Cyclohexadecen-1-one

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2003-11-18

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

The in vivo study on skin irritation with the registration substance was completed in 2003. Therefore, in compliance with Regulation (EC) 1907/2006 (REACH) performing an additional in vitro skin irritation study is considered scientifically not necessary.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2013

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

2001

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

448-300-4

EC Name:

-

Cas Number:

88642-03-9

Molecular formula:

C16H28O

IUPAC Name:

(6E)-cyclohexadec-6-en-1-one; (7Z)-cyclohexadec-7-en-1-one; (8E)-cyclohexadec-8-en-1-one; (8Z)-cyclohexadec-8-en-1-one

Test animals

Species:

rabbit

Strain:

other: Chbb:HM(SPF)

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 18 - 22 months
- Weight at study initiation: 2.7 - 3.0 kg
- Housing: individually in PPO cages (floor area: 2576 sq. cm) with perforated floor
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: approx. one week

ENVIRONMENTAL CONDITIONS
- Temperature: 20 +/- 3 °C
- Humidity: 55 +/- 15 %
- Air changes: 10 per hr
- Photoperiod: 12 / 12 hrs dark / hrs light

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

other: olive oil

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 g

VEHICLE
- Amount applied: ca. 0.1 mL for a better contact to the skin

Duration of treatment / exposure:

4 h

Observation period:

21 d

Number of animals:

3 females

Details on study design:

TEST SITE
- Area of exposure: back
- Type of wrap: 16-layer gauze patch (2.5 cm x 2.5 cm) was secured semi-occlusively with adhesive Gothaplast tape (2.5 cm wide) and fixed with Gothaplast tape (5 cm wide) loosely wound round the trunk

REMOVAL OF TEST SUBSTANCE
- Washing: with mild soap and lukewarm water
- Time after start of exposure: 4 h

OBSERVATION TIME POINTS
The skin reactions were read immediately and 1 h, 24 h, 48 h as well as 72 h after the termination of exposure as well as on day 7, 14 and 21

SCORING SYSTEM:
According to guideline and Draize scoring system:

Erythema and Eschar Formation Score
No erythema: 0
Very slight erythema (barely perceptible): 1
Well defined erythema: 2
Moderate to severe erythema: 3
Severe erythema (beef redness) to eschar formation preventing grading of erythema: 4
Maximum possible: 4

Oedema Formation Score
No oedema: 0
Very slight oedema (barely perceptible): 1
Slight oedema (edges of area well defined by definite raising): 2
Moderate oedema (raised approximately 1 mm): 3
Severe oedema (raised more than 1 mm and extending beyond area of exposure): 4
Maximum possible: 4

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 21 d

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

3.67

Max. score:

4

Reversibility:

fully reversible within: 21 d

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

fully reversible within: 21 d

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 21 d

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 21 d

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

3.33

Max. score:

4

Reversibility:

fully reversible within: 21 d

Irritant / corrosive response data:

7 days after the termination of exposure isolated scales were observed an the anterior left test field of animal No. 2425 as well as slight crusty scales an the middle and posterior left test field. Animals No. 2461 and No. 2462 showed flat, yellow scales an the whole anterior right test field.

14 days after the termination of exposure isolated, small scales were still recorded an the middle and posterior left test field of animal No. 2425. Animals No. 2461 and No. 2462 still showed isolated scales an the anterior right test fields.

21 days after the termination of exposure animals No. 2425, No. 2461 and No. 2462 were free of any signs of skin irritation.

Other effects:

- Other adverse local effects: none
- Other adverse systemic effects: not observed

Any other information on results incl. tables

Table 1

Animal No	Exposure	Test field	Ersthema formation observed after x hours after termination					Mean (24 -72 h)	Oedema formation after x hours after termination					Mean (24 -72 h)
			0	1	24	48	72		0	1	24	48	72
2425	3 min	Anterior le.	0	1	2	2	2		0	0	0	0	0
	1 h	Median le.	0	1	3	3	3		0	0	2	2	2
	4 h	Posterior le.	1	2	3	3	3	3.00	0	0	2	2	2	2.00
2461	4 h	Anterior le.		2	3	4	4	3.67		2	3	3	3	3.00
2462	4h	Anterior le.		2	4	4	4	4.00		1	4	3	3	3.33

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

Based on the results of this study, the test item was found to be irritating to rabbit skin.

Executive summary:

The skin irritant effect of the test item was investigated according to the method recommended in the OECD Guideline No. 404, "Acute Dermal Irritation/ Corrosion", 2002, and OECD document "Harmonised Integrated Classification System for Human Health and Environmental Hazards of Chemical Substances and Mixtures", 2001, modified. Based on a weight-of-the-evidence analysis of all existing relevant information carried out on the sponsor's own authority the in vivo testing of the test item was considered to be justified. During an initial test using one female albino rabbit a sequential application (exposure time 3 min, 1 h and 4 h) of the test item was carried out on one site of the left back area each. The skin was examined for signs of irritation straight after as well as 1 h, 24 h, 48 h and 72 h after the termination of exposure as well as on day 7, 14 and 21. Since the animal did show very well defined signs of skin Irritation but no full thickness destruction of the skin within the observation period of 21 days it was decided to carry out a confirmatory test with two additional animals in order to allow a categorization of the test item based on the classification criteria (CLP). Two female albino rabbits were exposed to the test item at one skin site on the back during the confirmatory test. After 4-hour exposure time the test item was removed and the skin was examined 1 h, 24 h, 48 h and 72 h after the termination of exposure as well as on day 7, 14 and 21. Skin reactions ranging from well defined to severe were observed in these animals, too. The observation period was extended to the complete reversibility of all effects on day 21 according to the sponsor's request. Under the experimental conditions described in this report the mean scores after the 4-hour exposure were:

Animal No	Erythema	Oedema
2425	3.00	2.00
2461	3.67	3.00
2462	4.00	3.33

 

Under the experimental conditions of this study, the mean score for erythema was 3.6 and for oedema 2.8. Based on the results of this study the test item is considered to be irritating to rabbit skin.