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SECTION 1. CHEMICAL IDENTIFICATION

CHEMINFO Record Number: 509
CCOHS Chemical Name: Lithium chloride

Synonyms:
Chlorure de lithium
LiCl
Lithium chloride anhydrous
Lithium chloride dihydrate
Lithium chloride monohydrate

Chemical Name French: Chlorure de lithium
Chemical Name Spanish: Cloruro de litio
CAS Registry Number: 7447-41-8
Other CAS Registry Number(s): 16712-19-9 16712-20-2 85144-11-2
RTECS Number(s): OJ5950000
EU EINECS/ELINCS Number: 231-212-3
Chemical Family: Lithium and compounds / inorganic lithium compound / lithium salt / alkali chloride
Molecular Formula: Cl-Li
Structural Formula: Li+ Cl-

SECTION 2. DESCRIPTION

Appearance and Odour:
White, odourless crystals, granules or crystalline powder; deliquescent (absorbs moisture from the air and forms wet solid or solution).(1)

Odour Threshold:
Odourless

Warning Properties:
POOR - lithium chloride is odourless.

Composition/Purity:
Lithium chloride exists as the anhydrous salt (CAS No. 7447-41-8) and as hydrated salts, lithium chloride monohydrate (LiCl.H20) (CAS No. 16712-20-2*) and lithium chloride dihydrate (LiCl.2H20) (CAS No. 16712-19-9). It is also reported in one source to exist as a trihydrate (LiCl.3H20) and as a pentahydrate ( LiCl.5H2O).(42) Lithium chloride (form not specified) is available in grades with purity of 99% and greater. It is also commercially available as a solution in water. *NOTE. Some sources give 85144-11-2 as the CAS No. for lithium chloride monohydrate.

Uses and Occurrences:
Lithium chloride is mainly used as the starting material for the production of lithium metal by molten salt electrolysis. It is also used as a chemical intermediate for lithium borohydride; component of fluxes and dipping baths for welding and brazing aluminum and light metal alloys; as a dehumidifier in air conditioning systems of the absorber type; desiccant (drying agent), e.g. for drying gases; as a catalyst; chlorinating agent for steroid substrates; electrolyte in dry cells; stabilizer in textile spinning solutions; antistatic finish for fabrics; as tracer in wastewater; and to add colour to fireworks compositions.(1,3,4,17,39)
Lithium chloride solution is used in large dehumidification systems in the air-conditioning industry; in deicer solutions; in low freezing solutions for fire extinguishers; as a catalyst; and in photosensitive developer compositions.(39)


SECTION 3. HAZARDS IDENTIFICATION

EMERGENCY OVERVIEW:
White, odourless crystals, granules or crystalline powder. Deliquescent. Does not burn or support combustion. During a fire, corrosive and toxic hydrogen chloride and chlorine gases, and lithium oxide may be formed by thermal decomposition or combustion. Generally has low toxicity following short-term exposure.



POTENTIAL HEALTH EFFECTS

Effects of Short-Term (Acute) Exposure

Inhalation:
Lithium chloride is unlikely to be inhaled, because it readily absorbs moisture from the air forming a wet solid. Exposure to any dust that is generated or to mists from solutions may be irritating, but is not expected to cause significant harmful effects.
There is no human or short-term exposure animal toxicity information available. No harmful effects were seen in rats in a 4-8 week inhalation study.

Skin Contact:
Lithium chloride is probably a mild irritant, based on limited animal information. The dust may have a drying effect, since it will absorb moisture from the skin. There is no human information available.
Lithium chloride is not expected to be absorbed through the skin.

Eye Contact:
Lithium chloride is probably a mild irritant, based on limited animal information. There is no human information available.

Ingestion:
Lithium chloride is not toxic if ingested, based on animal toxicity information. Some lithium salts (lithium carbonate or lithium citrate) are used therapeutically to treat psychiatric conditions. The occurrence of toxicity is related to the plasma concentration of the lithium ion and there is a narrow margin between toxic and therapeutic doses. Acute effects observed at 500 mg/day and higher include digestive problems, muscle cramps, and effects on the central nervous system (trembling, drowsiness and a dazed feeling). More severe toxic effects include kidney injury, coma, tremors, convulsion and death.(24,29,30) Persistent neurological effects have occurred following accidental or suicidal overdoses.(31) Ingestion is not a typical route of occupational exposure.

