Registration Dossier

Administrative data

Endpoint:
sensitisation data (humans)
Type of information:
other: human data
Adequacy of study:
supporting study
Study period:
2009-09-28 to 2009-10-30
Reliability:
other: not rated acc. to Klimisch
Rationale for reliability incl. deficiencies:
other: Relevant

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report Date:
2009

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:
A modified version of the Repeated Insult Patch Test was conducted on a panel of 113 subjects. The regimen comprised nine sequential 24 hour induction applications and two concurrently conducted 24- hour challenge applications, one on the initial induction site and one on a naive site.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
- Physical state: colourless liquid

Method

Type of population:
general
Ethical approval:
confirmed and informed consent free of coercion received
Subjects:
- Number of subjects exposed: 113 subjects (3 subjects dropped during the study)
- Sex: 33 males / 80 females
- Age: females: 18 - 75 years; males: 18 - 69 years
Inclusion criteria (satisfaction of all the following items was obligatory):
i. the candidate was at least eighteen years old, and
ii. agreed to comply fully with the scheduled study regimen, and
iii. expressed awareness that a participant would incur risks that would affect her/his well-being, and
iv. denied that the amount of the stipend had induced her/him to participate against her/his better judgement, and
v. had read the informed consent agreement, and
vi. had assured the interviewer that she/he had no questions about the informed consent's contents that had not been answered to her/his satisfaction, and
vii. had signed the consent form willingly and without reservation.
Exclusion criteria (any one of the following items was cause for rejection):
i. the candidate had an illness that contraindicated participation; or
ii. a condition that rendered the skin unsuitable for use in this study; or
iii. was suing dosages of medications that could alter the skin's tolerance; or
iv. had a documented history of intolerance to the category of products submitted for study; or
v. was a female who was pregnant or was breast feeding an infant.
This was a shared panel, i.e. the subjects were engaged in the evaluation of materials submitted by different sponsors.
Clinical history:
no data
Controls:
no data
Route of administration:
dermal
Details on study design:
TEST SOLUTION
42 % of the test material in glycerin was used for application.

TYPE OF TEST(S) USED: patch test (epicutaneous test)

ADMINISTRATION
- Type of application: partially-occlusive
- Description of patch / Removal of test substance: partially-occlusive patching devices consisting of a 2 cm x 2 cm absorbent pad centred on the adhesive-coated surface of a 2 cm x 4 cm plastic film were used to convey and maintain the product on the skin. The webril pad of a patching device was infused with 200 µL of the test material. The device with the product was placed firmly on the right side of the back of each subject. When the time came for removing the device, the device was peeled off the skin as gently as was feasible under the circumstances.

EXAMINATIONS
Examinations of the contact sites to grade the effects elicited by the product were conducted on Mondays, Wednesdays and Fridays. When a subject came in on a scheduled examination day, the technician examined the skin of the contact site.
i. if no adverse effect was detected, a "0" was recorded.
ii. if an adverse effect was detected, the technician entered a grade indicating her assessment of the response's intensity.
The subject was then examined again by a second techician to ascertain independently whether or not the site should be used again.
The scale used in this procedure to designate the intensities of those gross skin changes can be seen in table 1 in the field "Any other information on materials and methods incl. tables" below.

STUDY REGIMEN:
INDUCTION PHASE
Week 1
Monday: the skin of subjects were examined to ascertain that the skin was suitable for application. A freshly-prepared patching device was applied on its assigned site and the skin around the device was marked.
Tuesday: the patching device was removed.
Wednesday: the skin of the contact site was graded and the grade was recorded. A freshly-prepared patching device was applied on the same site.
Thursday: the patching device was removed.
Friday: the skin of the contact site was graded and the grade was recorded. A freshly-prepared patching device was applied on the same site. The subject was dismissed with instructions to remove the patching device on Saturday, to record the time of removal, and to return to the clinic on the following Monday for resumption of the regimen.

Week 2
Monday: the skin of the contact site was graded and the grade was recorded. The time at which the patch was removed on Saturday was recorded and a freshly-prepared patching device was applied on the same site.
Tuesday, Wednesday, Thursday, Friday: the procedures followed were the same as those followed on corresponding days during Week 1.

Week 3
The same procedure as in week 2 was followed.

Week 4
Monday: the skin of the contact site was graded and the grade was recorded. The time at which the patch was removed on Saturday was recorded.
If the subject had undergone all nine induction applications, she/he was dismissed after instructed as follows:
i)to report back on the following Monday to receive the challenge applications, and
ii) to notify the investigator should any significant changes occur in the skin of the contact site before Monday of the challenge week.
If the subject had not received the required number of induction applications and was deficient without valid reason, applications were continued (two applications could be made up). When the subject had undergone the required number of make up applications, she/he was dismissed after being instructed as stated above.

CHALLENGE PHASE
Week 5
Monday: the skin of the initial induction site was examined and ascertained to be free of any conditions that would have rendered it unfit for undergoing the challenge applications. A prepared device was applied on the initial induction site and a second prepared device was applied on a naive site. the skin around both devices was marked.
Tuesday: Both patching devices were removed. The skin of both contact sites was graded and grades were recorded.
Wednesday: the skin of both contact sites was graded and the grades were recorded. If follow-up was indicated, the subject was instructed to return on Thursday, otherwise the subject was dismissed from the study of this material.

FOLLOW-UP PHASE
Week 6 and Week 7
During the two weeks following the exit examination, the subjects were given the opportunity to relay any information concerning effects that were relevant to the characterization of the product as well as to communicate the need for treatment of persistent or newly-occurring responses.

Results and discussion

Results of examinations:
INDUCTION PHASE
No responses (grade 0) were noted on any of the 113 subjects who underwent at least one post-application examination. The absence of responses characterizes the product as one which is devoid of clinically significant skin-irritating propensities.
3 subject had dropped by week 2.

CHALLENGE PHASE
Original contact site: no responses (grade 0) were noted on any of the 110 subjects who participated in this phase of the study. The absence of responses characterizes the product as one which is devoid of clinically significant skin sensitizing propensities.
Naive contact site: no responses (grade 0) were noted on any of the 110 subjects who participated in this phase of the study. The absence of responses characterizes the product as one which is devoid of clinically significant skin sensitising propensities.

Applicant's summary and conclusion

Conclusions:
None of the subjects showed any response to the skin application of the product after challenge.
The tested mixture was found to be neither a clinically significant skin irritant nor a skin sensitizer under the conditions of this study.