p-menth-1-en-4-ol

Sensitisation data (human)

Administrative data

Endpoint:

sensitisation data (humans)

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Melaleuca oil (tea tree oil) dermatitis

Author:

Knight, T. E., Hausen B. M.

Year:

1994

Bibliographic source:

Journal of the American Academy of Dermatology, (1994) Vol. 30, No. 3, pp. 423-427

Materials and methods

Type of sensitisation studied:

skin

Study type:

study with volunteers

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

- Principle of test: Patch test
- Short description of test conditions: The patients were patch tested to the standard battery of 20 allergens, a 1% solution of pure Tea tree oil (TTO) in anhydrous ethyl alcohol, a 1% concentration of 11 of the constituent compounds found in highest concentrations in the essential oil of TTO, and a 5% concentration of d-carvone.
- Parameters analysed: Erythema and oedema reactions

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

p-menth-1-en-4-ol

EC Number:

209-235-5

EC Name:

p-menth-1-en-4-ol

Cas Number:

562-74-3

Molecular formula:

C10H18O

IUPAC Name:

4-methyl-1-(propan-2-yl)cyclohex-3-en-1-ol

Test material form:

liquid

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source: Haarman & Reimer, Holzminden, Germany
- Purity: at least 99%

Method

Type of population:

general

Ethical approval:

not specified

Subjects:

- Number of subjects exposed: 7
- Sex: male and female
- Age: 48 (2/7), 51 (1/7), 55 (1/7), 56 (1/7), 57 (1/7), 68 (1/7)
- Race: 2 Filipino, 5 probably white
- Demographic information: USA

Clinical history:

- History of allergy or casuistics for study subjects: The patients treated skin conditions, such as foot fungus, insect bites, hand rashes, dog scratches, and "pimples" of the legs. All patients initially had an eczematous dermatitis consisting of ill-defined plaques of erythema, edema, and scaling; in three patients vesiculation was also present
- Exposure history: All patients had applied 100% pure melaleuca oil which was commercially available.
- Any other allergic or airway disorders: not specified
- Smoking history: not specified

Controls:

Ethanol, olive oil, and a blank Finn Chamber patch was used. 20 control patients were treated.

Route of administration:

dermal

Details on study design:

TYPE OF TEST USED: patch test (epicutaneous test)

ADMINISTRATION
- Type of application: occlusive / semiocclusive /other: not specified
- Description of patch: not specified
- Vehicle / solvent: anhydrous ethyl alcohol, olive oil
- Concentrations: 1% solutions (100% pure TTO, the 11 constituent compounds of TTO); 5% (d-carvone); 5% and 10% (constituent compounds, 6/7 patients)
- Volume applied: not specified
- Testing/scoring schedule: reading 50 h after application
- Removal of test substance: Allergens were applied for 48 h

EXAMINATIONS
- Grading/Scoring system: not specified

Results and discussion

Results of examinations:

SYMPTOMS
- Frequency, level, duration of symptoms observed: Erythema and induration in one patient (1% group) and two patients (10% group), respectively.

NO. OF PERSONS WITH/OUT REACTIONS COMPARED TO STUDY POPULATION
- Number of subjects with positive reactions: 1; 2
- Number of subjects with negative reactions: 6; 4 (inframmammary/chest was not tested with one patient)
- Number of subjects with equivocal reactions: 3
- Number of subjects with irritating reactions: 3

RESULT OF CASE REPORT: The test substance was a less frequent sensitizer.

Any other information on results incl. tables

Table 1: Patch test results of terpinen-4 -ol

^Patient No	^Age (yr)/Sex/race	^Location of eczema	^Reactions
			^concentrations
			^1%	^10%
^1	^48/F/W	^Inframammary, chest	^N	^ND
^2	^56/F/W	^Arm	^N	^N
^3	^51/F/Fil	^Hands, arms, torso	^+2	^+2
^4	^68/F/W	^Legs	^N	^+2
^5	^57/M/W	^Arms, neck, face	^N	^N
^6	^55/M/Fil	^Groin, foot, chest	^N	^N
^7	^48/F/W	^Flanks, legs, arms	^N	^N

F = female; M = male; Fil = Filipino; W = White; N = negative; ND = not done; +2 = erythema and induration

Applicant's summary and conclusion

Conclusions:

The most common melaleuca oil allergen of the tested constituent compounds was d-limonene followed by aromadendrene and alpha-terpinene. Terpienen-4-ol was a less frequent sensitizer.

Executive summary:

The objective of the present study was to investigate which constituent compounds of melaleuca oil (tea tree oil) were responsible for allergic contact eczema in seven patients becoming sensitized. These seven patients were treated with Finn chambers in a patch test to a 1% solution (vol/vol) of melaleuca oil and 1% solutions (vol/vol) of 11 constituent compounds. From seven patients reacting to the 1% melaleuca oil solution, six patients also reaacted to d-limonene, five to alpha-terpinene and aromadendrene, two to terpinen-4 -ol, and one each to p-cymene and alpha-phellandrene. d-Carvone caused no reactions among the seven patients. The most common allergen was found to be d-limonene causing allergic contact eczema in the patients.