Lithium sulphate

Endpoint summary

Description of key information

Three weight of evidence approaches were obtained from handbook and/or published data regarding the acute oral toxicity of lithium sulfate. The LD50 (oral route) values are within the range of 300 and 2000 mg/kg bw.
In the acute dermal toxicity study conducted with lithium carbonate an LD50 value of above 3000 mg/kg bw  was determined. Based on a read-across approach the LD50 for lithium sulfate and its monohydrate can be assumed to be above 3000 mg/kg bw.
The acute inhalation toxicity study a LC50 of greater than 2 mg/L was determined when exposing Sprague Dawley rats to a single dose of  lithium carbonate. Based on the read-across approach the LC50 for lithium sulfate and its monohydrate is greater than 2 mg/L.

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:

weight of evidence

Study period:

1998

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Only handbook or published data available.

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

Sex:

not specified

Dose descriptor:

LD50

Effect level:

613 mg/kg bw

Based on:

test mat.

Interpretation of results:

Toxicity Category IV

Remarks:

Migrated information Criteria used for interpretation of results: EU

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 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

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1988-01-18 to 1988-06-24

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

1981

Deviations:

no

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 Breeding Laboratories, Inc., Raleigh, North Carolina
- Age at study initiation: male: 49 days; female: 55 days
- Weight at study initiation: male: 321.0 g - 242.9 g; female: 185.0 g - 199.5 g
- Housing: animals were housed individually in an elevated, stainless steel wire mesh cage
- Diet (e.g. ad libitum): ad libitum, Purina Certified Laboratory Chow
- Water (e.g. ad libitum): ad libitum, tap water


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.6 - 23.3
- Humidity (%): 43-64

- Air changes (per hr): 21.5

- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

inhalation: dust

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: plexiglass exposure chamber, which was operated in a dynamic mode
- Exposure chamber volume: 100 L

- Source and rate of air: The chamber was operated in dynamic mode with a consistent airflow of 35.8 litres per minute (Lpm). The chamber airflow rate was measured using a calibrated Dwyer 0-40 Lpm flowmeter and was recorded every 30 minutes. These conditions gave a calculated air change of 21.5 air changes per hour and a T99 value of 12.87.

- Method of particle size determination: Lithium carbonate dust was determined by sampling a measured volume of test atmosphere through an Andersen Cascade Impactor. The impactor stages each contained a pre-weighed glass-fiber filter designed to retain impacted particles of sequentially dimishing size. The quantity of dust collected on each filter was determined gravimetrically.

- Treatment of exhaust air: The exposure chamber air was exhausted through a HEPA filter.
- Temperature, humidity: 20.6 - 23.3 °C, 43-64 %



TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: Particle size determinations were performed twice during the exposure.
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): The MMAD and GSD of the test material aerosol were estimated from a standard second order polynomial least squares fit of the logarithm for each stage constant versus the cumulative weight distribution of the experimental data.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

The concentration of lithium carbonate in the exposure chamber was determined gravimetrically by collection of the dust on preweighed filters. Samples were collected at 5 Lpm for 2 minutes on a preweighed 25-mm Gelman Type A/E glass-fiber using a Thomas I

Duration of exposure:

4 h

Concentrations:

Gravimetric concentration: 2.17 mg/L

No. of animals per sex per dose:

5 male, 5 female

Control animals:

no

Statistics:

The MMAD and GSD of the test material aerosol were estimated from a standard second order polynomial least squares fit of the logarithm for each stage constant versus the cumulative weight distribution of the experimental data.

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 2 mg/L air

Exp. duration:

4 h

Mortality:

Two male animals died before the scheduled sacrifice. In addition to the typical signs, they exhibited wheezing, rough haircoat, rhinorrhea, and low body temperature (to the touch). Most animals were normal in appearance by Test Day 9 and all were normal by termination. There did not appear to be any substantive differences in the nature, or frequency of occurrence, of the abnormal observations of the surviving male animals and female animals.

Clinical signs:

other: During the exposure period, animals were observed with test compound on the fur, increased secretory responses, labored breathing, languid behaviour and squinted eyes. The signs were also exhibited at 30 and 60 minutes post-exposure. Crust on the eyelids

Body weight:

Body weight was decreased in all male animals and one female animal at Test Day 8 compared to the pre-exposure body weights. By Test Day 15, all surviving animals had gained weight relative to their body weights on Test Days 1 and 8.

