Lithium acetate

Endpoint summary

Description of key information

Dermal: The dermal LD50 of the test item is greater than 2000 mg/kg.

Oral: The oral LDLo of the test item was determined as 1500 mg/kg.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

no guideline followed

Principles of method if other than guideline:

- Parameters analysed / observed: The minimum lethal dose was investigated. The toxicity of the test substance was determined according to the survival of the animals and their general conditions. The animals were observed for 30 days after the administration of the solution.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

mouse

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 21 - 23 g
- Acclimation period: 10 days

Route of administration:

oral: gavage

Vehicle:

not specified

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 1 mL

No. of animals per sex per dose:

20

Control animals:

yes

Key result

Sex:

not specified

Dose descriptor:

LDLo

Effect level:

1 500 mg/kg bw

Based on:

test mat.

Gross pathology:

Animals that died revealed morphological changes of the lungs, brain and liver that were characterised as sharply expressed polyemia. Selective degeneration mainly affected liver, kidney and the nervous system. Morphological changes increased with the dosage of the test substance.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

According to Neretin et al. an LDLo of 1500 mg/kg bw was determined for mice.

Executive summary:

Lithium acetate was tested on 20 white mice per dose group in an acute toxicity study (Neretin, 1958). The LDLo- and LD100-levels in this study were 1500 mg/kg bw and 4000 mg/kg bw, respectively.

Animals that died revealed morphological changes of the lungs, brain and liver that were characterised as sharply expressed polyemia. Selective degeneration mainly affected liver, kidney and the nervous system. Morphological changes increased with the dosage of the test substance.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Quality of whole database:

reliable study report, sufficient for assessment

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

other justification

Justification for data waiving:

other:

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

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)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Lot/batch No.of test material: Reference No.: 434-01A; - FMC-T#: 1562

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage: Room temperature
- Stability: 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: Adult
- Weight at study initiation: 200-300 g
- Housing: Individually housed in stainless steel, suspended cages containing DACB indirect bedding.
- Diet: Purina Rodent Chow 5001 (pellets), ad libitum
- Water: Tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 - 20.6 °C
- Humidity: 51 - 56 %
- Photoperiod: 12-hour fluorescent light/dark cycle

Type of coverage:

occlusive

Vehicle:

water

Details on dermal exposure:

TEST SITE
- Area of exposure: From the Scapula to the pelvic region.
- % coverage: At least 10 % of the body surface
- Type of wrap if used: Gauze pad was secured with hypoallergenic tape and was covered with an elastic, plastic-lined bandage.

REMOVAL OF TEST SUBSTANCE
- Washing: Test sites were rinsed with water
- Time after start of exposure: 24 h

VEHICLE
- Amount(s) applied: 0.50 mL tap water

Duration of exposure:

24 hours

Doses:

2000 mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: Observations for toxicity were conducted 0.5, 1, 2, 3, 4 and 6 hours post-dosing, and daily thereafter. Dermal irritation were recorded on days 1, 3, 7 and 14. Body weights were recorded weekly.
- Necropsy of survivors performed: yes

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths were noted

Clinical signs:

All rats remained healthy during the study.

Body weight:

Immediately prior to dosing, body weights ranged from 223-266 g. All but one rat gained weight by day 14 of the study; this rat lost weight through day 7, then regained weight to return to its' pre-dosing weight.

Gross pathology:

No gross internal lesions were observed in any animal during necropsy.

Other findings:

Local irritation: The only irritation noted during the study was erythema in one female on study day 1.

Interpretation of results:

GHS criteria not met

Conclusions:

The dermal LD50 of the test material is greater than 2000 mg/kg.

Executive summary:

The acute dermal toxicity was assessed equivalent or similar to OECD guideline 402. Lithium acetate dihydrate was topically applied to five Sprague-Dawley rats per sex at a dosage level of 2000 mg/kg. The test material was in contact with the skin under an occlusive wrap for 24 hours. Observations for toxicity were conducted 0.5, 1, 2, 3, 4 and 6 hours post-dosing, and daily thereafter for 14 days. Dermal irritation was recorded in day 1, 3, 7 and 14. Body weights were recorded weekly. Gross necropsies were performed on all animals. No death were noted. All rats remained healthy during the study. All but one rat gained weight by day 14 of the study; this rat lost weight through day 7, then regained weight to return to its' pre-dosing weight. The only dermal irritation noted was erythema in one female on day 1. No gross lesions were revealed during necropsy. The dermal LD50 of the test item is greater than 2000 mg/kg.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

reliable study report, sufficient for assessment

Additional information

Acute oral toxicity

Lithium acetate was tested on 20 white mice per dose group in an acute toxicity study (Neretin, 1958). The LDLo- and LD100-levels in this study were 1500 mg/kg bw and 4000 mg/kg bw, respectively.

Animals that died revealed morphological changes of the lungs, brain and liver that were characterised as sharply expressed polyemia. Selective degeneration mainly affected liver, kidney and the nervous system. Morphological changes increased with the dosage of the test substance.

Acute inhalation toxicity
In accordance with column 2 of REACH Annex VIII, an acute inhalation toxicity study does not need to be conducted as two other routes for acute toxicity are provided. 

Acute dermal toxicity
Lithium acetate dihydrate was topically applied to five Sprague-Dawley rats per sex at a dosage level of 2000 mg/kg . The test material was in contact with the skin under an occlusive wrap for 24 hours. Observations for toxicity were conducted 0.5, 1, 2, 3, 4 and 6 hours post-dosing, and daily thereafter for 14 days. Dermal irritation was recorded in day 1, 3, 7 and 14. Body weights were recorded weekly. Gross necropsies were performed on all animals. No death were noted. All rats remained healthy during the study. All but one rat gained weight by day 14 of the study; this rat lost weight through day 7, then regained weight to return to its' pre-dosing weight. The only dermal irritation noted was erythema in one female on day 1. No gross lesions were revealed during necropsy. The dermal LD50 of the test item is greater than 2000 mg/kg.

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. The LDLo-value of 1500 mg/kg bw was used for the determination acute oral toxicity. As a result, the substance is to be classified as Cat. 4 (H302: Harmful if swallowed) but not considered to be classified for acute inhalation and dermal toxicity under Regulation (EC) No 1272/2008, as amended for the tenth time in Regulation (EU) No 2017/776.