Registration Dossier

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:
1979-02-15 to 1979-03-30
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1979
Report Date:
1979

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Principles of method if other than guideline:
Following a method from "Code of Federal Regulations", Title 16, Section 1500, 41
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Test material form:
solid

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Weight at study initiation: ca. 2.5 kg (males)
- Housing: The rabbits are kept in individual cages measuring 540 x 360 x 315 mm or in restraining devices which allow the back of the animal to be treated.
- Diet (e.g. ad libitum): ad libitum, 200 g of food is provided per animal per day in the form of granules (Granulés Lapin “entretien” SANDERS)
- Water (e.g. ad libitum): ad libitum
Animals were vaccinated against pasteurellosis and myxornatosis.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2 °C
- Humidity (%): 55 ± 20%
- Air changes (per hr): 12

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g

Duration of treatment / exposure:
single treatment, the treated was not rinsed
Observation period (in vivo):
Irritation scores were recorded at 1, 24, 48, 72, 96 hours and 7, 14 and 21 days after instillation.
Number of animals or in vitro replicates:
6 male rabbits
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): the test substance was not washed out

SCORING SYSTEM: Draize (see Table 1 in box “Any other information on materials and methods incl. tables”)

TOOL USED TO ASSESS SCORE: Ophtalmoscope of Heine (Miriflex C-00.13.101), slit lamp (Haag-Streit)


Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2.3
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Remarks on result:
positive indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Remarks on result:
positive indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #4
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Remarks on result:
positive indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #5
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Remarks on result:
positive indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #6
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Remarks on result:
positive indication of irritation
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
not fully reversible within: 21 days
Remarks on result:
positive indication of irritation
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
not fully reversible within: 21 days
Remarks on result:
positive indication of irritation
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: 48/72 h
Score:
1
Max. score:
2
Reversibility:
other:
Remarks:
Iris score not determinable on day 21
Remarks on result:
positive indication of irritation
Irritation parameter:
iris score
Basis:
animal #4
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
not fully reversible within: 21 days
Remarks on result:
positive indication of irritation
Irritation parameter:
iris score
Basis:
animal #5
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
not fully reversible within: 21 days
Remarks on result:
positive indication of irritation
Irritation parameter:
iris score
Basis:
animal #6
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
not fully reversible within: 21 days
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
not fully reversible within: 21 days
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2.7
Max. score:
3
Reversibility:
not fully reversible within: 21 days
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
not fully reversible within: 21 days
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #4
Time point:
24/48/72 h
Score:
2.7
Max. score:
3
Reversibility:
not fully reversible within: 21 days
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #5
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
not fully reversible within: 21 days
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #6
Time point:
24/48/72 h
Score:
2.7
Max. score:
3
Reversibility:
not fully reversible within: 21 days
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #4
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #5
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #6
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Remarks on result:
positive indication of irritation
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
of 6 animals
Time point:
24/48/72 h
Score:
2.7
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Remarks:
except 1 animal (day 7)
Remarks on result:
positive indication of irritation
Irritation parameter:
iris score
Basis:
mean
Remarks:
of 6 animals
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
not fully reversible within: 21 days
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
of 6 animals
Time point:
24/48/72 h
Score:
2.7
Max. score:
3
Reversibility:
not fully reversible within: 21 days
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
of 6 animals
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Remarks on result:
positive indication of irritation
Irritant / corrosive response data:
Severe irritation was observed in all animals. The effects in cornea, iris and conjunctiva were not reversible within 21 days in all animals, except corneal opacity in one animal. For individual results in cornea opacity, iris congestion, conjunctiva chemosis and redness (enanthema) please refer to Table 2 in box "Any other information on results incl. tables".

Any other information on results incl. tables

Table 2: Individual Eye Irritation Scores

Day 1 (24 hours) Day 2 (48 hours) Day 3 (72 hours) Day 21 Mean (24/48/72 hours)
Animal no. Corneal opacity Iris congestion Conjunctivae chemosis Conjunctivae enanthema Corneal opacity Iris congestion Conjunctivae chemosis Conjunctivae enanthema Corneal opacity Iris congestion Conjunctivae chemosis Conjunctivae enanthema Corneal opacity Iris congestion Conjunctivae chemosis Conjunctivae enanthema Corneal opacity Iris congestion Conjunctivae chemosis Conjunctivae enanthema
1 2 4 2 2 4 2 2 4 2 0(o) 1 1 1 2 1 4 2
2 2 4 3 2 4 3 3 4 2 2 1 2 1 2.3 1 4 2.7
3 3 n.d. 4 3 3 4 3 3 4 3 4 n.d. 3 2 3 1 4 3
4 3 4 3 3 4 3 3 4 2 3 1 1 1 3 1 4 2.7
5 3 1(?) 4 3 3 4 3 3 4 3 4 1 3 2 3 1 4 3
6 3 4 3 3 4 3 3 4 2 2 1 3 1 3 1 4 2.7

n.d. = The corneal opacitiy made the reading for the iris impossible

° = Circumcorneal injection + congestion of the iris

(?) The corneal opacity made the reading for this iris impossible

(o) = permanent myosis with reduced direct photomotor reflex

Applicant's summary and conclusion

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
In an in vivo eye irritation/corrosion study with rabbits, the test substance caused irreversible effects in the eye.
Executive summary:

In a primary eye irritation study, 0.1 g of the test item was instilled into the conjunctival sac of the right eye of six New Zealand White rabbits. Animals then were observed for 21 days. Irritation was scored by the method of Draize. Severe irritant effects were observed on the cornea, iris and conjunctiva. These symptoms were not reversible within 21 days. Based on the results, classification as Eye Dam. 1 (H318) in accordance with CLP regulation 1272/2008 is warranted.