Effects of Long-Term (Chronic) Exposure

Some lithium salts (lithium carbonate or lithium citrate) are orally administered therapeutically at doses of about 500-1800 mg/day for treatment of certain psychiatric conditions. There is considerable information available on the effects of therapeutic lithium administration on the skin, nervous system, kidneys and thyroid. In most cases the effects are reversible. The effects of lithium salts observed during therapeutic treatment protocols are not considered relevant to occupational exposures.

Carcinogenicity:

Lithium chloride is not expected to be carcinogenic. There is no human or animal information available.

The International Agency for Research on Cancer (IARC) has not evaluated the carcinogenicity of this chemical.

The American Conference of Governmental Industrial Hygienists (ACGIH) has no listing for this chemical.

The US National Toxicology Program (NTP) has not listed this chemical in its report on carcinogens.

Teratogenicity and Embryotoxicity:
Lithium chloride should not be considered a developmental toxin in occupational exposure situations based on evidence of developmental toxicity at doses that may be used therapeutically in pregnant mothers with certain psychiatric conditions.
A number of studies on the developmental effects caused by ingestion of therapeutic doses of lithium salts during pregnancy have been extensively reviewed by an expert committee on developmental and reproductive toxicity (Institute for Evaluating Health Risks (IEHR) in the United States). The evidence is considered sufficient to conclude that lithium salts, at therapeutic doses, can cause developmental toxicity in humans, with increased risk for major malformations (particularly cardiac) and possibly neonatal mortality.(13)
There are no well-conducted studies in animals that show developmental toxicity for lithium chloride or other lithium compounds, in the absence of maternal toxicity. The effects observed during therapeutic treatment with lithium salts are not considered relevant to occupational exposures.

Reproductive Toxicity:
There is insufficient evidence to conclude that lithium chloride is a reproductive toxin. No conclusions can be drawn from studies indicating that oral therapeutic doses of lithium compounds may affect libido and may impair sperm motility. The studies are limited by small numbers and by self-reporting biases.(13) Therapeutic exposures are not considered relevant to occupational situations.
Inadequate design or poor reporting limits most animal studies on the potential effects of lithium compounds on reproduction. In many cases, the animals were treated with high doses of lithium salts without consideration of whether the reported effects simply reflected generalized toxicity.(13)

Mutagenicity:
There is insufficient information available to conclude that lithium chloride is a mutagen. Negative results (chromosome aberrations and/or sister chromatid exchanges) were obtained in most studies on patients receiving lithium compounds therapeutically.(33,34,35,36,37) A positive result (chromosome breaks) was obtained in one study.(22) These studies are limited by small numbers and by concurrent exposures to other medications. Firm conclusions cannot be drawn from positive results in a study in live mice that is limited by poor reporting.

Toxicologically Synergistic Materials:
There is considerable information on the interaction of lithium salts used therapeutically and other medications.(14) In animal studies, sodium chloride decreased harmful effects observed following the ingestion of lithium chloride. A synergistic effect between lithium chloride and ethanol on the central nervous system was observed in one mouse study.

Potential for Accumulation:
Does not accumulate. The soluble salts of lithium, including lithium chloride, are completely absorbed in the small intestine and excreted in the urine, about 67% after 6-12 hours, then more slowly over a period of several days.(29,38) In people, approximately 95% is excreted in urine, 4-5% is excreted in sweat and less than 1% in feces.(29) The lithium ion also passes freely into human breast milk.(13)

Health Comments:
Lithium is considered an ultratrace element meaning that its established, estimated or suspected requirement in the human diet at less than 1 mg/day. The requirement for lithium in humans has not been proven, but is indicated from studies in animals. The requirement in humans is probably less than 25 microg/day while the average intake is reported to range from 100-2645 microg/day.(30,38)


SECTION 4. FIRST AID MEASURES

Inhalation:
If symptoms are experienced, remove source of contamination or move victim to fresh air. If symptoms persist, obtain medical advice.

