Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Toxicological information

Endpoint summary

Currently viewing:

Administrative data

Description of key information

Based on the results of the read across studies with lithium chloride and lithium carbonate as well as on the non-sensitising properties of acetic acid, it is concluded that lithium acetate is not skin sensitising.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

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
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
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.
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
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
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
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)
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.
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
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
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
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
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
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

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

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.

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
Reason / purpose for cross-reference:
reference to same 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:
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: 410-01d

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature
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
Route:
epicutaneous, occlusive
Vehicle:
water
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
Route:
epicutaneous, occlusive
Vehicle:
water
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):
no
Positive control results:
No positive control
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
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
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
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:
positive indication of skin sensitisation
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.
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 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.

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
HYPOTHESIS FOR THE ANALOGUE APPROACH
Lithium acetate completely dissociates in water forming lithium cation and the corresponding acetate anion. Thus, lithium salts with different anion moieties were found to be suitable candidates for read-across. (Eco)toxicological properties were extrapolated to different endpoints by using the lowest effect concentration.
For further information, please refer to the read-across justification in chapter 13.
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across: supporting information
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.5 mL LiCl (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
Remarks:
(FMC, 1997)
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0.5 mL LiCl (undiluted)
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Remarks:
(FMC, 1997)
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:
other: (FMC, 1997)
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:
other: (FMC, 1997)
Group:
positive control
Remarks on result:
positive indication of skin sensitisation
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

No skin sensitising study for lithium acetate is available. Therefore read across was performed to lithium carbonate and lithium chloride. A summary of the available studies for lithium carbonate and lithium chloride can be found below.

Sensitisation study 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 group of 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 sensitisation occurred; three test animals of the test group 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 this result, it can be assumed that lithium acetate is not a sensitiser.

Sensitisation study with lithium carbonate

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-sensitising when topically applied to Hartley guinea pigs.

Based on this result, it can be assumed that lithium aceate is not a sensitiser.

CONCLUSION

Based on the above study results, sensitising properties for lithium acetat can be excluded.

Acetic acid is an important industrial chemical that is also used in food industry as acidity regulator (E260). Its harmonised classification and labelling listed in Annex VI of Regulation (EC) No 1272/2008 does not include skin sensitising properties.

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 for skin sensitisation under Regulation (EC) No 1272/2008, as amended for the tenth time in Regulation (EU) No 2017/776.