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Diss Factsheets

Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1995-06-01 to 1995-06-28
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995
Report date:
1995

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
EPA OPP 81-6 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
Buehler test
Justification for non-LLNA method:
This study was conducted due to non-REACH regulatory requirements. With the existing data from this study not only being acceptable but of good quality (Klimisch Score 1), this study precludes the need for an additional LLNA study. In addition, a supplementary LLNA study would violate the ECHA objectives with regards to animal welfare.

Test material

Constituent 1
Chemical structure
Reference substance name:
Sodium fluoride
EC Number:
231-667-8
EC Name:
Sodium fluoride
Cas Number:
7681-49-4
Molecular formula:
FNa
IUPAC Name:
sodium fluoride
Test material form:
solid
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Lot/batch No.of test material: 199-7-4

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at room temperature
- Stability under test conditions: stable

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: young adults
- Weight at study initiation: males: 347- 402 grams; females: 296¬359 grams
- Housing: groupwise in suspended stainless steel caging with mesh floors
- Diet: ad libitum, Pelleted Purina Guinea Pig Chow
- Water: ad libitum, filtered tap water
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.9 - 21.7
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Induction
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
95 % w/w mixture with water were used at induction and challenge.
Day(s)/duration:
21
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Challenge
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
95 % w/w mixture with water were used at induction and challenge.
Day(s)/duration:
2
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
10
Details on study design:
RANGE FINDING TESTS:
A group of animals was used to determine the highest non-irritating concentration (HNIC) of test substance prior to the challenge dose. The fur was removed by clipping the dorsal area and flanks of each guinea pig. This area was divided into four test sites (two sites on each side of the midline) on each animal. The test substance was diluted with distilled water to yield concentrations of 95 %, 75 %, 50 % and 25 % w/w. Each concentration was applied to a test site using an occlusive 25 mm Hilltop Chamber. The sites were wrapped with non-allergenic Durapore adhesive tape. After 6 hours of exposure, the chambers were removed. Twenty-four hours after application, each site was evaluated for local reactions (erythema).

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 hours
- Test groups: Four-tenths of a gram of a 95 % w/w mixture of the test substance in distilled water was applied using an occlusive 25 mm Hilltop Chamber.
- Control group: This group was not treated.
- Site: left flank
- Frequency of applications: once each week
- Duration: 3 weeks
- Concentrations: 95 % w/w in water

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 2 days
- Exposure period: 2 days
- Test groups: A challenge dose was applied to a naive skin site using the same procedures as from the induction treatment.
- Control group: The group was treated like the test group.
- Site: right flank
- Concentrations: 95 % w/w in water
- Evaluation (hr after challenge): 24 and 48 hours
Challenge controls:
In addition to the test and positive control animals, 10 guinea pigs from the same shipment were maintained under identical environmental conditions and were treated with the HNIC of the test or positive control substance (five animals each) at challenge only.
Positive control substance(s):
yes
Remarks:
1-Chloro-2,4-Dinitrobenzene (DNCB)

Results and discussion

Positive control results:
Induction: Very faint to severe erythema (0.5-3) was noted at all positive control sites during the induction phase. Overall, the incidence and severity of irritation increased with each successive application. Eschar was evident at two sites following the second or third dose.

Challenge: Nine of ten positive control animals exhibited signs of a sensitization response (faint to moderate erythema [1-2]) 24 hours after challenge. At 48 hours, similar indications persisted in five of these animals. Very faint erythema (0.5) was noted at all other positive control sites following the challenge dose.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
95 % in distilled water
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
95 % in distilled water
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.04% in acetone
No. with + reactions:
9
Total no. in group:
10
Clinical observations:
faint to moderate erythema (1-2) in all animals
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
95 % in distilled water
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
95 % in distilled water
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.04 % in acetone
No. with + reactions:
5
Total no. in group:
10
Clinical observations:
faint to moderate erythema (1-2)
Remarks on result:
positive indication of skin sensitisation

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The test substance did not show any sensitising effects when applied to the skin of Hartley guinea pigs.
Executive summary:

The test substance was applied to ten healthy test guinea pigs and Dinitrochlorobenzene (DNCB, 0.08 % in 80 % aqueous ethanol) was applied to ten healthy positive control animals once each week for a three week induction period. Twelve days after the last induction, a challenge dose of the test and positive control substances at their highest non-irritating concentrations (95 % w/w mixture in distilled water and 0.04 % in acetone, respectively) was applied to a naive site on each guinea pig. Approximately 24 and 48 hours after each induction and challenge dose, the animals were scored for erythema. Two naive control groups (five animals for the test substance and five for the positive control substance) were maintained under the same environmental conditions and treated with the test or positive control substance at challenge only.

No irritation was observed at any of the test sites during the induction phase. Very faint to severe erythema (0.5 - 3) was noted at all positive control sites during the induction phase. Overall, the incidence and severity of irritation increased with each successive application. Eschar was evident at two sites following the second or third dose. No irritation was noted at any test or naive control sites following challenge. Nine of ten positive control animals exhibited signs of a sensitization response (faint to moderate erythema 1 - 2) 24 hours after challenge. At 48 hours, similar indications persisted in five of these animals. Very faint erythema (0.5) was noted at all other positive control sites following the challenge dose. Very faint erythema (0.5) was noted at one positive naive control site 24 hours after challenge. Irritation cleared from the affected site by 48 hours.

Based on these findings and on the evaluation system used, the test substance is not considered to be a contact sensitizer. The positive response to 0.04 % DNCB in acetone validates the test system used in this study.