Physicochemical Properties
| Molecular Formula | CLLI |
| Molecular Weight | 42.39 |
| Exact Mass | 41.984 |
| CAS # | 7447-41-8 |
| PubChem CID | 433294 |
| Appearance |
Deliquescent, cubic crystals, granules or crystalline powder White cubic crystals or powder; hygroscopic |
| Density | 2.06 |
| Boiling Point | 1382°C |
| Melting Point | 605 °C(lit.) |
| Flash Point | -4 °F |
| Index of Refraction | n20/D 1.381 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 1 |
| Rotatable Bond Count | 0 |
| Heavy Atom Count | 2 |
| Complexity | 2 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | [Cl-].[Li+] |
| InChi Key | KWGKDLIKAYFUFQ-UHFFFAOYSA-M |
| InChi Code | InChI=1S/ClH.Li/h1H;/q;+1/p-1 |
| Chemical Name | lithium;chloride |
| Synonyms | LiCl, Premium grade |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vitro | GSK3β inhibitors |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion Lithium may also be absorbed via the lungs. A systemic resorption of lithium was shown in a study on 27 intensive care unit patients, who were mechanically ventilated with lithium-chloride-coated heat and moisture exchangers for at least 5 days. Serum lithium was non-detectable at the first measurement, whereas 0.01-0.05 mM appeared in the blood from the 1st to the 4th day. In the following days, it remained at this level or increased to 0.1 mM. After cessation of the mechanical ventilation, serum lithium levels went back to undetectable levels within a few days. In a 7 year-old girl, the serum Li concentration rose to about 1 mM after a week, came back to 0.1 mM, rose to 3.9 mM on the 16th day and then returned to the usual low range (0.05-0.1 mM). The authors calculated that for adults, the daily amount of lithium chloride inhaled from a new heat and moisture exchanger (80% of the lithium content) can be considered equivalent to an oral dose of 100 mg/day of lithium chloride or 16 mg Li/day. ...After 20 minutes of ventilation more than 90% of the lithium chloride content of lithium-chloride-coated heat and moisture exchangers was deposited into the test lung of the breathing model. In rats, the levels of lithium in brain 24 hours after treatment with single doses of lithium chloride decreased in the following order: caudate > cerebral cortex >thalamus >hippocampus >cerebellum. After 7 or 14 daily doses of lithium chloride the concentrations of lithium were still highest in the cerebral cortex and caudate, and lowest in the cerebellum. Lithium chloride solution (24 mmol) administered to 7 healthy volunteers in single dose and multiple dose experiments. Mean biological T1/2 was approximately 19.8 hr. Absorption of Li from single oral dose had half-time of approximately 0.15 hr. Mean total body clearance was 27.6 mL/kg/hr. For more Absorption, Distribution and Excretion (Complete) data for LITHIUM CHLORIDE (16 total), please visit the HSDB record page. Biological Half-Life Lithium chloride solution (24 mmol) administered to 7 healthy volunteers in single dose and multiple dose experiments. Mean biological T1/2 was approximately 19.8 hr. The plasma half-life (in healthy volunteers) shows a considerable variability: from 5 to 40 hr, with most values between 15 and 30 hr, it depends on the duration of treatment as well as on kidney function and age. /Li+/ ...AFTER ORAL DOSES TO HUMAN SUBJECTS...THE TERMINAL ELIMINATION T/2 IS ABOUT 22 HR. /LITHIUM/ ... The clinical features and pharmacokinetics of 22 lithium overdoses are described. Effectiveness of different treatment regimens regarding elimination of lithium is discussed. Origin of overdose was due to deliberate poisoning or precipitated by concomitant diseases, coadministration of drugs, or combination of both. Treatment included supportive care, diuretics (15/22), hemodialysis (HD; 9/22), and mechanical ventilation (3/22). Severity of lithium intoxication was classified in 50% as I degrees, in 41% as II degrees, and in 9% as III degrees according to Hansen and Amdisen. Renal impairment on admission was diagnosed in 82% of the patients. Half-life of lithium in serum was 3.5 +/- 0.8 hr during the first HD, and 29 +/- 14 and 29 +/- 6 hr during therapy with diuretics or supportive treatment, respectively. Lithium clearance during HD was 160 +/- 15 mL/min, and renal clearance during HD or treatment with diuretics was approximately 20 and 15 +/- 9 mL/min, respectively. Renal lithium clearance was not influenced by HD therapy. There was no difference regarding half-life and clearance between the group that had an unspecific treatment or the group treated with diuretics. ... /Lithium NOS/ The usual elimination half-life is 12 to 27 hr, but it may rise to nearly 60 hr if renal excretion is compromised. /Li+/ |
