Uridine, 2'-deoxy-5-ethyl-, 3',5'-bis(4-chlorobenzoate)

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

August 31st, 2000 - January 5st, 2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Report date:

2009

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Uridine, 2'-deoxy-5-ethyl-, 3',5'-bis(4-chlorobenzoate)

EC Number:

607-566-3

Cas Number:

25137-84-2

Molecular formula:

C25H22Cl2N2O7

IUPAC Name:

Uridine, 2'-deoxy-5-ethyl-, 3',5'-bis(4-chlorobenzoate)

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

- Name of test material (as cited in study report): 2’DEOXY-5-ETHYL-URIDINE, 3’5’-BIS(4-CHLOROBENZOATE)
- Physical state: Solid (Whitish crystalline powder)
- Lot/batch No.: 2/98-G
- Expiration date of the lot/batch: June 2001
- Storage: At room temperature

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: supplied by, Charles River Italia S.p.A., (Como) and bred by P.O.A.D.A. Mandello Lario (CO)
- Age at study initiation: approximately 9 to 11 weeks
- Sex: females
- Housing: stainless steel cages measuring 69 x 45 x 51 cm
- Diet: anti-biotic free pelleted laboratory diet (Altromin MSK, A. Rieper, Bolzano, Italy) ad libitum
- Water: drinking water ad libitum
- Acclimation period: 10 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 15 to 21
- Humidity (%): 40 - 70
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated eye of the same animal

Amount / concentration applied:

0,1 g

Duration of treatment / exposure:

1, 24, 48 and 72 hours after dosing.

Observation period (in vivo):

1, 24, 48 and 72 hours

Number of animals or in vitro replicates:

3

Details on study design:

APPLICATION DOSE AND EXPOSURE TIME
- A 0.1 g aliquot of the test item was introduced into the right eye of each animai by gently pulling away the lower lid from the eyeball to form a cup into which the test item was placed. The lids were then held shut for a few seconds to prevent loss of the test item. The left eye remained untreated.

OBSERVATION PERIOD
Approximately 1, 24, 48 and 72 hours after dosing the animals were observed under standard conditions and the treated eye examined macroscopically for damage or irritation to the cornea, iris and conjunctivae using the untreated eye as a comparator control.

SCORING SYSTEM:
Conjunctivae
1 ) Reddening of the palpebral and bulbar conjunctivae
Blood vessels normal 0
Some blood vessels definitely hyperaemic (injected) 1
Diffuse, crimson colour, individual vessels not easily discernible 2
Diffuse, beefy red 3

2) Chemosis of the lids and/or nictitating membrane
No swelling 0
Any swelling above normal (including nictitating membranes) 1
Obvious swelling with partial eversion of the lids 2
Swelling with lids about half closed 3
Swelling with lids more than half closed 4

3) Discharge (Lachrymation)
No discharge 0
Any amount different from normal (does not include small amount observed in inner canthus of normal animals) 1
Discharge with moistening of the lids and hair just adjacent to the lids 2
Discharge with moistening of the lids and hair for a considerable area around the eye 3

Iris
Normal 0
Markedly deepened rugae, congestion, swelling, moderate circumcomeal hyperaemia, or injection, any of these or combination
of any thereof, iris stili reacting to light (sluggish reaction is positive) 1
No reaction to light, haemorrhage, gross destruction (any or all of these) 2

Cornea
1) Degree of opacity: (Area most dense taken for reading)
No ulceration or opacity 0
Scattered or diff se area of opacity (other than slight dulling of normal lustre), details of iris clearly visible 1
Easily discernible translucent area, details of iris slightly obscured 2
Nacreous area, no details of iris visible, size of pupil barely discernible 3
Opaque cornea, iris not discernible through the opacity 4

2) Area of cornea involved
One quarter (or less) but not zero 1
Greater than one quarter, but less than half 2
Greater than half, but less than three quarters 3
Greater than three quarters, up to whole area 4

2) Area of cornea involved
One quarter (or less) but not zero 1
Greater than one quarter, but less than half 2
Greater than half, but less than three quarters 3
Greater than three quarters, up to whole area 4

Cornea
1) Degree of opacity: (Area most dense taken for reading)
No ulceration or opacity 0
Scattered or diffuse area of opacity (other than slight dulling of normal lustre), details of iris clearly visible 1
Easily discernible translucent area, details of iris slightly obscured 2
Nacreous area, no details of iris visible, size of pupil barely discernible 3
Opaque cornea, iris not discernible through the opacity 4

2) Area of cornea involved
One quarter (or less) but not zero 1
Greater than one quarter, but less than half 2
Greater than half, but less than three quarters 3
Greater than three quarters, up to whole area 4

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Results 2

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Results 3

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Results 4

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 5

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 6

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 7

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 8

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 9

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 10

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 11

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 12

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

Stight redness (scores of 1 to 2) were observed in the treated eyes of all the three animals at examination performed approximately 1 and 24 hours after dosing. Slight chemosis (score of 1) and a slight corneal opacity (score of 1) were observed in 1 of the 3 animals approximately 1 hour after dosing. Complete recovery was observed at 48 hour post-dose examination.

Other effects:

Systemic effects: There was no indication of a systemic effect of treatment.

Applicant's summary and conclusion

Interpretation of results:

other: very slight irritant

Conclusions:

The results of this study indicate that the test item, 2’deoxy-5-ethyl-uridine,3’,5’-bis(4-chlorobenzoate), has a very slight irritant effect in the eye.

Executive summary:

The acute eye irritation of 2’deoxy-5-ethyl-uridine,3’,5’-bis(4-chlorobenzoate) was investigated in the rabbit.

A 0.1 g aliquot of the substance was introduced into the right eye of a total of 3 animals.

The resulting reaction to treatment was assessed 1, 24, 48 and 72 hours after dosing.

Slight conjunctival irritation was observed in the treated eyes of all the three animals at examination performed approximately 1 and 24 hours after dosing. Slight corneal opacity was also observed in the treated eye of 1 of the 3 animals approximately 1 hour after dosing. Complete recovery was observed at 48 hour post-dose examination.

There was no indication of a systemic effect of treatment.

Changes in body weight were not remarkable.

These results indicate that the test item, 2’deoxy-5-ethyl-uridine,3’,5’-bis(4-chlorobenzoate) chlorobenzoate), has a very slight irritant effect in the eye.