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Description of key information

Key value for chemical safety assessment

Bioaccumulation potential:
low bioaccumulation potential
Absorption rate - oral (%):
50
Absorption rate - dermal (%):
50
Absorption rate - inhalation (%):
100

Additional information

Assessment of the toxicokinetic behavior

 

Since no toxicokinetic studies are available for 3-[[3-[[(2-cyanoethyl)amino]methyl]-3,5,5-trimethylcyclohexyl]amino]propiononitrile (CAS 93940-97-7), the following assessment is based on the available physicochemical properties and results from other toxicological studies.

 

Physical chemical properties

3-[[3-[[(2-cyanoethyl)amino]methyl]-3,5,5-trimethylcyclohexyl]amino]propiononitrile is a clear, colourless, homogenous, viscous liquid at 20 °C and 1013.25 hPa with a molecular weight of 276.4203 g/mol. The test item has a high water solubility of 32 g/L at 20.0°C. The log Kow was determined to be 2.0 at 23°C and the dissociation constant of the test substance (pKa) is 7.2 at 20 °C. Due to the very low vapour pressure of the test substance (0.0000022 hPa at 20 °C, 0.0000042 hPa at 25 °C and 0.000083 hPa at 50 °C.), the volatility of the substance is rather very low. The test substance does not contain any functional groups sensitive to hydrolysis. Therefore hydrolysis is not expected. The surface tension of an aqueous preparation of the test item (β=1 g/l) at 20 °C was found to be 58 mN/m. The test item was surface active.

Adsorption

Gastrointestinal absorption:

The test item has a high water solubility of 32 g/L at 20.0°C. Therefore, it is predicted to be readily dissolved into the gastrointestinal fluids. According to structural properties, hydrolysis is not expected, indicating that the substance might be present in the GI tract for the time required for absorption. The small molecular weight of < 500 g/mol, and the moderate log Kow of 2 make the test item favourable for absorption in the GI tract. In line with this,single and repeated dosing via the oral route resulted in systemic toxic effects in rats. In an acute oral toxicity study, two out of three females died after administration of 2000 mg/kg bw, whereas animals receiving 500 mg/kg bw did not show any signs of mortality (LD50 > 500 - < 2000 mg/kg bw). Furthermore, animals receiving the high dose showed clinical signs and symptoms of intoxication, e.g., poor and impaired general state, dyspnea, cowering positions, piloerection and tremor. Repeated dosing with 150 mg/kg bw/day caused decreased body weights, imbalances in haematology and clinical chemistry parameters, as well as organ damage targeting, e.g., the liver, brain and kidneys. It is therefore assumed that the test substance or its possible metabolites become systemically available after absorption along the gastro-intestinal tract.

Respiratory absorption:

Due to the very low vapour pressure of the test substance (0.0000022 hPa at 20 °C, 0.0000042 hPa at 25 °C and 0.000083 hPa at 50 °C.), the volatility of the substance is rather very low and inhalation exposure to vapors is hence considered to be also low.

Dermal absorption:

With a very low vapour pressure, the test substance will not evaporate in significant amounts from the skin and will be available for absorption. The molecular weight of < 500 g/mol, the high water solubility and the moderate log Kow of 2 favour dermal uptake. Although the physical chemical data indicate dermal absorption potential, single dosing via the dermal route didn’t result in systemic toxic effects in rats up to the limit dose of 2000 mg/kg bw. This indicates that the substance is unlikely to be absorbed by the skin to an extend at which an acutely toxic internal dose is reached. However, the substance has been identified as a skin sensitizer in an LLNA. Thus, some uptake must have occurred although it may only have been a small fraction of the applied dose.

 

Distribution and Accumulation

Since the test substance is a relatively small water-soluble molecule, it probably diffuses through aqueous channels and pores. Therefore, a distribution into different organs is assumed. In line with this, target organ toxicity was detected (e.g., liver, brain and kidneys) in rats after repeated dosing with 150 mg/kg bw/day. Due to the moderate log Kow of 2, the test substance is unlikely to accumulate in adipose tissue with the repeated intermittent exposure patterns normally encountered in the workplace but may accumulate if exposures are continuous.

Metabolism

Using the OECD toolbox vs.4.2, the in vivo Rat metabolism simulator provided 11 potential simulated metabolites, as well as 11 simulated skin metabolites. Studies assessing genotoxicity (Ames test; BASF, 2006; HPRT test, BASF, 2018; MNT, BASF, 2018) were negative, i.e. there is no indication of a reactivity of the test substance or its metabolites with macromolecules under the chosen test conditions.

No further data available.

 

Excretion

No data available.

Based on the molecular weight of the parent compound and its water solubility, it is conjectured that the test substance would probably primarily undergo a renal elimination.