| Toxicity/Toxicokinetics |
Toxicity Summary IDENTIFICATION AND USE: Lithium chloride is a white cubic crystalline material. It is soluble in water, ethanol, acetone, pyridine and nitrobenzene. It is used to manufacture mineral waters; in pyrotechnics; soldering aluminum; in refrigerating machines. It is used as a dessicant. HUMAN EXPOSURE AND TOXICITY: Acute poisoning in man reported after 4 doses of 2 g each of lithium chloride, causing weakness, prostration, vertigo, and tinnitus. Chronic toxicity symptoms following ingestion of nonlethal doses of lithium chloride with low-sodium chloride diets are thirst and polyuria. Human volunteers (28 males, 25 females) were exposed to lithium chloride in spa water at a for 20 minutes/day, five days/week for two consecutive weeks. Serum lithium levels were compared to those of a control group of volunteers similarly exposed in spas without lithium. There were no differences between the serum lithium levels between lithium exposed volunteers and controls at any time interval (before lithium exposure and one hr after each weekly exposure). It is concluded that lithium is not absorbed through the skin during spa use. PAH-stimulated lymphocyte cultures from healthy adult volunteers were exposed to concentrations of lithium chloride. Tritiated thymidine was then added four hrs before harvesting. The mitotic index increased. The incidence of chromosomal breaks, gaps and satellite associations was increased in the presence of lithium chloride in the media. Acute intoxication can occur in the initial phase in a course of therapy, but also at any point of time during long-lasting treatment or after an acute overdose. Signs of toxicity include: anorexia, dry mouth, nausea, vomiting, diarrhea, tremor of the hands, faintness of musculature, thirst, leukocytosis, and concentration and memory disturbances (especially with older people). These phenomena are often seen in the initial phase of a course of treatment and usually disappear when treatment continues, except with the tremor of the hands. In elderly people, reversible delirious conditions can occur with confusion, restlessness, and ataxia.Serious toxic symptoms occur which include: fasciculations, muscle contractions, hyperreflexia and hypertonia, drowsiness, confusion, sometimes epileptiform insults, hypotension, coma, collapse. Independent of the plasma level, changes can occur in the ECG and in the EEC, with symptoms such as polyuria and polydipsia, seldom nephrogenic diabetes insipidus, ulcers of the leg, enhancement of acne and psoriasis, transient hyperglycemia, pruritus, and a metal taste. In about 5% of the cases, a (usually reversible) hypothyroidia develops. The vast majority of the studies on chromosomal damage in leukocytes, lymphocytes and bone marrow cells in patients do not indicate any increased risk by lithium therapy for chromosome aberrations or sister chromatid exchanges. Factors affecting the glomerular filtration rate have a significant influence on the clearance of lithium. Thus, subjects with chronic renal insufficiency are especially vulnerable to lithium exposure. Other conditions predisposing to lithium intoxication include advanced age, sodium depletion of different origin or use of certain drugs affecting the renal function. Moderately toxic; probable oral lethal dose (human 0.5-5 g/kg; between 1 oz and 1 pint (or 1 lb) for 70 kg person (150 lb). ANIMAL/ECOTOXICITY/ STUDIES: Lithium chloride was found to be irritating in the rabbit acute toxicity testing of the skin. It was moderately irritating in the Draize test in rabbit eyes. Inbred strains of male mice