Registration Dossier

Toxicological information

Eye irritation

Currently viewing:

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2010-05-18 to 2010-05-31
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2010

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
2002-04-24
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
signed 2009-11-12

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: granular
Details on test material:
- Name of test material (as cited in study report): Divanadium pentaoxide
- Trivial name: Vanadium pentoxide
- Molecular formula: V2O5
- Molecular weight: 181.88 g/mol
- Physical state: Solid; yellow-orange granules
- Storage condition of test material: Kept dry in closed containers
- Melting point: 690 °C
- Boiling point: Decomposes at 1750 °C
- Water solubility: 8 g/L [MSDS provided by the producer]
- Relative density: 3.36 [MSDS provided by the producer]

Test animals / tissue source

Species:
rabbit
Strain:
Himalayan
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: LPT Laboratory of Pharmacology and Toxicology GmbH & Co. KG, Branch Löhndorf, 24601 Löhndorf/Post Wankendorf, Germany
- Age at study initiation: Approx. 4 - 5 months
- Weight at study initiation: Animal 1: 2.1 kg; Animal 2: 2.3 kg; Animal 3: 2.5 kg
- Housing: For 8 hours following test item application, the animals were kept singly in restrainers which allowed free movement of the head but prevented a complete body turn, wiping of the eyes with the paws and excluded irritation of the eye by excrements and urine. During the acclimatisation period and after the 8-hour period in restrainers, the animals were kept singly in cages with dimensions of 380 mm x 425 mm x 600 mm (manufacturer: Dipl.Ing. W. EHRET GmbH, 16352 Schönwalde, Germany).
- Diet (ad libitum): Commercial diet, ssniff® K-H V2333 (ssniff Spezialdiäten GmbH, 59494 Soest, Germany)
- Water (ad libitum before and after the exposure period): Tap water
- Acclimation period: At least 20 adaptation days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 °C +/- 3 °C (maximum range)
- Relative humidity: 30% - 70% (maximum range; aim was 50% - 60%)
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg of the test item were administered into one eye each of three animals. The test item was placed into the conjunctival sac of the right eye of each animal after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second in order to prevent loss of the material. The left eye, which remained untreated, served as a control.
Duration of treatment / exposure:
1 hour (One hour after application the eyes were rinsed.)
Observation period (in vivo):
1, 24, 48 and 72 hours and 4 and 5 days after the administration
Number of animals or in vitro replicates:
3 male rabbits
Details on study design:
It is explicitly noted and in accordance with the guideline used, that the test was performed initially using one animal. As no corrosive or severe irritant effects were observed in this animal, 2 further animals were employed 24 hours after start of the initial test.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The eyes were rinsed with portions of 20 mL 0.9% aqueous NaCl solution, each.
- Time after start of exposure: 1 hour after administration

SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: The eyes were examined ophthalmoscopically with a slit lamp prior to the administration and 1, 24, 48 and 72 hours and 4 and 5 days after the administration. The eye reactions were observed and registered.
24 hours after administration, fluorescein (Fluorescein SE Thilo drops (ALCON PHARMA GmbH, 79108 Freiburg, Germany)) was applied to the eyes before being examined to aid evaluation of the cornea for possible lesions.

