Registration Dossier

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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Link to relevant study record(s)

Description of key information

For 3-isopropoxypropylamine,  no study is available for the determination of toxicokinetics, metabolism and distribution. Therefore, a qualitative assessment is performed on the basis of the physico-chemical properties of the substance.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential
Absorption rate - oral (%):
50
Absorption rate - dermal (%):
50
Absorption rate - inhalation (%):
100

Additional information

3 -isopropoxypropylamine, hereafter named IPOPA, is a liquid with a high water solubility, a moderate log Kow (0.49), a molecular weight of 118.19 g/mol and a moderate vapour pressure (40 hPa at 30°C). Its pKa is 10.14. The substance is found to be corrosive to the skin and skin sensitising.

Its chemical structure is an aliphatic carbon chain containing an ether and a primary amine as functional groups. Because of the amine group, the substance has an alkaline character. The ether group is chemically inert and therefore most of the chemical reactions involve the primary amine group.

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 IPOPA.

Absorption

Oral/GI absorption

Following its high water solubility, IPOPA 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. Also, based on its molecular weight which is <200 (118.19 g/mole) and the moderate log Kow, absorption by passive diffusion will be favoured.

Assuming a median intestinal pH value close to 7, the pKa of IPOPA 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 IPOPA will be hampered. The substance is corrosive and therefore it could enhance penetration by local necropsy of GI tissues. In the gastro-intestinal tract hardly any degradation of the substance is to be expected.

In an acute oral toxicity study, the oral LD50 in male/female Sprague-Dawley rats was determined to be 909 mg/kg bw in a study conducted similarly to OECD Guideline 401 (Manciaux, 1998). These observations may indicate significant absorption of the test substance.

The oral absorption factor is set to 50%, based on the anticipated hampered diffusion of IPOPA 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 40 HPa, IPOPA 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 low molecular weight (< 200) favour dermal absorption.

As IPOPA is a corrosive substance, absorption/penetration will be enhanced. In addition, IPOPA has been identified as a skin sensitiser. It can be concluded that uptake must have been occurred although it may only have been a small fraction of the applied dose.

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 IPOPA is set to 50%. The results of the toxicity studies do not provide reasons to deviate from this proposed value.

 

Distribution

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

 

Accumulation

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

 

Metabolism

Once absorbed, the aliphatic carbons as well as the primary nitrogen will undergo extensive hydroxylation, followed by rapid sulfation or glucuronidation. Direct conjugation at the nitrogen in the parent compound is expected. Also extensive cleavage of the ether bound is anticipated.

 

Excretion

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