Lithium acetate

Skin sensitisation

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 guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

1981

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Version / remarks:

1987

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 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

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Lot/batch No. of test material: Lot 0902

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature

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 (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 - 23.3°C
- Humidity (%): 37 % - 89 %
- Photoperiod (hrs dark / hrs light): 12 hours fluorescent light/ 12 hours dark

Study design: in vivo (non-LLNA)

Induction

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

Challenge

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)

Results

Results 1

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

Results 2

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

0.3 g test substance

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

None

Results 3

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

Results 4

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

0.3 g test substance

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

None

Results 5

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

Clinical observations:

None

Results 6

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

Any other information on results incl. tables

The challenge results for erythema are summarized below:

Erythema Scores^a
Group		0	1	2	3	4	Incidence^b	Severity^c
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:

not sensitising

Conclusions:

Under the conditions of this study, the test material lithium carbonate is non-sensitizing. Based on this result, it can be assumed that lithium posses no sensitizing properties.

Executive summary:

A skin sensitisation test in Hartley guinea pigs was performed according to OECD 406 and EU method B.6. 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.