(2S,3S,4R)-2-aminooctadecane-1,3,4-triol

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

29 january 2002 - 05 february 2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

OECD TG 404

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

1992

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

439-210-6

EC Name:

-

Cas Number:

554-62-1

Molecular formula:

C18H39NO3

IUPAC Name:

(2S,3S,4R)-2-aminooctadecane-1,3,4-triol

Test material form:

solid: particulate/powder

Details on test material:

SOURCE OF TEST MATERIAL
- Purity: 94.0 %

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at room temperature in the dark.

Specific details on test material used for the study:

Batch: 62630012
Expiry date: 01 November 2002

Test animals

Species:

rabbit

Strain:

New Zealand White

Remarks:

Albino rabbit (SPF-Quality)

Details on test animals or test system and environmental conditions:

Test animals
- Source: Charles River Deutschland, Kisslegg, Germany
- Age at study initiation: Animals used within the study were at least 6 weeks old
- Weight at study initiation: weights were between 1.0 and 3.5 kg
- Housing: Individually in labelled cages with perforated floors (Scanbur, Denmark, dimensions 53.5x63x38.5 cm). Acclimatisation period was at least 5 days before start of treatment under laboratory conditions.
- Diet: Standard laboratory rabbit diet (Charles River Breeding and Maintenance Diet for Rabbits,Altromin, Germany) approx. 100 g per day
- Water: Free access to tap-water

Environmental conditions
- A controlled environment was maintained in the room with optimal conditions considered as being approximately 15 air changes per hour, a temperature of 21±3°C, a relative humidity of 30-70% and 12 hours artificial fluorescent light and 12 hours dark per day.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

other: Ethanol

Controls:

yes, concurrent no treatment

Amount / concentration applied:

- Concentration applied: Each animal was treated by dermal application of 0.5 grams of the test substance.
- Vehicle: Since the test substance did not mix with water, the powdery test substance was moistened with watery ethanol (50% v/v), immediately before application, to ensure close contact with the animal's skin.

Duration of treatment / exposure:

4 hours

Observation period:

1, 24, 48 and 72 hours and 7 days after exposure

Number of animals:

3

Details on study design:

Treament
- Approximately 24 hours before treatment, the dorsal fur was clipped with electric clippers, exposing an area of approximately 150 square centimeters (10x15 cm^2). Whenever considered necessary, the treated skin areas were re-clipped at least 3 hours before the observations to facilitate scoring.
- A health inspection was performed prior to the commencement of treatment, to ensure that the animals were in a good state of health. Special attention was paid to the skin to be treated, which was intact and free from abnormalities.
- Each animal was treated by dermal application of 0.5 grams of the test substance. The test substance was moistened with 0.7 ml of the vehicle and applied to the skin of one flank, using a metalline patch of 2x3 cm. The patch was mounted on Micropore tape, which was wrapped around the abdomen and secured with Coban elastic bandage. Four hours after the application, the dressing was removed and the skin cleaned of residual test substance using water.

Obervation
- Mortality/Viability: twice daily
- Toxicity: at least once daily
- Body Weight: Day of treatment (prior to application)
- Irritation: The skin reactions were assessed at approximately 1, 24, 48 and 72 hours and 7 days after the removal of the dressings and test substance. The irritation scores and a description of all other (local) effects were recorded. Adjacent areas of the untreated skin of each animal served as controls

The irritation was assessed according to a numerical scoring system (according to guideline).

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal: 123

Time point:

24/48/72 h

Score:

1.7

Max. score:

2

Reversibility:

fully reversible within: 7 days

Results 2

Irritation parameter:

erythema score

Basis:

animal: 124

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 7 days

Results 3

Irritation parameter:

erythema score

Basis:

animal: 125

Time point:

24/48/72 h

Score:

1.7

Max. score:

2

Reversibility:

fully reversible within: 7 days

Results 4

Irritation parameter:

edema score

Basis:

animal: 123

Time point:

24/48/72 h

Score:

0.7

Max. score:

1

Reversibility:

fully reversible within: 7 days

Results 5

Irritation parameter:

edema score

Basis:

animal: 124

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 7 days

Results 6

Irritation parameter:

edema score

Basis:

animal: 125

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 7 days

Irritant / corrosive response data:

Irritation
Four hours exposure to 0.5 g of PHYTOSPHINGOSINE resulted in very slight to well-defined erythema and very slight to slight oedema in the treated skin-areas of the three rabbits. The skin irritation had resolved within 7 days after exposure in all animals. Scaliness was noted 7 days after the removal of the dressings and test substance.

Corrosion
There was no evidence of a corrosive effect on the skin.

Other effects:

Colouration
No staining of the treated skin by the test substance was observed.

Toxicity / Mortality
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Any other information on results incl. tables

Table1. Individual skin Irritation scores.

Animal#		123			124			125
Time after exposure		Erythema	Oedema	comments	Erythema	Oedema	comments	Erythema	Oedema	comments
1hour		2	1	-	2	2	-	2	2	-
24hour		2	1	-	2	1	-	2	1	-
48hour		2	1	-	2	1	-	2	1	-
72hour		1	0	-	2	1	-	1	1	-
7days		0	0	1	0	0	1	0	0	1

Table2. Mean value Irritaion scores.

Animal#		Mean 24-72hrs
		Erythema		Oedema
123		1.7		0.7
124		2.0		1.0
125		1.7		1.0

Table3. Animal Specifications

Animal#		Mean 24-72hrs
		Sex			Age(weeks)			Body weight(grams)
123		male			7-9			1421
124		male			7-9			1651
125		male			7-9			1493

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

acc. to CLP Regulation

Conclusions:

The test item phytosphingosine is slightly irritating to skin. Skin irritation resolved within 7 days after exposure in all animals. There was no evidence of a corrosive effect on the skin.

Executive summary:

Primary skin irritation/corrosion of phytosphingosine was investigated in rabbit (4 -hour semiocclusive application) and carried out according to OECD 404 and in compliance with GLP.

Four hours exposure to 0.5 g of phytosphingosine resulted in very slight to well-defined erythema and very slight to slight oedema in treated skin-areas of three rabbits. Skin irritation had resolved within 7 days after exposure in all animals. Moreover, there was no evidence of a corrosive effect on the skin. In conclusion, phytosphingosine is slighlty irritating to skin.

The study was considered reliable and adequate for hazard assessment of human health.