Lithium bromide

Endpoint summary

Description of key information

Based on the findings in the acute oral toxicity studies of lithium bromide, a LD50 range of greater than 500 to 1800 mg/kg bw/day could be derived. Under the conditions of the acute inhalation toxicity study, the four-hour LC50 for lithium bromide solution is greater than 15.57 mg/L (discriminating concentration). Based on the results in the acute dermal toxicity studies with lithium bromide, a LD50 greater than 2000 mg/kg (discriminating dose) in both male and female rats was derived.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1988-02-02 to 1988-02-16

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP study equivalent to guideline with minor insufficiencies.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

Please refer to section "Principles of method if other than guideline"

Principles of method if other than guideline:

Only three rodents per sex and dose were used. The limit test was conducted with a lower dose (500 mg/kg instead of at least 2000 mg/kg).

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Taconic Farms, Germantown, New York, US
- Age at study initiation: young adults
- Weight at study initiation: 209-263 g
- Fasting period before study: fasted overnight prior to dosing
- 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

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 68-71
- Humidity (%): 27-59
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 10 % (w/v) solution
- Amount of vehicle (if gavage): 1.0-1.3 mL


MAXIMUM DOSE VOLUME APPLIED: 1.3 mL

Doses:

500 mg/kg bw

No. of animals per sex per dose:

3 animals/sex/dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 3 hours after administration on the day of dosing and daily thereafter for fourteen days. Body weights were taken on the day of dosing and again on days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 500 mg/kg bw

Based on:

test mat.

Sex:

male/female

Dose descriptor:

LD0

Effect level:

> 500 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths.

Clinical signs:

The only clinical signs noted were chromorhinorrhea, diarrhea and abdominogenital staining during the first 24-hours post-dosing.

Body weight:

All rats gained weight by day 14 of the study.

Gross pathology:

There were no gross internal lesions observed in any animal at necropsy.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Under the study conditions a LD50 > 500 mg/kg bw was determined for lithium bromide.

Executive summary:

An acute oral toxicity study according to the non-definitive protocol of FMC was performed with lithium bromide. Sprague-Dawley rats (3 males and 3 females) were orally dosed with lithium bromide anhydrous as a 10.0 % (weight/volume) solution in tap water at a dosage level of 500 mg/kg bw. Observations for toxicity were conducted at approximately 3 hours after dosing and daily thereafter for fourteen days. Body weights were recorded on days 0, 7 and 14 of the study. A gross necropsy was performed on all animals. There were no deaths. The only clinical signs noted were chromorhinorrhea, diarrhea and abdominogenital staining during the first 24-hours post-dosing. All rats gained weight during the study. At necropsy, no gross internal lesions were observed. A LD50 of greater than 500 mg/kg bw could be derived. (FMC, 1988)

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1989

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Qualifier:

no guideline available

Principles of method if other than guideline:

Value was taken from handbook data

GLP compliance:

not specified

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

1 800 mg/kg bw

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The handbook publicated an oral LD50 of 1800 mg/kgbw/day in rats.

Executive summary:

The handbook publicated an oral LD50 of 1800 mg/kgbw/day in rats.

Reference 3

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1996-10-22 to 1997-01-22

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

February 24th 1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPP 81-1 (Acute Oral Toxicity)

Version / remarks:

November 1984

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Version / remarks:

December 29th 1992

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

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: 213-239 g
- Fasting period before study: fasted overnight prior to dosing
- Housing: individually housed in stainless steel suspended rat cages
- Diet (e.g. ad libitum): Purina Laboratory Rodent Chow 5001 (pellets), ad libitum
- Water (e.g. ad libitum): fresh tap water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 68-72
- Humidity (%): 39-69
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 54 wt % LiBr
- Amount of vehicle (if gavage): was individually calculated depending on the body weight

MAXIMUM DOSE VOLUME APPLIED: 0.29 mL

Doses:

2000 mg/kg bw

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: 0.5, 1, 2, 3, 4, 6 hours following dosing and daily thereafter for fourteen days. Weighing was conducted on days 0, 1 and 14
- Necropsy of survivors performed: yes
- other observations: clinical signs, body weight

Statistics:

The oral LD50 value and 95% confidence limits for separate and combined sexes was calculated using a modified Logit-Linear Regression Program written by Jim Gibbons, Texas Instruments Calculator Products Division.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

One of five females and no males died during the study.

