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Description of key information

The skin sensitization potential of target chemical [1R-(1α,2α,5β,8β)]-4,4,8-trimethyltricyclo[6.3.1.02,5]dodecan-1-yl acetate; (1R-(1alpha,2alpha,5beta,8beta))-4,4,8-Trimethyltricyclo[6.3.1.02,5]dodecanyl acetate (CAS No: 57082-24-3) was assessedin various experimental studies which were conducted on guinea pigs and humans for target chemical[1R-(1α,2α,5β,8β)]-4,4,8-trimethyltricyclo[6.3.1.02,5]dodecan-1-yl acetate; (1R-(1alpha,2alpha,5beta,8beta))-4,4,8-Trimethyltricyclo[6.3.1.02,5]dodecanyl acetate (CAS No: 57082-24-3) andits structurally similar read across substancesCedryl acetate (CAS No: 77-54-3) and 2-tert-butylcyclohexyl acetate (CAS No: 88-41-5). The predicted data usingQSAR toolbox and Danish QSAR databasehas 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 [1R-(1α,2α,5β,8β)]-4,4,8-trimethyltricyclo[6.3.1.02,5]dodecan-1-yl acetate; (1R-(1alpha,2alpha,5beta,8beta))-4,4,8-Trimethyltricyclo[6.3.1.02,5]dodecanyl acetate (CAS No: 57082-24-3) 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:
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:
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 Caryophyllen acetate (CAS No: 57082-24-3).
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 : [1R-(1α, 2α, 5β, 8β)]-4, 4, 8-trimethyltricyclo [6.3.1.02, 5] dodecan-1-yl acetate/ Caryophyllen acetate
- Molecular formula : C17H28O2
- Molecular weight : 264.4062 g/mol
- Smiles notation : CC(=O)O[C@@]12CCC[C@@](C)(CC[C@@H] 3[C@@H]1CC3(C)C)C2
- InChl : 1S/C17H28O2/c1-12(18)19-17-8-5-7-16(4,11-17)9-6-13-14(17)10-15(13,2)3/h13-14H,5-11H2,1-4H3/t13-,14+,16+,17-/m1/s1
- 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: 4%
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:4%
Amount: 0.025ml
Day(s)/duration:
on days 21 and 35
Adequacy of challenge:
not specified
No. of animals per dose:
30 (20: test group ; 10: control group)
Details on study design:
RANGE FINDING TESTS: The pretest was performed to determine the primary irritating threshold concentration of test substances at various concentrations (100, 30, 10 and 3%). In this test, a single application of 0.025 ml of each test concentration was simultaneously performed on one of the areas measuring 2 cm2 of the flank skin previously clipped and marked with a circular stamp. Reactions are read 24 h after the application of the test material. On the basis of pretest, the concentration selected for sensitization test was 4%.


MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 21
- Exposure period:24 hours
- Test groups: 20
- Control group: 10
- 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: 4%
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: 20 guinea pigs
- Control group: 10 guinea pigs
- Site: contralateral flank measuring 2 cm2
- Concentrations: Concentration:4%
Amount: 0.025ml
- Evaluation (hr after challenge): 24,48 and/or 72h.
Challenge controls:
Yes concurrent vehicle.
Positive control substance(s):
not specified
Reading:
1st reading
Hours after challenge:
72
Group:
test group
Dose level:
4% (0.025ml)
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No known signs of skin sensitization were observed.
Remarks on result:
no indication of skin sensitisation

No known signs of skin sensitization were observed.

Interpretation of results:
other: Not sensitizing
Conclusions:
The test material Caryophyllen acetate (CAS No: 57082-24-3) was considered to be not sensitizing on skin of guinea pigs at concentration of 4% 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 Caryophyllen acetate (CAS No: 57082-24-3).

 

The pretest was performed to determine the primary irritating threshold concentration of test substances at various concentrations (e.g, 100,30,10 and 3%). In this test, a single application of 0.025 ml of each test concentration was simultaneously performed on one of the areas measuring 2 cm2 of the flank skin previously clipped and marked with a circular stamp. Reactions are read 24 h after the application of the test material. On the basis of pretest, the concentration selected for sensitization test was 4 %.

 

On day 1 during induction, 0.1 ml of the Caryophyllen acetate (CAS No: 57082-24-3) was applied at concentrations of 4 % 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 chemical 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 4%.Thus the chemicalCaryophyllen acetate (CAS No: 57082-24-3) was considered to be not sensitizing on skin of guinea pigs at concentration of 4% 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 chemical [1R-(1α,2α,5β,8β)]-4,4,8-trimethyltricyclo[6.3.1.02,5]dodecan-1-yl acetate; (1R-(1alpha,2alpha,5beta,8beta))-4,4,8-Trimethyltricyclo[6.3.1.02,5]dodecanyl acetate (CAS No: 57082-24-3) 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 chemical [1R-(1α,2α,5β,8β)]-4,4,8-trimethyltricyclo[6.3.1.02,5]dodecan-1-yl acetate; (1R-(1alpha,2alpha,5beta,8beta))-4,4,8-Trimethyltricyclo[6.3.1.02,5]dodecanyl acetate (CAS No: 57082-24-3) and its structurally similar read across substanceCedryl acetate (CAS No: 77-54-3) and 2-tert-butylcyclohexyl acetate (CAS No: 88-41-5).The predicted data usingDanish QSAR databasethe has also been compared with the experimental data and summarized as below;