Skin Contact:
If irritation occurs, flush with lukewarm, gently flowing water for 5 minutes. If irritation persists, obtain medical advice. Completely decontaminate clothing, shoes and leather goods before re-use or discard.

Eye Contact:
DO NOT allow victim to rub eye(s). Let the eye(s) water naturally for a few minutes. Have victim look right and left, and then up and down. If particle/dust does not dislodge, flush with lukewarm, gently flowing water for 5 minutes or until particle/dust is removed, while holding the eyelid(s) open. If irritation persists, obtain medical attention. DO NOT attempt to manually remove anything stuck to the eye(s).

Ingestion:
NEVER give anything by mouth if victim is rapidly losing consciousness, is unconscious or convulsing. Have victim rinse mouth thoroughly with water. DO NOT INDUCE VOMITING. Obtain medical advice.

First Aid Comments:
Provide general supportive measures (comfort, warmth, rest).
Consult a doctor and/or the nearest Poison Control Centre for all exposures except minor instances of inhalation or skin contact.
All first aid procedures should be periodically reviewed by a doctor familiar with the material and its conditions of use in the workplace.



SECTION 5. FIRE FIGHTING MEASURES

Flash Point:
Not combustible (does not burn)

Lower Flammable (Explosive) Limit (LFL/LEL):
Not applicable

Upper Flammable (Explosive) Limit (UFL/UEL):
Not applicable

Autoignition (Ignition) Temperature:
Not applicable

Sensitivity to Mechanical Impact:
Not sensitive. Stable material.

Sensitivity to Static Charge:
Specific information is not available. Lithium chloride does not accumulate static charge. Since it does not burn, it will not be ignited by a static discharge.

Electrical Conductivity:
Not available

Minimum Ignition Energy:
Not applicable

Combustion and Thermal Decomposition Products:
Hydrogen chloride, chlorine and other toxic and irritating fumes and gases may be formed when lithium chloride is heated to decomposition. ??

Fire Hazard Summary:
Lithium chloride does not burn or support combustion and is not considered to be a fire hazard. During a fire, corrosive and toxic hydrogen chloride and chlorine gases, lithium oxide and other toxic and irritating fumes and gases may be formed by thermal decomposition.

Extinguishing Media:
Lithium chloride does not burn or support combustion. Use extinguishing media suitable for surrounding fire.

Fire Fighting Instructions:
Evacuate area and fight fire from a safe distance or a protected location. Approach fire from upwind. If possible, isolate materials not involved in the fire and protect personnel.
Move containers from fire area if it can be done without risk. Water can be used in flooding quantities as a spray or fog to keep fire-exposed containers cool and absorb heat to help prevent rupture. Water spray may also be used to knock down corrosive fumes which may be produced in a fire. Apply water from as far a distance as possible. Dike fire control water for appropriate disposal.

Protection of Fire Fighters:
Although lithium chloride is not hazardous, its thermal decomposition products including corrosive and toxic hydrogen chloride and chlorine gases may be given off in a fire. Do not enter without wearing specialized equipment suitable for the situation. Firefighter's normal protective clothing (Bunker Gear) will not provide adequate protection. Chemical protective clothing (e.g. chemical splash suit) and positive pressure self-contained breathing apparatus (NIOSH approved or equivalent) may be necessary.



NATIONAL FIRE PROTECTION ASSOCIATION (NFPA) HAZARD IDENTIFICATION

NFPA - Comments:
NFPA has no listing for this chemical in Codes 49 or 325.


