Linalool

Sensitisation data (human)

Administrative data

Endpoint:

sensitisation data (humans)

Remarks:

Repeated Insult Patch Test

Type of information:

experimental study

Adequacy of study:

key study

Study period:

5 October 2005 - 11 November 2005

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods

Remarks:

The human RIPT was done under usual accepted protocol for this type of study and was inspected by a quality assurance unit. Volunteers were informed and provided written consent. The study is highly reliable and relevant as it uses the most relevant species.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

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:

The skin of 135 human subjects, 45 male and 90 female, was repeatedly exposed (induction, rest, challenge phase) to three patches of which one was containing linalool in 1:3 EtOH:DEP. The other two patches contained the negative control (saline) and the vehicle. Erythema and also edema were assessed and scored after every application period and at 24, 48 and 72 hours after removal of patch in the challenge phase.

GLP compliance:

no

Remarks:

human test, but QUA inspected and audited

Test material

Test material information

Constituent 1

Reference substance name:

Linalool

EC Number:

201-134-4

EC Name:

Linalool

Cas Number:

78-70-6

Molecular formula:

C10H18O

IUPAC Name:

3,7-dimethylocta-1,6-dien-3-ol

Details on test material:

- Name of test material (as cited in study report):
H128-1 (Saline)
H128-2 (Linalool in 1:3 EtOH:DEP)
H128-3 (1:3 EtOH:DEP)
- Physical state: Liquid (clear)
- Composition of test material, percentage of components: 12.7% linalool in H128-2
- Storage condition of test material: Protect from light, keep in refrigerator
- Test conditions: Bring to room temperature prior to application to patches

Method

Type of population:

not specified

Ethical approval:

confirmed, but no further information available

Subjects:

- Number of subjects exposed: 135 (45 males and 90 females)
- Sex: Males and females

Clinical history:

- History of allergy or casuistics for study subject or populations: Not specified
- Symptoms, onset and progress of the disease: Not specified
- Exposure history: Not specified
- Aggravating factors both in home and workplace: Not specified
- Family history: Not specified
- Medical history: Not specified
- Any other allergic or airway disorders: Not specified
- Smoking history: Not specified

Controls:

Saline and the vehicle (1:3 EtOH:DEP) were used as control.

Route of administration:

dermal

Details on study design:

TYPE OF TEST(S) USED: patch test (epicutaneous test)

ADMINISTRATION
- Type of application: Occlusive
- Vehicle / solvent: Saline and the vehicle (1:3 EtOH:DEP) were used as control.
- Concentrations: 12.7% linalool
- Volume applied: 0.3 mL
- Testing/scoring schedule: See "Any other information o materials and methods incl. tables"
- Removal of test substance: After 24 hours

EXAMINATIONS
- Grading/Scoring system: See "Any other information o materials and methods incl. tables"

Results and discussion

Results of examinations:

SYMPTOMS
- Frequency, level, duration of symptoms observed: No symptoms except faint, minimal erythemas specified below were observed.

NO. OF PERSONS WITH/OUT REACTIONS COMPARED TO STUDY POPULATION
- Number of subjects with positive reactions: 0 (1sr reading, 24 hours after challenge), 1 (2nd reading, 48 hours after challenge), 1 (3rd reading, 72 hours after challenge), 0 (4th reading, 92 hours after challenge)
- Number of subjects with negative reactions: 118 (1st reading, 24 hours after challenge), 116 (2nd reading, 48 hours after challenge), 118 (3rd reading, 72 hours after challenge), 110 (4th reading, 92 hours after challenge)
- Number of subjects with equivocal reactions: 0 (1sr reading, 24 hours after challenge), 1 faint, minimal erythema (2nd reading, 48 hours after challenge), 1 faint, minimal erythema (3rd reading, 72 hours after challenge), 0 (4th reading, 92 hours after challenge)
- Number of subjects with irritating reactions: No irritating reactions were observed.


OTHER RESULTS:
- Number of subjects with positive reactions (negative control saline): 0/118 (1st reading, 24 hours after challenge), 1 faint, minimal erythema + 2 erythema/117 (2nd reading, 48 hours after challenge), 1 faint, minimal erythema/119 (3rd reading, 72 hours after challenge), 1 faint, minimal erythema/110 (4th reading, 92 hours after challenge)
- Number of subjects with positive reactions (negative control 1:3 EtOH:DEP): 0/118 (1st reading, 24 hours after challenge), 2 faint, minimal erythema/117 (2nd reading, 48 hours after challenge), 0/119 (3rd reading, 72 hours after challenge), 0/110 (4th reading, 92 hours after challenge)

Applicant's summary and conclusion

Conclusions:

This Repeated Insult Patch Test revealed that linalool only induces faint, minimal erythema in 1 out of 117 and 119 human subjects assessed at second and third reading after challenge. The negative control saline had 5 positive responses, while the vehicle produced 2 positive responses in 117 subjects at second reading. Maximum effect observed in controls was erythema. No classification is required when considering the criteria outlined in Annex I of Regulation (EC) No 1272/2008.

Executive summary:

The senstiziting potential of 12.7% linalool was tested in this human Repeated Insult Patch Test (RIPT). Saline and the vehicle (1:3 EtOH:DEP) were used as control. The skin of 135 human subjects, 45 male and 90 female, was repeatedly exposed (induction, rest, challenge phase) to three patches containing all three substances. During induction, 9 applications of the substance were done in three weeks. Following a rest period of 2 weeks, a challenge was done by application of the same substance on the other side (previously untreated) of the back. Erythema and also edema were assessed and scored after every application period (induction and challenge). In the challenge phase, reactions were scored at 0, 24, 48 and 72 hours after removal of patch with test substance. 119 subjects completed the study (36 male and 83 female).

 

During induction phase 6 reactions were noted for saline, 4 reactions for linalool, and 2 reactions for the vehicle. All reactions were faint, minimal erythema. Linalool only induces slight erythema in one out of 117 and 119 subjects assessed at second and third reading after challenge. 5 reactions after challenge (faint, minimal erythema to erythema) were seen in the saline group. 2 reactions (faint, minimal erythema) were observed in the vehicle group. No difference in effects was observed between application of the test substance and the control substances. When considering the criteria outlined in Annex I of Regulation (EC) No. 1272/2008, linalool will not have to be classified as a sensitiser up to a concentration of 12.7%.