Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
22 May 2002 and 07 June 2002
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficincies, which do not affect the quality of relevant results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2003
Report date:
2003

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Deviations:
no
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Chemical structure
Reference substance name:
Strontium titanium trioxide
EC Number:
235-044-1
EC Name:
Strontium titanium trioxide
Cas Number:
12060-59-2
Molecular formula:
O3Ti.Sr
IUPAC Name:
strontium(2+) oxotitaniumbis(olate)
Constituent 2
Reference substance name:
ST888YK
IUPAC Name:
ST888YK
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): ST888YK
- Physical state: White powder
- Lot/batch No.: 11423
- Expiration date of the lot/batch: March 2003
- Storage condition of test material: Room temperature
- Other: Composition: Metal oxide mixture

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Animals for this study were selected from a stock supply of healthy adult rabbits of the New Zealand White strain, obtained from Highgate Farm, Market Rasen, Lincolnshire, England.
They were in the weight range of 3.00 to 3.67 kg and at least eight weeks of age, prior to treatment (Day 1). All rabbits were acclimatised to the experimental environment for a period of at least five days prior to the start ofthe study.
The rabbits were selected without conscious bias for the study. They were housed individually in stainless steel cages with perforated floors at the Eye Research Centre, Eye, Suffolk, IP23 7PX.
A standard laboratory rabbit diet (Special Diet Services STANRAB (P) SQC pellet) and drinking water were provided ad libitum. The batch of diet used for the study was analysed by the supplier for nutrients, possible contaminants and micro-organisms likely to be present in the diet and which, if in excess of specified amounts, might have an undesirable effect on the test system. A dietary supplement of hay was given.
During the acclimatisation and study period the animals were given small soft white untreated wood blocks for environmental enrichment.
Results of routine physical and chemical examination of drinking water, as conducted by the supplier are made available to Huntingdon Life Sciences Limited.
Animal room environmental controls were set to maintain temperature within the range 15 to 23°C, and relative humidity within 40 to 70%. These environmental parameters were recorded and the permanent record archived with other departmental raw data. Lighting was controlled by means of a time switch to give 12 hours of artificial light (06:00 to 18:00 GMT) in each 24 hour period.
Each animal was identified by a numbered tag placed through the edge of one ear. This identification was unique within the Department throughout the duration of the study. Each cage was identified by a coloured label displaying the study number, animal number, phase of study and initials of the Study Director and Home Office licensee.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: The untreated eye was used as a comparison with the treated eye during assessment of ocular lesions.
Amount / concentration applied:
TEST MATERIAL
ST888YK was administered as supplied by the Sponsor.
The absorption of ST888YK was not determined.
The specific gravity of the test substance was approximated and the weight of ST888YK that occupied 0.1 mL was determined. Aliquots of this weight were prepared.
Duration of treatment / exposure:
The dose was instilled into the right eye by pulling the lower eyelid away from the eye ball to form a cup into which the test substance was dropped. The eyelids were then gently held together for one second.
Observation period (in vivo):
0, 1, 24, 48 and 72 hours; 7 days
Number of animals or in vitro replicates:
Three.
Details on study design:
The eyes of each animal were examined prior to instillation of the test substance to ensure that there was no pre-existing corneal damage, iridial inflammation or conjunctival irritation. Each animal was gently restrained.

OBSERVATIONS
Clinical signs
The behaviour of each rabbit was observed immediately following instillation of the test substance to allow assessment of the initial pain response by the criteria detailed in "any other information on materials and methods" below.
The animals were returned to their cages and checked at least twice during the first hour after dosing and at regular intervals throughout the day to ensure no severe injury passed unnoticed. Ocular reactions to treatment were assessed 1, 24, 48 and 72 hours and 7 days after treatment, according to the criteria
detailed in "any other information on materials and methods" below. Reactions not included below were described in detail.

An ophthalmoscope or pencil beam torch was used to facilitate inspection ofthe eyes.

Interpretation of results
The classification system of Kay and Calandra (1962)* was employed on this study. This system classifies ocular irritants thus:

Corneal scoring using the grade for degree of opacity density (A) and the grade for the area of cornea involved (B):

Corneal score =A x B x 5 (theoretical maximum = 80)

Iridial scoring using the grades for iritis (C):

Iridial score = C x 5 (theoretical maximum = 10)

Conjunctival score using the grade for conjunctival redness (D), chemosis grade (E) and grade for discharge (F):

Conjunctival score =(D + E + F) x2 (theoretical maximum =20)

The scores for each area are meaned for each time point and the highest total meaned score is used for the classification thus:

Total mean score Classification
0.0-0.5 Non-irritating
0.5 -2.5 Practically non-irritating
2.5 - 15 Minimally irritating
15 -25 Mildly irritating
25 -50 Moderately irritating
50-80 Severely irritating
80-100 Extremely irritating
100 - 110 Maximally irritating

* Kay, JH & Calandra, JC (1962) Interpretation of Eye Irritation Tests. Journal of the Society of Cosmetic Chemists.

