Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1999-04-12 to 1999-08-20
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1999
Report date:
1999

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1300 (Acute inhalation toxicity)
Version / remarks:
August 1998
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
May 1981
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Version / remarks:
December 1992
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Lithium Hydroxide monohydrate
EC Number:
603-454-3
Cas Number:
1310-66-3
Molecular formula:
H3LiO2
IUPAC Name:
Lithium Hydroxide monohydrate
Details on test material:
- Name of test material (as cited in study report): Lithium hydroxide monohydrate;
- Molecular formula: LiOH.H2O;
- Molecular weight: 41.96 g/mol;
- Physical state: White solid;
- Analytical purity: 99.99 %

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 laboratories;
- Age at study initiation: young adult animals;
- Weight at study initiation: 200 - 300 g/animal prior to exposure
- Fasting period before study: None
- Housing: Individually, in suspended stainless steel cages with wire mesh bottoms.
- Diet: Purina laboratory Rodent Chow 5001 (pellets) ad lib.;
- Water: Domestic water supply; untreated with additional chlorine or HCl; ad lib.;
- Acclimation period: Minimum of five calendar days;


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 23.9 °C ;
- Humidity (%): 30 - 70 %;
- Air changes (per hr):Not stated;
- Photoperiod (hrs dark / hrs light): 12 hrs light/dark cycle; from 6:00 a.m. to 6:00 p.m.

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
nose only
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: ADG nose-only exposure chamber;
- Exposure chamber volume: 11 L;
- Method of holding animals in test chamber: Individual polycarbonate nose-only tubes;
- Source and rate of air: Breathing grade compressed air; 39.1 L/min;
- Method of conditioning air: BGI Wright Dust Feeder II;
- System of generating particulates/aerosols: Compressed air dispersing the material into the exposure chamber;
- Method of particle size determination: Samples were drawn through a Sierra Series 218 cascade impactor;
- Treatment of exhaust air: Passing through an orifice tube system which continuously monitors air flow, then a commercial filter box;
- Temperature, humidity, pressure in air chamber: 20 °C; 35 % humidity;


TEST ATMOSPHERE
- Brief description of analytical method used: Sampling on Gelman Type A/E 37 mm glass fiber filters hold in cassettes.
- Samples taken from breathing zone: Centre of the chamber; directly above animal tube portals;

TEST ATMOSPHERE:
- Particle size distribution:
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): MMAD:4.68 - 4.69 µm; GSD: 2.7 to 2.74;


CLASS METHOD:
- Rationale for the selection of the starting concentration: To determine the inhalation LC50 value of the test material or to establish a non-lethal dosage level which is equal or greater than 5 mg/L or maximum attainable;
Analytical verification of test atmosphere concentrations:
yes
Remarks:
sampling on glass fiber filters; dividing filter weight gain by sample volume;
Duration of exposure:
4 h
Concentrations:
Nominal concentration. 12.7 mg/L;
Chamber airflow: 39.1 L/min;
Gravimetric concentration: 6.15 mg/L (mean)
No. of animals per sex per dose:
5 male; 5 female;
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observation: daily; weighing: on day 0, 7, and 14 after exposure;
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, necropsy findings;

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 6.15 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 3.4 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: calculated for LiOH anhydrous
Mortality:
As a result of the exposure, two animals had severe necrosis of the snout. The severity of necrosis caused respiratory difficulties for these animals. On Study Day 5, these animals were deemed to be in moribund condition and were humanely sacrificed.
Clinical signs:
other: Treatment-related clinical signs observed during the study included abdominogenital staining, alopecia on head/neck, ataxia, chromodacryorrhea, chromorhinorrhea, decreased feces, decreased locomotion, diarrhea, dyspnea, lacrimation, necrotic snout, oral d
Body weight:
Four surviving females and two males 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 male animals exhibited normal increases in body weight throughout the study.
Gross pathology:
There were no gross internal lesions observed in any animal at necropsy.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this study, the four-hour LC50 for lithium hydroxide monohydrate is greater than 6.15 mg/L (resp. greater than 3.4 mg/L lithium hydroxide anhydrous).
Executive summary:

The acute inhalation toxicity of lithium hydroxide monohydrate 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 hydroxide monohydrate. The animals were exposed for 4 hours at a mean concentration of 6.15 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 daily thereafter for 14 days. Individual body weights were recorded immediately prior to exposure on day 0 and on days 7, 14 and on day of unscheduled sacrifice. On day 14, all surviving animals were sacrificed and gross necropsy examinations were performed. Gross necropsies were also performed on animals that were humanely sacrificed. As a result of the exposure, two animals had severe necrosis of the snout. The severity of the necrosis caused respiratory difficulties for these animals. On Study Day 5, these animals were deemed to be in moribund condition and were humanely sacrificed. Treatment-related clinical signs observed during the study included abdominogenital staining, alopecia on head/neck, ataxia, chromodacryorrhea, chromorhinorrhea, decreased feces, decreased locomotion, diarrhea, dyspnea, lacrimation, necrotic snout, oral discharge, rales, squinting eyes, swollen snout, and unthriftiness. Other signs included unkempt fur and wet material on fur. All surviving animals were normal from day 11 through study termination. Four surviving females and two males 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 male animals exhibited normal increases in body weight throughout the study. There were no gross internal lesions observed in any animal at necropsy. Under the conditions of this study, the four-hour LC50 for Lithium hydroxide monohydrate is greater than 6.15 mg/L (resp. greater than 3.4 mg/L lithium hydroxide anhydrous).