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Description of key information

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 test item is miscible with water at 20.0°C in any ratio. Due to this high water solubility, it is predicted that the test item 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.
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.

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 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 test item is miscible with water at 20.0°C in any ratio. Due to this high water solubility, it is predicted that the test item 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 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 and the high water solubility and the small molecular weight indicates that the substance might be favourable 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 1397mg/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 test substance or its possible metabolites become systemically available after absorption along the gastro intestinal 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 sensitising after skin contact (BASF SE, 2008), further supporting the notion that there is a high bioavailability of the substance via the dermal route.

Distribution

Damages of spleen, adrenal gland, kidneys, stomach, eyes and lung appeared to be possible target organs in the combined repeated dose toxicity study with the reproduction / developmental toxicity screening test (BASF SE, 2013). Therefore, a distribution into these organs is assumed at toxic doses. Since the 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, 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 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 weights of its main constituents and its water solubility, it is conjectured that the test substance would probably primarily undergo a renal elimination.