Cinnamyl butyrate

Endpoint summary

Description of key information

Skin Sensitization:

No sensitization reactions were observed in any of the volunteers. Hence, Cinnamyl butyrate can be considered to be not sensitizing to human skin.

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:

weight of evidence

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 journals

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

To assess the dermal sensitization potential of cinnamyl butyrate in humans

GLP compliance:

not specified

Type of study:

other: Human Maximization study

Justification for non-LLNA method:

not specified

Specific details on test material used for the study:

- Name of the test material: Cinnamyl butyrate
- IUPAC name: (2E)-3-phenylprop-2-en-1-yl butanoate
- Molecular formula: C13H16O2
- Molecular weight: 204.267 g/mol
- Substance type: Organic
- Smiles: c1(\C=C\COC(CCC)=O)ccccc1
- Physical State: Colorless liquid

Species:

other: humans

Strain:

not specified

Sex:

male

Details on test animals and environmental conditions:

no data available

Route:

epicutaneous, occlusive

Vehicle:

petrolatum

Concentration / amount:

4% petrolatum, 2760 µg/cm2

Day(s)/duration:

five alternate-day 48-h periods

Adequacy of induction:

other: Patch sites were pre-treated for 24 h under occlusion with 5% aqueous sodium lauryl sulfate (SLS) for the initial patch only.

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

petrolatum

Concentration / amount:

% (2760 µg/cm2) cinnamyl butyrate in petrolatum

Day(s)/duration:

48 h

Adequacy of challenge:

other: Challenge applications were preceded by 30-min applications of 5% aqueous SLS under occlusion on the left side of the back.

No. of animals per dose:

29 healthy male volunteers

Details on study design:

MAIN STUDY

A. INDUCTION EXPOSURE
- No. of exposures: 5
- Exposure period: 48-h periods
- Test groups: 29 healthy volunteers
- Control group: no data available
- Site: forearms of all volunteers
- Frequency of applications: five alternate-day 48-h periods
- Duration: 48-h periods
- Concentrations: 4% (2760 µg/cm2) cinnamyl butyrate in petrolatum

B. CHALLENGE EXPOSURE
- No. of exposures: single
- Day(s) of challenge: Following a 10–14 day rest period
- Exposure period: 48 hours
- Test groups:
- Control group: A fifth site was challenged with SLS on the left and petrolatum controls on the right.
- Site: right side of the back
- Concentrations: undiluted
- Evaluation (hr after challenge): 48 hours

OTHER:
Patch sites were pre-treated for 24 h under occlusion with 5% aqueous sodium lauryl sulfate (SLS) for the initial patch only. Challenge applications were preceded by 30-min applications of 5% aqueous SLS under occlusion on the left side of the back.

Challenge controls:

no data available

Positive control substance(s):

not specified

Positive control results:

no data available

Reading:

1st reading

Hours after challenge:

48

Group:

test chemical

Dose level:

4% (2760 µg/cm2) cinnamyl butyrate in petrolatum .

No. with + reactions:

0

Total no. in group:

29

Clinical observations:

no sensitization reactions observed

Remarks on result:

no indication of skin sensitisation

Interpretation of results:

other: not sensitizing

Conclusions:

No sensitization reactions were observed in any of the volunteers. Hence, Cinnamyl butyrate can be considered to be not sensitizing to human skin.

Executive summary:

A maximization test was carried out to assess the dermal sensitization potential of Cinnamyl butyrate. Application of 4% (2760µg/cm²) cinnamyl butyrate in petrolatum was made under occlusion to the same site on the forearms of 29 healthy, male volunteers for five alternate-day 48-h periods. Patch sites were pre-treated for 24 h under occlusion with 5% aqueous sodium lauryl sulfate (SLS) for the initial patch only. Following a 10–14 day rest period, challenge patches were applied under occlusion to fresh sites for 48 h. Challenge applications were preceded by 30-min applications of 5% aqueous SLS under occlusion on the left side of the back, whereas the test material without SLS treatment was applied on the right side. A fifth site was challenged with SLS on the left and petrolatum controls on the right.

