[1α(E),2β]-1-(2,6,6-trimethylcyclohex-3-en-1-yl)but-2-en-1-one

Sensitisation data (human)

Administrative data

Endpoint:

sensitisation data (humans)

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

30 August 1982 to 29 October 1982

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1982

Report date:

1982

Materials and methods

Type of sensitisation studied:

skin

Study type:

study with volunteers

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The skin sensitising potential of the test substance was evaluated in the repeated insult patch test with 54 human volunteers. The substance, tested as 1% solution was applied for 24 hours 4 consecutive weeks for a total of 9 applications. Skin reactions were scored after 24 hours exposure. After 2 weeks rest period, the subjects were rechallenged at a virgin site for 24 hours and the reactions were scored over a period of 3 days.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

[1α(E),2β]-1-(2,6,6-trimethylcyclohex-3-en-1-yl)but-2-en-1-one

EC Number:

275-156-8

EC Name:

[1α(E),2β]-1-(2,6,6-trimethylcyclohex-3-en-1-yl)but-2-en-1-one

Cas Number:

71048-82-3

Molecular formula:

C13H20O

IUPAC Name:

[1α(E),2β]-1-(2,6,6-trimethylcyclohex-3-en-1-yl)but-2-en-1-one

Test material form:

liquid

Method

Type of population:

general

Ethical approval:

confirmed and informed consent free of coercion received

Subjects:

- 54 individuals
- Sex: Males: 5, Females: 49
- Age: 19-72
- Qualifying Criteria: (1) General well-being, (2) Willingness to cooperate, (3) Dependability and intelligence in following directions (4) Reading, understanding and signing informed consent statement to be subjected to the requirements and hazards associated with the test material and procedure.

Clinical history:

- Exclusion criteria: (1) Any visible skin diseased which might be confused with skin reactions from the test material, (2) Any subject participating in a patch test within six weeks of initiation of the study, (3) Candidates were only excluded if illness, condition could influence the course of the evaluation or compromise the validity of the test procedure, observations, and interpretations of the results.
- Subjects with known allergies, those who could be considered atopics and those who had previously reacted to soaps, deodorants, shaving creams, cosmetics, etc., were not intentionally excluded from the test population.

Route of administration:

dermal

Details on study design:

ADMINISTRATION
- Procedure: A series of nine applications, each 24 hrs duration was scheduled to be carried out during the induction period (week 1-4). After 24 hours the contact sites were examined and graded. Challenge applications on virgin sites on the upper back of all individuals were scheduled to be carried out during the challenge week (14 days after application of the last induction patch; week 6). The challenge patches were removed after 24 hours. The challenge sites were read and graded approximately 15 minutes following patch removal. The sites were re-examined and graded 24, 48, and 72 hours following patch removal.
- Patch: Parke-Davis Readi-Bandages, clear plastic patches, 1.5 x 1.5 inches (Lot No. WB6167), were used for patching in this study. 1% of the test substance was mixed with 99% of SDA-39C. 0.2 mL of the test solution was deposited on the patch, allowed to dry, applied and tested dry.
- Testing/scoring schedule:
Week 1: Day 1: Treated patches were applied; Day 2: Patches removed and discarded and contact sites were graded; Day 3: Contact sites were re-examined and freshly prepared patches were applied to the same site; Day 4: Patches removed and discarded and contact sites were graded and freshly prepared patches were applied to the same site; Day 5: Patches removed and discarded and contact sites were graded.
Week 2: Day 1: Holiday; Day 2: Treated patches were applied; Day 3: Patches removed and discarded and contact sites were graded; Day 4: Contact sites were re-examined and freshly prepared patches were applied to the same site; Day 5: Patches removed and discarded and contact sites were graded.
Week 3: Day 1: Treated patches were applied; Day 2: Patches removed and discarded and contact sites were graded; Day 3: Contact sites were re-examined and freshly prepared patches were applied to the same site; Day 4: Patches removed and discarded and contact sites were graded and freshly prepared patches were applied to the same site; Day 5: Patches removed and discarded and contact sites were graded.
Week 4: Day 1: Treated patches were applied; Day 2: Patches removed and discarded and contact sites were graded
- Grading/Scoring system: 0 -no visible irritation, or no difference from surrounding, untreated skin; 1 - erythema confined to the contact site and exceeding that of the untreated skin; 2 - erythema confined to the contact site and definitely exceeding that of untreated skin; papules may or may not be present; 3 - erythema with some degree of induration, papules may or may not be present; 4 - erythema, induration, with one or more complications such as extension beyond margins of contact area, vesiculation, ulceration.

Results and discussion

Results of examinations:

- Induction phase: Irritation as a result of the applications of the induction phase was observed in 7 individuals. In all of these individuals, the irritation and the characteristics of their responses were sufficient to classify this material as sensitizer. These responses persisted for a long time, actually intruding into the time scheduled for the challenge applications despite medication. Therefore, challenge applications in 6 of these individuals were refused by the panelists with the concurrence of the investigator.
- Challenge phase: One panelist, agreed to have the challenge application under occlusion and confirmation of a sensitization was obtained. Responses in the balance of the panel did not result from any of the induction or challenge applications.
- Using table IX from "Binomial Confidence Limits, Tables for Use with Binomial Samples", by Donald Mainland, Lee Herrera, and Marion I. Sutcliffe, Department of Medical Statistics, New York University, College of Medicine, 1956, the authors conclude that it is possible to state with 95% confidence that the material will be tolerated by no less than 75.07% and by as much as 84.62% of the population at risk.

Applicant's summary and conclusion

Conclusions:

The test substance, tested as a 1% solution, was found capable of sensitizing 7 out of 54 individuals.

Executive summary:

The skin sensitising potential of the test substance was evaluated in a repeated insult patch test with 54 human volunteers. The substance, tested as 1% solution, was applied for 24 hours 4 consecutive weeks for a total of 9 applications. Skin reactions were scored after 24 hours exposure. After 2 weeks rest period, the subjects were rechallenged at a virgin site for 24 hours and the reactions were scored over a period of 3 days. The substance was found to be capable of sensitizing 7 out of the 54 individuals.