Registration Dossier

Administrative data

Endpoint:
sensitisation data (humans)
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
From May 13 to June 20, 2002
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Remarks:
Well documented Human Repeat Insult Patch Test compliant with Good Clinical Practice regulations and using generally-accepted methods.

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 guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
Repeated Insult Patch Test: sensitization potential of the tested product is evaluated after repeated topical application under controlled occlusive patch study conditions.
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: Clear colourless liquid
- Storage Conditions: Ambient

Method

Type of population:
general
Ethical approval:
confirmed and informed consent free of coercion received
Subjects:
TEST SUBJECTS
- Total number enrolled: 116 (20 male, 96 female)
- Total number completed study: 107
- Age at study initiation:
From 18 to 44: 51 volunteers
From 45 to 64: 50 volunteers
> 65: 15 volunteers
- Race: Asian (4 volunteers), Black (6 volunteers), Caucasian (97 volunteers), Hispanic (9 volunteers)

Clinical history:
- Volunteers inclusion criteria:
Individuals eligible for inclusion in the study were those who:
1. were males or females, 18 years of age or older, in general good health;
2. 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;
3. were of any skin type or race providing the skin pigmentation would allow discernment of erythema;
4. had completed a patch study Medical Screening form as well as a Medical/Personal History form; and
5. had read, understood and signed an informed consent agreement.

- Volunteers exclusion criteria:
Individuals excluded from participation in the study were those who:
1. had any visible skin disease at the study site which, in the opinion of the investigative personnel, would have interfered with the evaluation;
2. were receiving systemic or topical drugs or medication which, in the opinion of the investigative personnel, would have interfered with the study results;
3. had psoriasis and/or active atopic dermatitis/eczema;
4. were females who were pregnant, planning to become pregnant during the study, or breastfeeding; and/or
5. had a known sensitivity to cosmetics, skin care products, or topical drugs as related to the material being evaluated.
Controls:
None
Route of administration:
dermal
Details on study design:
TYPE OF TEST(S) USED: patch test (epicutaneous test)

ADMINISTRATION
- Type of application: occlusive
- Description of patch: 2 cm x 2 cm Webril pad attached to a non-porous, plastic film adhesive bandage (3M medical tape), secured with hypoallergenic tape (Micropore) as needed.
- Vehicle / solvent: diethyl phthalate
- Concentrations: 10 % in diethyl phthalate
- Volume applied: 0.2 mL
- Testing/scoring schedule:
Induction phase: 9 consecutive applications, 48-hour intervals (72-hour if weekend). Subject who were absent during the 3-week, 9-patch 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).
Rest period: 10-15 days
Challenge phase: during the 6th week of the study
- Removal of patches: approximately 24 hours after each application
- Other: patches applied to the infrascapular area of the back, either to the right or left of the midline

EXAMINATIONS
During induction sites were evaluated at 48-hour intervals (72-hour if weekend). After challenge, evaluations were done after 48 and 72 hours of application.
Grading/Scoring system:
- = 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:
NO. OF PERSONS WITH/OUT REACTIONS COMPARED TO STUDY POPULATION
- Number of subjects with positive reactions: 0
- Number of subjects with negative reactions: 107
- Number of subjects with equivocal reactions: 0
- Number of subjects with irritating reactions: 0

OTHER RESULTS:
There were no adverse events reported.

Any other information on results incl. tables

Table 7.10.4/1: Sensitisation data

Reading

Hours after challenge

Group

Dose level

No. with + reactions

Total no. in group

Clinical observations

1st

24

test group

0.2 mL of tested substance at 10.0% in Diethyl Phthalate (DEP)

0

107

N/A

2nd

48

test group

0.2 mL of tested substance at 10.0% in Diethyl Phthalate (DEP)

0

107

N/A

 

107 volunteers completed the test. 9 volunteers discontinued the test.

Applicant's summary and conclusion

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

A panel of 116 male and female human volunteers participated in a repeat insult patch test in which a 10% solution of test material in Diethyl phthalate applied to the back of the subjects under occlusive patches. 107 subjects completed the study. During the induction phase nine patches were applied, separated by a 48-hour interval. The patches were removed 24 hours after application. Following a 10 -15 day rest period, a challenge patch was applied and the sites scored 48 and 72 hours after application.

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