Ammonium trivanadium octaoxide

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 2010-05-31

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

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:

Ammonium trivanadium octaoxide

EC Number:

235-384-0

EC Name:

Ammonium trivanadium octaoxide

Cas Number:

12207-63-5

Molecular formula:

NH4V3O8

IUPAC Name:

trivanadium(5+) ammonium octaoxidandiide

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): Ammonium trivanadium octaoxide
- Trivial name: Ammonium polyvanadate
- Molecular formula: NH4V3O8
- Molecular weight: 298.86 g/mol
- Physical state: Solid; yellow-orange powder
- Storage condition of test material: Kept cool and dry in tighly sealed containers

Test animals / tissue source

Species:

rabbit

Strain:

Himalayan

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: LPT Laboratory of Pharmacologyand 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: 2.4 kg; Animal 2: 2.3 kg; Animal 3: 2.3 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, ssniff7 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 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 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:

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.
No further information on the study design was stated.

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:

0

Max. score:

4

Results 2

Irritation parameter:

iris score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

animal# 1

Time point:

24/48/72 h

Score:

1.67

Max. score:

3

Reversibility:

fully reversible within: 5 days

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Results 5

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 this animal on test day 5.

Results 6

Irritation parameter:

iris score

Basis:

mean

Remarks:

animal #2

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 this animal on test day 5.

Results 7

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

animal #2

Time point:

24/48/72 h

Score:

2.67

Max. score:

3

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 this animal on test day 5.

Results 8

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 this animal on test day 5.

Results 9

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 this animal on test day 5.

Results 10

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 this animal on test day 5.

Results 11

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

animal #3

Time point:

24/48/72 h

Score:

2.67

Max. score:

3

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 this animal on test day 5.

Results 12

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 this animal on test day 5.

Irritant / corrosive response data:

Corneal opacity was observed in animal nos. two and three 24 hours (grade 2: Easily discernible translucent area, details of iris slightly obscured) and 48 hours to 4 days (grade 3: nacreous areas, no details of iris visible, size of pupil barely discernible) after instillation. The mean score per animal, following grading at 24, 48 and 72 h after installation of the test material was calculated ≤ 3.
The fluorescein test performed 24 hours after instillation revealed corneal staining in animal no. 2 (1/4 to 1/2 of the surface) and in animal no. 3 (up to 1/4 of the surface).
Irritation of the iris was observed in animal nos. two and three 24 hours (grade 1: Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia, or injection, iris reactive to light (a sluggish reaction is considered to be an effect)) and 48 hours to 4 days (grade 2: haemorrhage, gross destruction, or no reaction to light) after instillation. The mean score per animal, following grading at 24, 48 and 72 h after installation of the test material was calculated ≤ 2; in two of these three animals ≥ 1.5
Conjunctival redness was observed in all animals:
- animal no. 1: 60 minutes, 72 hours and 4 days (grade 1: some blood vessels hyperaemic (injected)) and 24 and 48 hours (grade 2: diffuse, crimson colour; individual vessels not easily discernible) after instillation;
- animal nos. 2 and 3: 60 minutes (grade 1: some blood vessels hyperaemic (injected)), 24 hours (grade 2: diffuse, crimson colour; individual vessels not easily discernible) and 48 hours to 4 days (grade 3:diffuse beefy red) after instillation. The mean score in two of three animals, following grading at 24, 48 and 72 h after installation of the test material was calculated > 2.5.
Chemosis was observed in all animals:
- animal no. 1: 24 and 48 hours (grade 1: some swelling above normal) after instillation;
- animal nos. 2 and 3: 24 hours to 4 days after instillation. The mean score in two of three animals, following grading at 24, 48 and 72 h after installation of the test material was calculated to be 2.
In addition, secretion was observed in all animals 60 minutes to 72 hours, in animal nos. 2 and 3 until 4 days after instillation.
Due to character and severity of the damages in the eyes of animal nos. 2 and 3 the study was discontinued for these animals 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 observed irritation, including iris lesions, cornea opacity, could be regarded as irreversible within a time period of 21 days.
According to the EC Regulation 1272/2008 and subsequent adaptations, the test item is classified as "irreversible effects on the eye" Category 1" (H318: Causes serious eye damage).