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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:
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 guidelineopen allclose all
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:
A valid skin sensitisation study according to OECD guideline 406 with lithium chloride is available.

Test material

Constituent 1
Chemical structure
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
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
undiluted, 0.5 mL
Day(s)/duration:
0-14 d/ 6h
Challenge
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
undiluted, 0.5 mL
Day(s)/duration:
day 28/ 6h
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):
no

Results and discussion

Positive control results:
No positive control

In vivo (non-LLNA)

Resultsopen allclose all
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
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
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
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
Group:
positive control
Remarks on result:
other: not indicated

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the condition of this study (Buehler test), the test material, lithium chloride revealed no sensitizing properties. Based on this result, it can be assumed that lithium is not sensitizing.
Executive summary:

In accordance with column 2 of REACH Regulation 1907/2006/EC Annex VII section 8.3. an in vivo sensitisation test does not need to be conducted if the available information indicates that the substance should be or is classified as corrosive to the skin. Lithium metal is corrosive and is labelled as such as it forms a strong base (lithium hydroxide) in contact with water or moist skin. Thus, results of a sensitisation study with lithium metal will be of no meaningful value because of local tissue damage due to corrosiveness. For estimation of the sensitisation potential of lithium / lithium ions a study with lithium chloride was used in a read-across approach.

As skin sensitisation study with lithium is not available, 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-sensitizing when topically applied to Hartley guinea pigs.

Based on the results obtained in this study and following a read across approach, it can be assumed that lithium is not sensitising and 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).