Reaction mass of lithium 3-hydroxy-2,2,4-trimethylpentanoate and lithium isobutyrate and sodium 3-hydroxy-2,2,4-trimethylpentanoate and sodium isobutyrate

Endpoint summary

Description of key information

No specific studies are available however based on physicochemical data, toxicity data and theoretical assessment, the basic toxicokinetics of the Reaction mass of lithium 3-hydroxy-2,2,4-trimethylpentanoate and lithium isobutyrate and sodium 3-hydroxy-2,2,4-trimethylpentanoate and sodium isobutyrate can be adequately characterised. The four components of the substance are acid salts which will dissociate under physiological conditions to generate the cations (lithium or sodium) and the corresponding acids (3-hydroxy-2,2,4-trimethylpentanoic acid or isobutyric (2-methylpropanoic) acid). These constituents are rapidly and extensively absorbed following oral exposure. Absorption following dermal exposure is likely to be less extensive. Rapid and extensive distribution is predicted. Sodium and lithium ions are not subject to metabolism, whereas the acid components will undergo metabolic processes.  Based on the theoretical assessment of the toxicokinetics, no bioaccumulation is predicted for the components of this substance. 

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

50

Absorption rate - dermal (%):

50

Absorption rate - inhalation (%):

100

Additional information

No specific studies are required. According to Column 1 of Annex VIII of the REACH regulation, assessment of the toxicokinetic behaviour of the substance (to the extent that can be derived from the relevant available information) is required and this is provided. An adequate assessment of the basic toxicokinetics of the substance can be made from the existing toxicity data and theoretical considerations, without the need for specific testing.

The substance is described as the reaction mass of the following main four components:

1. Lithium 3-hydroxy-2,2,4-trimethylpentanoate

2. Lithium isobutyrate [lithium 2-methylpropanoate]

3. Sodium 3-hydroxy-2,2,4-trimethylpentanoate

4. Sodium isobutyrate [sodium 2-methylpropanoate]

In the absence of specific data, the toxicokinetics (absorption, distribution, metabolism and excretion) of the substance components are addressed theoretically, below.

Absorption

The four components of the substance are acid salts which will dissociate under physiological conditions to generate the constituent cation (lithium or sodium) and the corresponding acids (3-hydroxy-2,2,4-trimethylpentanoic acid or isobutyric (2-methylpropanoic) acid).

Both lithium and sodium are rapidly and extensively absorbed from the gastrointestinal tract. As low molecular weight water-soluble organic acids, isobutyric acid and 3-hydroxy-2,2,4-trimethylpentanoic acid are also likely to be rapidly and extensively absorbed from the gastrointestinal tract.Data therefore indicate rapid absorption following oral administration, although the extent of absorption cannot be quantified. A default assumption of 50% oral absorption for the substance may be made for the purposes of risk assessment according to REACH Guidance.

Dermal absorption cannot be reliably quantified, but is likely to be significantly less extensive than for oral absorption. Dermal absorption of metal ions is generally very limited; the dermal absorption of isobutyric acid and 3-hydroxy-2,2,4-trimethylpentanoic acid may occur to some extent.Dermal absorption is therefore predicted, but is likely to be less rapid and extensive than oral absorption. In the absence of specific data, a default, conservative dermal absorption value of 50% may be assumed for the substance.

The Reaction mass of lithium 3-hydroxy-2,2,4-trimethylpentanoate and lithium isobutyrate and sodium 3-hydroxy-2,2,4-trimethylpentanoate and sodium isobutyrateis non-volatile; therefore inhalation exposure is not predicted unless the substance is used in situations in which liquid aerosols may be generated. If inhalation exposure were to occur, absorption is potentially extensive. A default assumption of 100% inhalation absorption may be made, if required, for the purposes of risk assessment.

Distribution

Based on water solubility, systemic distribution of absorbed sodium or lithium ions, isobutyric acid and 3-hydroxy-2,2,4-trimethylpentanoic acid is predicted. Lithium ions are known to be widely distributed; there is some evidence from the clinical use of lithium salts that lithium ions accumulate transiently in the central nervous system. Sodium ions are known to be widely distributed in the body; the plasma concentration of sodium is tightly regulated through the control of renal excretion.

Metabolism

Sodium and lithium ions are not subject to metabolism. 3-hydroxy-2,2,4-trimethylpentanoic acid may be metabolised to some extent in the liver to form the corresponding dicarboxylic acid (OECD QSAR Toolbox simulator). No hepatic metabolism is predicted for isobutyric acid; however this short-chain fatty acid is likely to be incorporated into normal metabolic processes.

Excretion

Lithium ions do not bind to plasma proteins and are subject to renal excretion. Sodium ions are present at relative high concentrations physiologically; the concentration is tightly controlled through the regulation of renal excretion. 3-hydroxy-2,2,4-trimethylpentanoic acid (and/or its predicted metabolite) are also likely to be rapidly excreted in the urine. Isobutyric acid is predicted to be incorporated into normal fatty acid metabolism and is excreted predominately as CO₂.

Bioaccumulation

Based on the theoretical assessment of toxicokinetics, no bioaccumulation is predicted for the components of this substance.