Registration Dossier

Administrative data

Endpoint:
sensitisation data (humans)
Type of information:
other: human data
Adequacy of study:
supporting study
Study period:
1993-01-18 to 1993-04-30
Reliability:
other: not rated acc. to Klimisch
Rationale for reliability incl. deficiencies:
other: relevant

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report date:
1993

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:
- Principle of test: a Human Repeat Insult Patch Test (HRIPT) was carried out on 97 volunteers with the test item according to the Shelanski/Shelanski method (Ref: Shelanski H A and Shelanski M V 1953. A New Technique of Human Patch Tests, Proc Sci Section Toil Group Assoc 19).
- Short description of test conditions: pads treated with the test item was applied to the upper arm of each subject. Patches were applied on monday, wednesday and friday of the first 3 weeks, called the `induction' or 'insult' period. Subjects were instructed to remove the patch after 24 hours. The test sites were scored before application of each subsequent patch and on the fourth monday of the test following the final insult patch application. Fourteen days after the ninth scoring visit challenge patches were applied to both arms of each subject. The results were graded 48 hours and 96 hours after application. Rechallenge was carried out with volunteers showing skin reactions.
- Parameters analysed / observed: skin reactions
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
2-[({[(1R,2S,5R)-5-methyl-2-(propan-2-yl)cyclohexyl]oxy}carbonyl)oxy]ethan-1-ol
EC Number:
701-039-2
Cas Number:
156324-78-6
Molecular formula:
C13H24O4
IUPAC Name:
2-[({[(1R,2S,5R)-5-methyl-2-(propan-2-yl)cyclohexyl]oxy}carbonyl)oxy]ethan-1-ol

Method

Type of population:
general
Ethical approval:
confirmed and informed consent free of coercion received
Subjects:
- Number of subjects exposed: 97 volunteers (92 volunteers completed the test)
- Sex: 18 males / 79 females
- Age: ≥21 years
Clinical history:
All subjects were required to complete a questionnaire before the start of the test.
Controls:
During the rechallenge volunteers were used as controls
Route of administration:
dermal
Details on study design:
TYPE OF TEST(S) USED: patch test (epicutaneous test)

ADMINISTRATION
- Concentrations: 100 % of the test item
- Volume applied: approx. 0.3 mL
- Type of application: semiocclusive
- Description of patch: 2 cm x 2 cm square Webril pads treated with the test item were located down the centre line of a piece of Blenderm tape. The patch strip was applied down the lateral surface of the upper arm of each subject and held in place (when necessary) by additional strips of Micropore adhesive tape.
- Testing/scoring schedule: patches were applied on monday, wednesday and friday of the first 3 weeks, called the `induction' or 'insult' period.
Scoring visit 1 was the first wednesday of the induction period. The test sites were scored before application of each subsequent patch and on the fourth monday of the test following the final insult patch application.
Fourteen days after the ninth scoring visit (i.e., the monday of the sixth week of the test), challenge patches were applied to both arms of each subject. The results were graded 48 hours and 96 hours after application.
- Removal of test substance: subjects were instructed to remove the patch after 24 hours.

RECHALLENGE
Three volunteers who showed reactions during the HRIPT at challenge to the test material were rechallenged with the test item on both arms for 24 hours.
Three other volunteers, who did not show significant reactions during the HRIPT, were patched with the test item on both arms for 24 hours as controls.
All patches were removed after 24 hours and skin reactions assessed 48 hours and 96 hours after application.

EXAMINATIONS
- Grading/Scoring system: please refer to the field "Attached background material" below

Results and discussion

Results of examinations:
NOTE: five volunteers dropped out from testing for reasons unrelated to the test

INDUCTION PERIOD:
- irritation recorded to the test item during induction was low in the majority of volunteers.
- a few volunteers developed stronger reactions. Three volunteers wore less than 9 induction patches of the test item because of irritation, but completed challenge.

