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Description of key information

Acute oral toxicity: LD50 of 613 mg Li2SO4/kg bw/day

Acute dermal toxicity: LD50 >3000 mg LiNO3/kg bw/day

Acute inhalation toxicity: Testing for acute toxicity via the inhalation route was not applicable as data on acute oral and acute dermal toxicity were available. According to REACH Regulation No. 1907/2006, Annex VIII, 8.5 data for a maximum of two routes of exposure need to be provided. Furthermore, considering the high melting point (1205 °C) and the very low vapor pressure (4.88E-022 Pa) of lithium phosphate, exposure by inhalation is unlikely.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1998
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Qualifier:
no guideline followed
Principles of method if other than guideline:
Only handbook or published data available. No guideline indicated.
GLP compliance:
not specified
Test type:
other: not indicated
Species:
rat
Strain:
not specified
Sex:
not specified
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
613 mg/kg bw
Based on:
test mat.
Remarks:
Li2SO4
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The publication of Walum et al. states a LD50 value of 613 mg/kg bw for rats.
Executive summary:

The publication was used to analyse the predictive power of animal tests for human toxicity. The Scandinavian Society of Cell Toxicology used lithium sulfate as one out of 50 reference substances. The LD50 value for rats was determined out of several studies and defined as 613 mg/kg bw.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Qualifier:
no guideline followed
Principles of method if other than guideline:
Only handbook or published data available. No guideline indicated.
GLP compliance:
not specified
Test type:
other: not indicated
Species:
mouse
Strain:
not specified
Sex:
male/female
Route of administration:
oral: unspecified
Vehicle:
not specified
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 190 mg/kg bw
Based on:
test mat.
Remarks:
Li2SO4
Remarks on result:
other: Walum et al.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
953 mg/kg bw
Based on:
test mat.
Remarks:
Li2SO4
95% CL:
> 822 - <= 1 103
Remarks on result:
other: Samoilov et al.
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Both publications state a LD50 of around 1000 mg/kg bw. Walum (1998) specifies a LD50 of 1190 mg/kg bw and Samoilov et al. (1970) a LD50 of 853 mg/kg bw for male and female albino mice.
Executive summary:

Both publications state a LD50 of around 1000 mg/kg bw. Walum (1998) specifies a LD50 of 1190 mg/kg bw and Samoilov et al. (1970) a LD50 of 853 mg/kg bw for male and female albino mice.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1999-03-26 to 1999-05-06
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
February 24th 1987
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Version / remarks:
January 1993
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Version / remarks:
August 1998
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature
- Stability under test conditions: Stable for a minimum of 30 days

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories
- Age at study initiation: young adults
- Weight at study initiation: 207-275 g
- Fasting period before study: yes
- Housing: Individually housed in stainless steel, suspended cages
- Diet: Purina Rodent Chow 5001 (pellets), ad libitum
- Water: Fresh tap water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 65-71
- Humidity (%): 50-61
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
- Amount of vehicle:
Dosage group 2000 mg/kg, males: 1.8 - 1.9 mL
Dosage group 2000 mg/kg females: 1.7 - 1.8 mL
Dosage group 1500 mg/kg males: 1.3 - 1.4 mL
Dosage group 1500 mg/kg females: 1.3 mL
Dosage group 1000 mg/kg males: 0.94 - 1.1 mL
Dosage group 1000 mg/kg females: 0.83 - 0.90 mL

Doses:
1000, 1500, 2000 mg/kg bw
No. of animals per sex per dose:
5 animals/dose/sex
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 0.5, 1, 2, 3, 4, 6 h following dosing and daily thereafter for 14 days
- Necropsy of survivors performed: Yes, any animal not surviving to termination were also necropsied.
- Clinical signs: 0.5, 1, 2, 3, 4, 6 h following dosing and daily thereafter for 14 days
- Body weight: Recorded on days 0, 7 and 14
Statistics:
The oral LD50 value and 95% confidence limits for separate and combined sexes were calculated using a modified Logit-Linear Regression Program written by Jim Gibbons, Texas Instruments Calculator Products Division.
Sex:
male
Dose descriptor:
LD50
Effect level:
1 317 mg/kg bw
Based on:
test mat.
Remarks:
LiNO3
95% CL:
>= 993 - <= 1 640
Sex:
female
Dose descriptor:
LD50
Effect level:
1 519 mg/kg bw
Based on:
test mat.
Remarks:
LiNO3
95% CL:
>= 1 179 - <= 1 859
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 426 mg/kg bw
Based on:
test mat.
Remarks:
LiNO3
95% CL:
>= 1 242 - <= 1 609
Mortality:
All deaths occurred within 5 days of dosing. Data is summarized below.
Clinical signs:
All deaths occurred within 5 days after dosing. The most significant clinical signs were twitching, rolling over in cage, recumbency, loss of muscle control, squinting eyes and tremors. All signs subsided by study day 6.
Body weight:
All survivors gained weight by day 14 of the study.
Gross pathology:
Red liquid was found in the stomach of one decedent and red liquid was found in the intestines of another decedent. Animals sacrificed at study termination on day 14 were found to be normal at necropsy.

