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Toxicity Profiles

Condensed Toxicity Summary for LITHIUM

NOTE: Although the toxicity values presented in these toxicity profiles were correct at the time they were produced, these values are subject to change. Users should always refer to the Toxicity Value Database for the current toxicity values.

May 1995

Prepared by Dennis M. Opresko, Ph.D., Chemical Hazard Evaluation and Communication Program, Biomedical and Environmental Information Analysis Section, Health Sciences Research Division, *, Oak Ridge, Tennessee.


*Managed by Martin Marietta Energy Systems, Inc., for the U.S. Department of Energy under contract No. DE-AC05-84OR21400.

Lithium is an alkali metal similar to magnesium and sodium in its properties (Birch, 1988; Arena, 1986) and has a molecular weight of 6.941 (Beliles, 1994). It does not occur in nature in its free form but is found in minerals such as spodumene, petalite, and eucryptite (Beliles, 1994). Lithium compounds are found in natural waters and in some foods. The average dietary intake is estimated to be about 2 mg per day (Beliles, 1994).

Inorganic salts or oxides of lithium have many uses. Lithium carbonate is used extensively as a therapeutic agent in the treatment of manic depressive affective disorders (Ellenhorn and Barceloux, 1988). Elemental lithium is a component of metal alloys; lithium hydride is used as a nuclear reactor coolant. Lithium hydroxide is used in alkaline storage batteries; lithium carbonate and lithium borate are used in the ceramic industry; and lithium chloride and fluoride are used in welding and brazing fluxes (Beliles, 1994). Lithium forms covalent bonds in organometallic compounds such as lithium stearate. Organo-lithium compounds are used as multipurpose greases, particularly in the automotive industry (Beliles, 1994).

Most common inorganic lithium compounds are water soluble to some extent: i.e., chloride, 454 g/L; carbonate, 13.3 g/L; hydroxide, 223 g/L; oxide, 66.7 g/L (Beliles, 1994)). Lithium hydride reacts with water to form a very basic solution of lithium hydroxide.

Soluble lithium compounds are readily absorbed through the gastrointestinal tract but not the skin; distribution is rapid to the liver and kidneys but slower to other organ systems (Jaeger et al., 1985). Lithium crosses the human placenta (ACGIH, 1991) and can also be taken up by infants through breast milk. Lithium is not metabolized and is excreted primarily in the urine.

The oral toxicity of most lithium compounds is relatively low; oral LD50 values for several compounds and animal species range from 422-1165 mg/kg. Case histories described by Gosselin et al. (1984) indicate that doses of 12-60 g (171-857 mg/kg/day for a 70 kg person) can result in coma, respiratory and cardiac complications, and death in humans. A single oral dose of 40 mg/kg produced toxic lithium blood levels in a patient with a history of prior lithium use (Marcus, 1980). In contrast, for chronic therapeutic use, the standard dose of lithium carbonate is 1-2 g/day (14-28 mg/kg/day).

Signs and symptoms of lithium toxicity include anorexia; nausea; diarrhea; alopecia; weight gain; thirst; pretibial edema (sodium retention); polyuria; glycosuria; aplastic anemia; tremors; acne; muscle spasm; and, rarely, dysarthria, ataxia, impaired cognition, and pseudotumor cerebri (Arena, 1986; Ellenhorn and Barceloux, 1988). Toxic effects that may appear after prolonged therapeutic use may include neurological symptoms, changes in kidney function, hypothyroidism, and leukocytosis.

The nervous system is the primary target organ of lithium toxicity. Neurologic effects occurring during prolonged therapy often include minor effects on memory, motor activity, and associative productivity (Kocsis et al., 1993). Movement disorders (myoclonus, choreoathetosis), proximal muscle weakness, fasciculations, gait disturbances, incontinence, corticospinal tract signs, and a Parkinsonian syndrome (cogwheel rigidity, tremor) have been reported (Sansone and Ziegler, 1985). Cases of severe lithium neurotoxicity, which may occur during chronic therapy as a result of increased lithium retention, may be characterized by disorientation, incoherence, paralysis, stupor, seizure, and coma (Hall et al., 1979). Permanent brain damage has occurred in several patients on long-term lithium therapy (Gosselin et al., 1984).

During chronic lithium therapy, changes in kidney function may appear as transient natriuresis, polydipsia/polyuria, nephrogenic diabetes insipidus, partial renal tubular acidosis, minimal change disease, and nephrotic syndrome (Ellenhorn and Barceloux, 1988). Degenerative changes may occur in the glomeruli or in the distal convoluted tubules or collecting ducts (Richman et al., 1980; Hestbech et al., 1977). In rare cases, acute renal failure may occur (Fenves et al., 1984).

Cohort studies indicate that the risk of major congenital malformations among women receiving lithium during early pregnancy is slightly higher (4-12%) than that among control groups (2-4%) (Cohen et al., 1994). Evidence also suggests that women on lithium therapy may have a higher risk of premature births. In animals, reproductive and developmental effects (decrease in litter size, decrease in live pups, reduced growth, and increased incidence of cleft palate) have been reported in rodents exposed to lithium salts during gestation (Marathe and Thomas, 1986; Sechzer et al., 1992; Szabo, 1970; Chernoff and Kavlock, 1982). Subchronic and chronic oral RfDs have not been derived for lithium.

Limited information is available on the inhalation toxicity of lithium compounds. Lithium hydride is a respiratory tract irritant. In occupationally exposed workers, concentrations between 1 and 5.0 mg/m3 caused severe eye and nasal irritation as well as skin irritation; concentrations of 0.025 mg/m3 or less caused no adverse effects (Beliles, 1994). In animal studies, concentrations above 10 mg/m3 for 4-7 hours resulted in inflammation of the eyes, partial sloughing of mucosal epithelium of the trachea, lesions of the nose and forepaws, and erosion of the nasal septum (Spiegl et al., 1956).

Lithium combustion aerosols are also respiratory tract irritants. In a study in which rats were exposed for 4 hours to an aerosol consisting of 80% lithium carbonate and 20% lithium hydroxide, signs of toxicity included anorexia, dehydration, respiratory difficulty, perioral and perinasal encrustation, ulcerative or necrotic laryngitis, focal to segmental ulcerative rhinitis often accompanied by squamous metaplasia, and in some animals, suppurative bronchopneumonia or aspiration pneumonia, probably secondary to laryngeal lesions (Greenspan et al., 1986). The LC50 (after 14 days) was estimated to be 1700 mg/m3 for males and 2000 mg/m3 for females. In a second study in which rats were exposed for 4 hours to an aerosol containing mostly lithium monoxide, some lithium hydroxide, and 12% lithium carbonate, the LC50 value (after 14 days) was 940 mg/m3 (Rebar et al., 1986). Four-hour exposure to an aerosol containing primarily lithium hydroxide with 23% lithium carbonate resulted in an LC50 of 960 mg/m3 (Rebar et al., 1986).

No information was found in the available literature on the subchronic, chronic, or developmental/reproductive toxicity of lithium compounds by the inhalation route. In addition, subchronic and chronic inhalation RfCs have not been derived for lithium.

Little information was found in the available literature on the carcinogenicity of lithium compounds. However, three patients on chronic lithium therapy developed leukemia, and one developed a thyroid tumor. Lithium has not been classified by EPA as to its potential carcinogenicity. Retrieve Toxicity Profiles Formal Version

Last Updated 10/31/97

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