Octadecanamide, N-[(1S,2S,3R)-2,3-dihydroxy-1-(hydroxymethyl)heptadecyl]-

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1994-10-31 to 1994-11-03

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1994

Report date:

1994

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

February 24, 1987

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Version / remarks:

December 1992

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Ceramide III

IUPAC Name:

Ceramide III

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

Ceramide III

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

- Source: Broekman Institute, Someren, The Netherlands
- Age at study initiation: approx. 8-14 weeks
- Weight at study initiation: 2100 - 2604 g
- Housing: individual housing in labelled cages with perforated floors (Scanbur, Denmark) and equipped with an automatic drinking system (ITL, Bergen, The Netherlands)
- Diet: ad libitum, standard laboratory rabbit diet (LKK-20, pellet diameter 4 mm, Hope Farms, Woerden, The Netherlands) approx. 100 g per day. In addition, hay (BMI Helmond, The Netherlands) was provided once a week.
- Water: ad libitum, tap-water diluted with decalcified water
- Acclimation period: at least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 50
- Air changes (per hr): 15
- Photoperiod: fluorescent light (120 lux) 12 hours daily

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent negative control

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 27 +-2 mg (a volume of approx. 0.1 ml)
- Concentration: undiluted

Duration of treatment / exposure:

24 hour

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- After 24 hours (immediately after fluorescein examination) both eyes of one animal was rinsed with approx. 50 ml tepid tap water per eye, using a velocity of flow which did not affect the eyes, to remove residual test substance.
SCORING SYSTEM: according to OECD guideline 405
TOOL USED TO ASSESS SCORE: Readings of ocular reactions were made 1 h, 24 h, 48 h, 72 h after treatment. Besides the eyes were examined for potential eye lesions 24 h by means of 2 % fluorescein-dilution.
It was washed out with 50 ml tepid tap-water per eye, using a velocity of flow which did not affect the eyes, to remove residual test substance.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal: #1, #2, #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 2

Irritation parameter:

iris score

Basis:

animal: #1, #2, #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 3

Irritation parameter:

conjunctivae score

Basis:

animal: #1, #2

Time point:

24/48/72 h

Score:

0

Max. score:

3

Results 4

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Results 5

Irritation parameter:

chemosis score

Basis:

animal: #1, #2, #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Other effects:

None described.

Any other information on results incl. tables

IRRITATION

Instillation of 27 mg (a volume of approx. 0.1 ml) into one eye of each of the animals resulted in effects in the iris and the conjunctivae.

The iridic irritation (grade 1) had resolved within 24 hours in all three animals. The irritation of the conjunctivae consisted of redness of the conjunctival tissues and had resolved within 24 hours in two animals and within 72 hours after instillation in the third animal. A small amount of discharge was also noted in the latter animal on day 1.

Remnants of the test substance were noted in the treated eyes on day 1 and/or 2.

CORROSION

There was no evidence of ocular corrosion.

COLOURATION

Remnants of the test substance were noted on the outside of the eyelids on day 1 and/or 2.

TOXIC SYMPTOMS / MORTALITY

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

The individual scores of each of the three animals and the average score (24, 48, 72 h) are given in the table below.

	CORNEA	IRIS	CONJUNCTIVAE	CHEMOSIS
Max. score	4	2	3	4
Time point (h)
1	0/0/0	1/1/1	0/0/1	0/0/1
24	0/0/0	0/0/0	0/0/2	0/0/0
48	0/0/0	0/0/0	0/0/1	0/0/0
72	0/0/0	0/0/0	0/0/0	0/0/0
Average 24, 48, 72	0	0	1	0

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this in vivo study, the test item was not irritating to the rabbit eye and thus, no classification is required.

Executive summary:

An acute eye irritation/corrosion study with Ceramide III in the rabbit was carried out in accordance with the OECD guideline No. 405, “Acute Eye Irritation/Corrosion” (February 24, 1987) and the EEC Directive 92/69 /EEC, B.5, “Acute Toxicity - Eye irritation” (December 1992).

Instillation of 27 mg of Ceramide III (a volume of approx. 0.1 ml) into an eye of each of three male New Zealand White albino rabbits resulted in effects on the iris and the conjunctivae in all animals. The untreated eye served as concurrent negative control. The irritation had resolved within 24 hours in two animals and within 72 hours after instillation in the third animal. The mean 24-72 h irritation score for all was 0.0 except for conjunctival redness (1.0) in one rabbit, which resolved completely after 72 h as described above.

No signs of systemic intoxication were observed during the study period.

In conclusion, Ceramide III was not irritating to the rabbit eye in this in vivo study.