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Toxicological information

Basic toxicokinetics

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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

Reference
Name:
Unnamed
Type:
Constituent
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 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.

Applicant's summary and conclusion