Divanadium trioxide

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2010-05-18 to 2010-06-04

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

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

, 2002-04-24

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

signed 2009-11-12

Test material

Test material information

Constituent 1

Reference substance name:

Divanadium trioxide

EC Number:

215-230-9

EC Name:

Divanadium trioxide

Cas Number:

1314-34-7

Molecular formula:

O3V2

IUPAC Name:

Divanadium trioxide

Test material form:

other: granules

Details on test material:

- Name of test material (as cited in study report): Divanadium trioxide
- Trivial name: Vanadium trioxide
- Molecular formula: V2O3
- Physical state: Solid, black granules
- Storage condition of test material: Kept dry in tightly sealed containers at room temperature
2

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. 3 - 4 months
- Weight at study initiation: Animal 1: 2.2 kg; Animal 2: 2.3 kg; Animal 3: 2.0 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
No further information on the test animals was stated.

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.
No further information on the amount/concentration applied was stated.

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 to 8 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 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 to 8 days after the administration. The eye reactions were observed and registered.
24 hours and 7 days 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

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 4 days

Results 2

Irritation parameter:

iris score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 7 days

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

1.67

Max. score:

2

Reversibility:

fully reversible within: 4 days

Results 5

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

animal #2

Time point:

24/48/72 h

Score:

0.67

Max. score:

1

Reversibility:

fully reversible within: 72 hours

Results 6

Irritation parameter:

iris score

Basis:

mean

Remarks:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Results 7

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 8 days

Results 8

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

animal #2

Time point:

24/48/72 h

Score:

1.67

Max. score:

2

Reversibility:

fully reversible within: 4 days

Results 9

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 6 days

Results 10

Irritation parameter:

iris score

Basis:

mean

Remarks:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Results 11

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 8 days

Results 12

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

animal #3

Time point:

24/48/72 h

Score:

1.67

Max. score:

2

Reversibility:

fully reversible within: 4 days

Other effects:

There were no systemic intolerance reactions.

Any other information on results incl. tables

Corneal opacity (grade 1: Scattered or diffuse areas of opacity (other than slight dulling of normal lustre), details of iris clearly visible) was observed in all animals 24 and 48 hours, in animal no. 1 until 72 hours and in animal no. 3 until 5 days after instillation. The mean score per animal, following grading at 24, 48 and 72 h after instillation of the test material was calculated ≤ 1. The irises were not affected by instillation of the test item (grade 0 in all three animals). Conjunctival redness, i.e. grade 1 (some blood vessels hyperaemic (injected)) or grade 2 (diffuse, crimson colour; individual vessels not easily discernible)) was observed in all animals 60 minutes up to 6 days, in animal nos. 2 and 3 until 7 days after instillation. The mean score per animal, following grading at 24, 48 and 72 h after instillation of the test material was calculated 2. Chemosis was observed in all animals 24 and 48 hours, i.e. grade 2 (Obvious swelling with partial eversion of lid) and 72 hours grade 1 (Some swelling above normal) after instillation. The mean score per animal, following grading at 24, 48 and 72 h after instillation of the test material was calculated < 2.

In addition, secretion was observed in all animals 24 to 6 days, in animal nos. 2 and 3 from 60 minutes after instillation.

The fluorescein test performed 24 hours after instillation revealed corneal staining in all animals (up to 1/4 of the surface). The fluorescein test performed 7 days after instillation did not reveal any pathological findings.

The effects observerd were fully reversible within 21 days of instillation (8 days). In accordance with EEC 67/548, the overall irritation results can be summarized as follows:

Opacity (cornea and iris), 1h after application: mean score=0.0

Opacity (iris), 24, 48 and 72h after application: mean score=0.0

Opacity (cornea), 24, and 48 h after application: mean score=1.0

Opacity (cornea), 72 h after application: mean score=0.66

Opacity (cornea), 4d after application: mean score=0.33

Opacity (cornea), 6d after application: mean score=0.0

 

Conjunctival redness, 1h after application: mean score=1.0

Conjunctival redness, 24, 48 and 72h after application: mean score=2.0

Conjunctival redness, 4d after application: mean score=1.33

Conjunctival redness, 7d after application: mean score=0.66

Conjunctival redness, 8d after application: mean score=0.0

 

Conjunctival chemosis, 1h after application: mean score=0.0

Conjunctival chemosis, 24 and 48h after application: mean score=2.0

Conjunctival chemosis, 72h after application: mean score=1.0

Conjunctival chemosis, 4d after application: mean score=0.0

Applicant's summary and conclusion

Interpretation of results:

other: Category 2 (irritating to eyes)

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

According to the EC-Commission directive 67/548/EEC and the results obtained under the present test conditions, Divanadium trioxide is non-irritating to eyes, hence, no labelling is required.

According to EC Regulation No. 1272/2008 and the mean scores in at least in 2 of 3 tested animals for corneal opacity (≥ 1) and conjunctival redness (≥ 2), divanadium trioxide produced reversible effects and needs to be classified for eye irritation Category 2 (H319: Causes serious eye irritation; if appropriately: Precautionary Statement Prevention: P264 + P280; Precautionary Statement Response P305 + P351 + P338, P337 + P313).