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:
2010-10-28 to 2010-11-25
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guidelinestudy reliable without restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011
Report Date:
2011

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
adopted 2002-04-24
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: crystalline
Details on test material:
- Name of test material (as cited in study report): Cobalt dichloride
- Physical state: solid
- Stability of test Item: stable under storage conditions
- Storage condition of test material: at room temperature (20 ± 5 °C, provided by Harlan Laboratories Ltd.).

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories U.K. Ltd., Hillcrest, Dodgeford Lane, Belton, Loughborough, Leics, LE12 9TE / UK
- Age at study initiation: 12 - 13 weeks
- Weight at study initiation: 2603 - 2702 g
- Housing: individually in stainless steel cages equipped with feed hoppers and drinking water bowls. A piece of wood (batch no. 102240, imported by
Indulab AG, Gams / Switzerland from ABEDD® - LAB & VET GmbH, 1160 Vienna / Austria) and a haystick 4642 (batch no. 80/09, Provimi Kliba AG,
4303 Kaiseraugst / Switzerland) were provided for environmental enrichment.
- Diet (ad libitum): pelleted standard Teklad Global High Fiber Rabbit Diet 2031C (batch no. 25/10, Provimi Kliba AG, 4303 Kaiseraugst / Switzerland)
- Water (ad libitum): community tap water from Füllinsdorf
- Acclimation period: under laboratory conditions after health examination. Only animals without any visual signs of illness were used for the study.

ENVIRONMENTAL CONDITIONS - Standard Laboratory Conditions
- Temperature: 17-23 °C
- Relative humidity: 30-70%
- Air changes: air-conditioned with 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12/12 (music played during the daytime light period)

Test system

Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): the test item was ground to a fine powder with a mortar and pestle. The test item was applied as a weight of 0.1 g/animal. The test item was applied with an eye glass to the conjunctival sac of the left 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 to prevent loss of test item. The right eye remained untreated and served as the reference control.
Duration of treatment / exposure:
not applicable
Observation period (in vivo):
approximately 1, 24, 48 and 72 hours, as well as 7, 10, 14, 17 and 21 days after administration
Number of animals or in vitro replicates:
3 male rabbits
Details on study design:
The eyes of the animals were examined one day prior to test item administration.

One animal was treated first. As neither a corrosive effect nor a severe irritant effect was observed after the 1- and 24-hour examinations, the test was completed using the two remaining animals.

REMOVAL OF TEST SUBSTANCE
The treated eyes were not rinsed after instillation.

SCORING SYSTEM: according to the Draize scale
Scleral reddening and ocular discharge were also assessed (scale for assessment can be seen in the field "Any other information on materials and methods incl. tables" below).

TOOL USED TO ASSESS SCORE:
Eye examinations were made with a Varta Cliptrix diagnostic-lamp (Roth AG, 4153 Reinach / Switzerland).

OBSERVATIONS:
- Viability / Mortality: daily from acclimatization of the animals to termination of the test.
- Clinical Signs (systemic): daily from acclimatization of the animals to termination of the test.
- Body Weights: at start of acclimatization, on the day of application and at termination of observation. Body weights of two animals were additionally recorded on test day 16 and 18.
-Necropsy: no necropsy was performed on the animals sacrificed at termination of observation.

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:
0
Max. score:
4
Remarks on result:
other: Moderate to marked reddening of the sclera and slight ocular discharge at 24, 48 and 72 hours after adminsitration.
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
2.67
Max. score:
3
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
2.67
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: Moderate reddening of the sclera and slight ocular discharge 24 hours after administration.
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:
1.33
Max. score:
3
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: Moderate to marked reddening of the sclera at 48 and 72 hours after administration.Slight to moderate ocular discharge at 24, 48 and 72 hours after administration.
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:
2.67
Max. score:
3
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
2.67
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Irritant / corrosive response data:
Moderate reddening and moderate to marked chemosis as well as slight to moderate ocular discharge were noted 1 hour after instillation of the test item.
In one animal, these signs gradually reversed until the 48-hour reading, when only slight redness of the conjunctive was noted. However, slight redness of the conjunctivae was noted in this animal until test day 22, the end of the observation period.
In the other two animals, moderate to marked redness of conjunctivae and sclerae and slight to marked chemosis of the conjunctivae, as well as slight to moderate discharge was observed throughout the entire observation period of 21 days after test item instillation. Additionally, white deposits were noted 7, 10, 14, 17 and 21 days after test item instillation in one animal and 7 and 21 days after instillation of the test item in the other animal.
In all three animals, the signs of ocular irritation had not reversed 21 days after instillation of the test item.
No abnormal findings were observed in the cornea or for the iris light reflex of any animal at any of the measurement intervals.
No staining produced by the test item was observed in the treated eyes.
No test item remnants were observed in the treated eyes of any animal at any of the reading times.
No corrosion of the cornea was observed at any of the reading times.
Other effects:
- Viability / Mortality: no intercurrent deaths occurred during the course of the study.
- Clinical signs: no clinical signs were recorded throughout the entire observation period.
- Body weights: the body weight of the animals was within the range commonly recorded for this strain and age.
- Macroscopic findings: no necropsy was performed at the end of the study.

Applicant's summary and conclusion

Interpretation of results:
Category 1 (irreversible effects on the eye)
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The instillation of cobalt dichloride into the eyes of three male young New Zealand white rabbits resulted in moderate to marked signs of eye irritation such as reddening and chemosis of the conjunctivae and reddening of the sclerae, as well as ocular discharge and white deposits in the eye. These signs of eye irritation were not reversible within 21 days after instillation of the test item.
According to the criteria specified by Directive 67/548/EEC and subsequent regulations, the test item is classified as risk of serious damage to eyes (R41).
According to the EC Regulation No. 1272/2008 and subsequent regulations, the test item is classified as Category 1.