CHALLENGE PERIOD / RECHALLENGE PERIOD:
Three volunteers developed reactions greater than mild erythema to the test item, as follows:
- one volunteer developed a mild erythema on the original arm and a mild erythema with oedema on the alternate arm at 48 hours. At 96 hours, both reactions were of mild erythema only.
Rechallenge: the volunteer developed a mild erythema on the left arm and a moderate spreading erythema on the right arm at 48 hours. At 96 hours the reactions on both arms were of mild
erythema.
Findings made during challenge were considered as an indication of an irritation reaction, which was confirmed during the rechallenge.
- one volunteeer developed a mild erythema on the original arm and a mild erythema with papules on the alternate arm at 48 hours. At 96 hours, no reaction was visible on the original arm and the reaction on the alternate arm remained as mild erythema with papules.
Rechallenge: the volunteer showed no sensitisation reactions to the test item at rechallenge
Findings made during challenge suggested a possible sensitisation reaction, which was not confirmed during the rechallenge.
- one volunteer developed moderate spreading reactions with oedema on both arms at 48 hours. At 96 hours a strong erythematous reaction with oedema was visible on the original arm and a moderate erythema with oedema was visible on the alternate arm.
Rechallenge: the volunteer developed strong spreading erythematous reactions with oedema and papules on both arms at 48 hours. At 96 hours the reaction on the left arm was of strong spreading erythema with oedema and vesicles and the reaction on the right arm was of moderate spreading erythema with oedema and vesicles.
Findings made during challenge suggested a possible sensitisation reaction, which was confirmed during the rechallenge.

The control volunteers participating in the rechallenge did not develop reactions to the test item.

Applicant's summary and conclusion

Conclusions:
Under the test conditions, one volunteer appeared to be sensitised to the test item (1/92 volunteers).
Executive summary:

A Human Repeat Insult Patch Test (HRIPT) was carried out on 97 volunteers with the test item according to the Shelanski/Shelanski method (Ref: Shelanski H A and Shelanski M V 1953. A New Technique of Human Patch Tests, Proc Sci Section Toil Group Assoc 19). Approximately 0.3 mL of 100 % substance was applied to a pad. Then, the pad was applied to the upper arm of each subject and held in place (when necessary) by strips of Micropore adhesive tape. The patch was removed 24 hours after start of treatment. Patches were applied on monday, wednesday and friday of the first 3 weeks (induction period). Fourteen days after the ninth scoring visit (ie, the monday of the sixth week of the test), challenge patches were applied to both arms of each subject. The results were graded 48 hours and 96 hours after application.

5 volunteers dropped out during the study.

During the induction period, irritation recorded to the test item was low in the majority of volunteers. A few volunteers developed stronger reactions. Three volunteers wore less than 9 induction patches of the test item because of irritation.

During the challenge period, three volunteers developed reactions greater than mild erythema to the test item. One volunteer developed a mild erythema on the original arm and a mild erythema with oedema on the alternate arm at 48 hours. At 96 hours, both reactions were of mild erythema only. At rechallenge the volunteer developed a mild erythema on the left arm and a moderate spreading erythema on the right arm at 48 hours. At 96 hours the reactions on both arms were of mild erythema. Findings made during challenge were considered as an indication of an irritation reaction, which was confirmed during the rechallenge.

Another volunteeer developed a mild erythema on the original arm and a mild erythema with papules on the alternate arm at 48 hours. At 96 hours, no reaction was visible on the original arm and the reaction on the alternate arm remained as mild erythema with papules. At rechallenge, the volunteer showed no sensitisation reactions to the test item at rechallenge Findings made during challenge suggested a possible sensitisation reaction, which was not confirmed during the rechallenge.

The third volunteer developed moderate spreading reactions with oedema on both arms at 48 hours. At 96 hours a strong erythematous reaction with oedema was visible on the original arm and a moderate erythema with oedema was visible on the alternate arm. At rechallenge, the volunteer developed strong spreading erythematous reactions with oedema and papules on both arms at 48 hours. At 96 hours the reaction on the left arm was of strong spreading erythema with oedema and vesicles and the reaction on the right arm was of moderate spreading erythema with oedema and vesicles. Findings made during challenge suggested a possible sensitisation reaction, which was confirmed during the rechallenge. The control volunteers participating in the rechallenge did not develop reactions to the test item.

In conclusion, one volunteer appeared to be sensitised to the test item (1/92 volunteers).