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Toxicological information

Acute Toxicity: inhalation

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Administrative data

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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988
Report date:
1989

Materials and methods

Test guideline
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

Test material

Constituent 1
Chemical structure
Reference substance name:
Lithium carbonate
EC Number:
209-062-5
EC Name:
Lithium carbonate
Cas Number:
554-13-2
Molecular formula:
CH2O3.2Li
IUPAC Name:
dilithium carbonate
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material: Lithium carbonate
- Molecular formula (if other than submission substance): Li2CO3
- Substance type: white powder
- Analytical purity: 99.4 %

Test animals

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): Exposure-time: 4 hours. 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 an a T99 value of 12.87.

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

Administration / exposure

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.

- System of generating particulates/aerosols: Following 240 minutes of exposure, the generation was discontinued and clean air was passed through the exposure chamber for an additional 30 minutes to clear the test material from the chamber. Afterwards, the chamber was opened and the animals were removed.

- 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 exhaust through a HEPA filter.
- Temperature, humidity: 20.6 - 23.3 °C, 43-64 %

TEST ATMOSPHERE
- 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 preweighted 25-mm Gelman Type A/E glass-fiber.
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.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 2 mg/L air
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 relative to their Test Days 1 and 8 body weights.
Gross pathology:
All animals surviving to the scheduled sacrifice were normal. 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 postmortem changes from potential treatment related lesions. Many of the lesions in these males were considered to probably be spontaneous postmortem 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.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Two male rats exposed to an actual concentration of 2.17 mg/L lithium carbonate died prior to termination. Their deaths were considered treatment-related. As no additional exposures were requested, the median lethal concentration (LC50) for this test substance was estimated as greater than 2 mg/L.
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 um). 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). By 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 with regard to acute toxicity according to Regulation (EC) No 1272/2008 (CLP).

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