Lithium nitrate

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1999-12-07 to 2000-02-14

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

2000

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

May 12th 1981

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 OPPTS 870.1300 (Acute inhalation toxicity)

Version / remarks:

August 1998

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Lithium nitrate

EC Number:

232-218-9

EC Name:

Lithium nitrate

Cas Number:

7790-69-4

Molecular formula:

HNO3.Li

IUPAC Name:

lithium nitrate

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 adults
- Weight at study initiation: 247-268 g
- Fasting period before study: no
- Housing: individually housed in stainless steel, suspended cages
- Diet (e.g. ad libitum): Purina Rodent Chow 5001 (pellets), ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 67-68
- Humidity (%): 52-61
- 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: a dynamically-operated, nose-only inhalation exposure chamber with 11 litres volume
- Method of holding animals in test chamber: housed in polycarbonate nose-only tubes during the exposure
- 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.
- Temperature, humidity, pressure in air chamber: Chamber, room air temperature and relative humidity were monitored continuously during the exposure with FMC wet/dry bulb hygrometers. Measurements were recorded at 30-minute intervals. The mean temperature and relative humidity in the chamber were 69 °F and 74 %, respectively. The mean temperature and relative humidity in the chamber room were 64 °F and 50 %, respectively.

TEST ATMOSPHERE
- Brief description of analytical method used: Chamber air samples were taken on German® Type A/E 37 mm glass fiber filters held in cassettes at approximately 40-minute intervals during the exposure to determine the airborne concentration of test material. The concentration was calculated by dividing the filter weight gain by the sample volume. The filters were then desiccated overnight and reweighed for determination of dry concentration. The dry concentration was then divided by the fraction of solids (0.32) to yield the formulation concentration.
- 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 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 2.82 liters per minute. The filters were then desiccated overnight and reweighed for determination of dry filter weight.
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): The mass median aerodynamic diameter (MMAD), geometric standard deviation (GSD) and the percent of aerosol less than or equal to 1,10, and 15 microns in size were determined by logarithmic-probability plotting.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

formulation concentration: 5.93 mg/L

No. of animals per sex per dose:

5 animals/sex/dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations 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
- body weight: once a week

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

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.93 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 dyspnea and lacrimation. All animals were normal on study day 1 and remained normal through study termination. Another sign noted that was attributed to animal exposure tube confinement was

Body weight:

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.

Other findings:

The results of the particle size distribution indicated the test material was respirable in size to the rat.

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 nitrate solution was greater than 5.93 mg/L.

Executive summary:

A group of five male and five female Sprague-Dawley rats was exposed to a respirable aerosol of lithium nitrate solution (30 %). Animals were exposed for 4 hours at a mean, formulation concentration of 5.93 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 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 noted during the study included dyspnea and lacrimation. All animals were normal from day 1 through study termination. All animals gained weight during 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 nitrate solution is greater than 5.93 mg/L. (FMC, 1999/2000)