Carvacrol

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)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

data is from peer reviewed journal.

Data source

Reference

Reference Type:

publication

Title:

Screening of fragrance materials for allergenicity in the guinea pig I. Comparison of four testing methods

Author:

G. KLECAK, H. GELEICK, and J. R. FREY

Year:

1977

Bibliographic source:

J. Soc. Cosmet. Chem., 2 8, 53-64 (February 1977)

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Open Epicutaneous Test

Principles of method if other than guideline:

An Open Epicutaneous Test (OET) was performed on guinea pigs to assess the skin sensitization potential of the given test chemical.

GLP compliance:

not specified

Type of study:

open epicutaneous test

Justification for non-LLNA method:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Carvacrol

EC Number:

207-889-6

EC Name:

Carvacrol

Cas Number:

499-75-2

Molecular formula:

C10H14O

IUPAC Name:

2-methyl-5-(propan-2-yl)phenol

Test material form:

liquid

Details on test material:

- Name of test material : 2-methyl-5-(propan-2-yl)phenol
- Common name : Carvacrol
- Molecular formula : C10H14O
- Molecular weight : 150.2196 g/mol
- Smiles notation : CC(C)c1ccc(C)c(O)c1
- InChl : 1S/C10H14O/c1-7(2)9-5-4-8(3)10(11)6-9/h4-7,11H,1-3H3
- Substance type: Organic
- Physical state: Liquid

In vivo test system

Test animals

Species:

guinea pig

Strain:

other: Himalayan white-spotted

Sex:

male/female

Details on test animals and environmental conditions:

- Source: Institute of Biomedical Research, Fullinsdorf Switzerland
- Weight at study initiation: 400-500g
- Diet (e.g. ad libitum): pelleted feed supplemented with green: Vegetables carrots and vitamin C in the drinking water, all available ad libitum.
- Water (e.g. ad libitum): ad libitum

Study design: in vivo (non-LLNA)

Induction

Route:

epicutaneous, open

Vehicle:

unchanged (no vehicle)

Concentration / amount:

0.1 ml of 3% solution

Day(s)/duration:

3 weeks (0-21 days)

Adequacy of induction:

not specified

Challenge

No.:

#1

Route:

epicutaneous, open

Vehicle:

unchanged (no vehicle)

Concentration / amount:

0.025 ml of 0.3%

Day(s)/duration:

on days 21 and 35

Adequacy of challenge:

other: the minimum irritating concentration was used for the challenge exposure

No. of animals per dose:

10 test guinea pigs
6 to 8 untreated controls

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 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 3%.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 21
- Exposure period:24 hours
- Test groups:6-8 guinea pigs
- Control group: 6 to 8 untreated controls
- 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:3%
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: 6 to 8 untreated controls
- Site: contralateral flank measuring 2 cm2
- Concentrations: Concentration:0.3%
Amount: 0.025ml
- Evaluation (hr after challenge): 24,48 and/or 72h.

Other: A concentration was considered allergenic when at least 2 out of the 8 animals of the concentration group concerned showed positive reactions with nonirritant concentrations used for challenge.

Challenge controls:

no data available

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:

0.0025 ml of 0.3%

Total no. in group:

8

Clinical observations:

signs of dermal sensitization observed

Remarks on result:

positive indication of skin sensitisation

Any other information on results incl. tables

Test chemical	OET		Allergenic reading
	Minimum sensitization concentration	Minimum eliciting concentration
Test chemical	3	1	+

Applicant's summary and conclusion

Interpretation of results:

other: sensitizing

Conclusions:

Signs of contact sensitization were observed in the guinea pigs after challenge exposure. Hence, the given test chemical can be considered to be sensitizing to skin.

Executive summary:

An Open Epicutaneous Test (OET) was performed on guinea pigs to assess the skin sensitization potential of the given test chemical. The pretest was performed to determine the primary irritating threshold concentration of test substance 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 3 %. On day 1 during induction, 0.1 ml of the test chemical was applied at concentrations of 3% in 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. Signs of contact sensitization were observed in the guinea pigs after challenge exposure. Hence, the given test chemical can be considered to be sensitizing to skin.