Registration Dossier

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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Endpoint:
basic toxicokinetics, other
Type of information:
other: Expert statement
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Expert statement

Data source

Reference
Reference Type:
other: Expert statement
Title:
Unnamed
Year:
2017
Report date:
2017

Materials and methods

Objective of study:
toxicokinetics

Test material

Constituent 1
Chemical structure
Reference substance name:
Lithium amide
EC Number:
231-968-4
EC Name:
Lithium amide
Cas Number:
7782-89-0
Molecular formula:
H2LiN
IUPAC Name:
lithium amide
Test material form:
solid

Results and discussion

Applicant's summary and conclusion

Conclusions:
Lithium amide reacts heavily with water and dissociates in water into lithium ions and ammonium ions. Both ions are distributed throughout the body and are mainly excreted unchanged via the kidneys. Due to the fast excretion, bioaccumulation is not to be assumed.
Executive summary:

Absorption

Following oral administration, the likelihood of systemic absorption through the walls of the intestinal tract depends on several physicochemical substance properties. In order to obtain a conclusive judgment of a substance’s potential to be able to reach the systemic circulation, important physicochemical factors such as molecular weight, water solubility and the log Pow value need to be considered. Generally, the smaller the molecule the more easily it may be absorbed through the walls of the gastrointestinal tract. As the molecular weight of the test substance is 22.96 g/mol, an uptake of the compound into the systemic circulation via the gastro-intestinal (GI) tract is very likely (ECHA, 2014). Furthermore the compound is highly hydrophilic (log Pow = 0.23) and its degradation products are water soluble.

Readily soluble ammonium or lithium salts are assumed to be completely and rapidly absorbed. The absorption process occurs via passive diffusion from the stomach or the intestine. The rate of absorption is most likely related to the gastric acidity. Ions that are not absorbed in the stomach will be rapidly absorbed in the small intestine.

Considering the low vapour pressure of lithium amide and the resulting low volatility, exposure of the substance as vapour is very limited if handled at room temperature. If inhaled, the high water solubility of the compound would lead to complete absorption of particles in the mucus lining of the respiratory tract. The extent of absorption via inhalation is further enhanced by the corrosive character of the test substance when in contact with water. Therefore complete absorption after inhalation is highly likely.

In general, substances with a molecular weight below 100 are favoured for dermal uptake. Above 500 the substances are considered to be too large to be readily absorbed through the skin. As the test substance has a molecular weight of 22.96 g/mol a dermal uptake is highly favoured. Furthermore the high water solubility of the test substance supports a moderate to high dermal absorption. But dermal penetration is confined by the high hydrophilicity together with the log Pow below 1. The poor lipophilicity will limit penetration into the stratum corneum and hence dermal absorption. When in contact with the skin moisture the dermal penetration will be increased by the skin corrosion. These pre-requisites lead to the conclusion that the test substance is bioavailable when placed in contact to the skin.

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 an 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 equilibration of 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 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.

Ammonium

After absorption, distribution of the ammonium ion throughout the body is expected based on their relatively low molecular weight. No accumulation in the body is anticipated based on its hydrophilic character. At physiological pH of the aqueous environment like the GI tract, the ammonium ion is in equilibrium with un-ionized ammonia, according to the following equation:

NH4++ H2O <--> NH3 + H3O+.

Ammonia is normally present in all tissues constituting a metabolic pool. Its distribution is pH dependent, since NH3 diffuses more easily than NH4+ ions. In general, NH4+ ions are considered to be less significant toxic compared to the non-ionized form ammonia. Rapid distribution occurs by systemic circulation to the intra- and extracellular water of different tissues.

The primary route of excretion is through the kidneys because of the high water solubility the small molecular weight and the ionisation of the substance.

Due to the fast excretion bioaccumulation is not to be assumed. Ammonium like lithium is not metabolised to any appreciable extent in the human body. In conclusion, ammonium in human body is quickly distributed and unchanged excreted. Thus, bioaccumulation can be excluded.