The G. Klecak {Curr. Probl. Derm., vo1.14, pp.152-171 (Karger, Basel 1985)} conducted an Open Epicutaneous Test (OET) of target chemical Caryophyllen acetate (CAS No: 57082-24-3).During the study, the pretest was performed to determine the primary irritating threshold concentration of test substances at various concentrations (e.g, 100,30,10 and 3%). In this test, a single application of 0.025 ml of each test concentration was simultaneously performed on one of the areas measuring 2 cm2 of the flank skin previously clipped and marked with a circular stamp. Reactions are read 24 h after the application of the test material. On the basis of pretest, the concentration selected for sensitization test was 4 %.On day 1 during induction, 0.1 ml of the Caryophyllen acetate (CAS No: 57082-24-3) was applied at concentrations of 4 % 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 chemical 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 4%.Thus the chemicalCaryophyllen acetate (CAS No: 57082-24-3) was considered to be not sensitizing on skin of guinea pigs at concentration of 4% in an Open Epicutaneous Test (OET).

 

The D.L.J. Opdyke {Food and Cosmetics Toxicology, 1979, Pages 191}carried outaHuman maximisation test in 25 volunteers to determine skin sensitization potential caused by the chemical [1R-(1α,2α,5β,8β)]-4,4,8-trimethyltricyclo[6.3.1.02,5]dodecan-1-yl acetate; (1R-(1alpha,2alpha,5beta,8beta))-4,4,8-Trimethyltricyclo[6.3.1.02,5]dodecanyl acetate (CAS No: 57082-24-3) Each subject was treated with 4% of Caryophyllen acetate (CAS No: 57082-24-3) in petrolatum dermally and later observed for any signs of contact allergy. None of the volunteer showed any signs of contact sensitization. Hence the chemical Caryophyllen acetate (CAS No: 57082-24-3) wasconsidered to be not sensitizing to theskin of human volunteers.

 

According to Danish QSAR database , the skin sensitization effects were estimated by using four different models i.e, Battery, Leadscope, SciQSAR and CASE Ultra for [1R-(1α,2α,5β,8β)]-4,4,8-trimethyltricyclo[6.3.1.02,5]dodecan-1-yl acetate; (1R-(1alpha,2alpha,5beta,8beta))-4,4,8-Trimethyltricyclo[6.3.1.02,5]dodecanyl acetate (CAS No: 57082-24-3) . Based on estimation, no skin sensitization reactions were observed in guinea Pig and Human. Therefore, [1R-(1α,2α,5β,8β)]-4,4,8-trimethyltricyclo[6.3.1.02,5]dodecan-1-yl acetate; (1R-(1alpha,2alpha,5beta,8beta))-4,4,8-Trimethyltricyclo[6.3.1.02,5]dodecanyl acetate (CAS No: 57082-24-3) was considered to be not sensitizing.

 

Another Open Epicutaneous Test (OET) was conducted by G. Klecak {Curr. Probl. Derm., vo1.14, pp.152-171 (Karger, Basel 1985)} for read across chemical Cedryl acetate (CAS No: 77-54-3).The test followed the same procedure as mentioned in previous study at concentration of 8%.It was observed that none of the guinea pigs induced contact sensitization at challenge concentration of 8%.Thus the chemicalCedryl acetate (CAS No: 77-54-3) was considered to be not sensitizing on skin of guinea pigs at concentration of 8% in an Open Epicutaneous Test (OET).

 

The above results were further supported by anotherHuman maximization test conducted byD.L.J. Opdyke {Food and Chemical Toxicology, Vol. 30, Pg. 13S, 1992} on 25 female volunteersto assess its skin sensitization potential.None of the female volunteers had developed any signs of skin sensitization. Hence the chemical 2-tert-butylcyclohexyl acetate (CAS No: 88-41-5) wasconsidered to be not sensitizing to theskin of female volunteers.

 

 

Based on the available data for the target chemical, supporting studies and read across substance,it can be concluded thatchemical [1R-(1α,2α,5β,8β)]-4,4,8-trimethyltricyclo[6.3.1.02,5]dodecan-1-yl acetate; (1R-(1alpha,2alpha,5beta,8beta))-4,4,8-Trimethyltricyclo[6.3.1.02,5]dodecanyl acetate (CAS No: 57082-24-3) is unable to cause skin sensitization and considered as not sensitizing . 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 [1R-(1α,2α,5β,8β)]-4,4,8-trimethyltricyclo[6.3.1.02,5]dodecan-1-yl acetate; (1R-(1alpha,2alpha,5beta,8beta))-4,4,8-Trimethyltricyclo[6.3.1.02,5]dodecanyl acetate (CAS No: 57082-24-3) and its structurally similar read across substanceCedryl acetate (CAS No: 77-54-3) and 2-tert-butylcyclohexyl acetate (CAS No: 88-41-5) were observed in various studies. From the results obtained from these studies it is concluded that the chemical [1R-(1α,2α,5β,8β)]-4,4,8-trimethyltricyclo[6.3.1.02,5]dodecan-1-yl acetate; (1R-(1alpha,2alpha,5beta,8beta))-4,4,8-Trimethyltricyclo[6.3.1.02,5]dodecanyl acetate (CAS No: 57082-24-3) is not likely to cause skin sensitization and hence can be classified as non-skin sensitizer.