Lithium carbonate

Endpoint summary

Additional information

Toxicokinetic Assessment of lithium carbonate

Lithium carbonate is an inorganic salt with a molecular weight of 73.89 g/mol. It is soluble in water (8.4 - 13 g/L). Hydrolysis of lithium carbonate produces basic solutions by generating lithium hydroxide and lithium hydrogen carbonate. The carbonate ion is the conjugate base of an extremely weak acid (carbonic acid) resulting in solutions with a pH of ca. 12.

Li2CO3 + H2O -> LiHCO3+ LiOH

The hydrogen carbonate ion (HCO3- (aq)), with its single negative charge, is a considerably weaker base resulting in solutions of pH ca. 8.5. With acid (decreasing pH) the respective lithium salt and carbon dioxide are formed. The partition coefficient (octanol / water) log Pow in order to assess the ratio of distribution in organic (lipid) and aqueous matrices cannot be determined for an inorganic salt, but is expected to be in the range of negative values.

Dermal absorption

Dermal absorption, the process by which a substance is transported across the skin and taken up into the living tissue of the body, is a complex process. The skin is a multilayered biomembrane with particular absorption characteristics. It is a dynamic, living tissue and as such its absorption characteristics are susceptible to constant changes. The barrier properties of skin almost exclusively reside in its outermost layer, the stratum corneum, which is composed of essentially dead keratinocytes. Upon contact with the skin, a compound penetrates into the dead stratum and may subsequently reach the viable epidermis, the dermis and the vascular network. During the absorption process, the compound may be subject to biotransformation. The stratum corneum provides its greatest barrier function against hydrophilic compounds, whereas the viable epidermis is most resistant to highly lipophilic compounds. Thus, the stratum corneum provides greatest barrier function against hydrophilic compounds, respectively water. Due to (1) the hydrophilic character of Lithium carbonate and (2) the barrier function of the stratum corneum against salts, dermal absorption can practically be excluded. Dermal toxicity values revealed LD50 values > 2000 mg/kg bw, which further supports this conclusion.

No significant elevation of serum lithium levels was reported in 53 healthy volunteers spending 20 minutes/day, 4 days/week for two consecutive weeks in a spa with a concentration of approximately 40 ppm (mg/L) lithium (generated from lithium hypochlorite) as compared with unexposed controls. This study result was expected due to the chemical properties of an inorganic lithium salt. Also other authors concluded that absorption of lithium through the skin is considered to be very poor.

In conclusion, the absorption of lithium through skin is considered to be poor. Thus, upon dermal contact, the bioavailability of lithium carbonate is expected to be very low and therefore negligible.

10% absorption will be appropriate for DNEL deduction as this presents a worst case.

Resorption after oral uptake

The absorption of lithium after oral intake, depending on the salt given can vary (e.g. 20 % for lithium from lithium carbonate).

In the stomach, due to gastric acid, an oral uptake of carbonate will result in neutralisation of its products of hydrolysis, i.e. – as described above – the respective lithium salt and carbon dioxide are formed. Soluble lithium compounds readily and almost completely absorbed from the gastrointestinal tract revealing peak plasma levels after single oral doses about 1-4 hours after administration. Soluble lithium compounds are readily and almost completely absorbed from the gastrointestinal tract. In the stomach, carbonate results in carbon dioxide.

Resorption after inhalation

The vapour pressure of lithium carbonate is negligible low and therefore exposure to vapour is toxicologically not relevant. If lithium reaches the lung it may be absorbed via the lung tissue but resorption after inhalation is assumed to be low due to the very low log Pow. Thus, upon inhalation, the bioavailability of lithium carbonate is expected to be low.

In summary: Upon inhalation, resorption and bioavailability of lithium carbonate is expected to be low.

Distribution, Metabolism and Excretion

Lithium:

Lithium is not bound to proteins, but is quickly distributed throughout the body water both intra- and extracellularly. Excretion of lithium is fast (> 50% and > 90% within 24 and 48 hours, respectively) and takes place almost completely via urine. However, trace amounts can still be found 1 to 2 weeks after the ingestion of a single lithium dose. Organ distribution is not uniform: Lithium is rapidly taken up by the kidney, but distributed more slowly into the liver, bone muscle or the brain. There is obviously a clear interaction between lithium and sodium excretion/retention in the kidney, altering the electrolyte balance in humans. A single oral dose of lithium ion is excreted almost unchanged through the kidneys. Due to the fast excretion bioaccumulation is not to be assumed. Lithium is not metabolised to any appreciable extent in the human body. In conclusion, lithium in human body is quickly distributed and excreted unchanged. Bioaccumulation can be excluded.

Carbonate:

Carbonate is contained in every mineral and health water, but contrary to various minerals, hydrogen carbonate can be produced by the human body. The major extracellular buffer in the blood and the interstitial fluid of vertebrates is the bicarbonate buffer system, described by the following equation: H2O + CO2 ↔ H2CO3 ↔ H+ + HCO3- Hydrogen carbonate has an acid neutralizing (alkalescent) effect and is responsible for the balancing of the pH-value in the body, e.g. it reduces the acid in the digestive system. Carbon dioxide diffuses rapidly into red blood cells, where it is hydrated with water to form carbonic acid. This reaction is accelerated by carbonic anhydrase, an enzyme present in high concentrations in red blood cells. The carbonic acid formed dissociates into bicarbonate and hydrogen ions. Most of the bicarbonate ions diffuse into the plasma. Thus, also without exposure to lithium carbonate, all species formed from carbonate (CO2, bicarbonate and hydrogen ions) naturally occur in the human body. Based on the low solubility, the systemic availability of carbonate from lithium carbonate is regarded as very low. Moreover, all species formed from carbonate by hydrolysis naturally occur in the human body. Thus, its toxicological relevance linked to the uptake of lithium carbonate is regarded as very low.