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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:
1993-10-18 to 1993-11-11
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report date:
1994

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
1981
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Version / remarks:
1987
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPP 81-6 (Skin Sensitisation)
Version / remarks:
1984
Deviations:
no
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. The availabe skin sensitisation study was performed according to OCED guideline 406 and is of good quality (reliability 1). 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:
Lithium carbonate
EC Number:
209-062-5
EC Name:
Lithium carbonate
Cas Number:
554-13-2
Molecular formula:
CH2O3.2Li
IUPAC Name:
dilithium carbonate
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): Lithium carbonate, Pharmaceutical Grade
- Physical state: Fine white powder
- Analytical purity: 99.2 %

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: HRP, Inc., Denver, PA
- Age at study initiation: Young adult
- Weight at study initiation: 301 g - 379 g
- Housing: individually housed in suspended polycarbonate cages
- Diet: ad libitum, Purina Guinea Pig Chow 5025
- Water: ad libitum, fresh tap water


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.9 - 23.3
- Humidity (%): 37 - 89
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: ethanol, acetone
Concentration / amount:
Test group: 0.3 g undiluted test material
Positive control group: 0.3 g test material plus 0.3 mL of 0.15 % DNCB in 80 % ethanol
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: ethanol, acetone
Concentration / amount:
Test group: 0.3 g undiluted test material
Positive control group: 0.3 g test material plus 0.3 mL of 0.15 % DNCB in 80 % ethanol
No. of animals per dose:
Test group: 20 (10 male, 10 female)
Positive control group: 10 (5 male, 5 female)
Challenge group: 10 (5 male, 5 female)
Details on study design:
The test material (0.3 g) was applied undiluted to each of 20 Hill Top Chambers®. In addition, 0.3 g test material plus 0.3 mL of 0.15 % DNCB in 80 % ethanol was applied to the test sites (left shoulder), and secured with hypoallergenic tape. Each animal was then wrapped with an elastic, plastic-lined bandage.
Six hours later, the bandage and chambers were removed and the test sites were wiped with clean gauze moistened with methanol. The test sites were then rinsed with tap water. The guinea pigs were dosed in this manner once weekly until a total of three applications had been administered. Following a 14 day rest period, the guinea pigs were challenged on a virgin site on the right shoulder in the manner described above.
Challenge controls:
An additional 10 naive animals each received 0.3 g of the test material for comparison.
Positive control substance(s):
yes
Remarks:
1-chloro-2,4-dinitrobenzene (DNCB)

Results and discussion

Positive control results:
Animals in the positive control group had slight erythema and edema following the initial induction application and all but one had well defined to moderate erythema and slight to mild edema following challenge.
No irritation was noted on any of the test or challenge control animals at any time during the study.

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.3 g test substance
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
None
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
other: challenge group
Dose level:
0.3 g test substance
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
None
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0.3 g test substance
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
None
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
other: challenge group
Dose level:
0.3 g test substance
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
None
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.3 g test substance and 0.3 mL of 0.15 % DNCB in 80 % ethanol
No. with + reactions:
10
Total no. in group:
10
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.3 g test substance and 0.3 mL of 0.15 % DNCB in 80 % ethanol
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: positive control. Dose level: 0.3 g test substance and 0.3 mL of 0.15 % DNCB in 80 % ethanol. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: None.
Reading:
1st reading
Hours after challenge:
24
Group:
other: positive control challenge
Dose level:
0.3 g test substance and 0.3 mL of 0.15 % DNCB in 80 % ethanol
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: other: positive control challenge. Dose level: 0.3 g test substance and 0.3 mL of 0.15 % DNCB in 80 % ethanol. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: None.
Reading:
2nd reading
Hours after challenge:
48
Group:
other: positive control challenge
Dose level:
0.3 g test substance and 0.3 mL of 0.15 % DNCB in 80 % ethanol
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: other: positive control challenge. Dose level: 0.3 g test substance and 0.3 mL of 0.15 % DNCB in 80 % ethanol. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: None.
Group:
negative control
Remarks on result:
not measured/tested

Any other information on results incl. tables

The challenge results for erythema are summarized below:

Erythema Scoresa

Group

 

0

1

2

3

4

Incidenceb

Severityc

Test Material

(24hr)

0

0

0

0

0

0/20

0

 

(48hr)

0

0

0

0

0

0/20

0

Challenge Control

(24hr)

0

0

0

0

0

0/10

0

 

(48hr)

0

0

0

0

0

0/10

0

Positive Control

(24hr)

0

1

1

8

0

9/10

2.7

 

(48hr)

0

1

5

4

0

9/10

2.3

a: Number animals exhibiting each score.

b: Number animals having scores greater than 1/ Total number animals challenged

c: Sum of (Number animals exhibiting each score x score)/ Total number animals challenged

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this study, the test material is non-sensitizing when topically applied to Hartley guinea pigs.
Executive summary:

A skin sensitisation test in Hartley guinea pigs was performed according to OECD 406 and EU method B.6 (Buehler test). Lithium carbonate Pharmaceutical Grade (0.30 g) was applied undiluted topically to the left shoulders (previously clipped free of hair) of 10 male and 10 female Hartley guinea pigs. The test material was left in contact with the skin for approximately six hours. The animals received three induction treatments one week apart. A concurrent positive control group of 10 animals was treated in a similar manner with DNCB (0.15 % weight/volume). 14 days after the third induction treatment, the animals were challenged with the test material at a virgin skin site. An additional 5 male and 5 female naive animals received 0.30 g of the undiluted test material (challenge control group). The positive control group was challenged with DNCB. Observations for skin reactions were recorded at initiation and termination. All animals remained healthy and gained weight during the study. No skin reactions were noted on any of the test or challenge control animals at any time during the study. Animals in the positive control group had slight erythema and edema following the initial induction application and all but one had well defined to moderate erythema and slight to mild edema following challenge. Under the conditions of this study, the test material is non-sensitizing when topically applied to Hartley guinea pigs.

Thus, based on the results obtained, lithium carbonate has not to be classified and labelled with respect to skin sensitisation according to Regulation (EC) No 1272/2008 (CLP).