Registration Dossier

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
8 November 1990 - 11 November 1990
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 deficiencies, which do not affect the quality of the relevant results.

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1991
Report Date:
1991
Reference Type:
publication
Title:
Acute Toxicological Evaluation of Cerium Fluoride
Author:
Lambert, C.E., Barnum, E.C. and Shapiro, R.
Year:
1993
Bibliographic source:
Int. J. Toxicol., 12(6): 632

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: FHSA 16 CFR 1500.42
Deviations:
no
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Appearance: light tan powdered solid

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Housing: Individually housed in suspended stainless steel caging with mesh floors
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum tap water supplied by automatic watering system
- Acclimation period: 5, 7 or 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 68 - 73 °C

IN-LIFE DATES: From: To: 8 November 1990 - 11 November 1990

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: the right eye of each rabbit remained untreated and served as control
Amount / concentration applied:
undiluted
Amount applied: 0.1 g
Duration of treatment / exposure:
The upper and lower lids were gently held together for 1 second post-installation to prevent loss of the test material.

Three of the treated eyes were rinsed 30 seconds post-installation.
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
6; 3 male, 3 female
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): three of the treated eyes were rinsed with saline.
- Time after start of exposure: 30 seconds post-exposure.

- Scoring system: according to the method of Draize. Ocular lesions were evaluated at 24, 48 and 72 hours post installation. Fluorescein was used at the 24 hour evaluation.

Draize Scale for Scoring Ocular Irritation. Eye scores further classified by system of Kay and Calandra.

1. CONJUNCTIVAE

(A) Redness (refers to palpebral and bulbar conjunctivae excluding cornea and iris)
Vessels normal............................................................................................................................................0
Vessels definitely injected above normal................................................................................................1
More diffuse, deeper crimson red, individual vessels not easily discernible....................................2
Diffuse beefy red.........................................................................................................................................3

(B) Chemosis
No swelling..................................................................................................................................................0
Any swelling above normal (includes nictitating membrane).............................................................1
Obvious swelling with partial eversion of lids.......................................................................................2
Swelling with lids about half closed.........................................................................................................3
Swelling with lids half closed to completely closed...............................................................................4

(C) Discharge
No discharge...............................................................................................................................................0
Any amount different from normal (does not include small amounts observed in inner
canthus of normal animals)......................................................................................................................1
Discharge with moistening of the lids and hairs just adjacent to lids...............................................2
Discharge with moistening of the lids and hairs a considerable area around the eye...................3

THE TOTAL SCORE = (A + B + C) x 2 MAXIMUM TOTAL = 20

2. IRIS

(D) Values
Normal.........................................................................................................................................................0
Folds above normal, congestion, swelling, circumcorneal injection (any or all
of these or combination of any thereof) iris still reacting to light
(sluggish reaction is positive).................................................................................................................1
No reaction to light, haemorrhage, gross destruction (any or all of these)....................................2

THE TOTAL SCORE = D x 5 MAXIMUM TOTAL = 10

3. CORNEA

(E) Degree of Opacity (most dense area used)
No opacity...................................................................................................................................................0
Scattered or diffuse areas, details of iris clearly visible......................................................................1
Easily discernible translucent areas, details of iris slightly obscured..............................................2
Opalescent areas, no details of iris visible, size of pupil barely discernible....................................3
Opaque, iris not discernible through the opacity................................................................................4

(F) Area of Cornea Involved
One quarter (or less) but not zero..........................................................................................................1
Greater than one quarter but less than half...........................................................................................2
Greater than half but less than three quarters......................................................................................3
Greater than three quarters, up to whole area.......................................................................................4

THE TOTAL SCORE = (E x F) x 5 MAXIMUM TOTAL = 80

MAXIMUM TOTAL SCORE POSSIBLE = 110

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0.11
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: Unwashed
Irritation parameter:
iris score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0.11
Max. score:
2
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: Unwashed
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0.56
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: Unwashed
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0.44
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: Unwashed
Irritation parameter:
other: discharge
Basis:
mean
Remarks:
of 3 animals
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0.67
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: Unwashed
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: n/a
Remarks on result:
other: Washed
Irritation parameter:
iris score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0
Max. score:
2
Reversibility:
other: n/a
Remarks on result:
other: Washed
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0.56
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Washed
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0.22
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: Washed
Irritation parameter:
other: discharge
Basis:
mean
Remarks:
of 3 animals
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0.11
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: Washed
Irritant / corrosive response data:
All treated eyes exhibited conjunctival irritation 24 hours post installation. With the exception of one washed eye, this had cleared 48 hours after installation. The remaining eye was free of irritation by 72 hours.
Other effects:
All animals appeared active and healthy. No signs of gross toxicity, adverse pharmacologic effects or abnormal behaviour were observed.

Any other information on results incl. tables

Table 1: Individual Results

Time Point (hours)

Rabbit Number

Cornea

Iris

Conjunctivae

Chemosis

Discharge

 

 

24

7758

7759

7760

7761

7762

7763

1*

0

0

0

0

0

0

0

1

0

0

0

2

1

2

2

1

1

2

1

1

1

1

0

2

1

3

1

0

0

 

 

48

7758

7759

7760

7761

7762

7763

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

1

0

0

0

0

0

0

0

0

0

0

0

0

0

0

 

 

72

7758

7759

7760

7761

7762

7763

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Rabbits 7761, 7762 and 7763 had the treated eye rinsed with 30 cc of saline solution 30 seconds post-installation.

*The area affected by the corneal opacity was judged to be one quarter (or less) but not zero and the area of the cornea involved was therefore given a score of 1.

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test material produced minor irritation effects to both the unwashed and washed eyes, all of which were reversible withing 72 hours. No classification is required under the conditions of this study.
Executive summary:

A primary eye irritation study was conducted in accordance with FHSA guideline16 CFR 1500.42.

0.1 g of the test material was instilled into the left eye of six New Zealand white rabbits, with three of the treated eyes being rinsed after 30 seconds with saline. The animals were observed for three days and the eyes examined at 24, 48 and 72 hours. Irritation was scored according to the method of Draize.

 

The test material produced minor irritation effects to both the unwashed and washed eyes, all of which were reversible withing 72 hours. No classification is required under the conditions of this study in accordance with EU criteria.