6-methylhept-5-en-2-one

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

No data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The results were taken from a review which discusses the Freund's Complete Adjuvant Test and the Open Epicutaneous Test. Data for about 300 fragrance raw materials were presented in tabular form.

Data source

Reference

Reference Type:

publication

Title:

The Freund's complete adjuvant test and the open epicutaneous test

Author:

Klecak G

Year:

1985

Bibliographic source:

Curr. Probl. Derm., vol. 14, 152-171, Karger, Basel

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Open epicutaneous test:
1. Pretest: establishing the primary irritating threshold concentration of the test substance
2. Main study:induction phase: a 3-week period of daily open applications of the test material usually to the same skin site (21 applications)challenge phase: induced and control animals are tested on day 21 and day 35 by topical application of the test substance if sensitisation has occurred

GLP compliance:

no

Remarks:

pre GLP

Type of study:

open epicutaneous test

Justification for non-LLNA method:

Existing OET of good quality that was generated before 11 October 2016.

Test material

Test material information

Constituent 1

Reference substance name:

6-methylhept-5-en-2-one

EC Number:

203-816-7

EC Name:

6-methylhept-5-en-2-one

Cas Number:

110-93-0

Molecular formula:

C8H14O

IUPAC Name:

6-methylhept-5-en-2-one

Details on test material:

- Name of test material (as cited in study report): methyl heptenone
- Analytical purity: no data given

In vivo test system

Test animals

Species:

guinea pig

Strain:

not specified

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 300 - 450g
- Diet: ad libitum
- Water: ad libitum

Study design: in vivo (non-LLNA)

Induction

Route:

epicutaneous, open

Vehicle:

other: not specified for methyl heptenone

Concentration / amount:

Pretest: 1; 3; 10; 30; 100 %; not specified for methyl heptenoneInduction: 0.3; 1; 3; 10; 30; 100%; not specified for methyl heptenone

Day(s)/duration:

20 days

Challenge

Route:

epicutaneous, open

Vehicle:

other: not specified for methyl heptenone

Concentration / amount:

Challenge: min. irritating concentration and three 3-fold serial dilutions (3% for methyl heptenone)

Day(s)/duration:

2 exposures, on days 21 and 35. The reactions are read after 24,48 and/or 72h

No. of animals per dose:

Pretest: 6-8 animals; Main study: 6-8 animals per dose in the main study; control: 10 animals

Details on study design:

Threshold irritation concentration:
- No. of exposures: 1
- Exposure period: 24 hours
- Control group: vehicle or negative control
- Site: clipped flank

MAIN STUDY

A. INDUCTION EXPOSURE
- No. of exposures: 21
- Control group: no pretreatment or vehicle (not specified for methyl heptenone)
- Site: clipped flank- Duration: 3 weeks
- Frequency of applications: daily

B. CHALLENGE EXPOSURE
- No. of exposures: 2
- Day(s) of challenge: 21, 35
- Site: clipped flank
- Evaluation (hr after challenge): 24, 48, 72

Challenge controls:

4 dilutions containing the minimal-irritant and maximal-non irritant concentration in non-pretreated or 21-day vehicle pretreated animals (no further data given)

Positive control substance(s):

not specified

Results and discussion

In vivo (non-LLNA)

Results

Results 1

Reading:

other: all readings

Hours after challenge:

24

Group:

test chemical

Dose level:

3%

No. with + reactions:

0

Total no. in group:

8

Clinical observations:

none

Remarks on result:

no indication of skin sensitisation

Results 2

Reading:

other: all readings

Group:

negative control

Dose level:

0

Total no. in group:

10

Clinical observations:

none specified

Remarks on result:

other: control result not specified

Results 3

Group:

positive control

Remarks on result:

not measured/tested

Any other information on results incl. tables

methyl heptenone was negative in the OET in guinea pigs.  

Applicant's summary and conclusion

Interpretation of results:

other: not classified

Remarks:

based on CLP criteria

Conclusions:

Under the conditions of this study, the substance was not found to be sensitising. Based on this result, Methylheptenone does not need to be classified as skin sensitiser in accordance with the criteria outlined in Annex I of the CLP Regulation (1272/2008/EC).

Executive summary:

Male and female guinea pigs, weighing 300-450g, were used in experimental groups of at least 6 guinea pigs for every concentration group. For controls 10 animals were used. Methylheptenone is applied epicutaneously, uncovered, undiluted and at concentrations of 30, 10, 3 and 1% or lower in a suitable vehicle. Constant volumes of each concentration were applied with a pipette or syringe on standard sites of the clipped flank of each animal. 1 day before starting the induction procedure, the threshold irritating concentration of methylheptenone was estimated on the guinea pigs subsequently used for the experimental group. A single application of 0.025 ml of each test concentration (e.g, 100,30,10 and 3%) was simultaneously performed on one of the sites measuring 2 cm2 of the flank skin previously clipped and marked with a circular stamp. Reactions were read 24 h after the application of the test material.

 

On day 1application of 0.1 ml of methylheptenone is performed to an site measuring 8 cm2 on the clipped flank skin of the guinea pigs. The applications were repeated daily for 3 weeks or done 5 times weekly during 4 weeks, usually on the same skin sites. The application sites were left uncovered and the reactions, if continuous daily applications were performed, were read 24 h after each application, or at the end of each week.

 

To determine whether or not contact sensitization was induced, all groups of guinea pigs previously treated for 21 days as described above, as well as 10 untreated, or only pretreated with the vehicle, controls were tested on days 21 and 35 on the contralateral flank with methylheptenone at the minimal irritating and some lower primary nonirritating concentrations. These tests were performed by applying with a pipette 0.025 ml of each concentration to skin sites measuring 2 cm2. The reactions were read after 24,48 and/or 72h. Methyl heptenone was negative in this OET in guinea pigs.  Based on this result, Methylheptenone does not need to be classified as skin sensitiser in accordance with the criteria outlined in Annex I of the CLP Regulation (1272/2008/EC).