Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
sensitisation data (humans)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
June - July 2010
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
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
data waiving: supporting information
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Justification for type of information:
Datas on human volunteers are available
Reason / purpose for cross-reference:
data waiving: supporting information
Reason / purpose for cross-reference:
data waiving: supporting information
Reference
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
Reason / purpose for cross-reference:
data waiving: supporting information

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report date:
2010

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 method used is an adaptation from that described by Marzulli and Maibach (Human Repeated Insult Patch Test for delayed contact hypersensitivity: HRIPT) - Marzulli F.N., Maibach H.I., Contact allergy: predictive testing in man, Contact dermatitis, 1976, 2, pp.1-17
GLP compliance:
no
Remarks:
study has been conducted in the spirit of the good Clinical Practice

Test material

Constituent 1
Reference substance name:
Cassava, ext.
EC Number:
296-251-0
EC Name:
Cassava, ext.
Cas Number:
92456-72-9
IUPAC Name:
Cassava, ext.
Test material form:
solid - liquid: aqueous solution
Details on test material:
Yellow liquid
Specific details on test material used for the study:
Tested diluted at 15% in water

Method

Type of population:
general
Ethical approval:
confirmed and informed consent free of coercion received
Subjects:
108 volunteers were included in the study, 4 volunteers discontinued for personal reasons independent of the study and no exclusion was decided by the investigator.
Controls:
A control site (without test products) served as control to avoid the possible intercurrent eftects not directly related to the test raw material.
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 standard (8 mm) (50 mm²)
Volume applied: 20 μL

The applications of the test raw material, the removal of the patches and the controls were peformed by the dermatologist or the technician in charge of the study.
- Induction phase: 3 consecutive weeks.
* application of the raw material to a perfectly delimited site, under patch on D1, D3, D5, D8, D10, D12, D15, D17, D19.
* patch removal
- after 48 h of contact on D3, D5, D10, D12, D17, D19.
- after 72h of contact on D8, D15, D22.

* controls: skin examination and questioning before patching on D1 and about 15 minutes (or more, if redness appeared after removal of the adhesive), after patch removal on D3, D5, D8, D10, D12, D15, D17, D19, D22.

- Rest period: 2 consecutive weeks at least (4 weeks at the most).
* no application of raw material.

- Ghallenge: 1 week,
* application of the raw material to a perfectly delimited virgin site and to the site defined for the induction phase, under patch on D36.
* patch removal after 48 h of contact on D38.
* controls: skin examination and questioning before patching on D36 and about 15 minutes (or more, if redness appeared after removal of the adhesive), after patch removal on D38, D39, D40 (48,72,96 h after application).

Confirmation of the compatibility (absence of irritant effect) and absence of allergenic potential
The expression of the results of the skin examination and questioning was that defined for this type of study in accordance with the corresponding procedure.
In case of reactivity:
- the main visible signs were noted, i.e. : Erythema, OEdema, Vesicle, Bulla, Papule, Scab, Dryness, Coloration, Soap effect.
The intensity of the erythema and oedema was assessed according to an ordinal scale: very slight, slight, moderate/ severe.
The appearance of the erythema was specified: diffuse, punctuated, peripheral (around the application site)
The importance of the number of vesicles and papules was assessed according to an ordinal scale:1 to 2 vesicles or papules, more than 2 vesicles or papules.
Bulla, scab, dryness, coloration and soap effect were described.
The importance of the dryness and coloration was assessed according to an ordinal scale: slight,moderate, severe.

- the main sensations of discomfort were described, i.e. : Heating, Stinging, Pruritus (itching).

The results were expressed:
- in percentage of reactive volunteers : for this calculation only the visible signs of reactivity were taken into account : erythema, oedema, vesicle, bulla, papule, scab.
- in a descriptive manner for the other visible signs or for the sensations of discomfort : when the frequency of appearance of these signs justified it, the percentage of reactive volunteers was possibly calculated.

interpretation:
All the volunteers included in the study were taken into account to confirm the skin compatibility of the test raw material as long as they were submitted at least to one post application examination at the defined time or else.
All the volunteers included in the study were taken into account to confirm the absence of allergenic potential of the test raw material (in absence of allergic reaction during the induction phase) as long as they were submitted to the challenge.
The interpretation of the results of the skin examination and questioning was that defined for this type of study in accordance with the corresponding procedure.
The possible reactions obserued during the induction phase were either irritation leactions or revelation of an allergy previously contracted or revelation of an allergy precociously induced by the test raw material.
The possible reactions obserued during the challenge on the "virgin" site were compared to those observed on the "induction" site at the same times. They were either irritation reactions or revelation of an allergy induced during the induction phase by the test raw material.
The natures, intensity, time of appearance, time of disappearance, location (induction site and/or virgin site) of the skin reaction were taken into account for the interpretation of the results.
To appreciate the skin compat¡b¡l¡ty and possible irritation reactions, the interpretation of the results, performed by the dermatologist, was absolute (referring to the experience of the investigator centre in this field and especially to the data acquired on products of same category tested under similar conditions). The test raw material could therefore have a very good, good, moderate or bad skin compat¡b¡l¡ty.
To appreciate the allergenic potential, the interpretation of the results was partly based on the allergenicity evaluation scale established by the ICDRG (International Contact Dermatitis Research Group) and took into account the visible reactions (clinical signs) and the possible reactions appeared on the control site:

NT : non tested
?+ : doubtful reaction, only slight erythema
+ : positive reaction (with no vesicle): efihema, infiltration, sometimes some papules
++ : strong positive reaction: presence of erythema, papules, vesicles
+++ : violent positive reaction: with presence of bullae
- : negative reaction
IR : irritation reaction

Results and discussion

Results of examinations:
Induction phase :
Type of rcacfivity on tle induction site : none
Number and percentage of reactive volunteers : 0 / 0%

Challenge phase :
Type of rcacfivity on tle induction site and virgin site : none
Number and percentage of reactive volunteers : 0 / 0%

Applicant's summary and conclusion

Conclusions:
Under the experimental conditions adopted the repeated applications of the raw material under occlusive patch induced no reaction of initation and the raw material has a very good skin compatibility.
Moreover, the repeated applications induced no allergic reaction,
Executive summary:

A panel of 108 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. 104 subjects completed the study.

During the induction or challenge phase, no skin reactions were observed.

Under the experimental conditions adopted the repeated applications of the raw material under occlusive patch induced no reaction of initation and the raw material has a very good skin compatibility.

Moreover, the repeated applications induced no allergic reaction,

Categories Display