The summarized mortality data:

    Male     Female     Combined
 Dosage Level (mg/kg bw)  No. dead / No. dosed  Dosage Level (mg/kg bw)  No. dead / No. dosed  Dosage Level (mg/kg bw)  No. dead / No. dosed
 2000  5/5  2000  5/5  2000  10/10
 1500  4/5  1500  2/5  1500  6/10
 1000  0/5  1000  0/5  1000  0/10
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Based on the results of the acute oral toxicity study of lithium nitrate an LD50 of 1317 (male), 1519 (female) and 1426 (Combined) mg/kg bw was derived.
Executive summary:

Groups of five male and female Sprague-Dawley rats were orally administered lithium nitrate by a 25% (w/v) preparation in tap water. Observations for toxicity were conducted 0.5, 1, 2, 3, 4, and 6 hours post-dosing, and daily thereafter for fourteen days. Body weights were recorded weekly and prior to necropsy. Gross necropsies were performed on all animals. All deaths occurred within 5 days of dosing. The most significant clinical signs were twitching, rolling over in cage, recumbency, loss of muscle control, squinting eyes and tremors. All signs subsided by study day 6; surviving rats remained healthy and gained weight until study termination. Red liquid was found in the stomach of one and in the intestine of another decedent. Animals sacrificed at study termination on day 14 were found to be normal at necropsy. The LD50 values determined were 1317 mg/kg in male rats, 1519 mg/kg in female rats, and 1426 mg/kg in combined sexes.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
613 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Justification for type of information:
Testing for acute toxicity via the inhalation route was not applicable as data on acute oral and acute dermal toxicity were available. According to REACH Regulation No. 1907/2006, Annex VIII, 8.5 data for a maximum of two routes of exposure need to be provided. Furthermore, considering the high melting point (1205 °C) and the very low vapor pressure (4.88E-022 Pa) of lithium phosphate, exposure by inhalation is unlikely.
Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1976-10-20
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
February 24th, 1987
Deviations:
yes
Remarks:
Four rabbits per dose (two rabbits per sex) instead of five rabbits per dose were used in the study. Two instead of three dose levels were tested in the study.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: Young adults
- Weight at study initiation: 2.42-2.82 kg
- Fasting period before study: No
- Housing: Individullay housed in suspended, wire-bottomed cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: At least 7 days
Type of coverage:
occlusive
Vehicle:
water
Details on dermal exposure:
TEST SITE
- Area of exposure: The whole back
- % coverage: 30 % of the total body surface area
- Type of wrap if used: Impervious plastic sheeting

REMOVAL OF TEST SUBSTANCE
- Washing: Yes
- Time after start of exposure: 24h after treatment

TEST MATERIAL
- Amount(s) applied: 2000, 3000 mg/kg bw
- Constant volume or concentration used: Yes
- For solids, paste formed: Yes, an aqueous slurry

VEHICLE
- water
Duration of exposure:
24 hours
Doses:
2000, 3000 mg/kg bw
No. of animals per sex per dose:
2 animals per sex per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Daily observations for mortality, local skin reactions and behavioural abnormalities
- Necropsy of survivors performed: Yes
- clinical signs: Daily
- body weight: Initial, 7- and 14-day body weights were recorded
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 3 000 mg/kg bw
Based on:
test mat.
Remarks:
Li2CO3
Sex:
male/female
Dose descriptor:
LD0
Effect level:
2 000 mg/kg bw
Based on:
test mat.
Remarks:
Li2CO3
Mortality:
No mortality occured within the 2000 mg/kg bw testing group.
One animal of the 3000 mg/kg bw testing group died. The cause of death was not evident.
Clinical signs:
The test material showed no irritating properties to the skin of the albino rabbit.
Body weight:
All animals gained weight throughout the study period.
Gross pathology:
Necropsy examination revealed advanced post mortem autolysis in the early died rabbit of the 3000 mg/kg bw testing group. No gross pathologic alterations were noted in any of the other rabbits.
Other findings:
No pharmacotoxic symptoms were exhibited by the rabbits following dermal exposure.
Interpretation of results:
GHS criteria not met
Conclusions:
In the acute dermal toxicity study an LD50 value of above 3000 mg/kg bw was determined.
Executive summary:

