Registration Dossier

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to generally valid procedures and according to GLP guidelines. All parameters described are closely related or comparable to guideline methods.

Data source

Reference
Reference Type:
other company data
Title:
Unnamed
Year:
1995
Report Date:
1995

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EPA OPP 81-6 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
Buehler test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Composite sodium fluoride; Technical sodium fluoride (NaF)
- Molecular formula (if other than submission substance): NaF
- Physical state: White powder
- Analytical purity: 95.6%
- Lot/batch No.: 199-7-4
- Stability under test conditions: stable
- Storage condition of test material: room temperature

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Davidson's Mill Farms, South Brunswick, NJ, USA
- Age at study initiation: no data
- Weight at study initiation: males, 347-402 g; females, 296-359 g
- Housing: Suspended stainless steel caging with wire mesh floors
- Diet (e.g. ad libitum): Pelleted Purina Guinea Pig Chow, ad libitum except during dosing
- Water (e.g. ad libitum): Filtered tap water was supplied ad libitum by automatic water dispensing system, ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.9-21.6
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12


Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
95% w/w mixture of composite NaF in distilled water
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
95% w/w mixture of composite NaF in distilled water
No. of animals per dose:
10 animals in a test group and 10 animals in a positive control group
5 animals in a test naive control group and 5 animals in a positve naive control group
Details on study design:
RANGE FINDING TESTS:
- A group of animals was used to determine the highest non-irritating concentration of composite NaF prior to the challenge dose. The test substance was diluted with distilled water to yield concentrations of 95%, 75%, 50% and 25% w/w and applied to skin test sites using an occlusive 25 mm Hilltop Chamber. After 6 hours of exposure, the chambers were removed. Twenty-four hours after application, each site was evaluated for local skin reactions.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 hours
- Test groups: 10 animals
- Control group: 5 naive animals - not treated at induction
- Site: left flank
- Frequency of applications: once each week
- Duration: 3 weeks
- Concentrations: 95% w/w mixture of composite NaF in distilled water

B. CHALLENGE EXPOSURE
- No. of exposures: one
- Day(s) of challenge: 20 days after last induction application
- Exposure period: 6 hours
- Test groups: 10 animals
- Control group: 5 naive animals
- Site: right flank
- Concentrations: 95% w/w mixture of composite NaF in distilled water
- Evaluation (hr after challenge): 24 and 48 hours after removal of challeng application


Challenge controls:
Five naive control animals were patched with 95% w/w mixture of composite NaF in distilled water for 6 hours at challenge. Test sites were evaluted at 24 and 48 hours after patch removal.
Positive control substance(s):
yes
Remarks:
0.04% dinitrochlorobenzene

Results and discussion

Positive control results:
Nine of 10 postive control animals exhibited signs of sensitization response (faint to moderate erythema; grades 1 to 2) 24 hours after challenge. At 48 hours, similar indications persisted in 5 of the animals. Very faint erythema (grade 0.5) was noted at all other positive control sites following challenge dose.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
95% w/w mixture of composite NaF in distilled water
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 95% w/w mixture of composite NaF in distilled water. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
95% w/w mixture of composite NaF in distilled water
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 95% w/w mixture of composite NaF in distilled water. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
95% w/w mixture of composite NaF in distilled water
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 95% w/w mixture of composite NaF in distilled water. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
95% w/w mixture of composite NaF in distilled water
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 95% w/w mixture of composite NaF in distilled water. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: none.
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.04% dinitrochlorobenzene
No. with + reactions:
9
Total no. in group:
10
Clinical observations:
faint to moderate erythema, grades 1 - 2
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: positive control. Dose level: 0.04% dinitrochlorobenzene. No with. + reactions: 9.0. Total no. in groups: 10.0. Clinical observations: faint to moderate erythema, grades 1 - 2.
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.04% dinitrochlorobenzene
No. with + reactions:
5
Total no. in group:
10
Clinical observations:
faint to moderate erythema, grades 1-2 persisted in 5 amimals; very faint erythema (grade 0.5) was noted at all other sites
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: positive control. Dose level: 0.04% dinitrochlorobenzene. No with. + reactions: 5.0. Total no. in groups: 10.0. Clinical observations: faint to moderate erythema, grades 1-2 persisted in 5 amimals; very faint erythema (grade 0.5) was noted at all other sites.
Reading:
1st reading
Hours after challenge:
24
Group:
other: naive positive control group
Dose level:
0.04% dinitrochlorobenzene
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: other: naive positive control group. Dose level: 0.04% dinitrochlorobenzene. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
48
Group:
other: naive positive control group
Dose level:
0.04% dinitrochlorobenzene
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
none-
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: other: naive positive control group. Dose level: 0.04% dinitrochlorobenzene. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: none-.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
Composite NaF is not considered to be a contact sensitizer.