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Description of key information

A toxicokinetic assessment was performed based on the available data of the substance. Furthermore, a publication (Askari, 1966) describing uptake of tetramethyl ammonium ions through biomembranes is available.

Key value for chemical safety assessment

Bioaccumulation potential:
low bioaccumulation potential
Absorption rate - oral (%):
100
Absorption rate - dermal (%):
100
Absorption rate - inhalation (%):
100

Additional information

A theoretical assessment, based on the physicochemical properties of the substance was performed.

A toxicant can enter the body via the lungs, the gastrointestinal tract, and the skin. In general, a compound needs to be dissolved before it can be taken up from the gastrointestinal tract after oral administration. Two characteristics of TMAH favor uptake via passive diffusion (passage of small water-soluble molecules through aqueous pores or carriage of such molecules across membranes with the bulk passage of water): (a) TMAH is highly soluble in water (> 1 kg/l); therefore the substance will dissolve into the gastrointestinal fluids. (b) TMAH has a low molecular weight (approximately 91.1521). Small molecules are easier taken up via diffusion. On the other hand, TMAH has a log Pow below 0 (<-1.4), which means the compound is hydrophobic. This characteristic will hamper penetration through lipid membranes. TMAH dissociates as soon as it comes in contact with the fluids of the gastro-intestinal tract, to form an OH--ion and a quaternary ammonium-ion. It is generally thought that ionized substances do not readily diffuse across biological membranes, but the absorption of ionic substances (i.e. acids and bases) is influenced by the varying pH of the GI tract. Also, it was shown by Askari, that radiolabelled TMAC (which will dissociate to form a positively charged quaternary ammonium ion and a chloride ion) was taken up by active transport and by passive diffusion into erythrocytes, demonstrating the potential of this compound to cross biomembranes. As TMAH also has a tetramethylammonium cation, TMAH is also expected to be able to cross biomembranes. For risk assessment purposes oral absorption of TMAH is set at 100%, based on its water solubility and its low molecular weight and experimental data. The oral toxicity data do not provide reason to deviate from the proposed oral absorption factor. Once absorbed, wide distribution of the test substance throughout the body is expected based on its high water solubility and low molecular weight. Absorbed TMAH is most likely excreted via urine. Based on the low partition coefficient of < -1.4, it is very unlikely that TMAH will accumulate in adipose tissue.

The vapour pressure of TMAH cannot be measured due to decomposition. No information on the particle size distribution is available. Therefore, it is assumed that TMAH can enter the respiratory tract. TMAH is mostly marketed in aqueous solution, of which aerosols may reach the respiratory tract. If TMAH reaches the tracheobronchial region, it is likely to be dissolved within the mucus lining the respiratory tract and to get absorbed due to its high water solubility and low molecular weight. Furthermore, due its high alkalinity it may damage the epithelium lining the respiratory tract, which will further promote systemic uptake of the substance. Based on the above data, for risk assessment purposes the inhalation absorption of TMAH is set at 100%.

TMAH is a white powder. When it comes in contact with the skin without additional water, uptake will be limited. However, given the fact that TMAH is very hygroscopic, it will take up water or dissolve into the surface moisture of the skin. The first layer of the skin, the stratum corneum, is a barrier for hydrophilic compounds. However, due to its corrosive properties, skin integrity will be affected leading to fast uptake of the substance. Furthermore, the ions formed after TMAH dissociates will influence its adsorption. The quaternary ammonium ion may bind to skin components which would slow the uptake. After the skin surface is damaged, TMAH will be absorbed easily due to its low molecular weight and high water solubility. Based on the above data, for risk assessment purposes the dermal absorption of TMAH is set at 100%. The results of the toxicity studies do not provide reasons to deviate from this proposed dermal absorption factor.

In a supporting uptake study with human erythrocytes by Askari (1966), it is shown that tetramethyl ammonium ions are taken up in the intracellular lumen both by passive diffusion and by a concentration-independent mechanism (receptor-mediated). Based on the physical/chemical properties of TMAH, absorption factors for this substance are derived to be 100% (oral), 100% (inhalation) and 100% (dermal) for risk assessment purposes. The bioaccumulation potential is expected to be low.