Lithium Citrate Tetrahydrate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1999-03-26 to 1999-05-06

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:

1999

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

February 24th 1987

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

January 1993

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

August 1998

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

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 material form:

solid: crystalline

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: 207-275 g
- Fasting period before study: yes
- Housing: individually housed in stainless steel, suspended cages
- Diet: Purina Rodent Chow 5001 (pellets), ad libitum
- Water: Fresh tap water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 65-71
- Humidity (%): 50-61
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

- Amount of vehicle (if gavage):
Dosage group 2000 mg/kg, males: 1.8 - 1.9 mL
Dosage group 2000 mg/kg females: 1.7 - 1.8 mL
Dosage group 1500 mg/kg males: 1.3 - 1.4 mL
Dosage group 1500 mg/kg females: 1.3 mL
Dosage group 1000 mg/kg males: 0.94 - 1.1 mL
Dosage group 1000 mg/kg females: 0.83 - 0.90 mL

Doses:

1000, 1500, 2000 mg/kg bw

No. of animals per sex per dose:

5 animals/dose/sex

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 h following dosing and daily thereafter for 14 days
- Necropsy of survivors performed: yes , any animal not surviving to termination were also necropsied.
- clinical signs: 0.5, 1, 2, 3, 4, 6 h following dosing and daily thereafter for 14 days
- body weight: was recorded on days 0, 7 and 14

Statistics:

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

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

1 317 mg/kg bw

Based on:

test mat.

95% CL:

>= 993 - <= 1 640

Effect levels 2

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

1 519 mg/kg bw

Based on:

test mat.

95% CL:

>= 1 179 - <= 1 859

Effect levels 3

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 426 mg/kg bw

Based on:

test mat.

95% CL:

>= 1 242 - <= 1 609

Mortality:

All deaths occurred within 5 days of dosing. Data is summarized below.

Clinical signs:

other: All deaths occurred within 5 days after dosing. The most significant clinical signs were twitching, rolling over in cage, recumbency, loss of muscle control, squinting eyes and tremors. All signs subsided by study day 6.

Gross pathology:

Red liquid was found in the stomach of one decedent and red liquid was found in the intestines of another decedent. Animals sacrificed at study termination on day 14 were found to be normal at necropsy.

Any other information on results incl. tables

The summarized mortality data:

Male		Female		Combined
Dosage Level (mg/kg bw)	No. dead / No. dosed	Dosage Level (mg/kg bw)	No. dead / No. dosed	Dosage Level (mg/kg bw)	No. dead / No. dosed
2000	5/5	2000	5/5	2000	10/10
1500	4/5	1500	2/5	1500	6/10
1000	0/5	1000	0/5	1000	0/10

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Based on the results of the acute oral toxicity study of lithium nitrate a LD50 of 1317 (male), 1519 (female) and 1426 (Combined) mg/kg bw was derived.

Executive summary:

Groups of five male and female Sprague-Dawley rats were orally administered lithium nitrate by a 25 % (w/v) preparation in tap water. Observations for toxicity were conducted 0.5, 1, 2, 3, 4, and 6 hours post-dosing, and daily thereafter for fourteen days. Body weights were recorded weekly and prior to necropsy. Gross necropsies were performed on all animals. All deaths occurred within 5 days of dosing. The most significant clinical signs were twitching, rolling over in cage, recumbency, loss of muscle control, squinting eyes and tremors. All signs subsided by study day 6; surviving rats remained healthy and gained weight until study termination. Red liquid was found in the stomach of one and in the intestine of another decedent. Animals sacrificed at study termination on day 14 were found to be normal at necropsy. The LD50 values determined were 1317 mg/kg in male rats, 1519 mg/kg in female rats, and 1426 mg/kg in combined sexes.