were used to determine whether genetic factors play a role in lithium toxicity. Significant differences were also observed between the mouse strains in the concentrations of lithium in plasma, heart, liver, kidney and brain 2 hr after a subcutaneous injection lithium chloride, but the lithium concentrations were not related in an obvious manner to lithium chloride toxicity. The results show that genetic factors can influence the toxicity and pharmacodynamics of lithium. Application of lithium chloride solution to rabbit's eye after mechanical removal of corneal epithelium to facilitate penetration caused no evident injury, but produced long lasting flattening of the cornea. A teratogenicity study was conducted in a group of 52 rats and 100 controls. The animals were administered lithium chloride (LiCl) in a in drinking water. The dose levels were evaluated to be just subtoxic in a for going study. No malformations or other defects in the lithium exposed litters. Neither were there any differences in size and weight among these and untreated controls. If the young were maintained at the same lithium concentration in the drinking water, 23 showed slightly lower growth, but developed finally into adult rats indistinguishable from normal rats. Significant inhibition of spermatogenesis was found in a study in immature rats after daily subcutaneous injections of lithium chloride for at least 15 days. Lithium chloride was negative in the Bacillus subtilis recombination assay without metabolic activation. Lithium chloride tested negative in the Ames test with Salmonella typhimurium strains TA 98, TA 100, TA 1535 and TA 1537 with or without metabolic activation. Lithium chloride at concentrations was administered to mice and bone marrow was extracted Lithium chloride induced chromosomal aberrations, but not sister chromatid exchanges. A 24 hour static bioassay was conducted in three species of fish: Oncorhynchus kisutch, Oncorhynchus tschawytscha, and Ptychocheilus orefonensis. Acclimatized fish were transferred to vessels in 4 L of water (3 fish per vessel) about 2 hrs prior to addition of test article. The fish were exposed to lithium chloride and observed for 24 hours. The times at which a fish lost its equilibrium or died were noted. Death was seen at 6.5-11 hrs and 2.5-6.5 hrs for Oncorhynchus kisutch and Oncorhynchus tschawytscha, respectively. In two separate tests with Ptychocheilus oregonensis, no signs of toxicity were observed. In a third test death was seen at 2.5-6.5 hrs. The lower limit of these ranges indicate the time that the last observation was made before death. The upper limit indicates the time that death was noted. Loss of equilibrium was not observed. The chronic administration of lithium chloride during the embryogenesis of Bufo arenarum toad has resulted in a teratological development and in some cases an irreversible blockade of morphogenesis. These results vary according to the embryonic stage, the duration of the treatment and the concentration used. The histological analysis of embryos treated non-chronically showed a series of mild-to-severe malformations. According to the results obtained, lithium would alter the gastrulation and organogenesis processes of this species, interfering with the normal succession of developmental stages. Interactions The aim of the present study was to investigate the effect of lithium on acute morphine-induced tolerance and dependence in an in vitro model of isolated guinea pig ileum which has been extensively used for the assessment of these effects of opioids. Morphine inhibited electrically stimulated twitch of ileum in a concentration-dependent manner (pD(2)=7.27+ or -0.16). Tolerance to this effect was induced by the incubation of ileum with 2xIC(50) of morphine for 2 hr that induced a degree of tolerance of 14.7. The co-incubation of ileum with morphine and lithium chloride (1 mM) reduced the degree of tolerance significantly (p<0.001) and restored the sensitivity of ileum to the morphine inhibitory effect. Lithium chloride can also reduce the expression of tolerance to morphine significantly (p<0.01). Dependence was induced by incubation with 4xIC(50) of