Lithium fluoride

Endpoint summary

Description of key information

Sodium fluoride did not show any sensitising effects when applied to the skin of Hartley guinea pigs in a Buehler assy. Lithium chloride was found to be non-sensitizing when topically applied to guinea pigs in a Buehler assay.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Reference 1

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

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.

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

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

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

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)

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.

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

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.

Reference 2

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1997-12-23 to 1998-03-30

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

1992

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Version / remarks:

1992

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPP 81-6 (Skin Sensitisation)

Version / remarks:

1984

Deviations:

no

Principles of method if other than guideline:

NA

GLP compliance:

yes

Type of study:

Buehler test

Justification for non-LLNA method:

Study was performed before LLNA method was described as OECD test guideline and before it could be established in the EU-REACH Regulation.

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Lot/batch No.of test material: 410-01d

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

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Final dilution of a dissolved solid, stock liquid or gel: 35 - 40 % LiCl aqueous solution

Species:

guinea pig

Strain:

Hartley

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Covance, Denver, PA
- Age at study initiation: Young adult
- Weight at study initiation: 301 g - 379 g
- Housing: individually housed in suspended polycarbonate cages
- Diet (e.g. ad libitum): ad libitum, Purina Guinea Pig Chow 5025
- Water (e.g. ad libitum): ad libitum, fresh tap water


ENVIRONMENTAL CONDITIONS
- Temperature: 18.9°C - 20°C
- Humidity: 32 % - 53 %
- Photoperiod: 12 hours fluorescent light/ 12 hours dark

Route:

epicutaneous, occlusive

Vehicle:

water

Concentration / amount:

undiluted / 0.5 mL

Day(s)/duration:

0, 7, 14 / 6 hours

Adequacy of induction:

not specified

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

water

Concentration / amount:

undiluted / 0.5 mL

Day(s)/duration:

Day 28 / 6 hours

Adequacy of challenge:

highest non-irritant concentration

No. of animals per dose:

Irritation Range-Finding Phase: 4
Induction and Challenge:
Test Group: 10
Naive Test Group: 10

Details on study design:

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 h
- Test groups: 0.5 mL undiluted test material
- Control group: -
- Site: right shoulder
- Frequency of applications: day 0, 7 and 14



B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: day 28
- Exposure period: 6 h
- Test groups: 0.5 mL undiluted test material
- Control group: 0.5 mL undiluted test material
- Site: left shoulder
- Evaluation (hr after challenge): 24 and 48 hours

Challenge controls:

Challenge controls were treated like the test group

Positive control substance(s):

no

Positive control results:

No positive control

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

0.5 mL undiluted

No. with + reactions:

3

Total no. in group:

10

Clinical observations:

Very faint erythema, usually nonconfluent

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

0.5 mL undiluted

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

None

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

0.5 mL undiluted

No. with + reactions:

4

Total no. in group:

10

Clinical observations:

Very faint erythema, usually nonconfluent

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

0.5 mL undiluted

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

None

Remarks on result:

no indication of skin sensitisation

Group:

positive control

Remarks on result:

not measured/tested

Interpretation of results:

GHS criteria not met

Conclusions:

Lithium chloride was found to be non-sensitizing when topically applied to guinea pigs in a study according to OECD 406 and EU method B.6.

Executive summary:

A skin sensitisation test in Hartley guinea pigs was performed according to OECD 406 and EU method B.6. Lithium chloride solution (0.5 mL undiluted) was applied to the right shoulder of each of ten male Hartley guinea pigs for a six hour exposure period at weekly intervals for three weeks. 14 days after the third induction treatment, the animals were challenged at a virgin skin site. The concentration of the test material chosen for challenge of the test group was the undiluted test material, which was the highest non-irritating concentration as determined during the range-finding phase of this study. An additional 10 male naive animals (naive test group) also received 0.5 mL of the undiluted test material for the challenge application. Observations for skin reactions were recorded approximately 24 hours after unwrapping each induction application and approximately 24 and 48 hours following unwrapping of the challenge application. Body weights were recorded at initiation and termination.

All animals remained healthy and gained weight during the study. No irritation was noted on animals in the test group following the first induction. Cumulative irritation was noted during successive inductions resulting in very faint to strong erythema. No evidence of sensitization occurred; three test animals displayed very faint erythema following challenge. Four animals in the challenge control group displayed very faint erythema during challenge. Because reactions were comparable between treated and naive animals at challenge, responses noted were attributed to irritation rather than sensitization reactions.

Under the condition of this study, the test material is judged to be non-sensitizing when topically applied to Hartley guinea pigs.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

No test is available for assessment of skin sensitising properties of lithium fluoride. Therefore read across was performed with two structurally similar substances in order to cover both ionic parts of the target substance (sodium fluoride, lithium chloride).

Buehler assay with sodium fluoride

The test was performed according to US EPA method OPP 81 -6. 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.

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.

Buehler assay with lithium chloride

A skin sensitisation test in Hartley guinea pigs was performed according to OECD 406 and EU method B.6. Lithium chloride solution (0.5 mL undiluted) was applied to the right shoulder of each of ten male Hartley guinea pigs for a six hour exposure period at weekly intervals for three weeks. 14 days after the third induction treatment, the animals were challenged at a virgin skin site. The concentration of the test material chosen for challenge of the test group was the undiluted test material, which was the highest non-irritating concentration as determined during the range-finding phase of this study. An additional 10 male naive animals (naive test group) also received 0.5 mL of the undiluted test material for the challenge application. Observations for skin reactions were recorded approximately 24 hours after unwrapping each induction application and approximately 24 and 48 hours following unwrapping of the challenge application. Body weights were recorded at initiation and termination.

All animals remained healthy and gained weight during the study. No irritation was noted on animals in the test group following the first induction. Cumulative irritation was noted during successive inductions resulting in very faint to strong erythema. No evidence of sensitization occurred; three test animals displayed very faint erythema following challenge. Four animals in the challenge control group displayed very faint erythema during challenge. Because reactions were comparable between treated and naive animals at challenge, responses noted were attributed to irritation rather than sensitization reactions. Under the condition of this study, the test material is judged to be non-sensitizing when topically applied to Hartley guinea pigs. Thus, based on the results obtained, lithium chloride has not to be classified and labelled with respect to skin sensitisation according to Regulation (EC) No 1272/2008 (CLP).

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. As a result the substance is not considered to be classified as skin sensitising under Regulation (EC) No 1272/2008.