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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:
Justification for type of information:
A clinical study on human volunteers show that the substance has no skin sensitization potential. See end-point 7.10.4
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:
August - october 2015
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
Type of sensitisation studied:
skin
Study type:
study with volunteers
Qualifier:
no guideline followed
Principles of method if other than guideline:
Repeated Insult Patch Test was performed to confirm that repeated applications of the product under maximized conditions, in healthy subjetcs, does not induce delayed contact allergy reactions. A secondary objective is to determine the irritating potential of the product first after a single application and second after repeated applications.
GLP compliance:
no
Remarks:
The study has been conducted in the spirit of the good Clinical Practice
Type of population:
general
Ethical approval:
confirmed and informed consent free of coercion received
Subjects:
110 healthy subjects were selected according to the inclusion and non-inclusion criteria, and 105 subjects completed study
Controls:
Patch without product
Route of administration:
dermal
Details on study design:
ADMINISTRATION
- Type of application: occlusive
- Application area: Scapular zones: homolateral (Induction site) and contralateral (challenge site)
- Description of patch: Finn's chamber occlusive (8 mm) (50 mm²)
- Volume applied: 25 μL
The studied product was applied to a cleansed (with physiological saline or water) and dry skin.
- Application frequency:
Induction phase: 3 times a week during 48 hours (72 h for the week-end)
Challenge phase: once during 48 hours
- Study schedule:
Induction phase: 3 weeks
Rest phase: 2 weeks
Challenge phase : 1 week

EXAMINATIONS
After each application, the patch is removed and the clinical examination is performed by the investigator 30 minutes later in order to eliminate the pressure and the occlusive effects. The resulf ot the examination if negative if the skin looks normal. The clinical examination is made on the back using the following criteria and scale:
Clinical criteria regarding the irritating potential (induction phase)
- Grading/Scoring system:
0 = No erythema, no edema
0.5 = very slight = erythema: barely perceptible: pinkish coloration of one part of the tested area and palpable and barely visible edema
1 =Slight = erythema: pinkish coloration of the complete tested area or rather visible on one part of the tested area, and palpable and visible edema
2 =obvious = obvious erythema covering the whole tested arean and obvious edema (thickness <1mm) with or without blister or vesible
3 = important = severe erythema covering all the tested area or obvious erythema diffusion outside the tested area, and severe edema (thickness > 1mm of diffusiong outside the tested area) with our without vesicle or blister.

Clinical criteria regarding the sensitizing potential ( challenge phase), the occurrence of allergic reactions was assessed according to the following scale:
Absence of reaction: ICDRG (International Contact Dermatitis Research Group) quotation : 0, numetic score quotation: 0
Doubtful reaction: ICDRG (International Contact Dermatitis Research Group) quotation : ?, numetic score quotation: 0.5
Erythema and edema: ICDRG (International Contact Dermatitis Research Group) quotation : +, numetic score quotation: 1
Erythema, edema and vesicles: ICDRG (International Contact Dermatitis Research Group) quotation :++, numetic score quotation: 2
Severe reaction with blister or post-blisters ulcerations: ICDRG (International Contact Dermatitis Research Group) quotation : +++, numetic score quotation: 3
A score superior or equal to 2 represents a contact allergy
Results of examinations:
under these study conditions, the test item shows a score 0.00. It canthus be considered as non irritating.

At the end of the 9 readings of the induction phase, the average score of each subject (Cumulative irritation index CII) is calculated by adding the scores obtained for each readings and by dividing this sum by the actual number of readings.The irritating potential of the product is estimated by calculating the mean of the reactions observed

during the induction phase in order to obain the Mean cumulative Irritation Inde (MCII). the obtained index allows to arbitrarily classify the studied product according to the following scale:

 M.C.I.I. Classe 
 M.C.I.I. < 0.25  Non irritating (NI)
 0.25 ≤M.C.I.I. < 0.50  Very slightly irritating (VSI)
0.5≤ M.C.I.I. < 1   Slightly irritating (SI)
 1 ≤M.C.I.I. < 2  Moderately irritating (MI)
M.C.I.I. ≥2   Irritating (I)

Challenge phase:

A possible reaction during the induction or challenge phase is assessed from 0 to 3 according to ICDRG (International Contact Dermatitis Research Group). During the Challenge phase, the reading is done 30 minutes after patch-tests removal and 48 hours later. The sensitizing potential of the product is assessed by the readings on D37 and D39 according to the following criteria reaction++ or +++ in the absence of added irritation phenomenon. The presence of only one case of active sensitization or controlateral

side leads to the conclusion "Potentially sensitizing product".

Under these study conditions, no reaction ++ nor +++ was observed, so the test item can be considered non sensitizing.

Conclusions:
Under these study conditions, the product can be considered non-irritating and non-sensitizing
Executive summary:

A panel of 110 male and female human volunteers participated in a repeat insult patch test in which a test product applied to the back of the subjects under occlusive patches. 105 subjects completed the study. During the induction or challenge phase, no skin reactions were observed. The test item showed a score of 0.01. It can thus be considered as non-irritating.

No reaction ++ nor +++ was observed, so the product can be considered as non-sensitizing.

Under these study conditions, the product can be considered non-irritating and non-sensitizing

Data source

Materials and methods

Results and discussion

Applicant's summary and conclusion