SECTION 9. PHYSICAL AND CHEMICAL PROPERTIES

Molecular Weight: 42.39 (anhydrous); 60.41 (monohydrate); 78.42 (dihydrate)

Conversion Factor:
Not applicable

Physical State: Solid
Melting Point: 613-614 deg C (1135.4-1137.2 deg F) (4,40); also reported as 610 deg C (1130 deg F) (41,42)
Boiling Point: 1360 deg C (2480 deg F) (1,40); also reported as 1382 deg C (2519.6 deg F) (3,4)
Relative Density (Specific Gravity): 2.07 at 25 deg C (water = 1) (1,4,42)
Solubility in Water: Very soluble (77-83 g/100 mL at 20 deg C (4,40); also reported as 45.2 g/100 mL at 20 deg C (3,41))
Solubility in Other Liquids: Soluble in methanol, ethanol, acetone, amyl alcohol, diethyl ether, pyridine and amines.(1,3,4,17)
Coefficient of Oil/Water Distribution (Partition Coefficient): Log P(oct) = -0.46 (estimated) (43)
pH Value: Neutral or slightly alkaline (1)
Viscosity-Dynamic: Not applicable
Surface Tension: Not applicable
Vapour Density: Not applicable
Vapour Pressure: Practically zero
Saturation Vapour Concentration: Not applicable
Evaporation Rate: Not applicable
Henry's Law Constant: Not available

SECTION 10. STABILITY AND REACTIVITY

Stability:
Normally stable.

Hazardous Polymerization:
Does not occur.

Incompatibility - Materials to Avoid:

NOTE: Chemical reactions that could result in a hazardous situation (e.g. generation of flammable or toxic chemicals, fire or detonation) are listed here. Many of these reactions can be done safely if specific control measures (e.g. cooling of the reaction) are in place. Although not intended to be complete, an overview of important reactions involving common chemicals is provided to assist in the development of safe work practices.


BROMINE TRIFLUORIDE or BROMINE PENTAFLUORIDE - rapidly attacks lithium chloride. Reaction may be violent.(44)

Hazardous Decomposition Products:
None reported.

Conditions to Avoid:
Generation of dust.

Corrosivity to Metals:
Lithium chloride (10-100% solutions) corrodes types 3003 and Cast B-356 aluminum, and copper at 21 deg C. Lithium chloride concentrations up to 30% corrode types 403, 410 and 430 stainless steel, and 100% solution corrodes types 1010 and 1020 carbon steel at 21 deg C.(45) Lithium chloride corrodes some stainless steels (types 316 and 317), copper-nickel and naval and admiralty brass at temperatures of 100 deg C and greater.(45) Lithium chloride (concentrations up to 100%) is not corrosive to some stainless steels (e.g. types 303, 304, 316, 317 and Carpenter 20Cb-3), Monel and bronze at 21 deg C. Lithium chloride concentrations up to 30% are not corrosive to nickel, Inconel and tantalum, and concentrations up to 60% are not corrosive to Hastelloy and titanium at 21 deg C.(45)

Corrosivity to Non-Metals:
Lithium chloride attacks some plastics, e.g. polyurethane, polybutylene terephthalate and ethylene vinyl acetate (EVA), and some elastomers, e.g. polyacrylate, polyurethane and flexible polyvinyl chloride (PVC).(46,47) Lithium chloride does not attack plastics, such as Teflon and other fluorocarbons, polyvinylidene fluoride (Kynar), chlorinated polyvinyl chloride (CPVC), polyvinyl chloride (PVC), polypropylene, nylon and high density polyethylene, and elastomers, such as nitrile Buna N (NBR), ethylene propylene, Viton and other fluorocarbons (e.g. Chemraz and Kalrez), chloroprene, styrene butadiene (SBR), natural rubber and low density polyethylene (LDPE).(46,47)

Stability and Reactivity Comments:
Lithium chloride is one of the most hygroscopic salts known.(17)


SECTION 11. TOXICOLOGICAL INFORMATION

LD50 (oral, 6-month-old male rat): 526 mg/kg (cited as 12.4 mmol/kg, as lithium) (2)
LD50 (oral, 6-week-old male rat): 840 mg/kg (cited as 19.8 mmol/kg, as lithium) (2)

LD50 (dermal, rat): 1488 mg/kg (5, unconfirmed)
LD50 (dermal, rabbit): 1629 mg/kg (5, unconfirmed)

Eye Irritation:

There is insufficient information available to assess the eye irritation potential of lithium chloride. There are no results from confirmed standard tests available.

