STI571 F8

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2005

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Test material form:

solid: particulate/powder

Details on test material:

Batch number: 022401

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Number and sex: 3 females.
Hygiene: Optimal hygienic conditions.
Room temperature: Average of 19.5 °C (continuous control and recording).
Relative humidity: Average of 63.1 % (continuous control and recording).
Light: Artificial light from 6 a.m. to 6 p.m.
Cages: Individual caging in metal wire cages, Ehret GmbH, D-79312 Emmendingen, type KK 016R, 79 cm x 59 cm bottom area, 38 cm height.
Feed: Altromin 2123 maintenance diet for rabbits, rich in crude fiber, ad libitum. Analysis of the feed for ingredients and contaminants is performed randomly by Altromin, D-32791 Lage, ermany.
Hay-briquettes (supplied by SSNIFF, D-59494 Soest) are offered additionally as a dietary supplement.
Water Tap: water from an automatic watering system, ad libitum.
Environmental Enrichment: Aspen wood boards during acclimatisation and observation period.
Acclimatisation: 5 days (animal No. 121) and 12 days (animals Nos. 122 and 123).
Identification: Individual labelling with felt-tipped pen on an ear pinna and cage labels.
Sacrifice of animals: The animals were killed by inhalation of 80 % CO2 + 20 % air.

Test system

Controls:

yes, concurrent no treatment

Amount / concentration applied:

The approximate equivalent of 0.1 mL of the test substance was administered per animal into
the conjunctival sacs of the right eyes by gently pulling the lower lids away from the eyeballs
for instillation. The eyes were held closed for about one second to prevent a loss of test substance.
The weighed amounts of the individual doses were 34, 30 and 30 mg.
The left eyes remained untreated and served as a control.
Firstly, the test substance was given to one animal. As no evidence for a serious damage to
the eye of this animal was found during the initial 72 hour observation period (no corrosive
effect), the test substance was administered to the other two animals subsequently.

Duration of treatment / exposure:

The approximate equivalent of 0.1 mL of "STI571 F8" was instilled into the conjunctival sac
of one eye of each of 3 New Zealand White rabbits.

Observation period (in vivo):

Both eyes of the animals were examined within 24 hours before the instillation and
approximately 1, 24, 48 and 72 hours p.a.
An additional examination was performed in 1/3 animals 7 d p.a.
A further examination by instillation of a fluorescein solution (Minims Fluorescein Sodium 2 %)
onto the cornea was performed in the animals 24 h p.a.
The whole eyes, especially the corneae, the irises and the conjunctivae were examined,
using an otoscope lamp.

Number of animals or in vitro replicates:

3

Details on study design:

Investigations
• Body weights: at the start and at the termination of the test.
• General signs of toxicity: once daily.
• Eye examinations: 1, 24, 48 and 72 h and 7 d after the administration (p.a.) of the test
substance (ending individually, when the animal was free of alterations).


Scoring scheme for eye lesions (Grades for ocular lesions)
CORNEA Opacity : degree of density (area most dense is taken for reading).
0 No ulceration or opacity.
1 Scattered or diffuse areas of opacity (except for slight dulling of normal lustre), details of iris clearly visible.
2 Easily discernible translucent area, details of iris slightly obscured.
3 Nacreous area, no details of iris visible, size of pupil barely discernible.
4 Opaque cornea, iris not discernible through the opacity.

IRIS
0 Normal.
1 Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia
or injection; any of these or combination of any thereof, iris still reacting to light (sluggish reaction is positive).
2 No reaction to light, haemorrhage, gross destruction (any of all these or all together).

CONJUNCTIVAE
Redness: (refers to the most severe effect of palpebral and bulbar conjunctivae in comparison to the control eye).
0 Blood vessels normal.
1 Some blood vessels definitely hyperaemic (injected).
2 Diffuse crimson colour, individual vessels not easily discernible.
3 Diffuse beefy red.

Chemosis: lids and/or nictating membranes.
0 No swelling.
1 Any swelling above normal (includes nictating membranes).
2 Obvious swelling with partial eversion of lids.
3 Swelling with lids about half closed.
4 Swelling with lids more than half closed.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.7

Max. score:

3

Reversibility:

fully reversible

Remarks:

Scores of "2" or "1" in all animals 1 h p.a., a score of "1" in all animals from 24 h until a maximum of 72 h p.a.

Results 2

Irritation parameter:

conjunctivae score

Remarks:

(chemosis)

Basis:

animal #1

Time point:

24/48/72 h

Score:

ca. 1

Max. score:

4

Reversibility:

fully reversible

Remarks:

A score of "3" in all animals 1 h p.a., decreasing afterwards and lasting until a maximum of 48 h p.a.

Results 3

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

2

Reversibility:

other: Not affected

Remarks on result:

no indication of irritation

Results 4

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

ca. 0.3

Max. score:

4

Reversibility:

fully reversible within: 48 h or 7 d p.a. the cornea was normal again.

Results 5

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

ca. 0.3

Max. score:

4

Reversibility:

fully reversible

Remarks:

A score of "3" in all animals 1 h p.a., decreasing afterwards and lasting until a maximum of 48 h p.a.

Results 6

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #2

Time point:

24/48/72 h

Score:

ca. 0.7

Max. score:

3

Reversibility:

fully reversible

Remarks:

Scores of "2" or "1" in all animals 1 h p.a., a score of "1" in all animals from 24 h until a maximum of 72 h p.a.

Results 7

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

4

Reversibility:

fully reversible within: 48 h or 7 d p.a. the cornea was normal again.

Results 8

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

2

Reversibility:

other: Not affected

Remarks on result:

other: Max. duration: 48 h; Max. value at end of observation period: 0 (related to all animals)

Results 9

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

ca. 1

Max. score:

4

Reversibility:

fully reversible

Remarks:

48 h or 7 d p.a. the cornea was normal again.

Results 10

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

2

Reversibility:

other: Not affected

Results 11

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #3

Time point:

24/48/72 h

Score:

ca. 1

Max. score:

3

Reversibility:

fully reversible within:

Remarks:

Scores of "2" or "1" in all animals 1 h p.a., a score of "1" in all animals from 24 h until a maximum of 72 h p.a.

Results 12

Irritation parameter:

conjunctivae score

Remarks:

chemosis

Basis:

animal #3

Time point:

24/48/72 h

Score:

ca. 1

Max. score:

4

Reversibility:

fully reversible within: A score of "3" in all animals 1 h p.a., decreasing afterwards and lasting until a maximum of 48 h p.a.

Irritant / corrosive response data:

Reversibility of any observed effect: Changes fully reversible within 7 days

Other effects:

No signs of systemic toxicity were observed in the animals
during the test period and no mortality occurred.


Ocular discharge was observed in all animals in the first 2
days.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

According to Commission Directive 2001/59/EC "STI571 F8" does not require
classification for eye irritation.