Phenethyl propionate

Endpoint summary

Description of key information

The target chemical 2-phenylethyl propanoate (CAS No: 122-70-3) was considered to be not sensitizing on skin of guinea pigs at challenge concentration of 8% in an Open Epicutaneous Test (OET).

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Data is from peer reviewed journal

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

An Open Epicutaneous Test (OET) was performed on guinea pigs to assess the skin sensitization potential of test chemical 2-phenylethyl propanoate (CAS No: 122-70-3).

GLP compliance:

not specified

Type of study:

open epicutaneous test

Justification for non-LLNA method:

not specified

Specific details on test material used for the study:

- Name of test material (IUPAC name): 2-phenylethyl propanoate
- Common name: Phenethyl propionate (PEP)
- Molecular formula: C11H14O2
- Molecular weight: 178.2296 g/mol
- Smiles notation: c1(CCOC(=O)CC)ccccc1
- InChl: 1S/C11H14O2/c1-2-11(12)13-9-8-10-6-4-3-5-7-10/h3-7H,2,8-9H2,1H3
- Substance type: Organic
- Physical state: Liquid

Species:

guinea pig

Strain:

not specified

Sex:

male/female

Details on test animals and environmental conditions:

- Weight at study initiation: 300-450g

Route:

epicutaneous, open

Vehicle:

other: ethanol, acetone, H20, petroleum, PEG and/or other suitable vehicles

Concentration / amount:

Concentration:100%, 30%, 10%, 3%, 1%, or 0.3%
Amount: 0.1ml

Day(s)/duration:

3 weeks (0-21 days)

Adequacy of induction:

not specified

No.:

#1

Route:

epicutaneous, open

Vehicle:

other: ethanol, acetone, H20, petroleum, PEG and/or other suitable vehicles

Concentration / amount:

Concentration:8%
Amount: 0.025ml

Day(s)/duration:

on days 21 and 35

Adequacy of challenge:

not specified

No. of animals per dose:

6-8 guinea pigs

Details on study design:

RANGE FINDING TESTS:

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 21
- Exposure period:24 hours
- Test groups:6-8 guinea pigs
- Control group:3 guinea pigs
- Site: an area measuring 8 cm2 on the clipped flank skin of the guinea pigs
- Frequency of applications: The applications are repeated daily for 3 weeks or done 5 times weekly during 4 weeks
- Duration: 21 days (3 weeks)
- Concentrations: 100%, 30%, 10%, 3%, 1%, or 0.3% in vehicle.
Amount: 0.1ml

B. CHALLENGE EXPOSURE
- No. of exposures: 2
- Day(s) of challenge: on days 21 and 35
- Exposure period:24 hours
- Test groups: 6-8 guinea pigs
- Control group: 3 guinea pigs
- Site: contralateral flank measuring 2 cm2
- Concentrations: Concentration:8%
Amount: 0.025ml
- Evaluation (hr after challenge): 24,48 and/or 72h.

Challenge controls:

Yes concurrent vehicle.

Reading:

1st reading

Hours after challenge:

72

Group:

test chemical

Dose level:

8% (0.025ml)

No. with + reactions:

0

Total no. in group:

8

Clinical observations:

No known signs of skin sensitization were observed.

Remarks on result:

no indication of skin sensitisation

Remarks:

skin reactions were evaluated at 24,48 and/or 72h.

Cellular proliferation data / Observations:

No known signs of skin sensitization were observed.

Interpretation of results:

other: Not sensitizing

Conclusions:

The test material 2-phenylethyl propanoate (CAS No: 122-70-3) was considered to be not sensitizing on skin of guinea pigs at concentration of 8% in an Open Epicutaneous Test (OET).

Executive summary:

An Open Epicutaneous Test (OET) was performed on guinea pigs to assess the skin sensitization potential of test chemical 2-phenylethyl propanoate (CAS No: 122-70-3).

 

On day 1 during induction, 0.1 ml of the 2-phenylethyl propanoate was applied at concentrations of 100%, 30%, 10%, 3%, 1%, or 0.3% in vehicle to an area measuring 8 cm2 on the clipped flank skin of the guinea pigs. The applications are repeated daily for 3 weeks or done 5 times weekly during 4 weeks, usually on the same skin sites. The application sites were left uncovered and the reactions, if continuous daily applications were performed, can be read 24 h after each application, or at the end of each week.

 

To determine whether or not contact sensitization was induced, all groups of guinea pigs previously treated for 21 days, as well as 10 untreated, or only pretreated with the vehicle, controls are tested on days 21 and 35 on the contralateral flank with the test material. This test was performed by applying with a pipette 0.025 ml of each concentration to skin areas measuring 2 cm2. The reactions were read after 24,48 and/or 72h.

