Lithium chloride

Endpoint summary

Description of key information

Acute toxicity data are available for all three ways of exposure:
LD50 (rat, oral): 526 mg/kg bw
LD50 (rat, dermal): > 2000 mg/kg bw
LD50 (rat, inhalation): 5570 mg/m³

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

Study period:

1980

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Reason / purpose for cross-reference:

reference to other study

Qualifier:

no guideline followed

Principles of method if other than guideline:

Only data from review article available. No guideline or method indicated.

GLP compliance:

not specified

Test type:

other: not applicable

Species:

rat

Strain:

not specified

Sex:

male

Details on test animals or test system and environmental conditions:

The rats were 3 weeks, 6 weeks, 3 months and 6 months old.

Details on oral exposure:

Lithium chloride was given intraperitoneally, subcutaneously and orally.

Doses:

No data

No. of animals per sex per dose:

No data

Control animals:

not specified

Details on study design:

No data

Statistics:

No data

Preliminary study:

Not applicable

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

526 mg/kg bw

Based on:

test mat.

Mortality:

No data

Clinical signs:

other: No data

Gross pathology:

No data

Other findings:

No data

In relation to age, LD50 was significantly higher in rats of 6 weeks after oral administration than LD50 in rats of 3 and 6 months. No differences were found following intraperitoneal and subcutaneous administration. In relation to route of administration, LD50 was significantly higher in rats of 3 and 6 weeks after oral administration than LD50 after intraperitoneal and subcutaneous administration. This difference was not found in rats of 3 and 6 months. It is concluded that age and route of administration are of significance for LD50 of Lithium chloride in the rat.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

According to the review article, the LD50 of lithium chloride is 526 mg/kg bw after oral administration to rats.

Executive summary:

According to the reviewarticle, the LD50 of lithium chloride is 526 mg/kg bw after oral administration to rats.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

526 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1999-03-23 to 1999-06-11

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

1981

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.2 (Acute Toxicity (Inhalation))

Version / remarks:

1992

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

Version / remarks:

1998

Deviations:

no

Principles of method if other than guideline:

NA

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories
- Weight at study initiation: males: 253 g to 319 g
- Housing: animals were individually housed in stainless steel suspended rat cages
- Diet (e.g. ad libitum): ad libitum, Purina Laboratory Rodent Chow 5001
- Water (e.g. ad libitum): ad libitum, fresh tap water
- Acclimation period: animals were acclimated for a minimum of 5 days prior to study start


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.3°C - 20.6°C
- Humidity (%): 53 % - 61 %
- Air changes (per hr): the exposure was conducted for 4 hours. At the end of the exposure, the chamber was cleared for approximately 10 minutes by drawing room air through it at the same flow rate (37.2 litres per minute) prior to removing the animals
- Photoperiod (hrs dark / hrs light): 12 hours fluorescent light/ 12 hours dark

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: The 11-liter ADG nose-only exposure chamber was made of anodized aluminium and was operated dynamically.
- Source and rate of air: The calculated 99 % equilibrium time for the chamber at a flow rate of 37.2 litres per minute was 1.4 minutes (equivalent to 1 "air change" every 18 seconds).

- Method of holding animals in test chamber: The test animals were assigned to and housed in individual polycarbonate nose-only tubes during the exposure. The tube position assignment ensured equal distribution of both sexes around the chamber.
- Method of particle size determination: The aerodynamic particle size distribution was determined by gravimetric analysis of the amount of test material collected on the impactor stages. The MMAD, GSD and the percent of aerosol less than or equal to 1, 10, and 15 microns in size were determined by logarithmic-probability plotting.

- Treatment of exhaust air: The chamber air was exhaust from the bottom of the chamber and passes through an orifice tube system which continuously monitored airflow and then through a commercial filter box.

- Temperature, humidity, in air chamber: 21.7 °C, 74 %


TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: Chamber air samples were also taken twice during the exposure to determine the aerodynamic particle size distribution of airbone material. The samples were drawn through a Sierra Series 218 cascade impactor at 2.82 litres per minute.

- MMAD (Mass median aerodynamic diameter)/GSD (Geometric st. dev.): less than or equal to 1, 10, and 15 microns in size were determined by logarithmic-probability plotting

Duration of exposure:

4 h

Concentrations:

mean concentration: 5.57 mg/L

No. of animals per sex per dose:

5

Control animals:

no

Statistics:

Particle size distributions will be determined, by log-probability plotting of the data and subsequent determination of the MMAD, GSD and other particle size parameters from the data plots. The LC50 and 95 % confidence limits will be determined, if applicable, by a suitable logit or probit analysis.

