Magnesium potassium titanium oxide

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

06 November-09 November 2000

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:

2001

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)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

(1987)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

436-900-9

EC Name:

-

Cas Number:

39290-90-9

Molecular formula:

Hill Empirical formula: K(0.2-0.7) Mg(0.4) Ti(1.6) O(3.7-3.95) CAS Empirical formula: K(0.2-0.7) Mg(0.4) Ti(1.6) O(3.7-3.95)

IUPAC Name:

Magnesium Potassium Titanium Oxide

Details on test material:

Batch: 0G99
White powder
Expiry date: 21 August 2001
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: Charles River Deutschland, Kisslegg, Germany.
- Age at study initiation: Animals used within the study were at least 6 weeks old
- Weight at study initiation: body weights were between 1.0 and 3.5 kg.
- Individually housed in labelled cages with perforated floors (Scanbur, Denmark, dimensions 53.3x63x38.5 cm) and equipped with an automatic drinking system.
- Standard laboratory rabbit diet (Charles River Breeding and Maintenance Diet for Rabbits, Altromin, Germany) approx. 100 g. per day. In addition, hay (BMI, Helmond, the Netherlands) was provided twice a week.
-Free access to tap water.
- Acclimatization period was 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%
- 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:

83.7 mg ± 1.2 mg of solid powdery test substance, 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 after instillation of the test substance.

Number of animals or in vitro replicates:

3 males.

Details on study design:

Each animal was treated by instillation of approximately 0.1 mL of the 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)

The eyes of each animal were examined approximately 1, 24, 48 and 72 hours 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)

In case 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:

conjunctivae score

Remarks:

(redness)

Basis:

animal #1

Time point:

other: average score over 24, 48 and 72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 h

Remarks on result:

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

Results 2

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #2

Time point:

other: average score over 24, 48 and 72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 h

Remarks on result:

other: Highest score (2) after 1 h

Results 3

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #3

Time point:

other: average score over 24, 48 and 72 h

Score:

0.7

Max. score:

3

Reversibility:

fully reversible within: 72 h

Remarks on result:

other: Highest score (2) after 1 h

Results 4

Irritation parameter:

chemosis score

Basis:

animal: #1 and #2

Time point:

other: average score over 24, 48 and 72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 h

Remarks on result:

other: Highest score (1) after 1 h

Results 5

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

other: average score over 24, 48 and 72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 h

Remarks on result:

other: Highest score (2) after 1 h

Results 6

Irritation parameter:

cornea opacity score

Remarks:

(opacity)

Basis:

animal: #1, #2, #3

Time point:

other: average score over 24, 48 and 72 h

Score:

0

Max. score:

4

Results 7

Irritation parameter:

iris score

Basis:

animal: #1, #2, #3

Time point:

other: average score over 24, 48 and 72 h

Score:

0

Max. score:

2

Reversibility:

fully reversible within: 24 h

Remarks on result:

other: Highest score (1) after 1 h

Irritant / corrosive response data:

Instillation of approximately 84 mg of the test substance (approximately 0.1 mL) into one eye of each of three rabbits resulted in irritation of the iris and the conjunctivae. Irritation of the conjunctivae was seen as redness, chemosis and discharge, which had completely resolved within 72 hours in two animals and within 48 hours in the other animal. Iridial irritation (grade 1) was observed on day 1 and had resolved within 24 hours.

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.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

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