Application of an unspecified amount of 30, 40 and 50% lithium chloride caused redness and swelling in the eyes of mice, which cleared on the second day.(6) No further details are available. In another study, which is not available in English, application of 100 mg for 24 hours caused severe irritation in rabbits.(5, unconfirmed)

Skin Irritation:

There is insufficient information available to assess the skin irritation potential of lithium chloride. There are no results from confirmed standard tests available.

Application of an unspecified amount of 30, 40 and 50% lithium chloride for an unreported time caused redness and swelling in mice, which cleared on the second day.(6) No further details are available. In another study, which is not available in English, application of 500 mg lithium chloride for 24 hours caused severe irritation in rabbits.(5, unconfirmed)

Effects of Short-Term (Acute) Exposure:

Relatively high oral doses (100 mg/kg/day and above) have resulted in decreased body weight, decreased lithium clearance and altered urine flow in male rats. One study showed kidney injury in male rats exposed to 100 mg/kg/day for 3 weeks.

Ingestion:
Male rats were given lithium chloride in the diet at concentrations of 20, 40 or 60 mmol/kg for 3-4 weeks. The approximate doses were 50, 100, or 150 mg/kg/day, as lithium chloride (8, 17 or 25 mg/kg/day, as lithium). There was a dose-related decrease in body weight gain (significance not reported). At the 2 high doses, there was increased water intake. At 150 mg/kg/day, some rats had a decrease in lithium clearance by the kidneys, decreased urine flow and increased serum lithium (significance not reported) indicating lithium intoxication.(7) Male rats (numbers not reported) were given a diet containing 0.4% lithium chloride for 15 or 30 days. The approximate dose was 240 mg/kg/day, as lithium chloride (40 mg/kg/day, as lithium). At day 4, there was an increase in urine production, and after 15 and 30 days, there was a significant decrease in body and adrenal weight. Detailed examination of the tissues indicated changes in the thyroid gland characteristic of decreased thyroid activity (hypothyroid) and a reduction in size of the seminal vesicles. No changes were noted in the adrenal glands, pancreas or testes.(8) This study is limited by the use of a single dose and animal numbers were not specified. Male rats were given lithium chloride in the diet at a concentration of 40 mmol/kg for 3 weeks. The approximate dose was 100 mg/kg/day, as lithium chloride (16.5 mg/kg/day, as lithium). The treatment caused a significant increase in water intake (5-fold) over the 3 weeks and enzyme and structural changes in the kidneys (dilations of distal tubules). Accompanying studies indicated that the kidney changes were caused by the lithium ions, not by the increase in urine production.(9) This study is limited by the use of a single exposure group. Male rats were given 3 single doses of 100, 200 or 300 mg/kg lithium chloride with 6 days between each dose. There were significant changes in behaviour (learned bar-pressing performance) at 200 and 300 mg/kg.(10)

Effects of Long-Term (Chronic) Exposure:

Long-term administration of relatively high oral doses of lithium chloride (150 mg/kg/day) has resulted in decreased body weight, decreased lithium clearance and altered urine flow in rats. Exposure for 1 year resulted in increased mortality and structural changes in the kidneys (dilated tubules, fibrosis and atrophy).

Inhalation:
Male rabbits were exposed to 0, 0.6 or 1.9 mg/m3 lithium aerosol, as lithium chloride, for 4-8 weeks (median diameter 1 micrometres; 6 hr/d, 5 d/wk). No significant effects were observed in the lungs.(15)

Ingestion:
Rats were given lithium chloride in the diet at 40 mmol/kg from birth (by exposure of the mothers during lactation) to 55-65 weeks of age. The approximate dose for adults was 150 mg/kg/day, as lithium chloride (25 mg/kg/day, as lithium). All treated rats survived the first 8 weeks of treatment, but by 55 weeks survival was 64% in males and 40% in females compared to 94% in controls. Treated animals had a significant increase in urine flow (at 50 weeks) and in renal concentrating ability, as well as a significant decrease in the clearance rate of lithium. Detailed examination of the kidneys showed dilated tubules, fibrosis and atrophy.(11) This study is limited by the use of only one exposure group. Male rats were given lithium chloride in the diet at a concentration of 60 mmol/kg for 3-5 weeks. The approximate dose was 150 mg/kg/day, as lithium chloride (25 mg/kg/day, as lithium). There was an increase in urine flow for the first 2 weeks, followed by decreased urine flow, decreased body weight and decreased lithium clearance by the kidneys. These effects were all reversed by adding sodium chloride to the drinking water.(7) No statistical evaluation of the data was reported. This study is limited by the use of only one exposure group.

