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Description of key information

The toxicokinetic behaviour of the test substance is qualitatively assessed based on its physico-chemical parameters. The absorption factors were determined to be : oral 50%, dermal 50% and inhalation 100%.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential
Absorption rate - oral (%):
Absorption rate - dermal (%):
Absorption rate - inhalation (%):

Additional information

The test substance (CAS No 63469-23-8) is a liquid with a high water solubility (miscible), a moderate log Kow (0.0931 at pH 11.5; at physiological pH the substance will be charged and hence more hydrophilic) and a moderate vapour pressure (64 Pa). Its pKa is 10.2. The substance is found to be corrosive to the skin and the eyes.

No toxicokinetic data (animal or human studies) are available on this substance. The data present in this dossier are based on physico-chemical parameters and will allow a qualitative assessment of the toxicokinetic behaviour of the test substance.


Oral/GI absorption

Following its high water solubility (100 g/L as limit value), the test substance will readily dissolve into the gastrointestinal fluids and subsequently pass through aqueous pores or be carried through the epithelial barrier by the bulk passage of water.

Based on its relatively low molecular weight (218 g/mole) and the moderate log Kow (0.0931), absorption by passive diffusion will be favoured.

The intestine is where absorption after oral administration is normally produced. Data on intestine pH for different species are rare and most stem from relatively old sources (ECHA guidance on IR&CSA, R.7c). Assuming a median intestinal pH value close to 7, the pKa of the test substance suggests that this substance will be predominantly in its ionized form at physiological pH. It is generally thought that ionized substances do not readily diffuse across biological membranes. Therefore it could be concluded that the diffusion across biological membranes of the test substance will be hampered.

The substance is corrosive and therefore it could enhance penetration by local necropsy of GI tissues.

The test substance has been tested in a subacute oral toxicity study (Combined repeated oral toxicity study with the reproduction/developmental toxicity screening test; OECD 422), a NOAEL of 100 mg/kg bw/d was derived.

In the gastro-intestinal tract hardly any degradation of the substance is to be expected. The oral absorption factor is set to 50%, based on the anticipated hampered diffusion of the test substance as an ionized substance. The results of the toxicity studies do not provide reasons to deviate from this proposed value.

Respiratory absorption

Given the vapour pressure of 64 Pa, the test substance is not a highly volatile substance and the availability for inhalation as a vapour is limited.

Once in the respiratory tract, the very hydrophilic substance may be retained within the mucus, and subsequently absorption may occur. Absorption directly across the respiratory tract epithelium by passive diffusion is favoured in view of the moderate log Kow value.

Based on the above considerations, the inhalatory absorption factor is set to 100%.

Dermal absorption

In view of its high water solubility and moderate log Kow, penetration into the lipid-rich stratum corneum and hence dermal absorption might be limited although its physical form (liquid) and relatively low molecular weight (218) favours dermal absorption.

As the test substance is a corrosive substance, absorption/penetration will be enhanced.

Generally default values of 10% and 100% are used for dermal absorption, based on molecular weight and log Kow value (ECHA guidance on IR&CSA, R.7c). The dermal absorption factor might therefore set to 100% (default), based on a molecular weight < 500 and a log Kow in the range of -1 to 4. However it is also generally acknowledged that dermal absorption will not be higher compared to oral absorption; as a result, the dermal absorption factor for the test substance set to 50%. The results of the toxicity studies do not provide reasons to deviate from this proposed value.


The high water solubility and low molecular weight predict that the substance will distribute widely through the body.

The log Kow value was experimentally determined to be 0.0931 (Tarran D.A., 2012). This study was performed on the non-ionised form of the substance, at pH 11.5 and hence the log Kow under environmental / physiological conditions is anticipated to be lower due to ionisation at pH values below the pKa of the substance (10.2). The substance is not likely to distribute into cells and hence the intracellular concentration is not expected to be higher than the extracellular concentration.


In view of the low log Kow and the high water solubility, the test substance is not expected to accumulate in the body (lung, adipose tissue, stratum corneum).


Once absorbed, extensive hydroxylation (aliphatic carbons) and oxidative deamination (tertiary amines), followed by rapid sulfation or glucuronidation is expected.


Given the high water solubility and relatively low molecular weight, the test substance and its metabolites will be mainly excreted via the urine.

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