Preliminary study:

NA

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.57 mg/L air

Based on:

test mat.

Mortality:

One female died on study day 1.

Clinical signs:

other: Treatment-related clinical signs observed during the study included chromodacryorrhea, chromorhinorrhea, decreased locomotion, dyspnea, lacrimation, oral discharge and squinting eyes. Other signs included abdominogenital staining of the fur, unkempt fur a

Body weight:

Three females lost weight during day 0 through day 7 weighing interval. These same animals gained weight during the day 7 through day 14 weighing interval. The remaining animals exhibited normal increases in body weight during the study.

Gross pathology:

There were no gross internal lesions observed in any animal at necropsy.

No other information

Interpretation of results:

study cannot be used for classification

Conclusions:

Under the conditions of this study, the 4-hour LC50 for Lithium chloride is greater than 5.57 mg/L.

Executive summary:

The acute inhalation toxicity of Lithium chloride in Sprague-Dawley rats was determined according to OECD Guideline 403 and EU method B.2. A group of five male and five female Sprague-Dawley rats was exposed to a respirable aerosol of Lithium Chloride. Animals were exposed for 4 hours at a mean concentration of 5.57 mg/L in a dynamically-operated, nose-only inhalation exposure chamber. Gravimetric airborne test material samples were taken frequently during the exposure. Particle size samples were taken twice during the exposure. Observations for toxicity and mortality were performed frequently during the exposure, upon removal of the rats from the chamber, at one hour post-exposure and twice daily thereafter for 14 days. Individual body weights were recorded immediately prior to exposure on day 0 and on days 7 and 14. On day 14, all surviving animals were sacrificed and gross necropsy examinations were performed. Gross necropsies were also performed on animals dying prior to study termination.

One animal died during the study. Treatment-related clinical signs observed during the study included chromodacryorrhea, chromorhinorrhea, decreased locomotion, dyspnea, lacrimation, oral discharge and squinting eyes. Most signs resolved by day 3 post-exposure and all surviving animals were normal from day 10 through study termination. Three females lost weight during the day 0 through day 7 weighing interval. These same animals gained weight during the day 7 through day 14 weighing interval. The remaining animals exhibited normal increases in body weight during the study. There were no gross internal lesions observed in any animal at necropsy.

Under the conditions of this study, the 4-hour LC50 for Lithium chloride is greater than 5.57 mg/L.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

5 570 mg/m³ air

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:

1994-10-13 to 1995-01-11

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

1992

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPP 81-2 (Acute Dermal Toxicity)

Version / remarks:

1984

Deviations:

no

Principles of method if other than guideline:

NA

GLP compliance:

yes

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: 0997

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

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 adult
- Weight at study initiation: 242 g to 299 g
- Housing: individually housed in stainless steel suspended rat cages
- Diet (e.g. ad libitum): ad libitum, Purina Rodent Chow 5001 (pellets)
- Water (e.g. ad libitum): ad libitum, fresh tap water
- Acclimation period: The animals were acclimated for a minimum of 5 calendar days prior to study start.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.6°C - 21.2°C
- Humidity (%): 56 % - 61%
- Photoperiod (hrs dark / hrs light): 12 hours fluorescent/ 12 hours dark

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: Dermal application on intact skin
- Type of wrap if used: 4 ply 4x4 inch gauze pad, hypoallergenic tape, elastic bandage, lined with plastic


REMOVAL OF TEST SUBSTANCE
- Washing (if done): The test material will be wiped away with a clean gauze pad moistened with tap water.
- Time after start of exposure: 24 hours

Duration of exposure:

24 hours

Doses:

Doses corresponding to a dosage level of 2000 mg/kg were individually calculated based on the body weight of each animal on the day of dosing.

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 and weighing: Observations for toxicity: approximately 0.5, 1, 2, 3, 4 and 6 hours following dosing and daily thereafter for 14 days; body weights: on days 0, 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, local irritation, necropsy

Statistics:

Not performed

Preliminary study:

NA

Key result

Sex:

male/female

Dose descriptor:

discriminating dose

Effect level:

> 2 000 mg/kg bw

Mortality:

There were no deaths.

Clinical signs:

other: All rats remained healthy during the study.