Teratogenicity, Embryotoxicity and/or Fetotoxicity:
There is insufficient evidence available to conclude that lithium chloride is a developmental toxin. In one limited study, oral exposure through pregnancy and lactation resulted in harmful effects in offspring of mice (reduced organ weights, increased enzyme levels) measured 2 weeks after weaning. It is not clear if the effects observed were from exposure during the pregnancy and/or during lactation. There are no well-conducted studies that show developmental toxicity for lithium chloride or other lithium compounds in the absence of maternal toxicity. For lithium compounds in general, the US Institute for Evaluating Health Risks (IEHR) concluded that there is adequate information to indicate that developmental toxicity can occur in rats and mice at doses from 19-89 mg/kg/day (cited as 2.71-12.67 mmol/kg/day), usually in the presence of maternal toxicity. In addition, IEHR concluded there is sufficient information that developmental toxicity can occur after birth based on developmental toxicity studies that included the period of lactation to weaning, and beyond, with lithium doses of 2.9-11.5 mg/kg/day (cited as 0.41-1.64 mmol/kg/day).(13)
Mice (number not specified) were given 1 mmol/L lithium chloride in the drinking water from preconception until the end of weaning. The reported dose during the pregnancy was 12.9 mg/kg/day, as lithium chloride (2.1 mg/kg/day, as lithium). At birth, there was no significant difference in litter size or weight. In the offspring, two weeks after weaning, there was a significant decrease in kidney weights of females, of testes weight in males and of brain weight for both sexes. There was also a significant increase in specific liver and heart enzymes (liver alcohol dehydrogenase and heart lactate dehydrogenase). There was no significant decrease in maternal weight and no other report of maternal toxicity.(18) This study is limited by the use of only one exposure group and the number/group was not specified. It is not clear if the effects observed were from exposure during the pregnancy and/or during lactation. Rats were given 20 mmol/L lithium chloride in the drinking water for 3-7 weeks before mating, through pregnancy and weaning. The approximate reported dose was 66-100 mg/kg/day, as lithium chloride (11-17 mg/kg/day, as lithium). No malformations were noted in the offspring. The same dose of lithium chloride administered over a 2-year period resulted in a transient decrease in water consumption in adult animals, which lasted a few days, but there were no other indications of effects on health or behaviour.(12) Thus, maternal toxicity would not be expected at this dose. The use of only one exposure group and limited reporting of observations limit this study.

