1-Butanone, 3-(dodecylthio)-1-[(1R,2S)-2,6,6-trimethyl-3-cyclohexen-1-yl]-, rel-

Sensitisation data (human)

Administrative data

Endpoint:

sensitisation data (humans)

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

From 12 July 2004 to 15 October 2004

Rationale for reliability incl. deficiencies:

other: FDA guideline

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Type of sensitisation studied:

skin

Study type:

study with volunteers

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: FDA Regulation: CFR Title 21, Part 312, Investigational New Drug Application

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: FDA Regulation: CFR Title 21, Part 50, Protection of Human Subjects

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: FDA Regulation: CFR Title 21 Part 56, Institutional review Boards

Deviations:

no

Principles of method if other than guideline:

Patch test

GLP compliance:

yes

Remarks:

Good Clinical Practices

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

456-350-3

EC Name:

-

Cas Number:

878665-13-5

Molecular formula:

C25H46OS

IUPAC Name:

3-(dodecylsulfanyl)-1-[(1S,2R)-2,6,6-trimethylcyclohex-3-en-1-yl]butan-1-one

Test material form:

not specified

Details on test material:

- Name of test material (as cited in study report): ST 48 C 03
- Analytical purity: 99.6%
- Lot/batch No.: SJMI1
- Storage condition of test material: ambient temperature

Specific details on test material used for the study:

- Storage condition of test material: ambient temperature

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: Preliminary study: 14. Main study: 113 (a sufficient number to provide 100 completed subjects)
- Sex: Preliminary study: 6 males, 8 females. Main Study: 23 male & 90 females
- Age: > 18 years old (57 % between 18 and 44 years old, 50.0 % between 45 and 64 years old, 6% > 65 years old)
- Race: no discrimination (Asian: 1.8%, black: 8.8%, Caucasian: 73.5%, Hispanic: 15%, other: 0.9%)

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:

None

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: Diethyl Phtalate (DEP).
- Concentrations: 1 %.
- Volume applied: 0.2 mL.
- Testing/scoring schedule: 1 reading 72 hours after induction application; 2 readings (48 anf 72 hours) after challenge application.

EXAMINATIONS
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

Results and discussion

Results of examinations:

There was no evidence of sensitization to ST 48 C 03 at 1% in DEP.

Any other information on results incl. tables

A total of 14 +113 subjects between the ages of 18 and 70 were enrolled and 13 +111 subjects completed the study.

The following table summarizes subject enrolment and disposition:

 

	Preliminary study	Main Study
Number enrolled	14	113
Number discontinued	1	7
Lost to follow-up	-	2
Voluntary withdrawal	1	4
Adverse event	-	1*
Number completed	13	106
* heart attack unrelated to study product

 

The summary of dermatologic response data for the main study 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*
-	109	108	106	99	101	92	89	88	86	11	106	106
?	0	1	1	5	7	14	15	18	19	3	0	0
+	0	0	1	1	0	2	2	1	1	0	0	0
TOTAL EVALUABLE	109	109	108	105	108	108	106	107	106	14	106	106
NUMBER ABSENT	1	1	2	4	1	1	3	2	3		0	0
NUMBER DISCONTINUED	3	3	3	4	4	4	4	4	4		7	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
-	86 (78.9%)
?	19 (17.4%)
+	4 (3.7%)

 

Applicant's summary and conclusion

Conclusions:

Under the conditions employed for this study, there was no evidence of sensitization and of irritation to the test material 1% in DEP

Executive summary:

ST 48 C 03 at 1% in Diethyl Phtalate (DEP) was evaluated to determine its ability to sensitize the skin of normal volunteer subjects using an occlusive Human Repeated Insult Patch Test (HRIPT) study. Occlusive testing is a severe condition improving dermal exposure & penetration that facilitates dermal reactions. 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.

 

A pilot study was conducted first with ST48 C 03 to determine the feasibility of testing on a larger population by evaluating its ability to sensitize the skin of normal volunteer subjects using an occlusive repeated insult patch study. 14 subjects were enrolled and 13 completed the study. There was no evidence of skin sensitization.

Approximately 3 weeks after the pilot study was completed, a main study was conducted for ST 48 C 03 at 1% in DEP under the same conditions as pilot. 113 subjects were enrolled and 106 subjects completed the study. There was no evidence of sensitization.

 

Under the conditions employed in this study, there was no evidence sensitization to ST 48 C 03 at 1% in DiethylPhtalate (DEP). In conclusion, the test material can be applied safely, at least to the concentration tested in that study (1%), to human skin without significant risk of adverse reactions.