Registration Dossier

Administrative data

Endpoint:
sensitisation data (humans)
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
From June 12 to July 21, 1998

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report Date:
1998

Materials and methods

Type of sensitisation studied:
skin
Study type:
study with volunteers
Principles of method if other than guideline:
Occlusive repeated insult patch study in humans
GLP compliance:
no
Remarks:
The test is in compliance with Good Clinical Practice

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
- Physical state: Fragrance/clear colorless liquid

Method

Type of population:
general
Ethical approval:
confirmed and informed consent free of coercion received
Subjects:
- Number of subjects exposed: 106 subjects completed the study (110 were enrolled)
- Sex: 92 females and 18 males
- Age: 18-71 years
- Race: 104 Hispanic; 6 White
Clinical history:
Inclusion Criteria:
1. Individuals 18 years of age or older.
2. Individuals free of any systemic or dermatologic disorder which, in the opinion of the investigative personnel, would have interfered with the study results.
3. Individuals with uniformly-colored skin on the infrascapular area of the back which would allow a discernible erythema.
4. Individuals who had completed a patch study Medical Screening form as well as a Medical/Personal History form.
5. Individuals who had read, understood and signed an Informed Consent agreement.

Exclusion Criteria:
1. Individuals with any visible skin disease at the evaluation site which, in the opinion of the investigative personnel, would have interfered with the evaluation.
2. Individuals receiving systemic or topical drugs or medication which, in the opinion of the investigative personnel, would have interfered with the study results.
3. Individuals who were under steroidal treatment for asthma.
4. Individuals with psoriasis and/or active atopic dermatitis/eczema.
5. Females who were pregnant, planning a pregnancy or nursing a child.
6. Individuals with a known sensitivity to cosmetics, skin care products or topical drugs as related to product being evaluated.
Controls:
None
Route of administration:
dermal
Details on study design:
TYPE OF TEST(S) USED: Patch test (epicutaneous test)

ADMINISTRATION
- Site: Patches were applied to the infrascapular area of the back, either to the right or left of the midline
- Type of application: Occlusive
- Description of patch: Non-porous, plastic film adhesive bandage with a 2 cm x 2 cm Webril pad. Secured with hypo-allergenic tape (Micropore) as needed.
- Vehicle / solvent: Diethyl Phthalate (DEP)
- Concentrations: 10 %
- Volume applied: 0.2 mL
- Testing/scoring schedule: Subjects participated over a 6-week period involving 3 phases: (1) Induction, (2) Rest, and (3) Challenge.
Induction phase: The induction phase consisted of nine (9) consecutive applications of the study material and subsequent evaluations of the study sites assessed. Prior to application of the patches, the sites were outlined with a skin marker, e.g., gentian violet. The subjects were required to remove the patches approximately 24 h after application. They returned to the facility at 48 h intervals to have the sites evaluated and identical patches reapplied. Patches applied on Friday were removed by subjects after 24 h and sites were evaluated on the following Monday, i.e., 72 h after patch application. Patches applied on the Friday before the Monday holiday were evaluated on the following Tuesday, 96 h after patch application.
Subjects who were absent once during the three (3)-week, nine (9)-patch induction phase received a make-up (MU) induction patch on the last induction visit. The MU applications were graded 48 h later at the MU scoring visit.
Rest period: 11-13 days
Challenge phase: The challenge phase was initiated during the sixth week of the study with identical patches applied to sites previously unexposed to the study material. These patches were removed by subjects after 24 h and the sites graded after additional 24 and 48 h periods, i.e., 48 and 72 h after application.

EXAMINATIONS
- = No reaction
? = Minimal or doubtful response, slightly different from surrounding normal skin
+ = Definite erythema. No oedema
++ = Definite erythema. Definite oedema.
+++ = Definite erythema. Definite oedema and vesiculation.

Statistical analysis: None

Results and discussion

Results of examinations:
One hundred ten (110) subjects between the ages of 18 and 71 were enrolled and 106 subjects completed the study. Three (3) subjects (Subject Entry Nos. 039, 052 and 079) voluntarily withdrew. One (1) subject (Subject Entry No. 009) failed to keep the scheduled visits and was lost to follow-up.

SYMPTOMS
- Frequency, level, duration of symptoms observed: None

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

Any other information on results incl. tables

Table 7.10.4/1: Repeated Insult Patch Study

 

Grade

Induction reading

Challenge reading

1

2

3

4

5

6

7

8

9

1

2

-

109

109

105

105

108

108

106

107

106

106

106

?

0

0

0

0

0

0

1

0

0

0

0

Total evaluable

109

109

105

105

108

108

107

107

106

106

106

Number absent

1

0

3

3

0

0

1

1

1

0

0

Number discontinued

0

1

2

2

2

2

2

2

3

4

4

 - = No reaction

? = Minimal or doubtful response, slightly different from surrounding normal skin 

Note: All Enrolled Subjects (n=110)

Applicant's summary and conclusion

Conclusions:
Under the condition of the study, the test material is not a skin sensitiser at 10%.
Executive summary:

A panel of 110 male and female human volunteers participated in a repeat insult patch test in which a 10 % solution of test material in Diethyl Phthalate (DEP) was applied to the infrascapular area of the back of the subjects under occlusive patches. 106 subjects completed the study. During the induction phase nine patches were applied, separated by a 48 h interval. The patches were removed 24 h after application. Following a 10-13 days rest period, a challenge patch was applied and the sites scored 48 and 72 hours after application.

There was no significant skin reactivity observed during the course of the study. Test material did not induce significant skin irritation nor show any evidence of induced allergic contact dermatitis in human subjects.

Under the conditions employed in this study, there was no evidence of sensitisation to the test material at 10 %.