Lithium chloride

Endpoint summary

Link to relevant study record(s)

Reference

Endpoint:

dermal absorption

Type of information:

other: expert statement

Adequacy of study:

key study

Study period:

2010

Reliability:

1 (reliable without restriction)

Conclusions:

The absorption of lithium through skin is considered to be very poor.

Executive summary:

Expert statement: Due to the chemical properties of an inorganic salt, the dermal absorption of lithium chloride is expected to be very poor. Based on (1) the hydrophilic character of lithium chloride 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. 10% absorption was used for DNEL deduction. Thus, this presents a worst case.

Description of key information

Lithium chloride is a highly soluble salt that dissociates in lithium and chloride ions in water.  After oral uptake, lithium chloride is readily and almost completely absorbed from the gastrointestinal tract. The absorption of lithium through the skin is considered to be very poor to negligible. Upon inhalation, resorption and bioavailability of lithium chloride is expected to be low. After absorption, lithium is quickly distributed and unchanged excreted. Bioaccumulation can be excluded. Chloride occurs ubiquitous and is an essential element of the human body and lithium has been used as a psychiatric drug for almost half a century. Thus, in the sum, the toxicological relevance of lithium chloride is also regarded as very low. 

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

Toxicokinetic Assessment of lithium chloride

Lithium chloride is an inorganic salt with a molecular weight of 42.395 g/mol. It is very soluble in water (569 g/L) and readily undergoes dissociation, forming lithium and chloride ions. 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 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 subjected 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 chloride and (2) the barrier function of the stratum corneum against salts, dermal absorption can practically be excluded. The dermal toxicity value revealed a LD50 > 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 (from lithium hypochlorite) as compared with unexposed controls. This study result was expected due to the chemical properties of an inorganic salt as lithium chloride. Also other authors concluded that absorption of lithium through the skin is considered to be very poor. 10 % absorption will be appropriate for DNEL deduction as this presents a worst case. In conclusion, the absorption of lithium through skin is considered to be poor. Thus, upon dermal contact, the bioavailability of lithium chloride is expected to be very low and therefore negligible.

Resorption after oral uptake

After oral administration lithium chloride is readily and almost completely absorbed from the gastrointestinal tract revealing lithium peak plasma levels after single oral doses at 30-60 minutes (i.e. faster than in case of lithium carbonate uptake due to the higher water solubility) and plateau levels were reached at 12-24 hours. After oral administration lithium chloride is readily and almost completely absorbed.

Resorption after inhalation

The vapour pressure of lithium chloride 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 inhalaltion is assumed to be low due to the very low log Pow. Thus, upon inhalation, the bioavailability of lithium chloride is expected to be low. Upon inhalation, resorption and bioavailability of lithium chloride 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. 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 and complete 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.

Chloride:

Chloride is also distributed throughout the body water, mainly extracellularly and to a low extent intracellularly. Chloride is filtered by the kidneys through the glomerulus and excreted from the renal tubular lumen by active transport systems, and also by passive diffusion. Chloride is the most abundant anion in humans and all animal species and it is an essential element being responsible for metabolism. Chloride is important for the regulation of the acid-base balance of the body, and maintains electrochemical neutrality by anion exchange with bicarbonate (the chloride shift) in the CO2 transport in the red blood cells and the osmotic tension of blood and tissues. Chloride is taken up daily as it is naturally present in drinking water and also a food and food additives. Based on the high solubility, the systemic availability of chloride from lithium chloride is assumed to be high. But due to its important role for metabolism, regulation of the acid-base balance, etc. and the daily uptake by drinking water and food, the toxi-cological relevance of chloride linked to the uptake of lithium chloride is regarded as very low.