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Description of key information

Since APD is a polar substance, highly water soluble and has a molecular weight below 500, its elimination mainly occurs rapidly via the kidneys. Taking into account all available data, the biological properties of APD are mainly related to its intrinsic alkalinity. APD has a low acute toxicity and is expected to have only a low potential to accumulate in biological systems.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

There were no experimental studies available in which the toxicokinetic properties of 2 -amino-1,3-propanediol (APD) were investigated. Therefore, whenever possible, toxicokinetic behaviour was assessed taking into account the available information on physicochemical and toxicological characteristics of APD according to the “Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance (ECHA, 2009)”.

 

Absorption and distribution

APD (91 g/mol) is solid in its pure state, is highly soluble in water (≥ 859 ≤ 898 g/L) and has a very low vapour pressure (0.01 Pa). The relatively low partition coefficient (log Kow) of -1.82 results in a low potential to accumulate in biological systems.

The acute oral toxicity of APD has been determined in rats. The rats received orally 5000 mg/kg bw APD via gavage (Lister, 1995). Four rats (4/10) died within 24 hours after administration. The four animals that died showed abnormal findings at gross necropsy including discoloration of the kidneys, liver, spleen and small intestine and signs of hemorrhaging in the stomach. Abnormal clinical signs were observed in all (10/10) animals; including piloerection and lethargy. Taking into consideration the dose administered (5000 mg/kg bw) and the nature of the effects observed, the main cause of acute toxicity was most probably local irritation due to the high alkalinity of the test substance.

No data on acute inhalation toxicity are available. As a consequence of the very low vapour pressure of 0.01 Pa, APD is essentially non inhalable. Therefore, exposure to humans via the inhalatory route is unlikely to occur.

In the dermal acute toxicity in rabbits (Lister, 1995), no mortality was reported and no clinical signs or unusual findings were noted at necropsy (LD50 > 2000 mg/kg). However, skin irritations at the test site likely due to the alkaline pH value were observed. For APD, a QSAR based modelling published by Potts and Guy (1992), taking into account molecular weight and low Kow, estimated a dermal permeability constant Kp of 2.56E-05 cm/h. Similar to the approach taken by Kroes et al. (2007), the maximum flux Imax (Imax = Kp [cm/h] x water solubility [mg/cm³]) was calculated, resulting in dermal absorption of 23 µg/cm²/h APD. Usually, this value is considered as indicator for a dermal absorption of 80% (Mostert and Goergens, 2011).As no systemic toxicity was found in the acute dermal toxicity study up to 2000 mg/kg bw,it is likely that systemic bioavailability of APD is rather limited.

 

Metabolism and excretion

According to the chemical structure of APD, it can be assumed that APD is not metabolised in-vivo. Modelling of potential metabolites via OECD QSAR toolbox v.2.0 (2010) confirms this assumption. No relevant metabolites were generated by the liver metabolism simulator, by the skin metabolism simulator or by the microbial metabolism simulator. Therefore, it seems to be very unlikely that APD will be metabolised by cytochrome P450 enzymes in-vivo.

Moreover studies on genetic toxicity in-vitro (Ames test, gene mutation in mammalian cells in-vitro, chromosome aberration in-vitro) were all negative, indicating that there is no evidence of reactivity under in-vitro test conditions. With respect to skin sensitisation data, there was no evidence of direct protein reactivity which would cause skin sensitisation. Since no interactions with proteins were determined and no relevant metabolites were generated via QSAR modelling, reactivity of the test substance is considered rather unlikely under in-vitro and in-vivo conditions.

Since APD is a polar substance, highly water soluble and has a molecular weight below 500, its elimination mainly occurs via the kidneys. Taking into account all available data, the biological properties of APD are mainly related to its intrinsic alkalinity. APD has a low acute toxicity and is expected to have only a low potential to accumulate in biological systems.

References:

Potts, R. and Guy, R. (1992) Predicting skin permeability. Pharm. Res. 9(5): 663-669

Kroes, R. et al. (2007) Application of the threshold of toxicological concern (TTC) to the safety evaluation of cosmetic ingredients. Food Chem. Toxicol. 45, 2533–2562

Mostert, V. and Goergens, A. (2011) Dermal DNEL setting: using QSAR predictions for dermal absorption for a refined route-to-route extrapolation. Society of Toxicology, Annual Meeting, ISSN 1096-6080 (http://www.toxicology.org/AI/PUB/Toxicologist11.pdf), 120(2): 107