Lithium hydroxide

Repeated dose toxicity: oral

Administrative data

Endpoint:

chronic toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

HYPOTHESIS FOR THE ANALOGUE APPROACH
Lithium hydroxide completely dissociates in water forming lithium cation and the corresponding hydroxide anion. Thus, lithium salts with different anion moieties and hydroxide compounds were found to be suitable candidates for read-across. (Eco)toxicological properties were extrapolated to different endpoints by using the lowest effect concentration.
For further information, please refer to the read-across justification in chapter 13.

Cross-reference

Reason / purpose for cross-reference:

read-across source

Reference

Endpoint:

chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1958, 1995, 2002

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: publication

Reason / purpose for cross-reference:

reference to same study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 452 (Chronic Toxicity Studies)

Principles of method if other than guideline:

No data

GLP compliance:

not specified

Remarks:

study was published in 1958

Species:

rat

Strain:

other: albino Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight:
females: 0.14 kg - 0.18 kg
males: 0.2 - 0.27 kg

Route of administration:

oral: drinking water

Vehicle:

water

Details on oral exposure:

10-12 g/0.1 kg/bw /day

Key result

Dose descriptor:

NOAEL

Effect level:

84.8 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: Worst case NOAEL Lithium chloride intake

Key result

Dose descriptor:

NOAEL

Effect level:

13.9 mg/kg bw/day (nominal)

Based on:

other: Lithium content of test material

Sex:

male/female

Basis for effect level:

other: Worst case Lithium intake

Key result

Dose descriptor:

NOAEL

Effect level:

2 other: mmol/kg bw/day

Based on:

other: Lithium content of test material

Sex:

male/female

Basis for effect level:

other: Worst case Lithium intake

Key result

Dose descriptor:

NOAEL

Effect level:

138.07 mg/kg bw/day (nominal)

Based on:

other: Based on lithium content of test material and calculated for LiNO3

Sex:

male/female

Basis for effect level:

other: Worst case Lithium intake

Critical effects observed:

not specified

Dose level 20 mmol lithium chloride / L:

This dose was just subtoxic; apart from slight initial disturbances, it caused no effects on health or behaviour in the adult animals over a period of up to two years.

Plasma levels: 1.5 - 2 mmol lithium

Dose level 50 mmol lithium chloride / L:

The animals appeared to be unchanged in aspect and behaviour for 3 to 5 days. Then they became progressively drowsy and asocial. They were difficult to rouse; when roused, their gait was staggering and hesitant and they rested again as soon as possible. When resting they showed fine muscular tremor and trembling; usually they sat for long periods by themselves anywhere in the box. A few days later they became unresponsive and were stuporous, with dull eyes and slightly erected, untidy and unkempt fur. They were visibly ill and emaciated. Death occurred within 2 to 3 weeks.

Plasma levels: 3 (behavioural changes) - 8 (death) mmol lithium

Conclusions:

In a 2-year study in rats ingesting drinking water containing lithium chloride in a concentration of 20 mmol no effects on health or behaviour were found, except slight, transitory initial disturbances. When a concentration of 50 mmol LiCl/L was administered, food and water intake was decreased within a few days, and the rats became progressively drowsy and asocial on the 3rd to 5th day. Their gait was staggering, and they had a fine muscular tremor. Simultaneously their weight began to drop. The deterioration progressed to stupor and death within 2-3 weeks.
Plasma levels at dose level 20 mmol/L: 1.5 - 2 mmol
Lithium Plasma levels at dose level 50 mmol/L: 3 (behavioural changes) - 8 (death) mmol Lithium.

The Lithium concentration of 20 mmol/L used in this chronic drinking water study, is comparable to the highest doses given temporarily to hospitalised patients (plasma lithium level about 2 mmol/L).

The daily water intake was 0.010 - 0.012 kg / 0.1 kg bw.
For worst case considerations, the daily Lithium intake in rat is 2.0 mmol/kg bw/day which is equivalent to 13.881 Lithium mg/kg bw/ day.
Thus, a worst case NO(A)EL of 13.9 mg Lithium/kg bw/ day can be derived.

Executive summary:

In a 2-year study in rats ingesting drinking water containing lithium chloride in a concentration of 20 mmol no effects on health or behaviour were found, except slight, transitory initial disturbances. When a concentration of 50 mmol LiCl/L was administered, food and water intake was decreased within a few days, and the rats became progressively drowsy and asocial on the 3rd to 5th day. Their gait was staggering, and they had a fine muscular tremor. Simultaneously their weight began to drop. The deterioration progressed to stupor and death within 2-3 weeks. Plasma levels at dose level 20 mmol/L: 1.5 - 2 mmol lithium plasma levels at dose level 50 mmol/L: 3 (behavioural changes) - 8 (death) mmol lithium. Based on the result, a worst case NOAEL of 2.0 mmol lithium /kg bw/day, corresponding to 13.9 mg lithium /kg bw/ day was derived and calculated to be 138 mg/kg bw/day for lithium nitrate.

Materials and methods

Test material

Test material information

Constituent 1

Reference substance name:

Lithium hydroxide

EC Number:

215-183-4

EC Name:

Lithium hydroxide

Cas Number:

1310-65-2

Molecular formula:

HLiO

IUPAC Name:

lithium hydroxide

Test material form:

solid

Results and discussion

Effect levels

Key result

Dose descriptor:

NOAEL

Effect level:

47.97 mg/kg bw/day (nominal)

Based on:

other: recalculated for LiOH

Sex:

male/female

Remarks on result:

other: based on LiCl (Trautner, 1958)

Target system / organ toxicity

Key result

Critical effects observed:

no