Clinical signs:

Clinical signs including abdominal gripping, abdominogenital staining, ataxia, oral discharge, chromodacryorrhea, chromorhinorrhea, decreased and no feces, dehydration, diarrhea, decreased locomotion, unthriftiness, lacrimation, rales, recumbency, twitching and vocalization were noted during the first seven days post-dosing.

Body weight:

All surviving rats gained weight by day 14 of the study.

Gross pathology:

The only finding at necropsy was blood, found in the stomach of the one rat which died on study day 1.

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results of the acute oral toxicity study with LiBr solution a LD50 > 2000 mg/kg bw could be derived for lithium bromide as such.

Executive summary:

The acute oral toxicity study according to OECD guideline 401 and EU method B.1 was performed with lithium bromide solution. Five Sprague-Dawley rats per sex were orally dosed with lithium bromide solution (undiluted) at a dosage level of 2000 mg/kg bw. Observations for toxicity were conducted at approximately 0.5, 1, 2, 3, 4 and 6 hours following dosing and daily thereafter for fourteen days. Body weights were recorded on days 0, 7 and 14 of the study, or upon discovery of death. A gross necropsy was performed on all animals. One of five females and no males died during the study. Clinical signs including abdominal gripping, abdominogenital staining, ataxia, oral discharge, chromodacryorrhea, chromorhinorrhea, decreased and no feces, dehydration, diarrhea, decreased locomotion, unthriftiness, lacrimation, rales, recumbency, twitching and vocalization were noted during the first seven days post-dosing. All surviving rats gained weight by day 14 of the study. The only finding at necropsy was blood in the stomach of the one rat which died on study day 1. Under the conditions of this study, an oral LD 50 value of greater than 2000 mg/kg bw could be derived for both male and female rats. (FMC, 1997)

Reference 4

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

not available

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study report is not detailed enough and documentation is not available, nevertheless the study was performed according to an OECD guideline and is scientifically acceptable.

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

water

Doses:

0 (vehicle), 670, 930, 1300, 1800, 2500 mg/kg bw/day

No. of animals per sex per dose:

5 animals/sex/dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 4 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

1 383 mg/kg bw

Based on:

test mat.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

1 600 mg/kg bw

Based on:

test mat.

Dead animals showed a decrease in locomotive activity, sedation and passivity. In addition, some of them demonstrated cyanosis, hypothermia and incomplete eyelid opening. From these findings, causes of death in these animals were suspected to be reduction in viability by inhibition of the central nervous system functions and disturbance of feeding behavior. Since some animals showed large amounts of nasal discharge and lacrimation before death, an abnormality in the body fluid balance could be added on a cause of death. There were no abnormal necropsy findings in dead animals, except for pale or small spleens in the males given 1300 mg/kg.

Most males and all females given 930 mg/kg or more showed decrease in locomotive activity after administration of lithium bromide, and some of them showed stereotyped behavior of rubbing the cage floor with their chins. With time, some animals became sedated, and some of them showed incomplete eyelid opening or an abnormal gait. These findings indicated that lithium bromide targets the central nervous system. Since most treated animals showed loose or mucous stool and diarrhea, and some demonstrated decrease of fecal volume several days after the treatment, the digestive system is also a target of lithium bromide toxicity. In addition, reddish tears, piloerection and salivation were found. These clinical signs disappeared by day 5 of observation, except for abdominal distention found until necropsy in surviving females given 2500 mg/kg.

Body weight gain of both sexes of animals was suppressed in the groups given 930 mg/kg and more. However, in the surviving females given 2500 mg/kg the body weight gain increased after withdrawal of the test substance.

No abnormalities were found on necropsy of the surviving animals.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Based on the results of the study LD50 values of 1383 mg/kg for males and 1600 mg/kg for females were estimated.

