Ammonium sodium vanadium oxide

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2013-02-25 to 2013-03-20

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adopted 2012-10-02

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

signed 2009-11-12

Test material

Test material information

Constituent 1

Reference substance name:

Ammonium sodium vanadium oxide

EC Number:

254-463-0

EC Name:

Ammonium sodium vanadium oxide

Cas Number:

39455-80-6

Molecular formula:

(NH4)NaV6O16

IUPAC Name:

ammonium sodium bis(tetraoxotrivanadoxan-3-oylolate)

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): Ammonium sodium vanadium oxide
- Molecular weight: 602.667 g/mol
- Physical state: orange powder, odourless
- Storage condition of test material: keep cool, dark and dry in tightly sealed containers.
- Melting point : decomposition at 50°C
- Water solubility: Soluble
- Relative density: 2.43 (OECD 109; Vanadium Consortium, 2012)

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: approximately 7 months
- Weight at study initiation: 2.28 - 3.03 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; before and after the exposure period): commercial diet, ssniff® K-H V2333 (ssniff Spezialdiäten GmbH, 59494 Soest, Germany)
- Water (ad libitum; before and after 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)
- 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:

One hour

Observation period (in vivo):

Prior to the administration and 1, 24, 48, 72 hours and 4 to 12 days after the administration

Number of animals or in vitro replicates:

3 female rabbits

Details on study design:

USE OF TOPICAL ANAESTHETICS AND SYSTEMIC ANALGESICS
8 hours after administration of the test item one animal was treated with 0.01 mg Buprenovet®/kg b.w. in conjunction with 0.5 mg Metacam®/kg b.w., subcutaneously.

INITIAL TEST AND CONFIRMATORY TEST
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: each eye was rinsed with 20 mL of 0.9% aqueous NaCl solution.
- Time after start of exposure: one hour after instillation

SCORING SYSTEM: according to the Draize scale
Any further lesions are listed.

TOOL USED TO ASSESS SCORE: the eyes were examined ophthalmoscopically with a slit lamp prior to the administration and 1, 24, 48, 72 hours and 4 to 12 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.

OBSERVATIONS:
General criteria: body weight of all animals was measured at the beginning 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:

other: 24, 48 and 72 hours

Score:

1.67

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: Corneal staining (3/4 to whole surface) was observed during the 24 hours fluorescein test. No pathological findings were made during the 7 days fluorescein test

Results 2

Irritation parameter:

iris score

Basis:

mean

Remarks:

animal #1

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

2

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

animal #1

Time point:

other: 24, 48 and 72 hours

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 5 days

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

animal #1

Time point:

other: 24, 48 and 72 hours

Score:

1.67

Max. score:

4

Results 5

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

animal #2

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

4

Remarks on result:

other: Corneal staining (1/2 to 3/4 of the surface) was observed during the 24 hours fluorescein test. No pathological findings were made during the 7 days fluorescein test

Results 6

Irritation parameter:

iris score

Basis:

mean

Remarks:

animal #2

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

2

Results 7

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

animal # 2

Time point:

other: 24, 48 and 72 hours

Score:

1.33

Max. score:

3

Reversibility:

fully reversible within: 4 days

Results 8

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

animal #2

Time point:

other: 24, 48 and 72 hours

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Results 9

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

animal #3

Time point:

other: 24, 48 and 72 hours

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 12 days

Remarks on result:

other: Corneal staining (3/4 to whole surface) was observed during the 24 hours fluorescein test. Corneal staining (up to 1/4 of the surface) was observed during the 7 days fluorescein test.

Results 10

Irritation parameter:

iris score

Basis:

mean

Remarks:

animal #3

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

2

Results 11

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

animal #3

Time point:

other: 24, 48 and 72 hours

Score:

3

Max. score:

3

Reversibility:

fully reversible within: 12 days

Results 12

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

animal #3

Time point:

other: 24, 48 and 72 hours

Score:

4

Max. score:

4

Reversibility:

fully reversible within: 10 days

Irritant / corrosive response data:

A single instillation of 100 mg Ammonium sodium vanadium oxide per animal into the conjunctival sac of the right eye of three rabbits caused the following changes:
Cornea opacity was observed in two animals:
- one animal: 60 minutes and 48 hours (grade 2), 24 hours (grade 3) after instillation;
- second animal: 24 hours to 4 days and 6 days to 7 days (grade 2), 5 days and 8 days to 11 days (grade 1) after instillation.

Conjunctivae redness was observed in all animals:
- one animal: 60 minutes and 48 hours (grade 2), 24 hours (grade 3), 72 hours and 4 days (grade 1) after instillation;
- second animal: 60 minutes and 24 hours (grade 2), 48 hours and 72 hours (grade 1) after instillation;
- third animal: 60 minutes and 4 days and 6 days to 7 days (grade 2), 24 hours to 72 hours (grade 3), 5 days and 8 days to 11 days (grade 1) after instillation.

Chemosis was observed in all animals:
- one animal: 60 minutes and 48 hours (grade 2), 24 hours (grade 3) after instillation;
- second animal: 60 minutes and 48 hours (grade 1), 24 hours (grade 2) after instillation;
- third animal: 60 minutes and 4 days and 6 to 7 days (grade 2), 24 hours to 72 hours (grade 4), 5 days and 8 days to 9 days (grade 1) after instillation.

The irises were not affected by instillation of the test item.

Other effects:

There were no systemic intolerance reactions concerning behaviour, body weight and food consumption.

Applicant's summary and conclusion

Interpretation of results:

Category II

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Ammonium sodium vanadium oxide is irritating to the eyes.
According to the EC-Commission directive 67/548/EEC and its subsequent amendments, ammonium sodium vanadium oxide is not classified as irritating to the eyes.
According to the EC-Regulation 1272/2008 and subsequent regulations, ammonium sodium vanadium oxide is classified in Category 2.