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Administrative data

Link to relevant study record(s)

Description of key information

There are no specific experimental data available concerning toxicokinetics, metabolism and distribution for CHEP. Based on the physicochemical properties of the substance and available ecotoxicological and toxicological information it is concluded that the substance is systemically bioavailable after oral, dermal and inhalative administration. The substance has a low potential for bioaccumulation.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

Assessment of the Toxicokinetic Behaviour

Since no toxicokinetic studies are available for the reaction mass of 2-piperazine-1-ylethanol and piperazine-1,4-diethanol and piperazine and water (CHEP), the following assessment is based on the available physicochemical properties and results from other toxicological studies. Furthermore some ADME studies are available from piperazine which is one constituent of the test substance. These can be taken into account because the physicochemical properties are similar for the three major constituents.

CHEP is a liquid, viscous, organic, colourless substance with a small molecular weight for each of the three main components (CAS 103-76-4: 130.1882 g/mol, CAS 122-93-3: 174.24 g/mol, CAS 110-85-0: 86.1356 g/mol) indicative for a favourable absorbance of the test item.


The partition coefficient of the test substance (Log Pow) is -1.55 at 23°C at pH 11.3. Based on this rather low partition coefficient the test substance is unlikely to bioaccumulate with the repeated intermittent exposure patterns normally encountered. However, this low log Pow value, the high water solubility and the small molecular weight indicate that the substance might be favourable for passive diffusion. In line with this, in an acute oral toxicity study with CAS 103-76-4, 5/5 females and 3/5 males died after administration of 5305 mg/kg bw and 1/5 males and 3/5 females died after administration of 4244 mg/kg bw, respectively. After administration of 3396 mg/kg bw 1/5 male and 2/5 females and at 1698 mg/kg bw 1/10 animals died (-> LD50 = 4244 mg/kg bw). Furthermore, animals receiving high and intermediate doses showed clinical signs and symptoms, including high stepping gait, motor excitation, intermittent respiration, abdominal position and paresis (hindlimb), immediately after application; piloerection, nose and eyes with reddish crusts, intermittent respiration, apathy and squatting posture until including day 3. These observations are in line with the low log Pow value, showing that the substance is systemically bioavailable when administered orally. It is therefore assumed that the test substance or its possible metabolites become systemically available after absorption along the gastro intestinal tract. These results are in line with the ADME study (Morrison, 1997) done in pig with piperazine (CAS 110-85-0) where the peak plasma level was found after 1 hour after administration.

Furthermore, bioavailability via the dermal route is also assumed but to a lower extend. The LD50 was estimated to be 8300 mg/kg bw in an acute dermal toxicity study with rabbits (CAS 110-85-0, BASF AG, 1977). The animals showed clinical signs such as cyanosis, diarrhea, salivation, mild convulsions, bleeding from mouth and nose, ataxia, loss of righting, abnormal stance, catatonia, ptosis, and decreased activity. Furthermore, the substance is corrosive (BASF AG, 2012) and sensitising after skin contact (EU Risk assessment for piperazine, 2005), further supporting the notion that there is a bioavailability of the substance via the dermal route.

It is shown that piperazine (CAS 110-85-0) induces occupational asthma due to exposure of piperazine (Hagmar, 1983). Therefore, as a worst case assumption, bioavailability via the inhalative route for CHEP is also assumed.


For piperazine (CAS 110-85-0, Morrison 1997) the highest radioactivity was found in kidneys and liver after oral administration to pig. Elimination of the activity in the kidney was rapid, with only 3% remaining of the 12h value post dosing. The elimination from the liver, skeleton, muscle, fat and skin was considerably slower with 10, 11, 24, 25% respectively remaining after 7 days in comparison with the 12 h levels.

Since neurotoxic effects were observed after oral application of piperazine to humans(EU Risk assessment, 2005) piperazine is assumed to enter the blood brain barrier.


Piperazine (CAS 110-85-0) was metabolized rapidly to naturally occurring materials in pig after oral administration, largely to polysaccharides and to lower extent amino acids (Hazelton, 1975). For the other two constituents of CHEP no data are available. Using the OECD toolbox vs.3.0, the liver metabolism simulator provided 19 potential simulated metabolites for CAS 103-76-4 and 25 metabolites for CAS 122-96-3, as well as 4 simulated skin metabolites each. A study assessing genotoxicity of the test substance (Ames-Test; BASF 2012) was negative, i.e. there is no indication of a reactivity of the test substance or its metabolites with macromolecules under the chosen test conditions.


In the ADME study with piperazine (Morrison, 1997) it was found that piperazine was eliminated to 57% via the urine mainly in the first 24 hours after oral administration. 16% was excreted in faeces. About one fourth of the totally administered amount can be considered as still retained in the body.

For the other two constituents of CHEP no data are available concerning excretion. Based on the molecular weights of these to constituents and their respective water solubilities, it is conjectured that the test substance would probably primarily undergo a renal elimination as seen for piperazine.