 

It was observed that none of the guinea pigs induced contact sensitization at challenge concentration of 8%.Thus the chemical2-phenylethyl propanoate (CAS No: 122-70-3) was considered to be not sensitizing on skin of guinea pigs at concentration of 8% in an Open Epicutaneous Test (OET).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Various studieshas been investigated for the test chemical2-phenylethyl propanoate (CAS No: 122-70-3)  to observe the potential for skin sensitization to a greater or lesser extent. The studies are based on in vivo experiments in guinea pigs and humans for target chemical2-phenylethyl propanoate (CAS No: 122-70-3) and its structurally similar read across substance Benzylformate(CAS No: 104-57-4).The predicted data usingDanish QSAR databasethe has also been compared with the experimental data and summarized as below;

 

An Open Epicutaneous Test (OET) was performed by G. Klecak (1985) and D. Belsito, D. Bickers, M. Bruze, P. Calow, M.L. Dagli, A.D. Fryer,H. Greim, Y. Miyachi, J.H. Saurat, I.G. Sipes (2012) for target chemical2-phenylethyl propanoate (CAS No: 122-70-3) on guinea pigs.On day 1 during induction, 0.1 ml of the 2-phenylethyl propanoate was applied at concentrations of 100%, 30%, 10%, 3%, 1%, or 0.3% in vehicle to an area measuring 8 cm2 on the clipped flank skin of the guinea pigs. The applications are repeated daily for 3 weeks or done 5 times weekly during 4 weeks, usually on the same skin sites. The application sites were left uncovered and the reactions, if continuous daily applications were performed, can be read 24 h after each application, or at the end of each week. To determine whether or not contact sensitization was induced, all groups of guinea pigs previously treated for 21 days, as well as 10 untreated, or only pretreated with the vehicle, controls are tested on days 21 and 35 on the contralateral flank with the test material. This test was performed by applying with a pipette 0.025 ml of each concentration to skin areas measuring 2 cm2. The reactions were read after 24,48 and/or 72h. It was observed that none of the guinea pigs induced contact sensitization at challenge concentration of 8%.Thus the chemical2-phenylethyl propanoate (CAS No: 122-70-3) was considered to be not sensitizing on skin of guinea pigs at concentration of 8% in an Open Epicutaneous Test (OET).

 

 

The D. L. J. Opdyke (1979) and. Belsito, D. Bickers, M. Bruze, P. Calow, M.L. Dagli, A.D. Fryer,H. Greim, Y. Miyachi, J.H. Saurat, I.G. Sipes (2012) reported Human Maximization test for chemical 2-phenylethyl propanoate (CAS No: 122-70-3) on 25 male volunteers in order to determine the skin sensitization potential caused by the chemical. 2-phenylethyl propanoate was applied at concentration of 8% (5520 µg/cm2) in petrolatum on skin of each subject and then observed for skin reactions. None of the subjects showed any cutaneous reaction. Therefore, 2-phenylethyl propanoate (CAS No: 122-70-3) was considered to be not sensitizing on the skin of 25 volunteers.

 

 

According to Danish QSAR database,theskin sensitization effects were estimated by using four different models i.e, Battery, Leadscope, SciQSAR and CASE Ultra for 2-phenylethyl propanoate (CAS No: 122-70-3). Based on estimation, no skin sensitization reactions were observed in guinea pigs and humans. Therefore, 2-phenylethyl propanoate (CAS No: 122-70-3) was considered to be non sensitizing.

 

 

 

The above results were supported by the experimental study carried out by D.W. Sharp (1978) in 10 Hartley albino guinea pigs forstructurally similar read across substance Benzylformate (CAS No: 104-57-4) by using Modified Draize Technique. Prior to the skin senitization test, the preliminary irritation tests were performed in 8 guinea pigs to determine concentrations suitable for sensitization test [injection challenge concentration(ICC) and application challenge concentration(ACC) ].As a result of the preliminary studies, the concentration selected for skin sensitization test were 0.25% for ICC and 20% for ACC. During 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 20 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, and apparent sensitization reactions confirmed 7 days later by a second and confirmatory challenge with controls included. At 24 hours after the first challenge and at the second and confirmatory challenge with 0.25% and 20%Benzyl formate, none of the rabbits showed positive results. Thus, it can be concluded that the Benzyl formate (CAS No: 104-57-4) was considered to be not sensitizing on guinea pigs.

 

 

Thus on the basis of available data for thetarget substance2-phenylethyl propanoate (CAS No: 122-70-3) andits structurally similar read across substance Benzylformate (CAS No: 104-57-4),it can be concluded thatchemical 2-phenylethyl propanoate (CAS No: 122-70-3) is unable to cause skin sensitization and considered as non skin sensitizer.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The skin sensitization potential of test substance 2-phenylethyl propanoate (CAS No: 122-70-3) andits structurally similar read across substance Benzylformate (CAS No: 104-57-4) were observed in various studies. From the results obtained from these studies it is concluded that the chemical 2-phenylethyl propanoate (CAS No: 122-70-3) is not likely to cause skin sensitization and hence can be classified as non skin sensitizer.