Registration Dossier

Administrative data

Endpoint:
sensitisation data (humans)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2004 to 2005
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted following current standard for this type of test and well documented report. There is no OECD guideline for this type of study.
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

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 available
Principles of method if other than guideline:
Standard repeat insult human patch test protocol followed.
GLP compliance:
yes
Remarks:
Good Clinical Practice

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): alpha-hexyl cinnamic aldehyde; Code H125-1
- Physical state: Clear transparent liquid
- Source: Research Institute for Fragrance Materials.

Method

Type of population:
general
Ethical approval:
other: Written Informed Consent was obtained; IRB review was not required
Subjects:
- Number of subjects exposed:138
- Sex: male 47, female 91
- Age: 18-64 years
- Race: no data
- Demographic information: no data
- Other: subjects were considered dependable and able to read and understand instructions. The subjects did not exhibit any physical or dermatological condition that would have precluded application of the test articles.
Clinical history:
no other data available
Controls:
Patches containing Saline and the vehicle, 1:3 Ethanol: Diethylphthalate, acted as controls
Route of administration:
dermal
Details on study design:
TYPE OF TEST(S) USED: patch test

ADMINISTRATION
- Type of application: occlusive
- Description of patch: 25mm Hill Top Chamber
- Vehicle / solvent: 1:3 ethanol:diethylphthalate
- Concentrations: 20% in vehicle
- Volume applied: 0.3ml
- Testing/scoring schedule: Induction: Patches were applied every Monday, Wednesday and Friday until 9 applications of the test article had been made. Challenge: After a rest of aproximately 10-14 days, challenge patches were applied to previously unpatched test sites. Scoring was done just prior to the next patch application during the induction period. For the challenge patch, scoring was done 24, 48, and 72 hours after application.
- Removal of test substance: Patches were removed 24hrs after each application for both induction and challenge patches.
- Other: Application to the back of each subject between the scapulae and waist, and to the left of the spinal mid-line. The test article was allowed to volatilize 15 to 40 minutes prior to patch application

EXAMINATIONS
- Grading/Scoring system: Scoring scale:
0 = no evidence of any effect
+ = Barely perceptible (minimal, faint, uniform or spotty erythema)
1 = Mild (pink, uniform erythema covering most of the contract site)
2 = Moderate (pink-red erythema uniform in the entire contact site)
3 = Marked (bright-red erythema with/without petechiae or papules)
4 = Severe (deep-red erythema with/without vesiculation or weeping)
- Statistical analysis: not applicable
- Other: During induction, if a subject developed a positive moderate reaction or greater during the induction phase or at the discretion of the Principal Investigator, if the skin response warranted a change in site, the patch was applied to a previously unpatched, adjacent site for the next application. If a 2-level reaction (or greater) occurred at the new site, no further applications were made. However, all reactive subjects were subsequently challenge patch tested.

Results and discussion

Results of examinations:
It was concluded that under the conditions of this study alpha-hexylcinnamaldehyde did not induce clinically maningful irritation or show any evidence of induced allergic contact dermatitis in 99% (102/103) of the test population

Generally transient, barely perceptible (+) to mild (1-level) non-specific test/patch test irritant (non-cumulative) responses were observed, occassionally accompanied by mild dryness (with and without erythema) and mild papular response (46/103).

One subject displayed mild erythema accompanied by moderate edema at both 48hr and 72hr readings. At 96hr reading it subsided to barely perceptible erythema accompanied by mild dryness. The subject was schedule to participate in rechallenge but was lost to follow up. After breaking codes it was noted that this subject reacted to both test materials and vehicle, and accordingly, results for this individual were considered inconclusive.

Saline did not induce clinically meaningful irritation or show any evidence of induced allergic contact dermatitis in any subject. The vehicle exhibited the same reaction as alpha-hexylcinnamaldehyde solution in the same subject. The vehicle did not induce clinically meaningful irritation or show any evidence of induced allergic contact dermatitis in any other subject.

Any other information on results incl. tables

none

Applicant's summary and conclusion

Conclusions:
Under the conditions of this study the test substance did not show evidence of induced allergic contact dermatitis in 99% of the test population.
Executive summary:

A panel of 138 male and female human volunteers participated in a repeat insult patch test in which a 20% solution of alpha-hexylcinnamaldehyde in 3:1 ethanol:diethylphthalate (0.3ml) was placed onto Hill Top Chambers and applied to the back of the subjects. Saline and vehicle control patches were also used. During the induction phase nine patch applications were made and these were removed 24hrs after application. Following a rest period, a challenge patch was applied and the sites scored 24, 48, and 72hrs after application. One subject displayed mild erythema accompanied by moderate edema at both 48hr and 72hr readings to both the test article and vehicle patches. At 96hr reading it subsided to barely perceptible erythema accompanied by mild dryness. The subject was scheduled to participate in rechallenge but was lost to follow up and the results for this indiviual were considered inconclusive. It was concluded that under the conditions of this study the test substance did not show evidence of induced allergic contact dermatitis in 99% of the test population.