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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 2011-06-01
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 propionate
- Physical state: slight purple/blue 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.

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: 11 weeks (male); 10 - 11 weeks (female)
- Weight at study initiation: 2775 g (male); 2864 - 3244 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 to 6 days 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. The test item was applied 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 and 14 days after administration
Number of animals or in vitro replicates:
1 male rabbits / 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:
1.67
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:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal #2
Time point:
other: 24, 48 and 72 hours
Score:
2.33
Max. score:
3
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: The animal was further affected up to at least 14 days after treatment.The ocular findings consisted of scleral and conjunctival reddening as well as discharge (with mucus) and were considered as being a secondary effect (infection).
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #2
Time point:
other: 24, 48 and 72 hours
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #3
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #3
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal #3
Time point:
other: 24, 48 and 72 hours
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #3
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritant / corrosive response data:
The instillation of cobalt propionate into the eye resulted in marked reddening of the conjunctivae in all animals 1 hour after treatment and persisted in all animals as slight to marked reddening until 72 hours after treatment. Slight to obvious swelling of the conjunctivae was noted in all animals 1 hour after treatment and persisted as slight in one female 24 hours later. Marked reddening of the sclerae was seen in all three animals 1 hour after treatment. The severity of the reddening decreased and was still present as slight 48 hours after treatment in all animals. One female was still affected with a slight reddening of the sclerae at the 72 hours. Ocular discharge appeared in both females at the 1-hour reading. These effects were reversible and were no longer evident 7 days after treatment in the male and one female.
One female was further affected up to at least 14 days after treatment. The ocular findings consisted of scleral and conjunctival reddening as well as discharge (with mucus) and were considered as being a secondary effect (infection). The local findings observed from 7 days after treatment were located at the corner of the treated eye (from the nictitating membrane side) and first appeared as reddened. Ten days after treatment, the reddening was still present, with
discharge (and mucus). The corner of the eye appeared purulent 12 days after treatment. By removing the pus, the affected site was reddened. The next observation was done 14 days after treatment and again a purulent area with reddening and discharge (with mucus) were seen. As these findings were considered as being a secondary effect (infection), the study was closed thereafter.
No abnormal findings were observed for the cornea or for the iris light reflex. No corrosion was observed. No staining of the treated eyes by the test item was observed. No test item remnants were observed.
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 propionate 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.