Executive summary:

A single dose oral toxicity test of lithium bromide was conducted in rats according to OECD test guideline 401. Oral administration of lithium bromide at doses more than 1300 mg/kg caused death after sedation and feed deprivation for 2-4 days. LD50 values were estimated to be 1383 mg/kg for males and 1600 mg/kg for females. (Hatano Research Institute, date not indicated)

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

500 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:

1996-08-14 to 1997-01-10

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

October 1984

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

December 29th 1992

Deviations:

no

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

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

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.

Key result

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.

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 methode 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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating conc.

Value:

15 570 mg/m³

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:

1999-03-18 to 1999-04-06

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

February 24th 1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

January 1993

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Version / remarks:

August 1998

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

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: 229-270 g
- 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): fresh tap water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 68-69
- Humidity (%): 51-56
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

Vehicle:

other: moistened with water (0.5 mL)

Details on dermal exposure:

TEST SITE
- Area of exposure: scapular to pelvic region
- Type of wrap if used: hypoallergenic wrap

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with water
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.46-0.54 g (Doses were based on individual body weights)
- Constant volume or concentration used: yes, a constant concentration was used.

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.5 mL

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

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: clinical signs (local irritation excluded) 0.5,1,2, 3,4, and 6 hours following dosing, and daily thereafter for 14 days. Weighing was performed on days 0, 7, 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, local Irritation (was recorded on days 1, 3, 7, 14)

Statistics:

The dermal LD50 value and corresponding 95% confidence limits were calculated using a modified Logit-Linear Regression Program written by Jim Gibbons, Texas Instruments Calculator Products Division.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths were noted.

Clinical signs:

All rats remained healthy during the study.

Body weight:

All rats gained weight by day 14 of the study.

Gross pathology:

No gross internal lesions were observed in any animal during necropsy.

Other findings:

Local irritation: The only irritation noted during the study was erythema on study day 1 in six animals and desquamation in four animals on day 3 and in one animal on day 7. All irritation resolved by study day 14.

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results of the acute dermal toxicity study with lithium bromide, a LD50 greater than 2000 mg/kg in both male and female rats was derived.

Executive summary:

The acute dermal toxicity according to OECD guideline 402 and EU method B.3 was performed with lithium bromide. Lithium bromide (anhydrous) was topically applied to five Sprague-Dawley rats per sex at a dosage level of 2000 mg/kg. The test material was in contact with the skin under an occlusive wrap for 24 hours. Observations for toxicity were conducted 0.5,1, 2, 3, 4, and 6 hours post-dosing, and daily thereafter for fourteen days. Dermal irritation was recorded on days 1, 3, 7 and 14. Body weights were recorded weekly. Gross necropsies were performed on all animals. No deaths were noted. All rats remained healthy and gained weight by day 14 of the study. The only irritation noted during the study was erythema on study day 1 in six animals and desquamation in four animals on day 3 and in one animal on day 7. All irritation resolved by study day 14. No gross lesions were revealed during necropsy. The LD50 is greater than 2000 mg/kg in both male and female rats when topically applied. (FMC, 1999)

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Additional information

Acute oral toxicity study

Key study

An acute oral toxicity study according to the non-definitive protocol of FMC was performed with lithium bromide. Sprague-Dawley rats (3 males and 3 females) were orally dosed with lithium bromide anhydrous by a 10.0 % (weight/volume) solution in tap water at a dosage level of 500 mg/kg bw. Observations for toxicity were conducted at approximately 3 hours after dosing and daily thereafter for fourteen days. Body weights were recorded on days 0, 7 and 14 of the study. A gross necropsy was performed on all animals. There were no deaths. The only clinical signs noted were chromorhinorrhea, diarrhea and abdominogenital staining during the first 24-hours post-dosing. All rats gained weight during the study. At necropsy, no gross internal lesions were observed. A LD50 of greater than 500 mg/kg bw could be derived. (FMC, 1988)

Supporting study

A single dose oral toxicity test of lithium bromide was conducted in rats according to OECD test guideline 401. Oral administration of lithium bromide at doses more than 1300 mg/kg caused death after sedation and feed deprivation for 2-4 days. LD50 values were estimated to be 1383 mg/kg for males and 1600 mg/kg for females. (Hatano Research Institute, no date indicated)

Supporting information

The handbook publicated an oral LD50 of 1800 mg/kgbw/day in rats.

