Lithium fluoride

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1996-08-14 to 1997-01-10

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1997

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

October 1984

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

December 29th 1992

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPP 81-3 (Acute inhalation toxicity)

Version / remarks:

November 1984

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Lithium bromide

EC Number:

231-439-8

EC Name:

Lithium bromide

Cas Number:

7550-35-8

Molecular formula:

BrLi

IUPAC Name:

lithium bromide

Test material form:

solid

Specific details on test material used for the study:

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

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, Kingston, NY
- Age at study initiation: 7-9 weeks (young adults)
- Weight at study initiation: 218-332 g
- Housing: individually housed in stainless steel suspended rat cages
- Diet (e.g. ad libitum): Purina Laboratory Rodent Chow 5001, ad libitum
- Water (e.g. ad libitum): fresh tap water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 67-71
- Humidity (%): 35-72
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

clean air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: The 11 L ADG nose-only exposure chamber was made of anodized aluminium and was operated dynamically.
- Method of holding animals in test chamber: Animals were housed in polycarbonate nose-only tubes.
- Source and rate of air: breathing grade compressed air; Chamber airflow of 28.1 L/min
- System of generating particulates/aerosols: TSI 6-jet atomizer
- 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 mass median aerodynamic diameter (MMAD), geometric standard deviation 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 exhausted from the bottom of the chamber and passed through an orifice tube system which continuously monitored airflow and then through a commercial filter box.
- Temperature, humidity, pressure in air chamber: Chamber and room air temperature and relative humidity were monitored continuously during the exposure with wet/dry bulb hygrometers. Measurements were recorded at 30 minute intervals.

TEST ATMOSPHERE
- Brief description of analytical method used: Chamber air samples were taken on desiccated GelmanType A/E 37 mm glass fiber filters held in cassettes. Samples were taken hourly during the exposure to determine the airborne concentration of test material.
- Samples taken from breathing zone: Yes, the samples were taken from the center of the chamber directly above the animal tube portals.

TEST ATMOSPHERE
- Particle size distribution: Chamber air samples were also taken twice during the exposure to determine the aerodynamic particle size distribution of airborne test material. The samples were drawn through a Sierra® Model 218 cascade impactor at 2.80 liters per minute.
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): The mass median aerodynamic diameter (MMAD), geometric standard deviation and the percent of aerosol 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 wet concentration: 15.57 mg/L
nominal exposure concentration: 16 mg/L

No. of animals per sex per dose:

five animals sex/dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for signs of toxicity and mortality at fifteen minute intervals during the first hour of exposure, hourly for the remainder of the exposure, upon removal from the chamber, at one hour post-exposure and daily thereafter for fourteen days.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

Particle size distributions were determined by log-probability plotting of the data and subsequent determination of the mass median aerodynamic diameter, geometric standard deviation and other particle size parameters from the data plots. The LC50 and 95% confidence limits were determined by a suitable logit or probit analysis.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 15.57 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

There were no deaths during the study.

Clinical signs:

other: Treatment-related clinical signs noted during the study included alopecia, chromodacryorrhea, chromorhinorrhea, decreased feces, decreased locomotion and oral discharge. Other signs attributed to excessive soiling as a result of animal tube confinement in

Body weight:

One female lost weight during the 7-14 day interval. At termination, all animals exhibited increases in body weight over their day 0 values.

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 acute inhalation toxicity study, the four-hour LC50 for lithium bromide solution was greater than 15.57 mg/L.

Executive summary:

The acute inhalation toxicity study according to OECD guideline 403 and EU method B.2 was performed with lithium bromide. A group of five male and five female Sprague-Dawley rats was exposed to lithium bromide solution for 4 hours at a concentration of 15.57 mg/L in a dynamically-operated, nose-only inhalation exposure chamber. Gravimetric airborne test material samples were taken hourly 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 and 14. On day 14, all animals were sacrificed and gross necropsy examinations were performed. All animals survived to study termination. Treatment-related clinical signs observed during the study included alopecia, chromodacryorrhea, chromorhinorrhea, decreased feces, decreased locomotion and oral discharge. All animals were in normal condition from day 2 of study through day 14 with the exception of one rat with alopecia from day 11 through 13 of the study. All animals gained weight during the study. No gross internal lesions were noted during necropsy. Under the conditions of this study, the four-hour LC50 for lithium bromide solution was greater than 15.57 mg/L.