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:
2011-05-17 to 2011-05-25
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study 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:
2002-04-24
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Cobalt powder
- Physical state: gray solid (very fine powder)
- Storage condition of test material: store in a cool, well-ventilated place away from incompatible materials. At room temperature (20 ± 5 °C, provided by Harlan Laboratories Ltd.).
- Stability of Test Item: stable under storage conditions.
- Particle size: D10: 1.2 µm; D50: 2.3 µm; D90: 4.3 µm
- Apparent density: 1.25 g/cm^3

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: 15 weeks (male); 14 weeks (females)
- Weight at study initiation: 2628 g (male); 2808 - 2840 g (females)
- Housing: individually in stainless steel cages
- Diet (ad libitum): pelleted standard Teklad Global High Fiber Rabbit Diet 2031C (batch no. 80/10, Provimi Kliba AG, 4303 Kaiseraugst / Switzerland); a piece of wood (batch no. 122201, imported by Indulab AG, Gams / Switzerland from ABEDD® - LAB & VET GmbH, 1160 Vienna / Austria) and a haystick 4642 (batch no. 37/10, Provimi Kliba AG, 4303 Kaiseraugst / Switzerland) were also provided for environmental enrichment.
- Water (ad libitum): community tap water from Füllinsdorf
- Acclimation period: Five days (male rabbit) or six days (females rabbits) under laboratory conditions, after health examination. Only animals without any visual signs of illness were used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature: 17-23 °C
- Relative humidity: 30-70%
- Air changes: 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 applied as a weight of 0.1 g/animal 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 days after administration
Number of animals or in vitro replicates:
1 male rabbit / 2 female rabbits
(a single animal (the male) 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.)
Details on study design:
The eyes of the animals were examined one day prior to test item administration.

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 the end of the observation period.
- Clinical Signs (systemic): daily from acclimatization of the animals to the end of the observation period.
- Body Weights: at start of acclimatization, on the day of application and at the end of tbe observation period.
- Pathology: no necropsy was performed on the animals sacrificed at termination of observation.
The animals were sacrificed by intravenous injection of 1.0 mL/kg body weight of a solution of 162 mg/mL sodium pentobarbitone into the ear vein and discarded.

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
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:
1.33
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
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:
2.33
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
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:
2.33
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
The instillation of cobalt powder into the eye resulted in moderate reddening of the conjunctivae in all animals 1 hour after treatment and persisted as slight to marked reddening until 72 hours after treatment. Slight to moderate reddening of the sclerae was observed in all animals 1 hour after treatment and persisted as slight to marked reddening until 72 hours after treatment. Slight ocular discharge was observed in the male animal 1 hour after treatment. All eye reactions were reversible and were no longer evident 7 days after treatment, the end of the observation period for all animals. No abnormal findings were observed in the cornea or for the iris light reflex. No corrosion was observed. No staining of the treated eyes by the test item was observed. Test item remnants were observed in the treated eyes of all animals 1 hour after treatment and persisted in one female animal until 24 hours after treatment.
Thus, the test item did not induce significant or irreversible damage to the rabbit eye.
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 weights were within the range commonly recorded for this strain and age.
- Pathology: no necropsy was performed at the end of the study.

Applicant's summary and conclusion

Interpretation of results:
Category II
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Cobalt powder is considered to be an eye irritant.
According to the criteria specified by Directive 67/548/EEC and subsequent regulations, the test item is not classified as eye irritant.
According to the EC Regulation No. 1272/2008 and subsequent regulations, the test item is classified as Category 2.