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Sensitisation data (human)

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Administrative data

Endpoint:
sensitisation data (humans)
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
01 Aug 2001 - 17 Jan 2002
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Well documented GCP study meeting basic scientific principles.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002
Report date:
2002

Materials and methods

Type of sensitisation studied:
skin
Study type:
study with volunteers
Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
other: 21 CFR Part 312
Qualifier:
according to guideline
Guideline:
other: 21 CFR Part 50
Qualifier:
according to guideline
Guideline:
other: 21 CFR Part 56
Principles of method if other than guideline:
Repeated Insult Patch Test of Y-15099 in Human Subjects (Modified Draize)
GLP compliance:
yes
Remarks:
GCP (good clinical practices)

Test material

Details on test material:
- Name of test material (as cited in study report): Y-15099
- Physical state: pale yellow liquid
- Analytical purity: 95.8%
- Purity test date: 2001-10-02
- Lot/batch No.: 18244-52
- Storage condition of test material: at room temperature

Method

Type of population:
general
Ethical approval:
confirmed and informed consent free of coercion received
Subjects:
- Number of subjects exposed: 108, but only 98 subjects completed the study
- Sex: Male and female subjects
- Age: 18 - 75 years (mean age 47.9 years)
- Race: The majority of subjects were Caucasian woman
Clinical history:
Study population inclusion criteria:
- 18 years of age or older, ingeneral good health
- free of any systemic or dermatologic disorder which, in the opinion of the investigative personnel, would have interfered with the study results or increase the risk of adverse events
- skin type or race providing the skin pigmentation would allow discernment of erythema
- completion of a patch study medical screening form as well as a medical/personal history form
- consent agreement
Study population exclusion criteria:
- visible skin disease
- systemic or topical drugs or medication interfering with the study
- asthma
- pregnancy/breast feeding
- known sensitivity to silicone, siloxane, silane, or cosmetics, skin care products, or topical drugs as related to the material being evaluated
Controls:
Positive control sides were treated with sodium lauryl sulfate 0.1% w/v aqueous solution and Texapon K-1296 (Lot No. 15044).
Route of administration:
dermal
Details on study design:
TYPE OF TEST(S) USED: standard repeated insult patch test (epicutaneous test) ;

INDUCTION
- Type of application: semiocclusive
- Number of exposures: 9 at 48-hour intervals (= 18-day period). Before each exposure, application sites were evaluated.
- Duration of exposure: 24 hours
- Description of patch: 2 cm x 2 cm Webril pad, fixed with hypoallergenic tape (Micropore).
- Vehicle / solvent: none
- Concentrations: undiluted
- Volume applied: 0.2 mL
- Application site: infrascapular area of the back, either to the right or left of the midline

When the positive control site to assess subject compliance had a grade of +D, application of SLS 0.1% aqueous solution control was discontinued.

CHALLENGE
- Type of application: semiocclusive
- Number of exposures: 1, after a 10-15 day resting period.
- Duration of exposure: 24 hours
- Application site: previously unexposed site
- Evaluation of application site: 24 and 48 hours after application

Compliance control only: material evaluated under occlusive patch conditions was applied to a 2 cm x 2 cm Webril pad attached to a non-porous, plastic film adhesive bandage (3M medical tape). The patch was secured with hypoallergenic tape (Micropore) as needed.

EXAMINATIONS
- Grading/Scoring system: no reaction (.); minimal or doubtful response (?); definite erythema, no edema (+); definite erythema, definite edema (++); definite erythema, definite edema and vesiculation (+++).

Results and discussion

Results of examinations:
SYMPTOMS
- Frequency, level, duration of symptoms observed: One subject experienced a serious non-product-related adverse effect.

NO. OF PERSONS WITH/OUT REACTIONS COMPARED TO STUDY POPULATION
- Number of subjects with positive reactions: 1
- Number of subjects with negative reactions: 96
- Number of subjects with equivocal reactions: 1

One subject presented evidence of possible sensitization at challenge. Sensitization was confirmed with rechallenge and provocative use.

Applicant's summary and conclusion

Conclusions:
Under the conditions employed in this study, there was evidence of sensitization to Y-15099.
Executive summary:

Y-15099 was evaluated as provided to determine its ability to sensitize the skin of normal volunteer subjects using a semi-occlusive standard repeated insult patch study procedure with nine 24 -hour induction applications and one 24 -hour challenge application. Ninety-eight subjects completed the study.

One subject presented evidence of possible sensitization at challenge. Re-challenge was conducted under semi-occlusive conditions 2 weeks later. Reactions of erythema and oedema with papules were present. Two weeks after completing re-challenge, the subject participated in a Provocative Use phase. Product application was stopped by the subject after 6 applications due to "itching and redness". She was observed the following day and presented erythema and papules spreading beyond the open application area. Sensitization was confirmed with re-challenge and provocative use. Under the conditions employed in this study, there was evidence of sensitization to Y-15099.