol OR Group CN Vapour Pressure < 0.001 Pa OR Group CNHal Aqueous Solubility < 0.001 g/L OR Group CNHal Aqueous Solubility < 0.1 g/L OR Group CNHal log Kow > 3.8 OR Group CNS log Kow < 0.5 OR Group CNS Melting Point > 120 C OR Group CNS Melting Point > 50 C by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "j"

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

Domain logical expression index: "k"

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

Domain logical expression index: "l"

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

Domain logical expression index: "m"

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

Domain logical expression index: "n"

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

Domain logical expression index: "o"

Similarity boundary:Target: NCCc1ccc(O)cc1
Threshold=50%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.0581

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.91

Interpretation of results:

other: Not sensitizing

Conclusions:

The chemical 4-(2-aminoethyl)phenol (CAS No: 51-67-2) was estimated to be not sensitizing to the skin of Pirbright White guinea pigs. Based on the estimated result 4-(2-aminoethyl)phenol (CAS No: 51-67-2) failed to induce skin sanitization effects and hence is considered to be not sensitizing to Pirbright White guinea pigs

Executive summary:

The skin sensitization potential of 4-(2-aminoethyl)phenol (CAS No: 51-67-2) was estimated using OECD QSAR toolbox version 3.3 with log Pow as the primary descriptor. The chemical 4-(2-aminoethyl)phenol (CAS No: 51-67-2) was estimated to be not sensitizing to the skin of Pirbright White guinea pigs. Based on the estimated result 4-(2-aminoethyl)phenol (CAS No: 51-67-2) failed to induce skin sanitization effects and hence is considered to be not sensitizing to Pirbright White guinea pigs and can be classified under the category ˋ Not Classified’ as per CLP regulation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Various studies has been investigated for the test chemical4-(2-aminoethyl)phenol (CAS No: 51-67-2) to observe the potential for skin sensitization to a greater or lesser extent. The studies are based on in vivo experiments in guinea pigs for target chemical4-(2-aminoethyl)phenol (CAS No: 51-67-2) and its structurally similar read across substancesMethylparaben (CAS No: 99-76-3) and Anisic 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;

 

The skin sensitization potential of 4-(2-aminoethyl)phenol (CAS No: 51-67-2) was estimated using OECD QSAR toolbox version 3.3 with log Pow as the primary descriptor. The chemical 4-(2-aminoethyl)phenol (CAS No: 51-67-2) was estimated to be not sensitizing to the skin of Pirbright White guinea pigs. Based on the estimated result 4-(2-aminoethyl)phenol (CAS No: 51-67-2) failed to induce skin sensitization effects and hence is considered to be not sensitizing to Pirbright White guinea pigs.

 

The Cosmetic Ingredients Review Expert Panel (CIR, 1984) conducted A repeated insult patch test (RIPT)for structurally similar read across substanceMethylparaben (CAS No: 99-76-3) on skin of 50 subjects (25M/25F) which supports the above mentioned result.During the induction exposure, 5% ofMethylparaben wasapplied to the skin of 50 subjects (25M/25F) for 4 to 8 hour every other day for 3 weeks (10 applications). Following a 3-week rest, the animals were challenged at same concentration used in induction for 24 to 48 hours.None of the subject showed any signs of contact allergy. HenceMethylparaben (CAS No: 99-76-3)was considered to be not sensitizing to the human’ skin.

 

The above results were further supported by the experimental study conducted byD.W. SHARP {Toxicology, 9 (1978) 261-271} forread across substanceAnisic alcohol (CAS No: 105-13-5)in 10 Inbred Hartley strain albino the guinea pigs according modified Draize sensitization test which supports the above mentioned result.The preliminary irritation tests were done in guinea pigs to determine concentrations suitable for sensitization testing [injection challenge concentration (ICC) and application challenge concentration(ACC)]. In the induction phase,the total dose was administered on one occasion as 4 intradermal injections, each 2.5 times the ICC (2.5X 0.25). Fourteen days later each animal was challenged intradermally in one flank and topically in the other with 0.1 ml aliquots of test substance at the respective ICC and ACC (0.25 and 10 respectively). Twenty-four hours later the reactions were observed. In the absence of sensitization reactions at first challenge the induction and challenge procedures were repeated, andapparent sensitization reactions confirmed 7 days later by a second challenge with controls included. Based upon the second challenge, it can be concluded that theAnisic alcohol (CAS No: 105-13-5)was considered to be non-sensitizingto the skin of albino Hartley guinea pigs at 0.25% ICC and 10% ACC concentrations.

 

Thus on the basis of available data for thetarget chemical4-(2-aminoethyl)phenol (CAS No: 51-67-2) and its structurally similar read across substancesMethylparaben (CAS No: 99-76-3) and Anisic alcohol (CAS No: 105-13-5),it can be concluded thatchemical 4-(2-aminoethyl)phenol (CAS No: 51-67-2) is unable to cause skin sensitization and considered as non-skin sensitizer. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The skin sensitization potential of test substance 4-(2-aminoethyl)phenol (CAS No: 51-67-2) and itsstructurallysimilar read across substancesMethylparaben (CAS No: 99-76-3) and Anisic alcohol (CAS No: 105-13-5) were observed in various studies. From the results obtained from these studies it is concluded that the chemical 4-(2-aminoethyl)phenol (CAS No: 51-67-2) is not likely to cause skin sensitization and hence can be classified as non-skin sensitizer.