morphine for 2 hr and was assessed based on naloxone-induced contractions (10(-5 )M). Lithium chloride (1 mM) can attenuate the development but not the expression of dependence to morphine as shown by the significant decrease in naloxone-induced contractions (p<0.05). ... ... Ovariectomized mice received estradiol dipropionate (2 ug per 100 g; sc) once a week or vehicle and drank tap water with 0.05% lithium chloride or plain tap water for 2 or 30 days. In animals treated with estradiol and lithium for a month, the incidence of atypical endometrial hyperplasia was significantly higher. In animals treated with estradiol and lithium for 2 days or for a month, uterine mass, the number of mitotic cells and BrdU-labelled cells in luminal epithelium, glandular epithelium, stromal and myometrial cells was markedly greater, whereas the levels of estrogen receptors-alpha, beta-catenin and glycogen synthase kinase-3beta were markedly lower in all uterine compartments, than in those in mice received estradiol with no lithium to drink. ... Mitochondrial preparations were made from male Wistar rat brains, and monoamine oxidase activity and protein content were measured. Varying concn of the enantiomers of tranylcypromine (+) and (-)-tranylcypromine were incubated with the enzyme source before the addition of substrate, and then the incubation was continued for 20 min at 37 °C. Substrates were either beta-phenylethylamine (0.03, or 0.21 mM) or serotonin (0.11 or 0.50 mM). Lithium was either added to the incubation medium at a concn of 1.5 mM/l (in vitro condition) or to the food at gradually incr concn for 3-4 wk (ex vivo condition), so that the serum lithium level at the time of testing was 0.6 to 0.9 mM/L. The (+)-enantiomer was 25 times more potent than its antipode as a monoamine oxidase inhibitor. Lithium enhanced the inhibitory effect of (-)-tranylcypromine on monoamine oxidase, but the effect depended significantly on the concn of substrate used (treatment x concn interaction. In the presence of (-)-tranylcypromine, Li significantly reduced the metabolism of beta-phenylethylamine under in vitro and ex vivo conditions as well as the metabolism of serotonin under in vitro conditions. Li failed, however, to influence the activity of monoamine oxidase significantly in the presence of (+)-tranylcypromine. /Lithium/ Eighteen cases of increased serum lithium concentrations after the addition of one of the cyclooxygenase (COX) 2 inhibitors to stable lithium therapy were retrieved from the U.S. Food and Drug Administration's Adverse Event Reporting System (AERS), 13 with rofecoxib and 5 with celecoxib. Serum lithium concentration increases of up to 99% and 448% with concomitant celecoxib and rofecoxib use, respectively, were reported. Thirty-six English-language literature articles report interactions between lithium and various NSAIDs. ... increased serum lithium concentration reports exist for aspirin, sulindac and 14 other NSAIDs, including celecoxib and rofecoxib. ... /Lithium therapy/ Non-Human Toxicity Values LD50 Rabbit oral 850 mg/kg LD50 Rat oral 757 mg/kg LD50 Mouse oral 1165 mg/kg LD50 Rat male oral 526-840 mg/kg bw (oral LD50 higher in rats of 6 weeks ols than in rats of 3 and 6 months of age). For more Non-Human Toxicity Values (Complete) data for LITHIUM CHLORIDE (13 total), please visit the HSDB record page. |
| References |
[1]. Biochemical reagents[M]//Methods of Enzymatic Analysis. Academic Press, 1965: 967-1037. |
| Additional Infomation |
Lithium chloride appears as colorless crystals or powder. Low toxicity. Lithium chloride is a metal chloride salt with a Li(+) counterion. It has a role as an antimanic drug and a geroprotector. It is an inorganic chloride and a lithium salt. A salt of lithium that has been used experimentally as an immunomodulator. See also: Lithium Cation (has active moiety) ... View More ... Mechanism of Action ...Intraperitoneal lithium chloride (LiCl) induces transient expression of inducible cAMP early repressor (ICER) and c-fos mRNAs in the rat adrenal cortex and increases plasma level of corticosterone; the cortical expression of ICER mRNA by LiCl occurs in a dose-dependent