Registration Dossier

Administrative data

Endpoint:
sensitisation data (humans)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: A study conducted according to standard protocols to assesses skin sensitization in humans by a reputable laboratory with expertise in this type of testing under good clinical practices. Data are sufficient for use to evaluate classification.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report Date:
2012

Materials and methods

Type of sensitisation studied:
skin
Study type:
study with volunteers
Test guideline
Qualifier:
no guideline required
Principles of method if other than guideline:
Induction by 24 hour dermal application (patch) followed by evaluation of the site 24-28 hour following patch removal for a total of 9 induction applications (3 times a week for 3 weeks). Following a 10-15 day rest period, a 24 hour challenge application with sites graded 24 and 48 hours following removal of patch.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
gas under pressure: liquefied gas

Method

Type of population:
general
Ethical approval:
confirmed and informed consent free of coercion received
Subjects:
- Number of subjects exposed: 123 (106 completed the study)
- Sex: 29 males and 94 females
- Age: at least 18 years of age
- Race: Any (american indian, asian, black, caucasian, hispanic, other)
- Inclusion criteria: Were males or females, 18 years of age or older, in general good health; Were free of any systemic or dermatologic disorder which, in the opinion of the investigative personnel, would have interfered with the study results or increased the risk of adverse events; Were of any skin type or race, providing the skin pigmentation would allow discernment of erythema; Had completed a medical screening procedure; and Had read, understood, and signed an informed consent agreement.
- Exclusion criteria: Had any visible skin disease at the study site which, in the opinion of the investigative personnel, would have interfered with the evaluation;Were receiving systemic or topical drugs or medication which, in the opinion of the investigative personnel, would have interfered with the study results; Had psoriasis and/or active atopic dermatitis/eczema; Were females who were pregnant, planning to become pregnant during the study, or breast-feeding; and/or Had a known sensitivity to cosmetics, skin care products, or topical drugs as related to the material being evaluated.
Controls:
An aqueous solution of 0.1% sodium lauryl sulfate was used to serve as a control and assess subject compliance
Route of administration:
dermal
Details on study design:
TYPE OF TEST(S) USED: repeated insult patch test

ADMINISTRATION
- Type of application: semiocclusive
- Description of patch: 2cm x 2cm Webril patch. The patches were applied to the infrascapular area of the back, either to the right or left of the midline. The pad is affixed to the skin with hypoallergenic tape (Micropore).
- Vehicle / solvent: none
- Concentrations: undiluted
- Volume applied: 0.2 ml
- Testing/scoring schedule: induction at 24 -48 hours following patch removal, challenge phase at 24 and 48 hours following patch removal

EXAMINATIONS
- Grading/Scoring system: (-) no reaction; (?) minimal or doubtful response, slightly different from surrounding skin; (+) definite erythema with no edema; (++) definite erythema, definite edema; (+++) definite erythema, definite edema and vesiculation

OUTLINE OF STUDY PROCEDURES
The Induction Phase consisted of 9 applications of the study material and subsequent evaluations of the patch sites. Prior to application of the patches, the sites were outlined with a skin marker, eg, gentian violet. Patches were applied on Mondays, Wednesdays, and Fridays for 3 consecutive weeks. The subjects were required to remove the patches approximately 24 hours after application. They returned to the facility at 48-hour intervals to have the sites evaluated and identical patches applied to the same sites. Patches applied on Friday were removed by subjects after 24 hours. The sites were evaluated on the following Monday, ie, 72 hours after patch application. Following the ninth evaluation, the subjects were dismissed for a rest period of approximately 10-15 days. Subjects who were absent once during the induction phase received a make-up (MU) patch at the last induction visit. The MU applications were graded 48 hours later at the MU visit, or were recorded as N9G (no ninth grading). Subjects who missed the ninth evaluation (N9G) but have had 9 patch applications were considered to have completed the induction phase.
The Challenge Phase was initiated during the sixth week of the study. Identical patches were applied to sites previously unexposed to the study material. The patches were removed by subjects after 24 hours and the sites graded after additional 24-hour and 48-hour periods (ie, 48 and 72 hours after application). Following a negative induction, a 48/72-hour sequence of “-/+,” “?/+,” or “+/+” resulted in an additional reading being performed at the 96-hour interval. Rechallenge was performed whenever there was evidence of possible sensitization. To be considered a completed case, a subject must have had 9 applications and no fewer than 8 subsequent readings during induction, and a single application and 2 readings during challenge. Only completed cases were used to assess sensitization.

Results and discussion

Results of examinations:
SYMPTOMS
- Frequency, level, duration of symptoms observed: no symptoms reported

NO. OF PERSONS WITH/OUT REACTIONS COMPARED TO STUDY POPULATION
- Number of subjects with positive reactions: 0
- Number of subjects with negative reactions = 106
- Number of subjects with equivocal reactions = 0
- Number of subjects with irritating reactions = 0

Applicant's summary and conclusion

Conclusions:
The test substance was evaluated as supplied under semi-occlusive conditions to determine its ability to sensitize the skin of volunteer subjects with normal skin using a repeated insult patch study respectively. One hundred six (106) subjects completed the study. Under the conditions employed in this study, there was no evidence of sensitization to the test substance.
Executive summary:

One hundred twenty-three (123) subjects between the ages of 18 and 68 were enrolled and 106 completed this repeated insult patch study. The material was applied under semi-occlusive patch conditions to a 2 cm x 2 cm Webril ™ pad, which delivered approximately 0.2 mL of study material. The pad was affixed to the skin with hypoallergenic tape (Micropore). The patches were applied to the infrascapular area of the back, either to the right or left of the midline. Sodium lauryl sulfate, 0.1% aqueous solution, served as a control to assess subject compliance. The induction phase consisted of 9 applications of the test substance (three times a week for three weeks) for 24 hours and subsequent evaluations of the patch sites. Following the ninth evaluation, the subjects were dismissed for a rest period of approximately 10-15 days. The challenge phase was initiated during the sixth week of the study. Identical patches were applied to sites previously unexposed to the study material. The patches were removed by subjects after 24 hours and the sites graded after additional 24-hour and 48-hour periods. No evidence of sensitization to the test substance was observed in this study.