Gross pathology:

All animals surviving to the scheduled sacrifice reacted normally. The finding of pale kidney in one female animal is considered sporadic in nature. In the male animals found dead, no histopathological evaluation was performed to distinguish spontaneous post mortem changes from potential treatment related lesions. Many of the lesions in these males were considered to be post mortem changes. The findings of sore and alopecia on the skin of one male animal were considered sporadic in nature. On this basis, the findings at necropsy of the two male animals which died on test were not considered related to treatment.

Interpretation of results:

study cannot be used for classification

Remarks:

Migrated information

Conclusions:

In this acute inhalation toxicity study a LC50 of greater than 2 mg/L was determined when exposing Sprague Dawley rats to a single dose of lithium carbonate.

Executive summary:

The acute inhalation toxicity of lithium carbonate in Sprague-Dawley rats was determined according to OECD Guideline 403 and EU method B.2. Five male and five female Sprague-Dawley rats received a single 4 hour whole-body exposure to a gravimetric concentration of 2.17 mg/L lithium carbonate.

The dust was determined to be generally respirable to the rat (73.3 % of particles less than 10 µm). Two male rats died as a result of treatment. Signs of treatment included test material on the fur, increased secretory responses, labored breathing, languid behaviour, squinted eyes and crust on the eyelids. The animals that died also exhibited wheezing, rough haircoat, rhinorrhea and low body temperature (to the touch). Test day 8 body weights in males were diminished compared to body weights immediately prior to exposure.

Based on the mortality results of this study using combined sexes, the median lethal concentration for a 4 hour exposure to lithium carbonate was estimated to be greater than 2 mg/L. As maximum attainable concentrations were applied without revealing indications for acute toxicity, lithium carbonate has not to be classified.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

2 000 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:

1976-10-20

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

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 ( two per sex) instead of five rabbits per dose were used in the study. Two instead of three dose levels were prepared 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 (if done): yes
- Time after start of exposure: 24h after treatment

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 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 and 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.

Mortality:

No mortality occured within the 2000 mg/kg bw testing group.
One animal died in the 3000 mg/kg bw testing group. The cause of death was not evident.

Clinical signs:

other: The test material showed no irritating properties to the skin of the albino rabbit.

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:

study cannot be used for classification

Remarks:

Migrated information

Conclusions:

In the acute dermal toxicity study conducted with lithium carbonate 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 Zealand white rabbits.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

3 000 mg/kg bw

Additional information

Acute toxicity: oral

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

All weight of evidences are leading to a classification of lithium sulfate and its monohydrate as harmful if swallowed. (Walum et al., 1998)

Acute toxicity: dermal

No acute dermal toxicity study was available for lithium sulfate and its monohydrate. Therefore read-across was performed using study results of a characteristically similar compound, lithium carbonate.

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 Zealand white rabbits. (Bio-Test, 1976)

Consequently, based on a read-across approach, the LD50 value of lithium sulfate and its monohydrate is assumed to be also above 3000 mg/kg bw.

Acute toxicity: Inhalation

No acute toxicity inhalation study was available for lithium sulfate and its monohydrate. Therefore read-across was performed using study results of a characteristically similar compound, lithium carbonate.

The acute inhalation toxicity of lithium carbonate in Sprague-Dawley rats was determined according to OECD Guideline 403 and EU method B.2. Five male and five female Sprague-Dawley rats received a single 4 hour whole-body exposure to a gravimetric concentration of 2.17 mg/L lithium carbonate.

The dust was determined to be generally respirable to the rat (73.3 % of particles less than 10 µm). Two male rats died as a result of treatment. Signs of treatment included test material on the fur, increased secretory responses, labored breathing, languid behaviour, squinted eyes and crust on the eyelids. The animals that died also exhibited wheezing, rough haircoat, rhinorrhea and low body temperature (to the touch). Test day 8 body weights in males were diminished compared to body weights immediately prior to exposure.

Based on the mortality results of this study using combined sexes, the median lethal concentration for a 4 hour exposure to lithium carbonate was estimated to be greater than 2 mg/L. As maximum attainable concentrations were applied without revealing indications for acute toxicity, lithium carbonate has not to be classified. (Hazleton, 1988)

Based on the read-across approach the LC50 value for lithium sulfate and its monohydrate can be assumed also to be greater than 2 mg/L.

Justification for selection of acute toxicity – oral endpoint
standard test animal (rat), result applicable for classification

Justification for classification or non-classification

Based on the data regarding acute toxicity, lithium sulfate and its monohydrate have to be classified and labelled as Xn, R22 (Harmful if swallowed) and as acute tox. cat. 4, H302 (harmful if swallowed) according to Directive 67/548/EEC (DSD) and Regulation (EC) No 1272/2008 (CLP), respectively.