Registration Dossier

Toxicological information

Sensitisation data (human)

Currently viewing:

Administrative data

Endpoint:
sensitisation data (humans)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 11 April to 20 May 2005
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: FDA guideline

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2005
Report Date:
2005

Materials and methods

Type of sensitisation studied:
skin
Study type:
study with volunteers
Test guidelineopen allclose all
Qualifier:
according to
Guideline:
other: FDA Regulation: CFR Title 21, Part 312, Investtigational New Drug Application
Deviations:
no
Qualifier:
according to
Guideline:
other: FDA Regulation: CFR Title 21, Part 50, Protection of Human Subjects
Deviations:
no
Qualifier:
according to
Guideline:
other: FDA Regulation: CFR Title 21 Part 56, Institutional review Boards
Deviations:
no
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): ST 05 C 05
- Substance type: pure active substance
- Analytical purity: 98.1 %
isomer composition: ca. 10-12 % cis- and 88-90 % trans- isomers
- Lot/batch No.: 2F32098
- Storage condition of test material: ambient temperature
- Expiration date of the lot/batch: 05 March 2007

Method

Type of population:
general
Ethical approval:
confirmed and informed consent free of coercion received
Remarks:
in compliance with FDA regulation (21 CFR Part 50)
Subjects:
- Number of subjects exposed: 118 (a sufficient number to provide 100 completed subjects)
- Sex: 20 male & 98 females
- Age: > 18 years old (49.2 % between 18 and 44 years old, 38.1 % between 45 and 64 years old, 12.7% > 65 years old)
- Race: no discrimination (Amerindian: 1, Asian: 2, black: 4, Caucasian: 96, Hispanic: 15)
Clinical history:
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 medical screening procedure; and
5. had read, understood and signed an informed consent agreement.

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 breast-feeding; and/or
5. had a known sensitivity to cosmetics, skin care products, or topical drugs as related to the material being evaluated.
Controls:
No positive control are performed on HRIPT.
Route of administration:
dermal
Details on study design:
TYPE OF TEST(S) USED: patch test (epicutaneous test)

ADMINISTRATION
The patches were applied to the infrascapular area of the back, either right or left of the midline.
- Type of application: occlusive
- Description of patch: Material evaluated under occlusive patch conditions was applied to a 2cm x 2cm Webril pad attached to a non-porous, plastic film adhesive bandage (3M medical tape). The patch was secured with hypoallergenic tape (Micropore), as needed.
- Vehicle / solvent: 75% Diethyl phtalate/25% Ethanol
- Concentrations: test material 20% in 75% Diethyl phtalate/25% Ethanol
- Volume applied: 0.2 ml
- Testing/scoring schedule: see "Any other information on materials and methods incl. tables"


EXAMINATIONS
Grading/Scoring system:
- = no reaction
? = Minimal or doubtful response, slightly different from surrounding normal skin
+= Definite erythema, No edema
++= Definite erythema, Definite edema
+++= Definite erythema, Definite edema and vesiculation
(See remarks on results including tables for more details)

Results and discussion

Results of examinations:
There were no adverse events reported during that study (See "Remarks on results including tables and figures" for more details on results)

Any other information on results incl. tables

118 subjects between the ages of 19 and 70 were enrolled and 111 subjects completed the study

The following table summarizes subject enrollment and disposition:

 

Number enrolled

118

Number discontinued

7

Lost to follow-up

3

Voluntary withdrawal

4

Number completed

111

 

The summary of response data is the provided in the following table:

 

 

Induction reading

MAKE-UP

Challenge phase (hours)

Response

1

2

3

4

5

6

7

8

9

48

72

96*

-

114

113

112

112

112

112

112

112

111

0

112

111

 

TOTAL EVALUABLE

114

113

112

112

112

112

112

112

111

0

112

111

 

NUMBER ABSENT

0

0

0

0

0

0

0

0

1

 

0

0

 

NUMBER DISCONTINUED

4

5

6

6

6

6

6

6

6

 

6

7

 

 

* = when required

- = no reactions

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

+ = definite erythema, no oedema

++ = definite erythema, definite edema

+++ = definite erythema, definite edema and vesiculation

D = damage to epidermis: oozing, crusting and/or superficial erosions

P =papularresponse > 50%

 

 

MAXIMUM ELICITED RESPONSE DURING INDUCTION

ALL SUBJECTS COMPLETING INDUCTION (N=112)

RESPONSE

N(%) SUBJECTS

-

112 (100.0%)

 

Applicant's summary and conclusion

Conclusions:
Under the conditions employed for this study, there was no evidence of sensitization and of irritation to ST 05 C 05 at 20% in 75% DEP/25% Ethanol.
Executive summary:

The test material at 20% in 75% DiethylPhtalate(DEP)/25% Ethanol was evaluated to determine its ability to sensitize the skin of normal volunteer subjects using an occlusive Human Repeated Insult Patch Test (HRIPT) study. HRIPT is a study that can detect weak sensitizers that require multiple applications to induce a cell-mediated (Type IV) immune response sufficient to cause an allergic reaction. HRIPT is a reproducible, standardized, quantitative patch evaluation procedure generally accepted to demonstrate that a particular material can be applied safely to human skin without significant risk of adverse reactions.

 

One hundred eleven appropriate subjects completed the study. Under the conditions employed in this study, there was no evidence of both sensitization and irritation to ST 05 C 05 at 20% in 75% DEP/25% Ethanol, even in the severe test conditions used i.e. occlusive testing and use of ethanol as co-solvent that both improve dermal exposure & penetration, therefore facilitating dermal reactions.

 

In conclusion, the test material can be applied safely, at least to the concentration tested in that study (20%), to human skin without significant risk of adverse reactions.