Cobalt Lithium Manganese Nickel Oxide

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

18 June 2007 to 28 June 2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to valid guidelines and the study was conducted under GLP conditions.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

480-390-0

EC Name:

-

Cas Number:

182442-95-1

Molecular formula:

LiCoNiMnO2 with the stoechiometry of Co+Ni+Mn equal to 1 and the ranges of the elements approximately as: Li: >0.90 - <1.20 Co: >0.0 - <0.50 Ni: >0.20 - <0.98 Mn: >0.0 - <0.50 O: 2

IUPAC Name:

Cobalt Lithium Manganese Nickel Oxide

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): Cellcore MX
- Physical state: solid
- Appearance: black powder
- Storage condition of test material: room temperature in the dark

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Age at study initiation: 12 - 20 weeks old
- Weight at study initiation: 2.0 - 3.5 kg
- Housing: individually in suspended cages
- Diet: ad libitum Certified Rabbit Diet
- Water: ad libitum access to mains drinking water
- Acclimation period: at least 5 days
Immediately before the start of the test, both eyes of the rabbits were examined for evidence of ocular irritation or defect with the aid of a light source from a standard ophthalmoscope. Only animals free of ocular damage were used.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 – 23 °C
- Humidity (%): 30 – 70 % (relative)
- Air changes (per hr): at least 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours light (06:00 to 18:00)

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: The left eye of each animal remained untreated and served as the control.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.05 mL of test material (weighing 100 mg)

Owing to the high pH of the test material (pH 11.0), and in order to minimise the pain on application of the test material, one drop of local anaesthetic (Tetracaine hydrochloride 0.5 %) was instilled into both eyes of the treated animals 1 to 2 minutes before treatment.

Duration of treatment / exposure:

Test material was placed into the conjunctival sac of the right eye, formed by gently pulling the lower lid away from the eyeball. The upper and lower lids were held together for about one second immediately after treatment, and then released.

Observation period (in vivo):

Assessment of ocular damage/irritation was made approximately 1, 24, 48 and 72 hours following treatment.
Initially a single animal was treated. After consideration of the ocular response produced in the first treated animal, two additional animals were treated.

Number of animals or in vitro replicates:

3 males

Details on study design:

SCORING SYSTEM:
- Immediately after administration of the test material, an assessment of the initial pain reaction was made according to the six point scale (see below).
- Assessment of ocular reaction at 1, 24, 48 and 72 hours was made according to the Draize scale (see below).
- Any other ocular effects were also noted

TOOL USED TO ASSESS SCORE:
Examination of the eye was facilitated by the use of a light source from a standard ophthalmoscope.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

of all three animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Results 2

Irritation parameter:

iris score

Basis:

mean

Remarks:

of all three animals

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Results 3

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

mean

Remarks:

of all three animals

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

of all three animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritant / corrosive response data:

- No corneal effects were noted.
- Iridial inflammation was noted in one treated eye one hour after treatment.
- Minimal to moderate conjunctival irritation was noted in all treated eyes one hour after treatment with minimal conjunctival irritation noted in all treated eyes at the 24-hour observation.
- All treated eyes appeared normal at the 48-hour observation.

Other effects:

Black staining on the fur was noted around all treated eyes throughout the study.

Any other information on results incl. tables

Table 1: Individual Scores for Ocular Irritation

Rabbit	1M (IPR = 2)				2M (IPR = 1)				3M (IPR = 0)
Time after treatment (hrs)	1	24	48	72	1	24	48	72	1	24	48	72
CORNEA
Opacity	0	0	0	0	0	0	0	0	0	0	0	0
Area	0	0	0	0	0	0	0	0	0	0	0	0
IRIS
Score	0	0	0	0	0	0	0	0	1	0	0	0
CONJUNCTIVAE
Redness	1	1	0	0	2	1	0	0	2	1	0	0
Chemosis	0	0	0	0	1	0	0	0	1	0	0	0
Discharge	1Sf	0Sf	0Sf	0Sf	1Sf	0Sf	0Sf	0Sf	1Sf	0Sf	0Sf	0Sf

IPR = initial pain reaction

Sf = black staining of the fur around the treated eye

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of the study, the test material induced only minimal reversible irritation to the eye in the New Zealand White rabbit. The test material was therefore considered to be not irritating in accordance with EU criteria.

Executive summary:

The eye irritancy potential of the test material was investigated in a study which was conducted under GLP conditions and in accordance with the standardised guidelines OECD 405 and EU Method B.5.

0.05 mL of test material (weighing 100 mg) was installed into the right eye of the New Zealand White rabbits. Assessment of ocular damage/irritation was made approximately 1, 24, 48 and 72 hours following treatment. Initially a single animal was treated. After consideration of the ocular response produced in the first treated animal, two additional animals were treated.

The application of the test material to the non-irrigated eye of three rabbits produced iridial inflammation in one eye, and minimal to moderate conjunctival irritation in all treated eyes, one hour after treatment. All treated eyes appeared normal at the 48-hour observation.

Under the conditions of the study, the test material induced only minimal reversible irritation to the eye in the New Zealand White rabbit. The test material was therefore considered to be not irritating in accordance with EU criteria.