Tetramethylammonium chloride

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

other: theoretical assessment

Adequacy of study:

key study

Study period:

2013

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: A theoretical assessment, non-GLP, based on the REACH guidance IR CSA, R.7, has been performed.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Principles of method if other than guideline:

Expert statement based on the (physico-chemical) properties of the substance.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Tetramethylammonium chloride

EC Number:

200-880-8

EC Name:

Tetramethylammonium chloride

Cas Number:

75-57-0

Molecular formula:

C4H12N.Cl

IUPAC Name:

N,N,N-trimethylmethanaminium chloride

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Results and discussion

Main ADME results

Type:

absorption

Results:

For risk assessment purposes an oral, dermal and inhalatory absorption of 100% for all exposure routes was derived.

Any other information on results incl. tables

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 gastro-intestinal tract after oral administration. Two characteristics of TMAC 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) TMAC is highly soluble in water (> 1 kg/l); therefore the substance will dissolve into the gastrointestinal fluids. (b) TMAC has a low molecular weight (approximately 109.6) and may easily diffuse. TMAC has a log Pow below 0 (< -1.6), thus the compound is hydrophobic. This characteristic will hamper penetration through lipid membranes. As soon as TMAC dissolves in the fluids of the gastro-intestinal tract, it will dissociate into a chloride-ion and a quaternary ammonium-ion. It is generally assumed 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 (also summarized under 7.1.1), that radiolabelled TMAC was taken up mainly by passive diffusion into erythrocytes, demonstrating the potential of this compound to cross biomembranes.

For risk assessment purposes oral absorption of TMAC 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 TMAC is most likely excreted via urine. Based on its low partition coefficient (< -1.6), it is very unlikely that TMAC will accumulate in adipose tissue. 

The low vapour pressure (< 1.3x10^-8Pa) indicates that it is not likely that TMAC will reach the nasopharyncheal region or subsequently the tracheo/bronchial/pulmonary region via inhalation of vapour. No information on the particle size distribution is available. Therefore, it is assumed that TMAC can enter the respiratory tract. TMAC is mostly marketed in aqueous solution, of which aerosols may reach the respiratory tract. If TMAC reaches the tracheobronchial region, it is likely to dissolve within the mucus lining the respiratory tract and to get absorbed due to its high water solubility and low molecular weight. Furthermore, due to its irritating properties 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 TMAC is set at 100% (2). TMAC is a white powder. When it comes in contact with the skin without additional water, uptake will be limited. However, given the fact that TMAC 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. TMAC has a log Pow <–1, suggesting that the substance is not likely to be sufficiently lipophilic to cross the stratum corneum, therefore dermal absorption is likely to be low. Furthermore, the ions formed after TMAC has dissolved might influence its adsorption. Especially the quaternary ammonium ion is likely to bind to skin components which would slow the uptake. It is however shown that TMAC is a skin irritant, so exposure of the skin will lead to damage of the skin integrity, enhancing penetration. After the skin surface is damaged, TMAC 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 TMAC is set at 100%. The results of the toxicity studies do not provide reasons to deviate from this proposed dermal absorption factor.