Assessment of pain response on instillation
The observed pain response following instillation of the test substance was reported separately.
Mortality and termination procedure
The animals were killed after completion ofthe observation periods.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Remarks:
3984 (male)
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: No effects noted.
Irritation parameter:
cornea opacity score
Basis:
animal #2
Remarks:
4117 (male)
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: No effects noted.
Irritation parameter:
cornea opacity score
Basis:
animal #3
Remarks:
4118 (male)
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: No effects noted.
Irritation parameter:
iris score
Basis:
animal #1
Remarks:
3984 (male)
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0
Max. score:
3
Reversibility:
other: No effects noted.
Irritation parameter:
iris score
Basis:
animal #2
Remarks:
4117 (male)
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0
Max. score:
3
Reversibility:
other: No effects noted.
Irritation parameter:
iris score
Basis:
animal #3
Remarks:
4118 (male)
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0
Max. score:
3
Reversibility:
other: No effects noted.
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #1
Remarks:
3984 (male)
Time point:
other: Mean of 24, 48 and 72 hours
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #2
Remarks:
4117 (male)
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #3
Remarks:
4118 (male)
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0.66
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
chemosis score
Basis:
animal #1
Remarks:
3984 (male)
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: No effects noted.
Irritation parameter:
chemosis score
Basis:
animal #2
Remarks:
4117 (male)
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: No effects noted.
Irritation parameter:
chemosis score
Basis:
animal #3
Remarks:
4118 (male)
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: No effects noted.
Irritant / corrosive response data:
OCULAR REACTIONS
Injection of the conjunctival blood vessels with or without very-slight or slight discharge was apparent during the first twenty-four hours after instillation. The injection was apparent in two animals at the 48-hour assessment and in one animal 24 hours later. No other ocular reaction was apparent in any animal at any time.
Instillation of the test substance gave rise to a moderate initial pain response in one animal; no pain response was evident in the other two animals.
Other effects:
CLINICAL SIGNS
There was no sign of toxicity or ill health in any rabbit during the observation period.

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The highest total mean score was 4.0 occurring at the one hour observation; accordingly under the criteria of Kay and Calandra (1962) ST888YK was classified as "minimally irritating" to the eye.
The test material is not considered to be classified as irritating to eyes according to Regulation (EC) No 1272/2008.
Executive summary:

A study was performed to assess the eye irritation potential of ST888YK to the rabbit. The method followed was that described in:

EEC Methods for the determination of toxicity, Annex to Directive 92/69/EEC (Official Journal No. L383A, 29.12.92), Part B, Method B.5. Acute toxicity (eye irritation).

OECD Guideline for the Testing of Chemicals No. 405, "Acute Eye Irritation/Corrosion", Adopted 24 February 1987.

EPA Health Effects Test Guidelines OPPTS 870.2400 Acute Eye Irritation EPA 712-C-98-195. August 1998.

Three rabbits were each administered a single ocular dose of a volume of 100 mg of the test substance. Reactions to treatment were assessed 1, 24, 48 and 72 hours and seven days after instillation.

Injection of the conjunctival blood vessels with or without very-slight or slight discharge was apparent during the first twenty-four hours after instillation. The injection was apparent in two animals at the 48-hour assessment and in one animal 24 hours later. No other ocular reaction was apparent in any animal at any time.

Instillation of the test substance gave rise to a moderate initial pain response in one animal; no pain response was evident in the other two animals.

The means of scores for the ocular reactions at approximately 24, 48 and 72 hours after administration, calculated separately for each animal, are summarised below:

Animal number

Corneal opacity

Iridial lesions

Conjunctival

Redness

Chemosis

3984

0.0

0.0

1.0

0.0

4117

0.0

0.0

0.3

0.0

4118

0.0

0.0

0.7

0.0

EC R36 trigger values*

≥ 2 < 3

≥ 1 < 2

≥ 2.5

≥ 2

EC R41 trogger values*

≥ 3

= 2

 

 

* Classification triggered if any value is attained by two or more animals.

The total mean scores (according to the system of Kay and Calandra (1962)) are summarised below:

 

Time after instillation of ST888YK

Area of eye

1 hour

24 hours

48 hours

72 hours

7 days

Cornea

0.0

0.0

0.0

0.0

0.0

Iritis

0.0

0.0

0.0

0.0

0.0

Conjunctiva

4.0

3.3

1.3

0.7

0.0

Total mean score

4.0

3.3

1.3

0.7

0.0

The highest total mean score was 4.0 occurring at the one hour observation; accordingly under the criteria of Kay and Calandra (1962) ST888YK was classified as "minimally irritating" to the eye.

Categories Display