Supporting study

The acute oral toxicity study according to OECD guideline 401 and EU method B.1 was performed with lithium bromide solution. Five Sprague-Dawley rats per sex were orally dosed with lithium bromide solution (undiluted) at a dosage level of 2000 mg/kg bw. Observations for toxicity were conducted at approximately 0.5, 1, 2, 3, 4 and 6 hours following dosing and daily thereafter for fourteen days. Body weights were recorded on days 0, 7 and 14 of the study, or upon discovery of death. A gross necropsy was performed on all animals. One of five females and no males died during the study. Clinical signs including abdominal gripping, abdominogenital staining, ataxia, oral discharge, chromodacryorrhea, chromorhinorrhea, decreased and no feces, dehydration, diarrhea, decreased locomotion, unthriftiness, lacrimation, rales, recumbency, twitching and vocalization were noted during the first seven days post-dosing. All surviving rats gained weight by day 14 of the study. The only finding at necropsy was blood in the stomach of the one rat which died on study day 1. Under the conditions of this study, an oral LD 50 value of greater than 2000 mg/kg bw could be derived for both male and female rats. (FMC, 1997)

The test substance was classified and labelled for acute toxicity Cat.4 as the majority of the data (except for one supporting study from 1997) are leading to classification and labelling. The key study presents the worst-case result.

Acute inhalation toxicity study

An acute inhalation toxicity study according to OECD guideline 403 and EU methode 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 is greater than 15.57 mg/L. (FMC, 1997)

Acute dermal toxicity study

Key study

The acute dermal toxicity according to OECD guideline 402 and EU method B.3 was performed with lithium bromide as solid. Lithium bromide (anhydrous) was topically applied to five Sprague-Dawley rats per sex at a dosage level of 2000 mg/kg. The test material was in contact with the skin under an occlusive wrap for 24 hours. Observations for toxicity were conducted 0.5, 1, 2, 3, 4, and 6 hours post-dosing, and daily thereafter for fourteen days. Dermal irritation was recorded on days 1, 3,7 and 14. Body weights were recorded weekly. Gross necropsies were performed on all animals. No deaths were noted. All rats remained healthy and gained weight by day 14 of the study. The only irritation noted during the study was erythema on study day 1 in 6 animals and desquamation in four animals on day 3 and in one animal on day 7. All irritation resolved by study day 14. No gross lesions were revealed during necropsy. The LD50 is greater than 2000 mg/kg in both male and female rats when topically applied. (FMC, 1999)

Supporting study

Lithium bromide solution was tested for acute dermal toxicity according to OECD guideline 402 and EU method B.3. Lithium bromide solution was topically applied to five Sprague-Dawley rats per sex at a dosage level of 2000 mg/kg bw. The test material was in contact with the intact skin for 24 hours under an occlusive wrap. Observations for toxicity were conducted at approximately 0.5, 1, 2, 3, 4 and 6 hours following dosing and daily thereafter for fourteen days. A description of local irritation was recorded on days 1, 3, 7 and 14. Body weights were recorded on days 0, 7 and 14 of the study. A gross necropsy was performed on all animals. There were no deaths. All rats remained healthy and gained weight by day 14 of the study. The only irritation noted during the study was desquamation in one rat on study day 3. There were no gross internal lesions noted during necropsy. Under the conditions of this study lithium bromide has a LD50 value greater than 2000 mg/kg bw. (FMC, 1997)

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on available data on acute toxicity, the test item has to be classified and labelled as acute tox. cat. 4, H302 (harmful if swallowed) according to Regulation (EC) No 1272/2008 (CLP), as amended for the tenth time in Regulation (EU) No 2017/776.