manner; adrenal induction of ICER expression is delayed compared with c-fos expression; dexamethasone pretreatment (4 mg/kg) blocks corticosterone release and adrenocortical ICER induction either by systemic LiCl (76 mg/kg) or by restraint stress; and intracerebroventricular LiCl (127 ug/5 uL) is sufficient for adrenocortical, but not medullary, ICER induction. ... Lithium, through modulating basic cellular signalling pathways, is capable of modulating several neurotransmitter systems in the brain such as cholinergic, serotonergic, noradrenergic and dopaminergic pathways. /Lithium NOS/ Lithium may also slightly alter the reuptake and presynaptic storage of catecholamines in directions consistent with incr inactivation of the amines. /Li+/ In animal brain tissue, Li+ at concn of 1 to 10 mEq/L inhibits the depolarization-provoked and Ca+2-dependent release of norepinephrine and dopamine, but not serotonin, from nerve terminals. Li+ may even enhance the release of serotonin, especially in the limbic system, at least transiently. The ion has little effect on catecholamine-sensitive adenylyl cyclase activity or on the binding of ligands to monoamine receptors in brain tissue, although there is some evidence that Li+ can inhibit the effects of receptor-blocking agents that cause supersensitivity in such systems. Li+ can modify some hormonal responses mediated by adenylyl cyclase or phospholipase C in other tissues, including the actions of antidiuretic and thyroid-stimulating hormones on the actions of antidiuretic and thyroid-stimulating hormones on their peripheral target tissues. In part, the actions of Li+ may reflect its ability to interfere with the activity of both stimulatory and inhibitory GTP-binding proteins (Gs and Gi) by keeping them in their less active alpha-beta-gamma trimer state. /Li+/ For more Mechanism of Action (Complete) data for LITHIUM CHLORIDE (12 total), please visit the HSDB record page. Therapeutic Uses /Expl ther:/ A salt of lithium that has been used experimentally as an immunomodulator Drug Warnings Lithium may also be absorbed via the lungs. A systemic resorption of lithium was shown in a study on 27 intensive care unit patients, who were mechanically ventilated with lithium-chloride-coated heat and moisture exchangers for at least 5 days. Serum lithium was non-detectable at the first measurement, whereas 0.01-0.05 mM appeared in the blood from the 1st to the 4th day. In the following days, it remained at this level or increased to 0.1 mM. After cessation of the mechanical ventilation, serum lithium levels went back to undetectable levels within a few days. In a 7 year-old girl, the serum Li concentration rose to about 1 mM after a week, came back to 0.1 mM, rose to 3.9 mM on the 16th day and then returned to the usual low range (0.05-0.1 mM). The authors calculated that for adults, the daily amount of lithium chloride inhaled from a new heat and moisture exchanger (80% of the lithium content) can be considered equivalent to an oral dose of 100 mg/day of lithium chloride or 16 mg Li/day. Since the ion also is secreted in human milk, women receiving Li+ should not breast-feed infants. /Li+/ ... A well-established regimen can be complicated by occasional periods of Na+ loss, as may occur with an intercurrent medical illness or with losses or restrictions of fluids and electrolytes; heavy sweating may be an exception due to a preferential secretion of Li+ over Na+ in sweat. Hence, patients taking Li+ should have plasma concn checked at least occasionally. /Li+/ Side effects including nausea, diarrhea, daytime drowsiness, polyuria, polydipsia, weight gain, fine hand tremor, and dermatological reactions including acne are common even in therapeutic dose ranges. /Li therapy/ For more Drug Warnings (Complete) data for LITHIUM CHLORIDE (18 total), please visit the HSDB record page. |
Solubility Data
| Solubility (In Vitro) |
H2O : ≥ 100 mg/mL (2359.05 mM) DMSO : 25 mg/mL (589.76 mM; with sonication) |
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 23.5905 mL | 117.9523 mL | 235.9047 mL | |
| 5 mM | 4.7181 mL | 23.5905 mL | 47.1809 mL | |
| 10 mM | 2.3590 mL | 11.7952 mL | 23.5905 mL |