Sodium 5-oxo-1-palmitoyl-L-prolinate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

02.June.2008-23.June.2008

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Sodium 5-oxo-1-palmitoyl-L-prolinate

EC Number:

261-406-3

EC Name:

Sodium 5-oxo-1-palmitoyl-L-prolinate

Cas Number:

58725-33-0

Molecular formula:

C21H38NNaO3.Na

IUPAC Name:

sodium (2S)-1-hexadecanoyl-5-oxopyrrolidine-2-carboxylate

Test material form:

liquid

Details on test material:

• Sponsor’s identification: LCA08009 • Date received : 14 May 2008
• Container : plastic flask (n=1) • Form : liquid
• Quantity : 142.44 g (container + contents) • Colour : brown
• Batch n° : LCA08009 • Storage : room temperature
• Production date: - • Expiry date: -
• CAS No: - • Purity: 30% It was identified under the code number: PH-08/0227.

The test item was considered as 100% for the study.
Informations concerning the identity, purity and stability of the test item are the responsibility of the Sponsor. A safety data sheet and an information data sheet concerning the test item were provided by the study monitor.

Specific details on test material used for the study:

Sponsor's identification: LCA08009
Date received: 14 May 2008
Container : plastic flask (n=1)
Form: liquid
Quantity : 142.44 g (containers+ contents)
Colour: brown
Batch n : LCAO8009
Storage : room temperature
Purity: 30%
It was identified under the code number: PH-08/0227.
The test item was considered as 100% for the study.
Informations concerning the identity, purity and stability of the test item are the responsibility of the Sponsor. An information data sheet and a safety data sheet concerning the test item were provided by the study monitor.

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Animal
One female albino New Zealand rabbits was supplied by the Elevage de Gérome (Quartier Labaste - F40260 Linxe). It was kept during a minimal 5-day acclimatisation period. During the test, the animal weighed between 2.60 kg and 3.05 kg. At the beginning of the test, the animal was 12 weeks old.

Housing
The animal was kept in an individual box installed in conventional air conditioned animal husbanding; the environmental conditions were:
- temperature: between 19°C and 23°C - relative humidity: between 38% and 62% - lighting time: 12 hours daily - rate of air exchange: at least ten changes per hour

Food and drink
Drinking water (tap-water from public distribution system) and foodstuff (SDS- C15) were supplied freely. Microbiological and chemical analyses of the water were carried out once every six months by the Institut Européen de l'Environnement de Bordeaux (I.E.E.B.).

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes

Amount / concentration applied:

0.1 mL of the test item was instilled, as supplied, into the conjunctival sac of one eye.

Duration of treatment / exposure:

Until natural elimination

Observation period (in vivo):

Ocular examinations were performed on both right and left eyes 1 hour, 24, 48 and 72 hours following
treatment

Number of animals or in vitro replicates:

One animal
Initially, a single animal was treated. After consideration of the ocular responses produced in the first
treated animal, two additional animals were not treated.

Details on study design:

0.1 mL of the test item was instilled, as supplied, into the conjunctival sac of one eye. The other eye
remained untreated serving as control.
Initially, a single animal was treated. After consideration of the ocular responses produced in the first
treated animal, two additional animals were not treated.
Grading of reactions
Ocular examinations were performed on both right and left eyes 1 hour, 24, 48 and 72 hours following
treatment.
NOTE :
If no reaction is observed 72 hours after instillation, the study is terminated. In case of persistent reactions, additional
observations can be carried out from D4 to D21 in order to determine the reversible character of the lesions observed.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

ca. 2.3

Reversibility:

fully reversible

Results 2

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

ca. 2

Reversibility:

fully reversible

Results 3

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

ca. 0

Results 4

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

ca. 2

Reversibility:

not fully reversible within: still noted at D21 (moderate intensity)

Irritant / corrosive response data:

The ocular reactions observed during the study have been moderate and partially reversible:
- at the conjunctivae level: a moderate redness associated with a moderate chemosis, registered 1 hour after the test item instillation and totally reversible at D21,
- at the corneal level: a moderate opacity, registered 24 hours after the test item instillation, and still noted at the end of the observation time (moderate intensity).
Moreover, a corneal neo-vascularisation was noted between D7 and D17.

Applicant's summary and conclusion

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

The results obtained, under these experimental conditions, enable to conclude that the test item LCA08009:
- is highly irritant for the eye (Max, O.I = 54) according to the classification established in the
Journal Officiel de la République Française dated July 10", 1992.
- and, must be classified R41 "Risk of serious damage to eyes" taking into account the irreversibility of the reactions, according to the criteria for the classification, packaging and labelling of dangerous substances in compliance with the E.E.C. Directive n° 67/548, 2001/59 and 9945. It must be characterised by the symbol “Xi' and the danger label “irritant”. In accordance with the Globally Harmonized System (COMC2007)355 final), the test item must be classified in category “irreversible effects on the eye'. The signal word “Danger' and hazard statement H318 “Causes serious eye damage' are required.

Executive summary:

The test item LCA08009 was instilled as supplied, into the eye of one New Zealand rabbit at the dose of 0.1 mL. The experimental protocol was established on the basis of the official method as defined in the OECD, guideline n° 405 dated April 24", 2002 and the test method B.5 of the directive 2004/73/EC.

The ocular reactions observed during the study have been moderate and partially reversible: - at the conjunctivae level: a moderate redness associated with a moderate chemosis, registered 1 hour after the test item instillation and totally reversible at D21, - at the corneal level: a moderate opacity, registered 24 hours after the test item instillation, and still noted at the end of the observation time (moderate intensity), Moreover, a corneal neo-vascularisation was noted between D7 and D7.

In conclusion, the result obtained, under these experimental conditions, enable to conclude that the test item LCA08009 must be classified R41 "Risk of serious damage to eyes" taking into account the irreversibility of the reactions, according to the criteria for the classification, packaging and labelling of dangerous substances in compliance with the E.E.C. Directive in 67/548, 2001/59 and 99/45. It must be characterised by the symbol “Xi” and the danger label "irritant, In accordance with the Globally Harmonized System (COMC2007)355 final), the test item must be classified in category 1 "irreversible effects on the eye'. The signal word “Danger' and hazard statement H318 “Causes serious eye damage” are required.