Registration Dossier

Administrative data

epidemiological data
Type of information:
other: human data
Adequacy of study:
supporting study
Study period:
2009-09-28 to 2009-10-02
other: not rated Klimisch
Rationale for reliability incl. deficiencies:
other: Relevant

Data source

Reference Type:
study report
Report Date:

Materials and methods

Endpoint addressed:
skin irritation / corrosion
Test guideline
no guideline followed
Principles of method if other than guideline:
The capability of the test item to elicit visible skin damage was tested during a human patch test. 52 subjects participated in the study. The patch was applied to the skin of the back for 48 hours. After removal of the patch the skin site was graded 30 to 60, 24 and 48 hours after patch removal using a grading scale.
GLP compliance:
not specified

Test material

Test material form:
other: liquid
Details on test material:
- Physical state: colourless liquid


Type of population:
Ethical approval:
confirmed and informed consent free of coercion received
Details on study design:
HYPOTHESIS TESTED: to determine whether the test item (2%) is capable of eliciting visible skin damage during a forty-eight-hour period of contact.

- Type: Clinical tests

STUDY PERIOD: 2009-09-28 to 2009-10-02

- Selection criteria:
Inclusion criteria (satisfaction of all the following items was obligatory)
a) volunteer with phototype I, II, III
b) healthy subjects aged between 18 and 70 years.
c) males and females
d) provide signed Informed Consent
e) females of childbearing age must declare to use effective means of contraception for at least three months before beginning of the study and must maintain it throughout the study and for three months after its completion.
f) subjects whose medical examination confirmed their suitability for participation in the study.
g) according to the procedures of the Investigating laboratory, the wash-out period for each subject will be 1 month minimum time-lapse from the last participation in any clinical study involving a patch test on the back.
Exclusion criteria (any one of the following items was cause for rejection)
a) current use of immunosupressive drugs and/or an organ transplant;
b) current use of topical or systemic anti-inflammatory drugs for a defined medical condition; e.g. aspirin, ibuprofen, corticosteriods;
c) application within the last months of any-inflammatory drug to skin area to be used in testing;
d) insulin-dependant diabetes;
e) asthma suffering
f) currently receiving allergy injections, final injection within the last week, or experts to begin injections during the course of the study;
g) treatment for malignancy (of any kind) within the last six months;
h) immune deficiency or autoimmune disease;
i) lactating or known to be pregnant;
j) bilateral mastectomy, mastectomy within the last year; axillary lymph nodes (both arms) removed for any reason;
k) skin disorder affecting the test area which, in the supervisor's / designate's judgement, would interfere with grading / assessment of skin responses;
l) subjects with clinically significant dermographism or skin disorder that could compromise evaluation of skin reactions;
m) subjects with disorders which may be aggravated by the application of test materials (e.g. psoriasis, vitiligo);
n) intensive exposure to sunlight (natural or artificial) during 1 month preceding the study;
o) intensive treatment with systemic retinoids or topical retinoids applied on the test area less than 1 month before the current study;
p) vaccination during 3 weeks preceding the study or intention to be vaccinated during the course of the study;
q) a condition or medication which, in the investigator's judgement, makes the subject ineligible or places the subject at undue risk (if the potential subject is under the care of a physician, approval to participate may be sought from that physician, at the investigator's discretion and/or in accordance with regulatory requirements);
r) current participation in another clinical study of any kind;
s) unwillingness or inability to give informed consent or to otherwise comply with protocol requirements;
t) subjects who had been deprived of their freedom by administrative or legal decision or who are under guardianship;
u) subjects who cannot be contacted in case of emergency;
v) subjects with excessive skin reactivity to patch materials;
w) subjects with a history of side effects to cosmetics.
Exposure assessment:
Details on exposure:
42 % of the test material in glycerin was used for application.

Occlusive patching devices were used to apply approximately 200 µL of the test item (2%) to the skin of the left upper back of each subject and to maintain it on its assigned site on each subject. These devices consisted of a 2 cm x 2 cm webril cotton square applied directly to the skin and secured in place with Hypafix® Tape.
The device was scheduled to be removed gently as circumstances permitted in the clinic by an experienced technician after forty-eight hours.

Daily regimen:
Day 1: skin of subjects were examined to ascertain that the skin was suitable for application. The occlusive patching device, as described above, was applied on its designated contact site and the skin around the device was marked. The subject was instructed to return at the same time the next day.
Day 2: the patch was examined to ascertain whether it was maintaining good contact on its assigned site. The subject was instructed to return at the same time the next day.
Day 3: the patch was removed. After a 30 to 60 minute waiting period, the contact site was examined and graded. The subject was instructed to return at the same time the next day.
Day 4: the contact site was examined and graded. The subject was instructed to return at the same time the next day.
Day 5: the contact site was examined and graded. The subject was dismissed from the study with instructions to notify the investigator immediately should the skin of the contact site manifest any change for the worse during the ensuing weeks.

Grading was performed in accordance with the following steps and scale.
1. Evaluation of erythema.
2. Evaluation of the presence of palpable elevated lesions.
3. Descriptions of other aspects concerning the test site.

Additional signs noted (when present) included vesicles, papules, bullae, desquamation, dryness, hyperpigmentation, soap effect, and spreading.

Grading scale:
No reaction = 0
Slight erythema, hardly visible, spotty or diffuse = 1
Moderate erythema, with well defined edges = 2
Severe erythema, possibly spreading beyond test site = 3
Oedema or papules with or without erythema = 4
Oedema and vesicles or bullae with or without erythema = 5
Caustic reaction (ulceration) = 6

PII index scale (PII range / irritancy level / irritancy category):
≤0.50 / essentially non-irritating / not a skin irritant
0.51 - 1.00 / virtually non-irritating / not a skin irritant
1.01 - 2.00 / minimally irritating / not a skin irritant
>2.00 moderately irritating / Primary skin irritant

Results and discussion

- no complaint was volunteered by any of the subjects when they returned for inspection of the patches twenty-four hours after they were first applied.
- no adverse effect was detected on any of the 52 subjects (grade 0).
Confounding factors:
no data
Strengths and weaknesses:
no data

Applicant's summary and conclusion

None of the subjects showed adverse effects during the study (grade 0).
The absence of responses characterizes the tested mixture as one which does not possess clinically significant primary irritating propensities.