Phenethyl isobutyrate

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Justification for type of information:

data is from peer reviewed journals

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Fragrance material review on phenethyl isobutyrate

Author:

D. McGinty, C.S. Letizia, A.M. Api

Year:

2012

Bibliographic source:

Food and Chemical Toxicology, 50, (2012), S416–S419

Reference 2

Reference Type:

publication

Title:

A toxicological and dermatological assessment of aryl alkyl alcohol simple acid ester derivatives when used as fragrance ingredients

Author:

The RIFM Expert Panel- D. Belsito , D. Bickers , M. Bruze , P. Calow , M.L. Dagli , A.D. Fryer ,H. Greim , Y. Miyachi , J.H. Saurat , I.G. Sipes

Year:

2012

Bibliographic source:

Food and Chemical Toxicology, 50, (2012), S269–S313

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Human maximization test

Principles of method if other than guideline:

Human maximization test was carried out to determine the allergenic potential of Phenethyl isobutyrate

GLP compliance:

not specified

Type of study:

other: Human maximization test

Justification for non-LLNA method:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Phenethyl isobutyrate

EC Number:

203-116-1

EC Name:

Phenethyl isobutyrate

Cas Number:

103-48-0

Molecular formula:

C12H16O2

IUPAC Name:

2-phenylethyl 2-methylpropanoate

Test material form:

liquid

Details on test material:

Name of the test chemical: Phenethyl isobutyrate
IUPAC Name:2-phenylethyl 2-methylpropanoate
Molecular Formula:C12H16O2
Molecular Weight: 192.26 g/mol
Smiles: c1(CCOC(C(C)C)=O)ccccc1
InChI: 1S/C12H16O2/c1-10(2)12(13)14-9-8-11-6-4-3-5-7-11/h3-7,10H,8-9H2,1-2H3
Substance Type: Organic
Physical State: Colorless to slightly yellow liquid

Specific details on test material used for the study:

Name of the test chemical: Phenethyl isobutyrate
IUPAC Name:2-phenylethyl 2-methylpropanoate
Molecular Formula:C12H16O2
Molecular Weight: 192.26 g/mol
Substance Type: Organic
Physical State: Colorless to slightly yellow liquid

In vivo test system

Test animals

Species:

other: humans

Strain:

not specified

Sex:

male

Study design: in vivo (non-LLNA)

Induction

Route:

epicutaneous, occlusive

Vehicle:

petrolatum

Concentration / amount:

2% (1380 microgram/sq.cm)

Day(s)/duration:

5 alternate days 48 hour periods

Adequacy of induction:

other: Before induction exposure, the patch sites were pre- treated for 24 h with 5% aqueous sodium lauryl sulfate (SLS) under occlusion.

Challenge

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

petrolatum

Concentration / amount:

2% (1380 microgram/sq.cm)

Day(s)/duration:

48 hours

Adequacy of challenge:

other: The challenge site was pretreated for 1 h with 10% SLS

No. of animals per dose:

25 healthy male volunteers

Details on study design:

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 5
- Exposure period: 48 hours
- Test groups: 25 male volunteers
- Control group:
- Site: forearm
- Frequency of applications: 5 alternate days 48 hour periods
- Duration: 48 hours
- Concentrations: 2% in petrolatum


B. CHALLENGE EXPOSURE
- No. of exposures: single
- Day(s) of challenge: after 10 days of rest
- Exposure period: 48 hours
- Test groups: 25
- Control group:
- Site: fresh site on the back
- Concentrations: 2% in petrolatum
- Evaluation (hr after challenge): The challenge site was evaluated at 48 and 72 hours

OTHER: Before induction exposure, the patch sites were pre- treated for 24 h with 5% aqueous sodium lauryl sulfate (SLS) under occlusion. The challenge site was pretreated for 1 h with 10% SLS.

Positive control substance(s):

not specified

Results and discussion

In vivo (non-LLNA)

Results

Reading:

1st reading

Hours after challenge:

72

Group:

test chemical

Dose level:

2% in petrolatum

No. with + reactions:

0

Total no. in group:

25

Clinical observations:

no reactions observed

Remarks on result:

no indication of skin sensitisation

Applicant's summary and conclusion

Interpretation of results:

other: not sensitizing

Conclusions:

Phenethyl isobutyrate failed to induce sensitization reactions after 72 hours of challenge exposure in 25 healthy male volunteers.
Hence, Phenethyl isobutyrate can be considered to be not sensitizing to skin

Executive summary:

Human maximization test was carried out to determine the allergenic potential of Phenethyl isobutyrate.

 

2% (1380 microgram/sq.cm) test chemical in petrolatum was applied under occlusion to the same site of the forearms of 25 healthy male volunteers for 5 day alternate 48 hour periods. Prior to induction exposure, the patch sites were pretreated for 24 h with 5% aqueous sodium lauryl sulfate (SLS) under occlusion. After a rest period of 10 days, the challenge patches were applied to the fresh sites on the backs of the volunteers for 48 hours.The challenge site was pretreated for 1 h with 10% SLS. The patch sites were evaluated after 48 and 72 hours.

Phenethyl isobutyrate failed to induce sensitization reactions after 72 hours of challenge exposure in 25 healthy male volunteers.

Hence, Phenethyl isobutyrate can be considered to be not sensitizing to skin.