Registration Dossier

Administrative data

Description of key information

Calcium fluoride was found to be non-irritant in a modern proprietary guideline and GLP-compliant study (Prinsen, 2002) and was found to be a slight eye irritant in a modern proprietary guideline and GLP-compliant study (Prinsen, 2002).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
19-22 November 2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Proprietary, GLP and guideline-compliant study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system 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 1924 and 1985 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. Upon arrival the rabbits were checked for overt signs of ill health and anomalies.
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
water
Controls:
no
Amount / concentration applied:
0.5 g of CaF2 moistened with 0.5 ml water.
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
3
Details on study design:
Three days prior to the start of the study, the hair was removed from the backs and flanks of the animals using electric clippers. The clipping was repeated if considered necessary. A skin site suitable for application was chosen, then a small cup loaded with 0.5 g of test substance and moistened with 0.5 ml water was placed on the skin. The cup was fixed to the selected application site using adhesive tape. The entire trunk of the rabbit was wrapped with self-adhesive gauze to keep the cup in place and minimise evaporation. The gauze was additionally fastened with two strips of tape. After a 4 hour exposure period, the cups were removed and the test site cleaned with moistened tissue. Approximately 1 hour later the resulting skin reactions were evaluated by the method of Draize. Further skin readings were made at 24, 48 and 72 hours after treatment.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: mean 24-72 hours
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: mean 24-72 hours
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: mean 24-72 hours
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: mean 24-72 hours
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: mean 24-72 hours
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: mean 24-72 hours
Score:
0
Max. score:
4
Irritant / corrosive response data:
No skin reactions (i.e. scores of 0 were given for erythema formation and oedema formation) were seen in any of the three rabbits at any time point.
Other effects:
No other effects reported

At 1 -72 hours after treatment, no signs of dermal irritation were observed in any of the three rabbits.

Interpretation of results:
GHS criteria not met
Conclusions:
According to EC-standards, calcium fluoride is not irritating or corrosive to skin.
Executive summary:

Calcium fluoride was tested for acute dermal irritating properties in three New Zealand White rabbit, according to OECD Guideline 404. The skin was exposed to the test substance for 4 hours under semi-occlusive conditions. At 1 -72 hours after treatment, no signs of dermal irritation were observed in any of the three rabbits. According to EC criteria, calcium fluoride is not irritating or corrosive to skin.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
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
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
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.
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.
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.

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

Interpretation of results:
GHS criteria not met
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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

Calcium fluoride was tested for acute dermal irritation in New Zealand White rabbit, according to OECD Guideline 404. The skin was exposed to the test substance for 4 hours under semi-occlusive conditions. At 1-72 hours after treatment, no signs of dermal irritation were observed in any of the three rabbits (Prinsen, 2002).

Eye irritation

Calcium fluoride was tested for acute eye irritation 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.

Respiratory irritation

There is no evidence of respiratory irritation either from the available animal data or from experience of use.


Justification for selection of skin irritation / corrosion endpoint:
Reliable GLP and test guideline compliant study

Justification for selection of eye irritation endpoint:
Reliable GLP and test guideline compliant study

Justification for classification or non-classification

Calcium fluoride was found to be non-irritating to skin and a mild eye irritant in guideline-compliant studies; the results do not trigger classification of the substance as 'Irritant' according to the CLP Regulation (1272/2008/EC). There is no evidence of respiratory irritation either from the available animal data or from experience of use. No classification is therefore proposed.