Reaction mass of 3,5,6,6-tetramethyl-4-methyleneheptan-2-one and (E)-3,4,5,6,6-pentamethylhept-3-en-2-one

Sensitisation data (human)

Administrative data

Endpoint:

sensitisation data (humans)

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1980

Report date:

1980

Materials and methods

Type of sensitisation studied:

skin

Study type:

study with volunteers

Remarks:

patch test

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Eight materials were evaluated for the sensitisation potential in humans after dermal contact. The materials were diluted to the appropriate concentration of 15% and applied to the skin on semi-occlusive patches (0.2ml and 3.3 cm2 (1.5 inch)). Fifty-four panellists were exposed to all 8 materials for 24 hours, Monday, Wednesday and Friday for a total of 9 induction applications. After a 2 weeks rest period, the panellists received a challenge patch at a virgin site for 24 hours, followed by readings over a 3-day period. Panellists exhibiting positive reactions to challenge patches were re-challenged at virgin sites after another two weeks rest period, and scored over a 3-day period.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of (E)-3,4,5,6,6-pentamethylhept-3-en-2-one and 3,5,6,6-tetramethyl-4-methyleneheptan-2-one

EC Number:

946-245-5

Molecular formula:

C12H22O

IUPAC Name:

Reaction mass of (E)-3,4,5,6,6-pentamethylhept-3-en-2-one and 3,5,6,6-tetramethyl-4-methyleneheptan-2-one

Test material form:

liquid

Details on test material:

According to ECHA communication with reference to Annotation number: SUB-C-2114629169-42-01/F, the substance ID for Koavone has been changed with EC# from 939-627-8 to 946-245-5, and the IUPAC name from Reaction mass of (3R,5R)-3,5,6,6-tetramethyl-4-methylideneheptan-2-one and (3R,5S)-3,5,6,6-tetramethyl-4-methylideneheptan-2-one and (E)-3,4,5,6,6-pentamethylhept-3-en-2-one to Reaction mass of (E)-3,4,5,6,6-pentamethylhept-3-en-2-one and 3,5,6,6-tetramethyl-4-methyleneheptan-2-one.

Method

Subjects:

- Number of subjects exposed: 55 (54 completed the study)
- Sex: male (8) and female (47)
- Age: females: from 16 to 78, males: from 20 to 72
- Race: Caucasian
- Demographic information: local population

Exclusion criteria:
1) Any visible skin disease which might be confused with skin reactions from the test material
2) Any subject participating in a patch test within 6 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 interpretation of the results
4) Any panellist participating in any other product evaluation during the course of the test.

Route of administration:

dermal

Details on study design:

TYPE OF TEST(S) USED: patch test (epicutaneous test)
ADMINISTRATION
- Type of application: semiocclusive
- Description of patch: Parke-Davis Readi-Bandages, clear plastic patches, 1 1/2 x 1 1/2 inches (Lot. No. WB6167), from which the sides were removed to provide semi-occlusive cover.
- Vehicle / solvent: Diluent 80-017
- Concentrations: 15.0% v/v
- Volume applied: 0.2 mL (deposited on the patch, allowed to dry, applied and tested dry)
- Testing/scoring schedule: A series of 9 alternate day applications, each of 24 hours duration, on Monday, Wednesday and Friday for 3 weeks in the induction phase; the reactions were scored on Tuesday, Thursday and Saturday. After 2 weeks rest period, a virgin site was challenged for 24 hours and scored after a 3-day period.
- Removal of test substance: after 24-hours contact, the patches were removed and discarded.

EXAMINATIONS
- 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 exceeing 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:

SYMPTOMS
Frequency, level, duration of symptoms observed: two cases of score 1 erythema were reported among 54 subjects after applications # 7 and 8, respectively, during the induction phase. No further skin reactions were observed.

NO. OF PERSONS WITH/OUT REACTIONS COMPARED TO STUDY POPULATION
Number of subjects with positive reactions: 0
Number of subjects with negative reactions: 54
Number of subjects with equivocal reactions: 0
Number of subjects with irritating reactions: 2

Under the test conditions, the test substance, tested as 15.0% v/v in Diluent 80-017, was found incapable of eliciting any visible consistent irritation in any of the individuals.

Applicant's summary and conclusion

Conclusions:

Application of 0.2 mL with 15% test substance applied at 7.62 cm2 was not sensitising under the conditions of the test in 54 subjects.

Executive summary:

The skin sensitising potential of the substance was evaluated in the repeated insult patch test with 54 human volunteers. The substance, tested as 15% solution (v/v) in 0.2 mL was applied to 7.62 cm² for 24 hours on Monday, Wednesday and Friday for 3 consecutive weeks for a total of 9 applications. This resulted in 200 mg * 0.15 / 7.62 = 3.94 mg/cm². 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.

Two cases of mild erythema (score 1) were reported after the 7th and the 8th exposure in the induction phase. No further skin reactions were noted.

The substance was found incapable to elicit any visible consistent irritation in any of the panellists.