Lithium hydroxide

Endpoint summary

Additional information

Toxicokinetic Assessment of lithium hydroxide and lithium hydroxide monohydrate

Lithium hydroxide anhydrous is an inorganic hygroscopic compound with a molecular weight of 23.95 g/mol. It is very soluble in water (71 to 125 g/L). Lithium hydroxide monohydrate is an inorganic compound with a molecular weight of 41.96 g/mol. It is even more soluble in water (189 to 223 g/L). Both are strong alkaline substances that dissociates completely in water and form lithium ions and hydroxyl ions resulting in increasing pH solutions:

LiOH <-> Li+ + OH-

The hydroxide ion may react with free H+ or any acidic species that may be present, forming water:

OH- + H+ <-> H2O, K = 10E14 (25°C)

Solubility of lithium hydroxide in water is affected by pH, temperature and the presence of other species in solution, e.g. increased pH causes decreased solubility because a higher hydroxyl ion concentration and less solid lithium hydroxide that can dissociate into free metal ions and hydroxyl ions. With acid (decreasing pH) the respective lithium salt is 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 inorganic compounds, but is expected to be in the rage 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. Upon dermal exposure, corrosive substances cause skin and tissue damage and can easily be absorbed and become systemically available. In case of dermal exposure to non-corrosive solutions, the uptake of lithium hydroxide is expected to be low as the stratum corneum provides greatest barrier function against hydrophilic compounds, respectively water. Due to (1) the hydrophilic character of lithium hydroxide and (2) the barrier function of the stratum corneum against the respective ions, dermal absorption can practically be excluded. For this reason the uptake of lithium hydroxide is expected to be limited under non-corrosive conditions (i.e. not in case of accidents).

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. Thus, the 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 in case of non-corrosive solutions. Thus, upon dermal contact, the bioavailability of Lithium is expected to be very low and therefore negligible.

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

Resorption after oral uptake

In the stomach, due to gastric acid, an oral uptake of non-corrosive solutions will result in neutralisation and the respective lithium salt is formed. The absorption of lithium after oral intake, depending on the salt given can vary (e.g. 20 % for lithium from lithium carbonate). 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, the respective lithium salt is formed.

Resorption after inhalation

The vapour pressure of lithium hydroxide (respective lithium hydroxide monohydrate) 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 hydroxide 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 penetrated 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 unchanged excreted. Bioaccumulation can be excluded.

Hydroxyl ion:

The hydroxide ion may react with free H+, forming water which is toxicological not relevant.