Reproductive Toxicity:
There is insufficient evidence to conclude that lithium chloride is a reproductive toxin. Factors such as poor reporting, small numbers of animals, lack of reporting on generalized toxicity, and the use of only a single dose limit the available studies.
Female rats were given lithium chloride in the drinking water at 20 mmol/L for 3-7 weeks before mating. The approximate reported dose was 66-100 mg/kg/day, as lithium chloride (11-17 mg/kg/day, as lithium). There was a significant decrease in the number of corpora lutea in the ovaries, but there was no effect on pregnancy outcome. The same dose of lithium chloride administered over a 2-year period resulted in a transient decrease in water consumption, which lasted a few days, but no other effects on health or behaviour.(12) This study is limited by the use of only one exposure group and limited reporting of observations. Female mice were given 0.4% lithium chloride in their diet for 15 days. The approximate dose was 480 mg/kg/day, as lithium chloride (79 mg/kg/day, as lithium). By day 8, all of the treated mice had an abnormal fertility cycle.(19) This study is limited by lack of reporting on generalized toxicity, which would be expected at the high dose used, and use of a single dose. Mice (number/group not specified) were given 1 mmol/L lithium chloride in the drinking water from conception until the end of weaning. The reported dose during the pregnancy was 12.9 mg/kg/day, as lithium chloride (2.1 mg/kg/day, as lithium). In the offspring, two weeks after weaning, there was a significant decrease in kidney weights of females, of testes weight in males and of brain weight for both sexes. There was no significant decrease in maternal weight and no other report of maternal toxicity. In a second part of the study, maternal exposure (5/group) during lactation resulted in decreased brain and testes weights in males and increased liver alcohol dehydrogenase in both sexes.(18) This study is limited by the use of only one exposure group and the small number of animals/group in the lactation only experiment. In a poorly reported study, mating pairs of mice were given lithium chloride in their drinking water at 0, 10, 20, 30, 50 or 100 mmol/L starting either at 3 or 6 weeks of age, through mating, pregnancy and lactation. The approximate doses were 0, 85, 170, 255, 425 or 850 mg/kg/day, as lithium chloride (0, 14, 27, 41, 68 or 136 mg/kg/day, as lithium). Mice given 100 mmol/L survived, but did not reproduce. At 50 mmol/L, mice had fewer litters and the intervals between litters were longer (significance not reported).(20) Despite the authors reporting of no adverse effects in the parent animals, general toxicity would be expected at this dose.

Mutagenicity:
There is insufficient information available to conclude that lithium chloride is a mutagen. No firm conclusions can be drawn from a positive result in a study using live mice, which is limited by poor reporting.
In a study using live mice, oral exposure to lithium chloride in olive oil resulted in a dose-dependent, significant increase in chromosome aberrations in bone marrow. The same treatment caused no increase in sister chromatid exchanges.(21) Conclusions cannot be drawn from this study because the number of animals tested and cells evaluated were not reported.
A positive result (chromosome aberrations) was obtained in cultured human lymphocytes.(22) A positive result (DNA synthesis inhibition) was obtained in cultured mammalian cells, without metabolic activation.(23) Negative results (gene mutation, DNA damage) were obtained in bacteria, with and without metabolic activation.(16,24,25) A weak positive result (aneuploidy) was obtained in yeast.(26) In another study with yeast, lithium chloride caused changes in the meiotic process.(27)

Toxicological Synergisms:
Sodium chloride decreases effects from ingestion of lithium chloride.(7) A synergistic effect between lithium chloride and ethanol on the central nervous system was observed in one mouse study.(28)


