Lithium sulphate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

other: expert statement

Adequacy of study:

key study

Study period:

2013

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

other: expert statement

Title:

Unnamed

Year:

2013

Materials and methods

Principles of method if other than guideline:

Expert statement

Test material

Test material information

Constituent 1

Reference substance name:

Lithium sulphate

EC Number:

233-820-4

EC Name:

Lithium sulphate

Cas Number:

10377-48-7

Molecular formula:

H2O4S.2Li

IUPAC Name:

lithium sulphate

Constituent 2

Reference substance name:

lithium sulfate

IUPAC Name:

lithium sulfate

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): no bioaccumulation potential based on study results
Lithium sulfate dissociates in water into lithium ions and sulfate ions. Both ions are distributed throughout the body and are mainly excreted (80 - 90 %) unchanged via the kidneys. Due to the fast excretion, bioaccumulation is not to be assumed.

Executive summary:

Dermal absorption

The stratum corneum provides its greatest barrier function against hydrophilic compounds, whereas the viable epidermis is most resistant to highly lipophilic compounds. When considering lithium sulfate it can be expected that the uptake will be limited and practically excluded. This is due to the hydrophilic character of lithium sulfate and the barrier function of the stratum corneum against ions. It is supported by an acute dermal toxicity study that revealed a LD50 value of > 3000 mg/kg bw without any local or systemic effects for the structural and chemical similar compound lithium carbonate. Further no sensitisation could be detected in a Buehler test with guinea pigs which supports the conclusion of a very limited absorption of lithium sulfate through the skin.

This is also supported by a study conducted in a spa with lithium. 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, upon dermal contact, the absorption of lithium sulfate through skin and its bioavailability are considered to be very poor.

Resorption after oral uptake

Upon oral uptake, lithium sulfate will reach the stomach in form of lithium ions and sulfate ions. Lithium ions and sulfate ions will be readily and almost completely absorbed from the gastrointestinal tract due to there low molecular weight. Additionally, the low log Pow below -1 of both ions favours absorption by passive diffusion and therefore they can cross lipophilic membranes. They are also small and water soluble enough to be carried through the epithelial barrier by the bulk passage of water. This assumption is proved with a LD50 of 1065 mg/kg bw observed from clinical and /or autopsy data obtained from humans.

 

Resorption after inhalation

The vapour pressure of lithium sulfate is negligible and therefore exposure to vapour is toxicologically not relevant. If lithium ions reach the lung they 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 sulfate is expected to be low.

 

Distribution, Metabolism and Excretion

Lithium:

Lithium does not bind to protein and as a small cation it is quickly distributed throughout the body water both intra- and extracellularly, replacing normal cations (as K+, Na+). Lithium ions effects in the cell level are presumed to be related to interferences with processes that involve these ions such as renal tubular transport and ion channels involved in neurotransmission. Lithium has a large volume of distribution of 0.6 – 0.9 L/kg (for a 70 kg human a 42 L of volume of distribution). Because of its large volume of distribution, lithium shifts into the intracellular compartment of cells. With long-term use, the intracellular concentration of lithium increases, which thereby results in increased total body lithium load. The intracellular concentration is not reflected by the plasma level, which measures only the extracellular fluid concentration. Organ distribution is not uniform: lithium is rapidly taken up by the kidney (there is obviously a clear interaction between lithium and sodium excretion/retention altering the electrolyte balance in humans). Penetration is slower into the liver, bone and muscle. Its passage across the blood-brain barrier is slow and upon equilibration the CSF lithium level reaches only approximately half the plasma concentration.

The primary route of excretion is through the kidneys. Lithium is filtered by the glumeruli and 80 % of the filtered lithium is reabsorbed in the tubules, probably by the same mechanism of sodium reabsorption. Lithium is excreted primarily in urine with less than 1 % being eliminated with the feces.

The renal clearance of lithium is proportional to its plasma concentration. The excretion of lithium ions is considered to be fast. About 50 % of a single dose of lithium is excreted in 24 hours and about 90 % in 48 hours. However, trace amounts can still be found 1 to 2 weeks after the ingestion of a single lithium dose. A single oral dose of lithium ion is excreted almost unchanged through the kidneys. A low salt intake resulting in low tubular concentration of sodium will increase lithium reabsorption and might result in retention and intoxication. Renal lithium clearance is under ordinary circumstances, remarkably constant in the same individual but decreases with age and falls when sodium intake is lowered.

Due to the fast excretion bioaccumulation is not 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.

 

 

Sulfate

Sulfate is a natural and necessary constituent in the bodies of humans and other animals. In humans, serum sulfate levels range from 0.25 to 0.38 mmol/L. Sulfate is involved in a number of biochemical activities including the production of chondroitin sulfate and sulfation of exogenous chemicals. It relevant for detoxication by liver and improve digestion.

As a small ion, sulfate may be distributed into the blood and the extracellular compartments due to its high water solubility. Because of the good solubility sulfate will not come into contact with intracellular metabolising enzymes, so intracellular metabolism of the test substance is highly unlikely. The primary excretion route is assumed to be the kidneys. It is filtered by the kidneys through the glomerulus and excreted from the renal tubular lumen by active transport systems or by passive diffusion. Due to the fast excretion bioaccumulation is not assumed.