Lithium potassium titanium oxide

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

16 July-06 August 2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study has been performed according to OECD and EC guidelines and according to GLP principles.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

(1992)

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

(1987)

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Version / remarks:

(1998)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Lithium Potassium Titanium Oxide

EC Number:

445-620-6

Cas Number:

39318-30-4

Molecular formula:

Hill Empirical formula: K(0.5-0.7) Li(0.27) Ti(1.73) O(3.8-3.95) CAS Empirical formula: K(0.5-0.7) Li(0.27) Ti(1.73) O(3.8-3.95)

IUPAC Name:

Lithium Potassium Titanium Oxide

Details on test material:

Batch: 2D82A
White powder, crystal structure
Expiry date: 31 May 2003
Test substance storage: At 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
- Animals: Albino Rabbit, New Zealand White, (SPF-Quality). Earmark.
- Source: Harlan, Horst, The Netherlands
- Age at study initiation: Animals used within the study were at least 6 weeks old
- Weight at study initiation: body weights were at least 1.0 kg.
- Housing: Individually in labelled cages with perforated floors (Scanbur, Denmark, dimensions 56x44x37.5 cm).
- Diet: Standard laboratory rabbit diet (Teklad Global Rabbit Diet, code 2030, Harlan, Blackthorn, England) approx. 100 g. per day.. In addition, hay (BMI, Helmond, the Netherlands) was provided twice a week.
- Water: Free access to tap water.
- Acclimatization period: at least 5 days before start of treatment under laboratory conditions.

A health inspection was performed prior to commencement of treatment, to ensure that the animals were in a good state of health. Special attention was paid to the eyes, which were free from any abnormality.

All certificates of analysis (diet and water) are retained in the NOTOX archives.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21±3ºC
- Humidity (%): 30 - 70%
Deviations from the maximum level for relative humidity (with a maximum of 27%) occurred which might have been caused by cleaning procedures in the room. Based on laboratory historical data this protocol deviation was considered not to have affected the study integrity.
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light and 12 hours darkness per day

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: The other eye of the test animal remained untreated and served as the reference control.

Amount / concentration applied:

Average of solid test substance: 92.5 mg (range 90.8-94.2 mg), a volume of approximately 0.1 mL.

Duration of treatment / exposure:

Single instillation on Day 1.

Observation period (in vivo):

The eyes of each animal were examined approximately 1, 24, 48 and 72 hours and 7, 14 and 21 days after instillation of the test substance.

Number of animals or in vitro replicates:

3 animals of one sex

Details on study design:

Each animal was treated by instillation of approximately 0.1 mL of test substance, in the conjunctival sac of one of the eyes 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 the test substance. The other eye remained untreated and served as the reference control.

Immediately after the 24 hour observation, a solution of 2% fluorescein in water (adjusted to pH 7.0) was instilled into both eyes of each animal to quantitatively determine corneal epithelial damage. Any bright green stained area, indicating epithelial damage, was estimated as a percentage of the total corneal area.

OBSERVATIONS:
Mortality/viabiity: twice daily
Toxicity: at least once daily
Body weight: Day of treatment (prior to instillation) and at termination

The eyes of each animal were examined approximately 1, 24, 48 and 72 hours and 7, 14 and 21 days after instillation of the test substance.
The irritation scores and a description of all other (local) effects were recorded.The irritation was assessed according to the following numerical scoring system. At each observation, the highest scores given were recorded:

CORNEAL IRRITATION
Opacity: degree of density (area most dense taken for reading)
0: No ulceration or opacity (may include slight dulling of normal luster)
1: Scattered or diffuse areas of opacity, details of iris clearly visible
2: Easily discernible translucent area, details of iris slightly obscured
3: Nacreous area, no details of iris visible, size of pupil barely discernible
4: Opaque cornea, iris not discernible through the opacity

Area of cornea involved:
0: No ulceration or opacity
1: One quarter or less but not zero
2: Greater than one quarter, but less than half
3: Greater than half, but less than three quarters
4: Greater than three quarters, up to whole area

IRIS
0: Normal
1: Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia, or injection, any of these or combination thereof, iris still reacting to light (sluggish reaction is positive)
2: No reaction to light, hemorrhage, gross destruction (any or all of these)

CONJUNCTIVAL IRRITATION
Redness (refers to palpebrae and sclera, excluding cornea and iris):
0: Blood vessels normal
1: Some blood vessels definitely hyperaemic (injected)
2: Diffuse, crimson color, individual vessels not easily discernible
3: Diffuse beefy red

Chemosis (refers to lids and/or nictitating membranes):
0: No swelling
1: Any swelling above normal (includes nictitating membranes)
2: Obvious swelling with partial eversion of lids
3: Swelling with lids about half closed
4: Swelling with lids more than half closed

Discharge:
0: No discharge (may include small amounts observed in inner canthus of normal animals)
1: Any amount different from normal and/or lacrimation
2: Discharge with moistening of the lids and hairs just adjacent to lids
3: Discharge with moistening of the lids and hairs (considerable area around the eye)

Where standard lighting was considered inadequate for observing minor effects, eye examinations were performed using an ophthalmic examination lamp.
In cases of equivocal results when comparing the treated and untreated eyes, the illustrated guide from the Consumer Product Safety Commission, Washington, D.C. 20207 was used for additional control purposes.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 3

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 5

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 6

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

fully reversible within: 24 h

Remarks on result:

other:

Remarks:

Highest score (1) at 1 h

Results 7

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.3

Max. score:

3

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: Highest score (2) at 1 h and 24 h

Results 8

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 21 days

Remarks on result:

other: Highest score (2) at 1 h

Results 9

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.3

Max. score:

3

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: Highest score (2) at 1 h and 24 h

Results 10

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 h

Remarks on result:

other:

Remarks:

Highest score (1) at 1 h

Results 11

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 h

Remarks on result:

other:

Remarks:

Highest score (1) at 1 h

Results 12

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 h

Remarks on result:

other:

Remarks:

Highest score (1) at 1 h

Irritant / corrosive response data:

Instillation of approximately 93 mg of the test substance (approximately 0.1 mL) into one eye of each of three rabbits resulted in effects on the iris and conjunctivae. Iridial irritation (grade 1) was observed in one animal and had resolved with 24 hours. Irritation of the conjunctivae was seen as redness and chemosis, which had completely resolved within 7, 14 or 21 days in all animals.

No corneal opacity was observed, and treatment of the eyes with 2% fluorescein, 24 hours after test substance instillation revealed no corneal epithelial damage in any of the animals.

There was no evidence of ocular corrosion.

Other effects:

Remnants of the test substance were present in the eyes of all animals on day 1 and on the outside of the eyelids of all animals during the study period.

No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Applicant's summary and conclusion

Interpretation of results:

other: Not irritating

Remarks:

according to EU 1272/2008

Conclusions:

Terracess L is not irritating to eye (single instillation of 0.1 mL solid test substance in rabbit eye).
Terracess L does not have to be classified and has no obligatory labelling requirement for eye irritation.