Registration Dossier

Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vitro
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Cross-reference
Reason / purpose:
data waiving: supporting information
Reference
Endpoint:
sensitisation data (humans)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
May- June 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Remarks:
Human Repeat Insult Patch Test using generally-accepted methods
Reason / purpose:
data waiving: supporting information
Reason / purpose:
data waiving: supporting information
Type of sensitisation studied:
skin
Study type:
study with volunteers
Qualifier:
according to
Guideline:
other: Marzulli-Maibach
Deviations:
no
Principles of method if other than guideline:
Human Repeated Insult Patch Test was performed to determine the irritation and/or sensitization potential of the tested product after repeated topical application under occlusive patch test conditions to the skin of human subjects with all type of skin.
GLP compliance:
no
Remarks:
Good Clinical Practice
Type of population:
general
Ethical approval:
confirmed, but no further information available
Subjects:
- Number of subjects empanelled: 115
- Number of subject satisfactorili completed the test procedure: 112 (one subject was discontinued during the test procedure)
- Sex: 93 Females; 22 Males
- Age: 18-70 years
- The subjects chosen were 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 article or determination of potential effects of the test article.
Controls:
Patch containing no product was applied to serve as a non-treated control
Route of administration:
dermal
Details on study design:
Type of application: Total occlusive
- Application area: The back: homolateral (Induction site) and contralateral (challenge site)
- Description of patch: Haye's chamber occlusive patch
- Vehicle / solvent: No data
- Concentrations: pure
- Volume applied: 25 μL
- Testing schedule:
Induction phase: A sufficient amount of the tested product to cover the surface of the patch was placed into a Haye's chamber occlusive patch and applied to the back of each subject between the scapulae and waist, adjacent to the spinal mid-line. This procedure was performed by the investigator and repeated every Monday, Wednesday and Friday until 9 applications.
The subjects were instructed to remove patch 48h after application on Sundays.
The subjects returned to test facility and the patch was removed each Tuesday and Thursday then the site was scored by the investigator just prior to the next patch application.
If subject developed a positive reaction of a level 2 erythema or greater during the Induction phase or if, at the discretion of the investigator, the skin response warranted a change in site, the patch was applied to a previously unpatched, adjacent site for the next application. If a level 2 reaction or greater occurred at the new site, no further applications were made. However, any reactive subjects were subsequently Challenge patch tested.

Challenge phase:
After a rest period of 2 weeks (no application of the test article), the Challenge patch was applied to a previously unpatched (virgin) and patched (inductal) site. The site was scored 30 minutes, 24 and 48 hours after the removal. All subjects were instructed to report any delayed skin reactivity that occurred after the final Challenge patch reading.

EXAMINATIONS
- Grading/Scoring system:
Induction phase: Dermal responses for the Induction phase of the study were scored according to the following scale:
- = No evidence of any effect
1 = Mild (Pink, uniform erythema covering most of the contact 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)
All other observed dermal sequelae (eg. oe, dryness, hypo or hyperpigmentation) were appropriately recorded on the data sheet and described as mild, moderate or severe.

Challenge phase: Dermal responses for the Challenge phase of the study were scored according to the following criteria of I.C.D.R.G. (the International Contact Dermatitis Research Group):
- = Negative
+? = Doubtful reaction a (Slight erythema)*
+ = Weak (non-vesicular) reaction**
++ = Strong (oedematous or vesicular) reaction
+++ = Extreme (bullous or ulcerative)***
NT = Not tested
IR = Irritant reaction of different types
* ?+ is a questionable faint or macular (non-palpable) erythema and is not interpreted as proven allergic reaction
** + is a palpable erythema, suggestive of a slight oedematous reaction
*** From coalescing vesicles
Results of examinations:
NO. OF PERSONS WITH/OUT REACTIONS COMPARED TO STUDY POPULATION
During the induction phase:
- Number of subjects with positive reactions: 3
- Number of subjects with negative reactions: 109

During the challenge phase:
- Number of subjects with positive reactions: 0
- Number of subjects with negative reactions: 112
Conclusions:
Under the conditions of repeated insult (occlusive) patch test procedure conducted in a panel of 112 volunteers with all type of skin, the product was "dermatologist-tested" and did not induce clinically significant nor show any evidence of induced allergic contact dermatitis in human subject.
The product can be considered as "hypoallergenic"
Executive summary:

A panel of 112 men and women human volunteers participated in a repeat insult patch test in which a test item applied as such, to the back of the subjects under occlusive patches.

Under the conditions of repeated insult (occlusive) patch test procedure conducted in a panel of 112 volunteers with all type of skin, the product was "dermatologist-tested" and did not induce clinically significant nor show any evidence of induced allergic contact dermatitis in human subject.

The product can be considered as "hypoallergenic"

Data source

Materials and methods

Results and discussion

Applicant's summary and conclusion