Lithium hydroxide

Skin sensitisation

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1998

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

1992

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Version / remarks:

1992

Deviations:

no

Test guideline 3

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:

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

Test material information

Constituent 1

Reference substance name:

Lithium chloride

EC Number:

231-212-3

EC Name:

Lithium chloride

Cas Number:

7447-41-8

Molecular formula:

ClLi

IUPAC Name:

Lithium chloride

Details on test material:

- Name of test material (as cited in study report): Lithium chloride solution
- Physical state: Clear liquid
- Analytical purity: 40.8 % (Specification: 38 - 42 %)
- Composition of test material, percentage of components: 35 - 40 % LiCl, aqueous solution

In vivo test system

Test animals

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 (°C): 18.9°C - 20°C
- Humidity (%): 32 % - 53 %
- Photoperiod (hrs dark / hrs light): 12 hours fluorescent light/ 12 hours dark

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

epicutaneous, occlusive

Vehicle:

water

Induction 2

Concentration / amount:

Irritation Range-Finding Phase: undiluted, 50 %, 25 % and 10 % in tap water
Induction Phase: undiluted, 0.5 ml
Challenge Phase: undiluted, 0.5 ml

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

water

Challenge 2

Concentration / amount:

Irritation Range-Finding Phase: undiluted, 50 %, 25 % and 10 % in tap water
Induction Phase: undiluted, 0.5 ml
Challenge Phase: undiluted, 0.5 ml

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
- Duration: 0-14 d



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): 6 h

Challenge controls:

No challenge controls

Positive control substance(s):

yes

Remarks:

1-chloro-2,4-dinitrobenzene (DNCB)

Results and discussion

Positive control results:

DNCB was proven to be an effective sensitizing agent when topically applied to Hartley guinea pigs.

In vivo (non-LLNA)

Results

Results 1

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

Results 2

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

Results 3

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

Results 4

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

Results 5

Group:

positive control

Remarks on result:

positive indication of skin sensitisation

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the condition of this study (Buehler test), the test material is judged to be non-sensitizing when topically applied to Hartley guinea pigs. Based on this result, it can be assumed that lithium hydroxide is not a sensitiser.

Executive summary:

In accordance with column 2 of REACH Regulation 1907/2006/EC Annex VII section 8.3. an in vivo test does not need to be conducted if the available information indicates that the substance should be classified for skin corrosivity, or the substance is a base (pH ≥ 11.5). Lithium hydroxide anhydrous and its monohydrate are corrosive and form base in contact with water with strong alkaline pH (≥ 11.5). Thus, respective studies are not required. Instead, a study with lithium chloride was used for read-across.

A skin sensitisation study with lithium hydroxide is not available. Consequently, read across was applied using study results obtained from 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 of the test group 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 lithium chloride is judged to be non-sensitising when topically applied to Hartley guinea pigs.

Lithium hydroxide (respectively lithium hydroxide monohydrate) was found non-sensitizing when read-across from this study was applied that was performed with lithium chloride according to OECD 406 and EU method B.6. Based on the results obtained, lithium hydroxide (respectively lithium hydroxide monohydrate) has not to be classified and labelled with respect to skin sensitisation according to Directive 67/548/EEC (DSD) and Regulation (EC) No 1272/2008 (CLP).