 

No sensitization reactions were observed in any of the volunteers. Hence, Cinnamyl butyrate can be considered to be not sensitizing to human skin.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin Sensitization:

Various studies were reviewed for dermal sensitization potential of Cinnamyl butyrate to ascertain its degree of sensitization. The studies include human and predicted data for the target chemical as well its structurally similar read across chemicals,Citronellyl isobutyrate [CAS: 97-89-2] and Cinnamyl propionate[CAS: 103-56-0].

A maximization test was carried out (Food and Chemical Toxicology, 45, (2007), S62–S65) to assess the dermal sensitization potential of Cinnamyl butyrate. Application of 4% (2760µg/cm2) cinnamyl butyrate in petrolatum was made under occlusion to the same site on the forearms of 29 healthy, male volunteers for five alternate-day 48-h periods. Patch sites were pre-treated for 24 h under occlusion with 5% aqueous sodium lauryl sulfate (SLS) for the initial patch only. Following a 10–14 day rest period, challenge patches were applied under occlusion to fresh sites for 48 h. Challenge applications were preceded by 30-min applications of 5% aqueous SLS under occlusion on the left side of the back, whereas the test material without SLS treatment was applied on the right side. A fifth site was challenged with SLS on the left and petrolatum controls on the right.  

No sensitization reactions were observed in any of the volunteers. Hence, Cinnamyl butyrate can be considered to be not sensitizing to human skin.

The skin sensitization potential of Cinnamyl butyrate was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor. Cinnamyl butyrate was predicted to be non sensitizing to the skin of male Dunkin- Hartley guinea pigs.

Skin sensitization effects were also estimated by four different models i.e, Battery, Leadscope, SciQSAR and CASE Ultra used within Danish QSAR database for Cinnamyl butyrate. Based on estimation, no skin sensitization reactions were observed in guinea pigs and humans. Therefore, cinnamyl butyrate was considered to be non sensitizing.

The experimental and estimated results are in agreement with each other indicating a strong possibility of cinnamyl butyrate being not sensitizing to skin.

These results are supported by the experimental study summarized in Food and Cosmetics Toxicology, Volume 16, Supplement 1, 1978, Pages 693; for the structurally similar read across substance, CITRONELLYL ISOBUTYRATE [CAS: 97-89-2]. 25 volunteers were exposed to test chemical at concentration of 4% in petrolatum for 48 hours and then observations were made for any skin reactions.

None of the subject elicited any skin sensitizing reactions. Hence, Citronellyl isobutyrate (CAS No: 97-89-2) was considered to be not sensitizing to the skin of 25 volunteers.

The above results are further supported by the experimental study summarized in Food and Chemical Toxicology, 45, (2007), S1–S23; for the structurally similar read across substance, Cinnamyl propionate[CAS: 103-56-0]. Application of 4% (2760µg/cm2) cinnamyl propionate in petrolatum was made under occlusion to the same site on the forearms of 25 healthy, male volunteers for five alternate-day 48-h periods. Patch sites were pretreated for 24 h with 5% aqueous sodium lauryl sulfate (SLS) under occlusion before induction exposure. After 10 days rest period, challenge application given for 48hr having same concentration as induction exposure.

Challenge applications were preceded by 30-min applications of 5% aqueous SLS under occlusion on the left side of the back, whereas the test material without SLS treatment was applied on the right side. A fifth site was challenged with SLS on the left and petrolatum controls on the right.

No sensitization reactions were observed in any of the volunteers. Hence, Cinnamyl propionate can be considered to be not sensitizing to human skin.

Based on the available data for the target as well as read across substances and applying the weight of evidence approach,Cinnamyl butyrate was not sensitizing to skin.Comparing the above annotations with the criteria of CLP regulation, test chemical can be classified under the category “Not Classified”.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Available data for Cinnamyl butyrate suggests that it is not likely to cause any dermal sensitization to skin.

Cinnamyl butyrate can be considered to be not sensitizer to skin and can be classified under the category “Not Classified” as per CLP regulation.