OTHER OBSERVATIONS: Any further lesions not covered by the scoring system were recorded. Body weight of all animals was measured at the beginning of the study and at the end of the study. Behaviour and food consumption were monitored.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: Due to character and severity of the damages in the eyes of the animal the study was discontinued for animal 1 on test day 6.
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
1.33
Max. score:
2
Reversibility:
not reversible
Remarks on result:
other: Due to character and severity of the damages in the eyes of the animal the study was discontinued for animal 1 on test day 6.
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
2.33
Max. score:
3
Reversibility:
not reversible
Remarks on result:
other: Day 4 and 5: Eye swollen, could not be opened. Due to character and severity of the damages in the eyes of the animal the study was discontinued for animal 1 on test day 6.
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: Due to character and severity of the damages in the eyes of the animal the study was discontinued for animal 1 on test day 6.
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
2.67
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: Due to character and severity of the damages in the eyes of the animal the study was discontinued for animal no. 2 on test day 5.
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
not reversible
Remarks on result:
other: Due to character and severity of the damages in the eyes of the animal the study was discontinued for animal no. 2 on test day 5.
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
not reversible
Remarks on result:
other: Day 4: Eye swollen, could not be opened. Due to character and severity of the damages in the eyes of the animal the study was discontinued for animal no. 2 on test day 5.
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: Due to character and severity of the damages in the eyes of the animal the study was discontinued for animal no. 2 on test day 5.
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
2.67
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: Due to character and severity of the damages in the eyes of the animal the study was discontinued for animal no. 3 on test day 5.
Irritation parameter:
iris score
Basis:
mean
Remarks:
Animal #3
Time point:
24/48/72 h
Score:
1.67
Max. score:
2
Reversibility:
not reversible
Remarks on result:
other: Due to character and severity of the damages in the eyes of the animal the study was discontinued for animal no. 3 on test day 5.
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
not reversible
Remarks on result:
other: Day 4: Eye swollen, could not be opened. Due to character and severity of the damages in the eyes of the animal the study was discontinued for animal no. 3 on test day 5.
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: Due to character and severity of the damages in the eyes of the animal the study was discontinued for animal no. 3 on test day 5.
Irritant / corrosive response data:
Corneal opacity was observed in all animals:
- animal no. 1: 24 hours (grade 1), 48 hours (grade 2) and 72 hours (grade 3) after instillation;
- animal nos. 2 and 3: 24 hours (grade 2) and 48 and 72 hours (grade 3) after instillation.
The mean score per animal, following 24, 48 and 72 h after instillation of the test material was calculated ≤ 3.

The fluorescein test performed 24 hours after instillation revealed corneal staining in all animals (1/4 to 1/2 of the surface).

Irritation of the iris was observed in all animals:
- animal no. 1: 24 and 48 hours (grade 1) and 72 hours (grade 2) after instillation;
- animal no. 2: 24 to 72 hours (grade 2) after instillation;
- animal no. 3: 24 hours (grade 1) and 48 and 72 hours (grade 2) after instillation.
The mean score per animal, following grading at 24, 48 and 72 h after instillation of the test material was calculated ≤ 1.5 in one animal; in two of these three animals ≥ 1.5.

Conjunctival redness was observed in all animals:
- animal no. 1: 60 minutes (grade 1), 24 and 48 hours (grade 2) and 72 hours (grade 3) after instillation;
- animal no. 2: 60 minutes (grade 2) and 24 to 72 hours (grade 3) after instillation;
- animal no. 3: 60 minutes (grade 1) and 24 to 72 hours (grade 3) after instillation.
The mean score in two of three animals, following grading at 24, 48 and 72 h after instillation of the test material was calculated to be 3.

Chemosis was observed in all animals:
- animal nos. 1 and 3: 24 to 72 hours (grade 2) after instillation;
- animal no. 2: 60 minutes (grade 1) and 24 to 72 hours (grade 2) after instillation.
The mean score in all three animals, following grading at 24, 48 and 72 h after instillation of the test material was calculated to be 2.

In addition, secretion was observed in animal no. one 24 hours to 72 hours, in animal nos. two and three 60 minutes to 72 hours after instillation.

Due to character and severity of the damages in the eyes of the animal the study was discontinued for animal 1 on test day 6 and animal nos. 2 and 3 on test day 5.
Other effects:
There were no systemic intolerance reactions.

Applicant's summary and conclusion

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
The test item is severly irritating to the eyes.
According to the Regulation (EC) No 1272/2008 and subsequent regulations, the test item is severly irritating to the eyes (Category 1).