trans-1-(1-oxohexadecyl)-4-[(1-oxohexadecyl)oxy]-L-proline

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2007-12-11 to 2008-03-03

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

trans-1-(1-oxohexadecyl)-4-[(1-oxohexadecyl)oxy]-L-proline

EC Number:

255-490-0

EC Name:

trans-1-(1-oxohexadecyl)-4-[(1-oxohexadecyl)oxy]-L-proline

Cas Number:

41672-81-5

Molecular formula:

C37H69NO5

IUPAC Name:

1-palmitoyl-4-(palmitoyloxy)-L-proline

Details on test material:

- form: powder
- colour : white
- batch number: 0724300010
- re-test date: 2010-08-30
- storage: room temperatue

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Three male albino New Zealand rabbits were supplied by the Elevage de Gérome (Quartier Labaste –F40260 Linxe). They were kept during a minimal 5-day acclimatisation period. During the test, the animals weighed between 2.99 kg and 3.45 kg. At the beginning of the test, the animals were 13 to 14 weeks old.
Each animal was kept in an individual box installed in conventional air conditioned animal
husbanding; the environmental conditions were:
- temperature : between 19°C and 22°C
- relative humidity : between 40% and 67%
- lighting time: 12 hours daily

Drinking water (tap-water from public distribution system) and foodstuff 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:

not required

Amount / concentration applied:

0.1 g of the test item was instilled into the conjunctival sac of one eye.

Duration of treatment / exposure:

One instillation, no rinsing.

Observation period (in vivo):

observation until 7 days after the instillation

Number of animals or in vitro replicates:

3

Details on study design:

After the 5-day acclimation period of the animals, 0.1 g of the test item was instilled 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 at D7, two additional animals were treated.
Ocular examinations were performed on both right and left eyes 1 hour, 24, 48 and 72 hours following treatment according to the following s
Eye examinations are carried out using the scale of lesion scores in the following scale :
CHEMOSIS (A)
• No swelling .................................................................................................................................. 0
• Slight swelling, including the nictitating membrane.............................................................. 1
• Swelling with eversion of the eyelid ......................................................................................... 2
• Swelling with eyelid half-closed ............................................................................................... 3
• Swelling with eyelid more than half-closed ............................................................................ 4
DISCHARGE (B)
• No discharge ............................................................................................................................... 0
• Slight discharge (normal slight secretions in the inner corner not to be
taken into account) ........................................................................................................................ 1
• Discharge with moistening of the eyelids and neighbouring hairs..................................... 2
• Discharge with moistening of the eyelids and large areas around the eye........................ 3
REDNESS (C)
• Blood vessels normal ...................................................................................... ........................... 0
• Vessels significantly more prominent than normal ............................................................... 1
• Vessels individually distinguishable with difficulty
- Generalised red coloration....................................................................... ................................ 2
- Generalised deep red coloration ........................................................................... ................... 3
IRIS (D)
• Normal ....................................................................................................................... .................. 0
• Iris significantly more wrinkled than normal, congestion,
swelling of the iris which continues to react to light, even slowly............................................ 1
• No reaction to light, haemorrhage, significant damage
(any or all of these characteristics)................................................................................................ 2
CORNEA: DEGREE OF OPACITY (E)
• No modification visible either directly or after
instillation of fluorescein (no loss of glint or polish) .................................................................... 0
• Translucent areas (diffuse or disseminated), iris details clearly visible .................. ............... 1
• Easily identifiable translucent area, iris details slightly obscured............................................. 2
• Opalescent area, no iris details visible, pupil outline scarcely distinguishable ...................... 3
• Total corneal opacity, completely obscuring the iris and pupil................................................. 4
CORNEA: EXTENT OF OPACITY (F)
• Opaque area present but covering one quarter or less............................................ ............... 1
• Between one quarter and half................................................................................................ ........ 2
• Between half and three quarters .................................................................................................... 3
• Between three quarters and the entire surface............................................................................. 4

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 1.23

Max. score:

2

Reversibility:

fully reversible

Results 2

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 1.67

Max. score:

2

Reversibility:

fully reversible

Results 3

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 0.23

Max. score:

1

Reversibility:

fully reversible

Results 4

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 1.57

Max. score:

2

Reversibility:

fully reversible

Irritant / corrosive response data:

The ocular reactions observed during the study have been slight to moderate, and totally reversible in the three animals:
- at the conjunctivae level: a slight to moderate redness, noted 24 hours after the test item instillation and totally reversible between D6 and D9, associated with a slight to moderate chemosis, noted 1 hour after the test item instillation and totally reversible between D4 and D7,
- at the corneal level: a moderate opacity, registered 24 hours after the test item instillation and totally reversible between D4 and D21,
- at the iris level: a congestion noted between D2 and D4 in one animal.
It was noted in one animal a corneal neo-vascularisation between D2 and D4. Moreover, it was noted a whitish secretion, requiring a physiological saline rinse, in only one animal at D2.

Any other information on results incl. tables

The results obtained, under these experimental conditions, enable to conclude that the test substance: - is moderately irritant for the eye (Max. O.I = 20.0) according to the classification established in the Journal Officiel de la République Française dated July 10th, 1992. - and, must not be classified 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 99/45. No symbol and risk phrase are required. In accordance with the Globally Harmonized System (COM(2007)355 final), the test item must be classified in category 2 “Irritating to eye”. The signal word “Warning” and hazard statement H319 “Causes serious eye irritation” are required.

Applicant's summary and conclusion

Interpretation of results:

moderately irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The results obtained, under these experimental conditions, enable to conclude that the test substance:
- is moderately irritant for the eye (Max. O.I = 20.0) according to the classification established in the Journal Officiel de la République Française dated July 10th, 1992.
- and, must not be classified 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 99/45. No symbol and risk phrase are required.
In accordance with the Globally Harmonized System (COM(2007)355 final), the test item must be classified in category 2 “Irritating to eye”. The signal word “Warning” and hazard statement H319 “Causes serious eye irritation” are required.

Executive summary:

The results obtained, under these experimental conditions, enable to conclude that the test substance: - is moderately irritant for the eye (Max. O.I = 20.0) according to the classification established in the Journal Officiel de la République Française dated July 10th, 1992. - and, must not be classified 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 99/45. No symbol and risk phrase are required. In accordance with the Globally Harmonized System (COM(2007)355 final), the test item must be classified in category 2 “Irritating to eye”. The signal word “Warning” and hazard statement H319 “Causes serious eye irritation” are required.