Registration Dossier

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
19-22 November 2002
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Proprietary, GLP and guideline-compliant study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002
Report Date:
2002

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Calcium fluoride (CaF2), a white powder, stored at ambient temperature.

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
The animals were young adult female SPF bred New Zealand White albino rabbits, obtained from Centre Lagro, France. They underwent 12 days quarantine/acclimatisation prior to the study commencing. The rabbits weighed between 2026 and 2081 g at study initiation. Rabbits were housed individually in stainless steel cages, and were identified by ear marks. The rabbits were subject to a 12 hour light/dark cycle, and the temperature during testing was 20±3°C, with approximately 10 air changes per hour. Humidity ranged from 45-99.9%; the upper limit was higher than 70% due to wet cleaning of the animal room and/or meteorological circumstances. The rabbits were fed standard laboratory rabbits diet ad libitum (SDS Special Diets services, England). Tap water was also available ad libitum. Both eyes of the rabbits were examined just before testing. Only rabbits without observable eye defects were used.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
Approximately 0.075 g (ca 0.1 ml).
Duration of treatment / exposure:
After administration of the test substance, the eye lids were gently held closed for at least one second to prevent loss of material. 1 hour after treatment, test substance was still present in the conjunctival sac - these remnants were removed when the eye lids were manipulated during examination of the eye.
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
3
Details on study design:
The non-GLP Chicken Enucleated Eye Test was performed first, this test did not show severe signs of irritation therefore the in vivo test was carried out. The test substance was applied to the eye of one rabbit, severe signs of irritation were not seen after 1 hour therefore the test immediately continued with the remaining 2 rabbits. Approximately 0.1 ml of the test substance was instilled into the conjunctival sac of one eye per rabbit. The upper and lower eyelids were held closed for at least 1 second before releasing, to prevent loss of material. The other eye remained untreated, serving as a control. The reactions of the eyes were assessed at 1, 24, 48 and 72 hours after treatment.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: Mean values scored at 24, 48 and 72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: Mean values scored at 24, 48 and 72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
other: Mean values scored at 24, 48 and 72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: Mean values scored at 24, 48 and 72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: Mean values scored at 24, 48 and 72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: Mean values scored at 24, 48 and 72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #1
Time point:
other: Mean values at 24, 48 and 72 h
Score:
0
Max. score:
3
Reversibility:
fully reversible within: 24 hours
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #2
Time point:
other: Mean values scored at 24, 48 and 72 h
Score:
0.3
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #3
Time point:
other: Mean values scored at 24, 48 and 72 h
Score:
0
Max. score:
3
Reversibility:
fully reversible within: 24 hours
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: Mean values scored at 24, 48 and 72 h
Score:
0
Max. score:
4
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: Mean values scored at 24, 48 and 72 h
Score:
0
Max. score:
4
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: Mean values scored at 24, 48 and 72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
At 1 hour after treatment, slight redness and slight or moderate swelling of the conjunctivae were observed in the rabbits. At 24 hours after treatment, slight redness of the conjunctivae was observed in one rabbit only. At 48 and 72 hours after treatment, no signs of eye irritation were observed in any of the three rabbits. See table 1.
Other effects:
No other effects were reported.

Any other information on results incl. tables

At one hour after treatment, amounts of the test substance were still present in the conjunctival sac. Upon manipulation of the eye lids during eye examination, the remnants of substance were removed.

Individual scores awarded to the ocular lesions elicited by Calcium fluoride.

Animal no.

Corneal effects

Iris

Conjunctivae

Discharge

score

area

redness

swelling

1 hour

1

0

0

0

1

1

0

2

0

0

0

1

2

0

3

0

0

0

1

1

0

24 hours

1

0

0

0

0

0

0

2

0

0

0

1

0

0

3

0

0

0

0

0

0

48 hours

1

0

0

0

0

0

0

2

0

0

0

0

0

0

3

0

0

0

0

0

0

72 hours

1

0

0

0

0

0

0

2

0

0

0

0

0

0

3

0

0

0

0

0

0

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
According to EU criteria, calcium fluoride is not irritating to eyes.
Executive summary:

Calcium fluoride was tested for acute eye irritating properties in New Zealand White rabbits, according to OECD Guideline 405. Calcium fluoride caused slight erythema and slight to moderate conjunctival chemosis. At 48 hours all eye effects had resolved completely. According to the EU criteria, calcium fluoride is not irritating to eyes.