SECTION 16. OTHER INFORMATION

Selected Bibliography:
(1) Lithium chloride. The Merck index: an encyclopedia of chemicals, drugs and biologicals. Edited by M.J. O'Neil, et al. 13th ed. Merck and Company, 2001. p. 991
(2) Petersen, K.P. Effect of age and route of administration on LD50 of lithium chloride in the rat. Acta Pharmacologica et Toxicologica. Vol. 47 (1980). p. 351-354
(3) Kamienski, C.W., et al. Lithium and lithium compounds. Kirk-Othmer encyclopedia of chemical technology. John Wiley and Sons, 2004. Available at: <www.mrw.interscience.wiley.com/kirk/kirk_search_fs.html> (Subscription required)
(4) Wietelmann, U., et al. Lithium and lithium compounds. In: Ullmann's encyclopedia of industrial chemistry. 7th ed. John Wiley and Sons, 2002. Also available at: <www.mrw.interscience.wiley.com/ueic/ueic_search_fs.html> (Subscription required)
(5) National Institute for Occupational Safety and Health (NIOSH). Lithium chloride. Last updated: 2003-05. In: Registry of Toxic Effects of Chemical Substances (RTECS(R)). [CD-ROM]. Canadian Centre for Occupational Health and Safety (CCOHS). Also available at: <http://ccinfoweb.ccohs.ca/rtecs/search.html> {Subscription required}
(6) Neretin, V.I., The comparative toxicity of certain lithium compounds in acute experiments on animals. Pharmacology and Toxicology. Vol. 21 (1958). p. 419-422
(7) Thomson, K. The effect of sodium chloride on kidney function in rats with lithium intoxication. Acta Pharmacologica et Toxicologica. Vol. 33 (1973). p. 92-102
(8) Chatterjee, S., et al. Morphological changes in some endocrine organs in rats following chronic lithium treatment. Anatomischer Anzeiger. Vol. 170 (1990). p. 31-37
(9) Ottosen, P.D., et al. Lithium-induced morphological changes in the rat kidney at different levels of urine flow. Pharmacology and Toxicology. Vol. 63 (1988). p. 108-113
(10) Chrislip, D.W., et al. Effects of acute oral administration of lithium compounds on multiple schedule performance in rats. Neurobehavioral Toxicology and Teratology. Vol. 7, no. 1 (Feb. 1985). p. 39-42
(11) Christensen, S., et al. Lithium-induced uraemia in rats: survival and renal function and morphology after one year. Acta Pharmacologia et Toxicologia. Vol. 58 (1986). p. 339-347
(12) Trautner, E.M., et al. The effects of prolonged sub-toxic lithium ingestion on pregnancy in rats. Australian Journal of Experimental Biology. Vol. 36 (1958). p. 305-322
(13) Moore, J.A. An assessment of lithium using the IEHR evaluative process for assessing human developmental and reproductive toxicity of agents. Reproductive Toxicology. Vol. 9, no. 2 (1995). p. 175-210
(14) Baldessarini, R.J. Drugs and the treatment of psychiatric disorders. In : Goodman & Gilman's The Pharmacological Basis of Therapeutics. Edited by A.G. Gilman, et al. 9th ed. McGraw-Hill. 1996. p. 446-449
(15) Johansson, A., et al. Rabbit lung after inhalation of lithium chloride. Journal of Applied Toxicology. Vol. 8, no. 5 (Oct. 1988). p. 373-375
(16) Haworth, S., et al. Salmonella mutagenicity test results for 250 chemicals. Environmental Mutagenesis. Vol. 5, suppl. 1 (1993). p. 1-142
(17) Lewis, Sr., R.J., ed. Lithium chloride. Hawley's condensed chemical dictionary. [CD-ROM]. 14th ed. John Wiley and Sons, Inc., 2002
(18) Messiha, F.S. Maternally-mediated developmental lithium toxicity in the mouse. General Pharmacology. Vol. 24, no. 1 (1993). p. 9-15
(19) Banerji, T.K., et al. Acute lithium treatment suppresses the proestrus LH surge in mice: chronic lithium leads to constant diestrus. Brain Research. Vol. 380 (1986). p. 176-180
(20) Mroczka, D.L., et al. Effect of lithium on reproduction and postnatal growth of mice. Biology of the Neonate. Vol. 43 (1983). p. 287-296
(21) Sobti, R.C., et al. Frequency of sister chromatid exchanges (SCEs) and chromosome aberrations (CAs) caused by three salts of lithium (in vivo). Cytologia. Vol. 54 (1989). p. 245-248
(22) De la Torre, R., et al. The in vivo and in vitro effects of lithium on human chromosomes and cell replication. Teratology. Vol. 13, no. 2 (Apr. 1976). p. 131-138
(23) Painter, R.B., et al. The HeLa DNA-synthesis inhibition test as a rapid screen for mutagenic carcinogens. Mutation Research. Vol. 92 (1982). p. 427-437
(24) Kanematsu, N., et al. Rec assay and mutagenicity studies on metal compounds. Mutation Research. Vol. 77 (1980). p. 109-116
(25) Nishioka, H. Mutagenic activities of metal compounds in bacteria. Mutation Research. Vol. 31 (1975). p. 185-189
(26) Zimmerman, F.K., et al. Induction of chromosome loss by mixtures of organic solvents including neurotoxins. Mutation Research. Vol. 224 (1989). p. 287-303
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Information on chemicals reviewed in the CHEMINFO database is drawn from a number of publicly available sources. A list of general references used to compile CHEMINFO records is available in the database Help.


Review/Preparation Date: 2005-11-25



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