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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2013-02-25 to 2013-03-12
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
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

Constituent 1
Chemical structure
Reference substance name:
Sodium metavanadate
EC Number:
237-272-7
EC Name:
Sodium metavanadate
Cas Number:
13718-26-8
Molecular formula:
NaVO3
IUPAC Name:
sodium metavanadate
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): Sodium metavanadate
- Molecular formula: NaVO3
- Molecular weight: 121.93 g/mol
- Physical state: white powder, odourless
- Storage condition of test material: keep cool, dark and dry in tightly sealed containers.
- Water solubility: 211 g/L
- Relative density: 2.84 [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: 2.50 - 2.85 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 6 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
Sixty minutes prior to test item administration, 0.01 mg Buprenovet®/kg b.w. were administered by subcutaneous injection to all animals to provide a therapeutic level of systemic analgesia to avoid or minimize pain and distress.
Five minutes prior to the test item administration, one or two drops of Ophtocain®, a topical anaesthetic, was applied to each eye of all animals, to the right eye, in which the test item was to be applied, and to the left eye, which served as control.
In addition, 8 hours after administration of the test item all animals were 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 6 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.

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

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
3.33
Max. score:
4
Reversibility:
fully reversible within: 6 days
Remarks on result:
other: Corneal staining (3/4 to whole surface) was observed during the 24 hours fluorescein test.
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
0.67
Max. score:
2
Reversibility:
fully reversible within: 4 days
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
fully reversible within: 6 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
fully reversible within: 6 days
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 5 days
Remarks on result:
other: Corneal staining (1/2 to 3/4 of the surface) was observed during the 24 hours fluorescein test.
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
2.67
Max. score:
3
Reversibility:
fully reversible within: 5 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 6 days
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 5 days
Remarks on result:
other: Corneal staining (3/4 to whole surface) was observed during the 24 hours fluorescein test.
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 5 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 4 days
Irritant / corrosive response data:
A single instillation of 100 mg Sodium metavanadate per animal into the conjunctival sac of the right eye of three rabbits caused the following changes:
Cornea opacity was observed in all animals:
- one animal: 24 and 72 hours (grade 3), 48 hours (grade 4), 4 and 5 days (grade 1) after instillation;
- second and third animal: 24 hours to 4 days (grade 1) after instillation.

The irises (grade 1) were observed in animal no. one 48 and 72 hours after instillation.

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

Chemosis was observed in all animals:
- one animal: 60 minutes and 4 to 5 days (grade 1), 24 to 72 hours (grade 4) after instillation;
- second animal: 60 minutes and 4 days (grade 1), 24 hours (grade 4), 48 hours (grade 3), 72 hours (grade 2) after instillation;
- third animal: 24 hours (grade 3), 48 hours (grade 2), 72 hours (grade 1) after instillation.
Other effects:
There were not any systemic intolerance reactions concerning behaviour, body weight and food consumption.

Applicant's summary and conclusion

Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
Sodium metavanadate is irritating to the eyes.
According to the EC-Regulation 1272/2008 and subsequent adaptations, sodium metavanadate is classified as rritating to the eyes (Category 2).

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