3,3,5-trimethylcyclohexan-1-one

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1998

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

(1992)

Deviations:

yes

Principles of method if other than guideline:

The study was performed in accordance with the Study protocol No. 16925 TAL and subsequent amendments, with the following deviation from the agreed Study Protocol:
- at the request of the Sponsor, no classification of the test substance was performed,
- the body weight of 2/3 animals, at beginning of the study, was outside of the target ranges specified in the protocol.
These minor deviations were not considered to compromise the validity or integrity of the study.

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

3,3,5-trimethylcyclohexan-1-one

EC Number:

212-855-9

EC Name:

3,3,5-trimethylcyclohexan-1-one

Cas Number:

873-94-9

Molecular formula:

C9H16O

IUPAC Name:

3,3,5-trimethylcyclohexan-1-one

Details on test material:

- Name of test material (as cited in study report): 3,3,5-trimethylcyclohexanone
- Physical state: colorless liquid
- Analytical purity: 98.5 %
- Lot/batch No.: 9801P0062
- pH: 9.9
- Storage condition of test material: at room temperature and protected from light

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevage Cunicole de Val de Selle, 90160 Prouzel, France.
- Weight at study initiation: mean of 2.2 +-0.1 kg
- Housing: individually in polystrene cages (35 cm x 55 cm x 32 cm or 48.2 cm x 58 cm x 36.5 cm). Each cage was equipped with a food container and a water bottle.
- Diet (e.g. ad libitum): animals had free access to 112 C pelleted diet (UAR, 91360 Villemoisson-sur-Orge, France)
- Water (e.g. ad libitum): Drinking water was filtered by a FG Millipore membrane (0.22 micron), ad libitum
- Acclimation period: at least 5 days
Bacteriological and chemical analysis or the water and diet, including the detection of possible contaminants (pesticides, heavy metals and nitrosamines), are performed regularly by external laboratories.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18+-3
- Humidity (%): 30-70
- Air changes (per hr): approximately 12 cycles/h of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:

semiocclusive

Preparation of test site:

abraded

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated skin served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.5 ml

Duration of treatment / exposure:

Right flank: approximately 4 h
Left flank: 3 minutes

Observation period:

1, 24, 48 and 72 h after removal of dressing

Number of animals:

3

Details on study design:

Doses of 0.5 ml of the test substance were placed on a 4 cm2 dry gauze pad (cooperative Pharmaceutique Francaise, 77000 Melun, France) which was then applied to the animals flanks.
The test substance and the gauze pad were held in contact with the skin by means of an adhesive hypoallergenic aerated semi-occlusive dressing (Laboratories de Pansement et d'Hygiene, 21300 Chenove, France) and a restraining bandage (Coheban, Laboratoires 3M Sante, 92245 Malakoff, France).
As possible irritant effects were anticipated, the test substance was evaluated in one animal in a first assay. Since the test substance was not irritant in this assay, it was subsequently applied to two additional animals.
Animals were examined for changes of behavior and their dermal irritation was evaluated according to a scoring scale described in Table 1.

Results and discussion

In vivo

Results

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 72 h

Score:

0

Max. score:

0

Remarks on result:

other: due to a lack of dermal irritaiton the study was ended after 72 h

Irritant / corrosive response data:

No cutaneous reactions were observed during the study.

Any other information on results incl. tables

No cutaneous reactions were observed during the study.

Table 1: Individual cutaneous examinations and mean values of the scores recorded at each reading for animal No. 1 (application for 3 min).

Rabbit number	Dermal irritation	Scores				Mean irritation score (1)	Interpretation (+) (-)
		1 h	24 h	48 h	72 h
		D1	D2	D3	D4
01	Erythema	0	0	0	0	0.0	(-)
	Oedema	0	0	0	0	0.0	(-)
	Other	*	*	*	*

(1)       mean of scores on days 2, 3 and 4

(+)       irritant according to E.E.C. criteria

(-)       non-irritant according to E.E.C criteria

*        none

Table 2: Individual cutaneous examinations and mean values of the scores recorded at each reading for each animal (application for 4 h).

Rabbit number	Dermal irritation	Scores				Mean irritation score (1)	Interpretation (+) (-)
		1 h	24 h	48 h	72 h
		D1	D2	D3	D4
01	Erythema	0	0	0	0	0.0	(-)
	Oedema	0	0	0	0	0.0	(-)
	Other	*	*	*	*
02	Erythema	0	0	0	0	0.0	(-)
	Oedema	0	0	0	0	0.0	(-)
	Other	*	*	*	*
03	Erythema	0	0	0	0	0.0	(-)
	Oedema	0	0	0	0	0.0	(-)
	Other	*	*	*	*

(1)       mean of scores on days 2, 3 and 4

(+)       irritant according to E.E.C. criteria

(-)       non-irritant according to E.E.C criteria

*        none

Applicant's summary and conclusion

Conclusions:

Under the conditions of an OECD 404 GLP study 3,3,5-Trimethylcyclohexanone is non-irritant when applied topically to rabbits.

Executive summary:

In a primary dermal irritation study, three male New Zealand White rabbits were dermally exposed to 0.5 ml of undiluted 3,3,5 -Trimethylcyclohexanone (98.5 % purity) under semi-occlusive conditions for 4 hours to 6 cm² of the body surface area. Animals then were observed for 72 h.  Irritation was scored following the OECD and EC guidelines.

No cutaneous reactions were observed.

In this study 3,3,5 -Trimethylcyclohexanone is not a dermal irritant.