Registration Dossier

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2007-03-05 to 2007-05-29
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study performed according to OECD Guideline 405 (Acute Eye Irritation / Corrosion) and EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion) without deviations.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report Date:
2007

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Remarks:
The testing facility indicated that the protocol was followed without deviation.
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Remarks:
The testing facility indicated that the protocol was followed without deviation.
GLP compliance:
yes (incl. certificate)
Remarks:
Certificate given by the Department of Health of the Government of the United Kingdom

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): VRT-753136 hcl
- Molecular formula: not applicable
- Molecular weight: not applicable
- Smiles notation: not applicable
- InChl: not applicable
- Structural formula attached as image file: not applicable
- Substance type: no data
- Physical state: white powder
- Analytical purity: 100 area %
- Impurities: 0.03 area% of unknowns
- Composition of test material, percentage of components: no data
- Isomers composition: no data
- Purity test date: 2006-09-15
- Lot/batch No.: Batch number 25515/Lot No. AF6-001
- Expiration date of the lot/batch: 2008-05
- Stability under test conditions: no data
- Storage condition of test material: room temperature
- Other: no data

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Obtained from Highgate Farm, Market Rasen, Lincolnshire, England.
- Age at study initiation: Approximately 12 to 15 weeks of age, prior to treatment (Day 1).
- Weight at study initiation: 2.88 - 3.18 kg
- Housing: The rabbits were housed individually in plastic cages with perforated floors.
- Diet: Each rabbit was offered 125 g of a standard laboratory rabbit diet (Rabbit GD Diet Pellets supplied by Highgate Farm) per day. A dietary supplement of hay was offered during acclimatisation until two days prior to dose instillation, for the remainder of acclimatisation and throughout the study observation period whole-meal bread was offered.
- Water: Drinking water was provided ad libitum.
- Acclimation period: Approximately two to three weeks prior to the start of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 to 20 deg C
- Humidity (%): 40 to 70%
- Air changes (per hr): Not applicable
- Photoperiod (hrs dark / hrs light): Lighting was controlled by means of a time switch to give 12 hours of artificial light (06:00 to 18:00 GMT) in each 24 hour period.

IN-LIFE DATES:
- From: 2007-03-07 To: 2007-03-23

Test system

Vehicle:
not specified
Controls:
other: The untreated eye was used as a comparison with the treated eye during assessment of ocular lesions.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): Administered a single ocular dose of a volume of 0.1 mL of the test substance weighing approximately 65 mg.
- The specific gravity of the test substance was approximated and the weight of VRT-753136 hcl that occupied 0.1mL was determined. Aliquots of this weight were prepared.


VEHICLE
- Amount(s) applied (volume or weight with unit): no data
- Concentration (if solution): no data
- Lot/batch no. (if required): no data
- Purity: no data
Duration of treatment / exposure:
Single ocular dose
Observation period (in vivo):
8 days
Number of animals or in vitro replicates:
Three rabbits
Details on study design:
Treatment Procedure:
- The eyes of each animal were examined prior to instillation of the test substance to ensure that there was no pre-existing corneal damage, iridial inflammation or conjunctival irritation. Each animal was gently restrained. The dose was instilled into the right eye by pulling the lower eyelid away from the eye ball to form a cup into which the test substance was dropped. The eyelids were then gently held together for one second before releasing; the left eye remained untreated.

REMOVAL OF TEST SUBSTANCE
- Washing: no data
- Time after start of exposure: no data

SCORING SYSTEM:
- Eye irritation scoring was performed according to Draize and is described in the Table for "Grading of Ocular Lesions" in OECD guideline 405.



TOOL USED TO ASSESS SCORE:
- An ophthalmoscope and a pencil beam torch were used to facilitate inspection of the eyes.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 1 hour
Score:
4.7
Max. score:
110
Remarks on result:
other: Minimally irritating
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24 hours
Score:
1.3
Max. score:
110
Remarks on result:
other: Practically non-irritating
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 48 hours
Score:
0
Max. score:
110
Reversibility:
other: not applicable
Remarks on result:
other: Non-irritating
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 72 hours
Score:
0
Max. score:
110
Reversibility:
other: not applicable
Remarks on result:
other: Non-irritating
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: means scores over 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: observation of corneal opacity
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: means scores over 24, 48 and 72 hours
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Remarks on result:
other: observation of iridial lesions
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: means scores over 24, 48 and 72 hours
Score:
0.3
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: observation of conjunctival redness
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: means scores over 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: observation of conjunctival chemosis
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: means scores over 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: observation of corneal opacity
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: mean scores over 24, 48 and 72 hours
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Remarks on result:
other: observation of iridial lesions
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: mean scores over 24, 48 and 72 hours
Score:
0
Max. score:
3
Reversibility:
other: not applicable
Remarks on result:
other: observation of conjunctival redness
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: mean scores over 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: observation of conjunctival chemosis
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
other: mean scores over 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: observation of corneal opacity
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: mean scores over 24, 48 and 72 hours
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Remarks on result:
other: observation of iridial lesions
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: mean scores over 24, 48 and 72 hours
Score:
0.3
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: observation of conjunctival redness
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: mean scores over 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: observation of conjunctival chemosis
Irritant / corrosive response data:
Injection of the conjunctival blood vessels was apparent during the first 24 hours after instillation; slight or moderate discharge was evident at the one hour observation. The treated eye of all animals were overtly normal 48 hours after instillation.
Instillation of the test substance gave rise to a moderate initial pain response in the sentinel animal; local ocular anaesthesia (1% amethocaine hydrochloride) was employed for the subsequent animals.
Other effects:
There was no sign of toxicity or ill health in any rabbit during the observation period.

Any other information on results incl. tables

Not applicable

Applicant's summary and conclusion

Conclusions:
Instillation of VRT-753136 hcl gave rise to a “minimally irritating” response and the test substance did not require labelling with the risk phrase R36, “Irritating to eyes”, in accordance with Commission Directive 2001/59/EC.
Executive summary:

Not applicable