The acute dermal toxicity study was performed with lithium carbonate. Four male and four female New Zealand white rabbits were treated (a 24-hour occlusive dermal application) with an aqueous lithium carbonate slurry at dose levels of 2000 mg/kg bw and 3000 mg/kg bw. One animal from the 3000 mg/kg bw testing group died under non-evident circumstances. Clinical signs or dermal symptoms were not observed during the 14 days post-treatment observation period. No effects on body weight gain were noted for these groups. Specific macroscopic alterations related to the toxic effect of lithium carbonate were not found. The acute dermal LD50 value was determined to be above 3000 mg/kg bw in male and female New Zealnd white rabbits and 2000 mg/kg bw can be determined as the discriminating dose.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
3 000 mg/kg bw

Additional information

Acute toxicity via oral route

An acute oral toxicity study with lithium phosphate was not available. Consequently read-across was applied using characteristically similar compounds. A weight of evidence approach was performed with read-across data from lithium sulfate and lithium nitrate.

Read-across with lithium sulfate (Walum 1998, Samoilov 1970)

Three weight of evidence approaches were available for lithium sulfate anhydrous regarding rats, mice and humans (for human data please refer to section 7.10.5). Rats were the most sensitive species with an LD50 of 613 mg/kg bw obtained from an overview article regarding the predictive power of animal testing for human toxicity from Walum (1998). The Scandinavian Society of Cell Toxicology used lithium sulfate as one out of 50 reference substances. The article further states an LD50 value of 1190 mg/kg bw for mice. This value was supported by a Russian publication regarding the comparative toxicity of some lithium salts from Samoilov (1970). Here a value of 953 mg/kg bw (CI: 822 - 1103 mg/kg bw) for mice was stated. For humans Walum (1998) stated a mean oral lethal dose of 1065 mg/kg bw. The data was obtained from clinical observations and /or autopsy data.

Read-across with lithium nitrate (FMC, I99-2283, 1999)

Groups of five male and female Sprague-Dawley rats received lithium nitrate orally by a 25% (w/v) preparation in tap water. Observations for toxicity were conducted 0.5, 1, 2, 3, 4, and 6 hours post-dosing, and daily thereafter for fourteen days. Body weights were recorded weekly and prior to necropsy. Gross necropsies were performed on all animals. The LD50 values in mg/kg bw and the corresponding 95% confidence limits are as follows: Male: 1317 (993-1640); Female: 1519 (1179-1859); Combined: 1426 (1242-1609). All deaths occurred within 5 days of dosing. The most significant clinical signs were twitching, rolling over in cage, recumbency, loss of muscle control, squinting eyes and tremors. All signs subsided by study day 6; surviving rats remained healthy and gained weight until study termination. Red liquid was found in the stomach of one and in the intestines of another decedent. Animals sacrificed at study termination on day 14 were found to be normal at necropsy.

Acute toxicity via inhalation:
Additional testing by inhalation route is not applicable as data for oral and dermal toxicity study were available. According to the REACH Regulation (EC) No 1907/2006, Annex VIII, 8.5.1 only information on two application routes needs to be provided, with test item administration via the most appropriate route. In addition, low inhalation exposure is expected due to the high melting point (1205 °C) and low vapour pressure (4.88E-022 Pa) of the test item.

Acute toxicity via dermal route:

An acute dermal toxicity study with lithium phosphate was not available. Consequently read-across was applied using a characteristically similar compound, lithium carbonate.

Read-across with lithium carbonate (Industrial BIO-TEST, 8530-09465, 1976)

The acute dermal toxicity study was performed with lithium carbonate. Four male and four female New Zealand white rabbits were treated (a 24-hour occlusive dermal application) with an aqueous lithium carbonate slurry at dose levels of 2000 mg/kg bw and 3000 mg/kg bw. One animal from the 3000 mg/kg bw testing group died under non-evident circumstances. Clinical signs or dermal symptoms were not observed during the 14 days post-treatment observation period. No effects on body weight gain were noted for these groups. Specific macroscopic alterations related to the toxic effect of lithium carbonate were not found. The acute dermal LD50 value was determined to be above 3000 mg/kg bw in male and female New Zealnd white rabbits and 2000 mg/kg bw can be determined as the discriminating dose.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008:
The available experimental test data with the read-across substances are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on available data on acute toxicity, the test substance is classified as cat. 4, H302 (Harmful if swallowed) according to Regulation (EC) No 1272/2008 (CLP), as amended for the tenth time in Regulation (EU) No 2017/776.