Acetic acid, anhydride, reaction products with 1,5,10-trimethyl-1,5,9-cyclododecatriene

Sensitisation data (human)

Administrative data

Endpoint:

sensitisation data (humans)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

10 October 2011 to 18 November 2011

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Remarks:

Api, 2002, Sensitisation methodology and primary prevention of the Research Institute for Fragrance Materials, Dermatology, 205, 84-87

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2011

Materials and methods

Type of sensitisation studied:

skin

Study type:

study with volunteers

Test guideline

Qualifier:

according to guideline

Guideline:

other: Modified Shelanski-Shelanski human patch test (Proc.Sci.Sect. Toilet Goods Assoc.19:46, 1953).

GLP compliance:

yes (incl. QA statement)

Remarks:

Good Clinical Practice

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

482-330-9

EC Name:

-

Cas Number:

144020-22-4

Molecular formula:

C17H26O

IUPAC Name:

1-[(1E,5Z,9Z)-2,5,10-trimethylcyclododeca-1,5,9-trien-1-yl]ethan-1-one; 1-[(1R)-2,5,10-trimethylcyclododeca-2,5,9-trien-1-yl]ethan-1-one; 1-[(1R)-4,9-dimethyl-12-methylidenecyclododeca-4,8-dien-1-yl]ethan-1-one; 1-[(1S)-2,5,10-trimethylcyclododeca-2,5,9-trien-1-yl]ethan-1-one; 1-[(1S)-4,9-dimethyl-12-methylidenecyclododeca-4,8-dien-1-yl]ethan-1-one

Method

Type of population:

general

Ethical approval:

confirmed and informed consent free of coercion received

Remarks:

All subjects signed an Informed Concent Form in compliance with 21 CFR

Subjects:

- Number of subjects exposed: initiated with 112 subjects, 7 subjects discontinued study participation for reasons unrelated to the test material, 105 subjects completed the study
- Sex: male and female
- Age: between 18 and 70
- Race: not specified
- Demographic information: not specified

Clinical history:

Subjects were in good health as determined by a Panelist Profile/Medical History
Subjects with no visible or known pre-existing skin diseases that might be confused with a skin reaction from the test material, or which may be reasonably expected to affect the outcome of the study. This included subjects with psoriasis or active eczema, even if currently controlled through medication.
Subjects who do not report a history of acute or chronic dermatologic, medical, or physical conditions that could interfere with dermal scoring

Route of administration:

dermal

Details on study design:

TYPE OF TEST(S) USED: patch test (epicutaneous test)

ADMINISTRATION
- Type of application: occlusive (Occlusive Strip with Flexcon®, TruMed Technologies Inc., Burnsville Minnesota)
- Description of patch: a 3.63 cm2 modified Shelanski – Shelanski human patch test method
- Vehicle / solvent: EtOH:DEP (1:3)
- Concentrations: 10% w/w
- Volume applied: 0.2 ml
- Testing/scoring schedule: Patches were applied to the same site on the upper back (between the scapulae) on Monday, Wednesday and Friday for a total of 9 applications during the Induction Period. The sites were graded by a CRL technician for dermal irritation 24 hours after removal of the patches by the subjects on Thuesday and Thursday and 48 hours after removal of the patches on Saturday. Following approximately a 2-week rest period, the challenge patches were applied to previously untreated test sites on the back. After 24 hours the patches were removed by a CRL technician and the test sites were evaluated for dermal reactions. The test were re-evaluated at 48 and 72 hours. Subjects exhibiting reactions during the Challenge Phase of the study may have been asked to return for a 96-hour reading.
- Removal of test substance: In the Induction Period by the subjects on Thuesday, Thursday and Saturday. 24 h after the Challenge Phase by the CRL technician
- Other: The test material was applied to the patch as received and allowed to evaporate for at least 30 minutes, but no longer than 90 minutes, prior to patch application.

EXAMINATIONS
- Grading/Scoring system: 0: No visible skin reaction; ±: Barely perceptible erythema; 1+: Mild erythema; 2+: Well defined erythema; 3+: Severe erythema and edema; 4+: Erythema and edema with vesiculation.

Results and discussion

Results of examinations:

SYMPTOMS
- Frequency, level, duration of symptoms observed: none

NO. OF PERSONS WITH/OUT REACTIONS COMPARED TO STUDY POPULATION
- Number of subjects with positive reactions: 0
- Number of subjects with negative reactions: 105
- Number of subjects with equivocal reactions: 0
- Number of subjects with irritating reactions: 0

Applicant's summary and conclusion

Conclusions:

Application of 0.2 mL with 10% test substance applied at 3.63 cm2 was not sensitising under the conditions of the test in 105 subjects.

Executive summary:

The induction phase took place on Monday, Wednesday and Friday till 9 applications had been made in approximately 3 weeks. The amount of volume applied was 0.2 ml, test concentration used was 10% and the applied surface was 3.63 cm2. During the induction patches were placed on the upper back (between the scapulae). The subjects removed the patches 24 hours after application themselves. After removal, 24 hours the skin was not treated, except for the 48 hours treatment free period after the Friday application. Two weeks after the final induction treatment, a challenge patch was applied to a virgin right of the back and removed after 24 hours. Reactions to the challenge were assessed after 24, 48, 72 and 96 hours. None of the 105 subjects tested was sensitised by the sample. It was therefore concluded that the test substance is not sensitising at the concentration used.