N-(2-aminoethyl)-1,3-propanediamine

Endpoint summary

Description of key information

For N3-amine, no toxicokinetic studies are on-hand. However, based on the available data of the source substance N4-amine following conclusions are made to characterize also the target substance N3-amine (for read-across justification please refer to IUCLID chapter 13).
N4-amine is a liquid, viscous, organic, colourless substance with a small molecular weight of 174.2871 g/mol, indicative for a favorable absorbance. The source substance is miscible with water at 20.0°C in any ratio. Due to this high water solubility, it is predicted that N4-amine is readily dissolved into the gastrointestinal fluids. An oral and dermal absorption is assumed. A distribution to several organs after repeated oral administration is indicated since damages in these organs were found (study acc. to OECD 422). Due to the relatively low vapor pressure of the source substance (2.2 hPa at 20°C), the volatility of the substance is rather low and inhalation exposure to vapors is hence considered to be low. Furthermore, some data on N3/N4-amine as second source substance are available. N3/N4-amine is a clear yellowish liquid with a small molecular weight of 113.162 g/mol, indicative for a favorable absorbance. This source substance is miscible with water at 20.0°C in any ratio. Due to this high water solubility, it is predicted that N3/N4-amine is readily dissolved into the gastrointestinal fluids. An oral and dermal absorption is assumed. Although the vapor pressure of N3/N4-amine (26.4 hPa at 20°C) is moderate, an inhalation risk test showed no mortality, when 12 rats were exposed for 8 hours to an atmosphere that has been saturated at 20 degrees. Therefore, the exposure to vapors is considered to be of low risk. Furthermore, 8 hours exposure to the target substance N3-amine to an atmosphere that has been saturated at 20 degrees centigrade did not result in mortality in rats.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

Assessment of the Toxicokinetic Behaviour (source substance N4-amine / target substance N3-amine)

Since no toxicokinetic studies are available for N4-amine, the following assessment is based on the available physicochemical properties and results from other toxicological studies:

N4-amine is a liquid, viscous, organic, colourless substance with a small molecular weight of 174.2871 g/mol, indicative for a favourable absorbance of the test item.

The source substance is miscible with water at 20.0°C in any ratio. Due to this high water solubility, it is predicted that the source substance is readily dissolved into the gastrointestinal fluids.

Due to the relatively low vapour pressure of the test substance (2.2 hPa at 20°C), the volatility of the substance is rather low and inhalation exposure to vapors is hence considered to be low.

 

Adsorption

The partition coefficient of the source substance (Log Pow) is -1.55 at 23°C at pH 11.3. For the target substance N3-amine, a Log Pow of -1.67 at 23°C at pH 10.9 was identified (BASF AG, 2014). Furthermore, the target substance was shown to be miscible in water in any ratio at 20 °C (BASF AG, 2014). Based on the rather low partition coefficients source substance and target substance are unlikely to bioaccumulate with the repeated intermittent exposure patterns normally encountered. However, this low log Pow value and the high water solubility and the small molecular weight indicates that the source substance might be favorable for passive diffusion. In line with this, in an acute oral toxicity study, 5/5 males and females and 4/5 females died after administration of 1397 mg/kg bw and 1/5 males died after administration of 950 mg/kg bw, respectively, whereas animals receiving 647 mg/kg did not show any signs of mortality (-> LD50 = 1140 mg/kg). Furthermore, animals receiving high and intermediate doses showed clinical signs and symptoms, including poor general state, apathy, abdominal or lateral position, spastic gait, atonia, and diarrhea. 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 source substance or its possible metabolites become systemically available after absorption along the gastrointestinal tract.

Furthermore, bioavailability via the dermal route is also assumed since the LD50 was estimated to be 190 mg/kg bw in an acute dermal toxicity study with rabbits (BASF AG, 1977). The animals showed clinical signs such as apathy, dyspnea, cyanosis, tremor, piloerection, blood-coloured urine with hematoma and poor general state. Furthermore, the substance is corrosive (BASF AG, 1977) and sensitizing after skin contact (BASF SE, 2008), further supporting the notion that there is a high bioavailability of the source substance via the dermal route.

For the target substance a similar acute oral toxicity (LD50-rat: 654 mg/kg bw) and a comparable acute dermal toxicity (LD50-rabbit: 184 mg/kg bw) were observed (BASF AG, 1977). Due to this, it is assumed that there is also high bioavailability of the target substance via the oral and the dermal route of ingestion. N3-amine is also corrosive after skin contact (BASF AG, 1977).

 

Distribution

Damages of spleen, adrenal gland, kidneys, stomach, eyes and lungappeared to be possible target organs in the combined repeated dose toxicity study with the reproduction / developmental toxicity screening test of the source substance (BASF SE, 2013). Therefore, a distribution into these organs is assumed at toxic doses. Since N4-amine is a small water-soluble molecule it probably diffuses through aqueous channels and pores.

 

Metabolism

Using the OECD toolbox vs.3.0, the liver metabolism simulator provided 21 potential simulated metabolites were found for the source substance, as well as 22 simulated skin metabolites. Studies assessing genotoxicity (Ames-Test; BASF 2012, HPRT test in vitro; BASF 1997, Chromosome aberration in vitro; BASF 1997) were negative, i.e. there is no indication of a reactivity of N4-amine or its metabolites with macromolecules under the chosen test conditions. With reference to the target substance, no genotoxic potential was identified in the AMES-Test (BASF AG, 1990), too. No further data available.

 

Excretion

No data available.

Based on the molecular weights of its main constituents and its water solubility, it is conjectured that the source substance and test substance would probably primarily undergo a renal elimination.

 

Conclusive remark on ADME of the target substance based on available data

Based on the similarity of the source substance (N4 -amine) and the target substance (N3 -amine) given information are satisfactory to evaluate this issue in an adequate manner.