Gross pathology:

There were no gross internal lesions observed in any animal at necropsy.

Other findings:

NA

Mean body weights:

	Day 0	Day 7	Day 14
Female	295 ± 6.9	342 ± 7.9	397 ± 10.2
Female	263 ± 15.9	270 ± 18.8	287 ± 14.2

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study the LD50 is greater than 2000 mg/kg in male and female rats when topically applied.

Executive summary:

The toxic effects of Lithium chloride in Sprague-Dawley rats were investigated according to OECD Guideline 402 and EU method B.3 on acute dermal toxicity. Lithium Chloride (moistened with tap water) was topically applied to five Sprague-Dawley rats/sex at a dosage level of 2000 mg/kg. The test material was in contact with the intact skin for 24 hours under an occlusive wrap. Observations for toxicity were conducted at approximately 0.5, 1, 2, 3, 4 and 6 hours following dosing and daily thereafter for 14 days. A description of local irritation was recorded on days 1, 3, 7 and 14. Body weights were recorded on days 0, 7 and 14 of the study. A gross necropsy was performed on all animals.

There were no deaths. All rats remained healthy and gained weight during the study. No irritations were noted on any of the test sites. All animals appeared normal at necropsy.

Under the conditions of this study, the LD50 is greater than 2000 mg/kg in male and female rats when topically applied.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

Acute oral toxicity

According to a review article, the LD50 of Lithium chloride is 526 mg/kg bw after oral administration to rats. This results fits to data obtained for other lithium salts like Li2CO3.

Acute inhalation toxicity

Two acute inhalation toxicity studies were determined in Sprague-Dawley rats according to OECD Guideline 403 and EU method B.2. In these studies a group of five male and five female Sprague-Dawley rats was exposed to a respirable aerosol of Lithium Chloride. Animals were exposed for 4 hours at a mean concentration of 5.57 mg LiCl/L (and 5.53 mg LiCl/L) in a dynamically-operated, nose-only inhalation exposure chamber. Observations for toxicity and mortality were performed frequently during the exposure, upon removal of the rats from the chamber, at one hour post-exposure and twice daily thereafter for 14 days.

A single mortality occured in one study. Treatment-related clinical signs observed during the study included chromodacryorrhea, chromorhinorrhea, decreased locomotion, dyspnea, lacrimation, oral discharge and squinting eyes. Most signs resolved by day 3 post-exposure and all surviving animals were normal from day 10 through study termination. Three females lost weight during the day 0 through day 7 weighing interval. These same animals gained weight during the day 7 through day 14 weighing interval. The remaining animals exhibited normal increases in body weight during the study. There were no gross internal lesions observed in any animal at necropsy.

At the other test all animals survived to study termination. Treatment-related clinical signs observed during the study included chromodacryorrhea, chromorhinorrhea and decreased feces. All animals were normal from day 2 of study through study termination. All animals gained weight during the study. No treatment related gross internal lesions were noted during necropsy.

In conclusion, it could be shown in two inhalation studies, performed with the concentrations of 5.53 mg/L and 5.57 mg/L that the LC50 is higher than 5.57 mg/L (5570 mg/m3).

Acute dermal toxicity

The toxic effects of Lithium chloride in Sprague-Dawley rats were investigated according to OECD Guideline 402 and EU method B.3 on acute dermal toxicity. Lithium Chloride (moistened with tap water) was topically applied to five Sprague-Dawley rats/sex at a dosage level of 2000 mg/kg. The test material was in contact with the intact skin for 24 hours under an occlusive wrap. Observations for toxicity were conducted at approximately 0.5, 1, 2, 3, 4 and 6 hours following dosing and daily thereafter for 14 days. A description of local irritation was recorded on days 1, 3, 7 and 14. Body weights were recorded on days 0, 7 and 14 of the study. A gross necropsy was performed on all animals.

There were no deaths. All rats remained healthy and gained weight during the study. No irritations were noted on any of the test sites. All animals appeared normal at necropsy.

In conclusion, the LD50 was found to be greater than 2000 mg/kg in male and female rats when topically applied.

Justification for classification or non-classification

Based on the results of the acute oral toxicity study, lithium chloride is classified and labelled as acutely toxic cat. 4 (H302: Harmful if swallowed) according to Regulation (EC) No 1272/2008 (CLP).

Based on the results of the acute dermal and acute inhalation toxicity study, the test substance is not subjected to classification and labelling according to Regulation (EC) No 1272/2008 (CLP).