Registration Dossier

Diss Factsheets

Administrative data

basic toxicokinetics
Type of information:
other: expert statement
Adequacy of study:
key study
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Theoretical assessment taking all currrently available relevant information into account, based on the REACH Guidance: Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.7c Endpoint specific guidance. Since this is a theoretical assessment, the Klimisch value cannot be 1.

Data source

Reference Type:
study report
Report date:

Materials and methods

GLP compliance:

Test material

Constituent 1
Chemical structure
Reference substance name:
Tetraethylammonium hydroxide
EC Number:
EC Name:
Tetraethylammonium hydroxide
Cas Number:
Molecular formula:
N,N,N-triethylethanaminium hydroxide

Results and discussion

Main ADME results
For risk assessment purposes, 50% is used for oral absorption and 100% is used for dermal and inhalation absorption

Applicant's summary and conclusion

For risk assessment purposes, 50% is used for oral absorption and 100% is used for dermal and inhalation absorption
Executive summary:

A substance can enter the body via the gastrointestinal tract, the lungs, and the skin. In general, a compound needs to be dissolved before it can be taken up from the gastrointestinal tract after oral administration. TEAH is marketed in aqueous solution, at 35%. Two characteristics of TEAH 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). First, TEAH is highly soluble in water (at least 350 g/L), therefore the substance will readily dissolve into the gastrointestinal fluids. Secondly, TEAH has a low molecular weight

(approximately 147). Small molecules are easier taken up via diffusion. On the other hand, TEAH has a partition coefficient below 0 (log Pow = -3.8), which means the compound is highly hydrophilic. This characteristic will hamper penetration through lipid membranes. TEAH ionizes in aqueous solution. Thus, as soon as it comes in contact with the fluids of the gastro-intestinal tract, an OH--ion and a quaternary ammonium-ion are formed. It is generally assumed that ionized substances do not readily diffuse across biological membranes, but the varying pH of the GI tract may have influence on the absorption of the ions. Although its water solubility and its low molecular weight favour uptake, its low partition coefficient and its ionic form will hamper uptake. Therefore, for risk assessment purposes oral absorption of TEAH is set at 50%. 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 TEAH is most likely excreted via urine. Based on the low partition coefficient, the potential of TEAH to bioaccumulate in adipose tissue is expected to be low. The vapour pressure of TEAH was calculated to be low (8.14 E-7 Pa). The particle size distribution of TEAH is not relevant, as TEAH is not available as such. Furthermore it should be taken into account that TEAH is marketed in aqueous solution,

thus aerosols may be formed. Therefore, it is assumed that TEAH can enter the respiratory tract. If TEAH reaches the tracheobronchial region, it is likely to be dissolved within the mucus lining of the respiratory tract and to get absorbed due to its high water solubility and low molecular weight. Furthermore, due its high alkalinity (pH >13 at 35% solution) 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 TEAH is set at 100%. TEAH will take up water or dissolve into the surface moisture of the skin. Furthermore, it is considered that TEAH is exclusively marketed as aqueous solution, in this

state uptake is facilitated. The first layer of the skin, the stratum corneum, is a barrier for hydrophilic compounds. The ions formed after TEAH ionizes

will influence its adsorption. The quaternary ammonium ion may bind to skin components which would limit the uptake. However, due to its corrosive properties, skin integrity will be affected leading to fast uptake of the substance. Once the skin surface is damaged, TEAH 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 TEAH is set at 100%. The results of the toxicity studies do not provide reasons to deviate from this proposed dermal absorption factor.

Categories Display