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Description of key information

Key value for chemical safety assessment

Bioaccumulation potential:
low bioaccumulation potential

Additional information

The urinalysis indicated that the urine concentrations of AMPD were proportional to the administered dose (Rasoulpour and Andrus, 2011).

There were no experimental studies available in which the toxicokinetic properties of 2-amino-2-methyl-1,3-propanediol (AMPD) were investigated.Therefore, whenever possible, toxicokinetic behaviour was assessed taking into account the available information on physicochemical and toxicological characteristics of AMPDaccording to “Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance (ECHA, 2009)”. AMPD (105.14 g/mol) is a white crystalline mass in its pure state, is highly soluble in water (2500 g/L at 20 °C; Merck Index) and has a very low vapour pressure (0.159 Pa at 25 °C; QSAR data). The relatively low partition coefficient (log Kow) of < -3.8) results in a low potential to accumulate in biological systems.

Acute oral toxicity studies have been conducted in rats and mice. In an acute toxicity study performed in 1969, rats were orally administered AMPD and observed for signs of toxicity for 14 days (reviewed in Burnett et al., 2009). The mortality in the 10200, 15400, 23100 and 34600 mg/kg bw groups was 0/4, 1/4, 4/ and 4/4. The rats in the 23100 mg/kg bw group died within the first week and those in the 34600 mg/kg bw group died 45 min to 3 h after administration. The LD50 value was calculated to be 17000 mg/kg bw. Also mice were administered AMPD via the oral route and kept for observation for 7 days (Rubenkoenig, 1955). In the 2000, 2500, 3500, 5000 and 7000 mg/kg bw dose groups, the mortality was 0/10, 1/10, 5/10, 7/10 and 10/10, respectively. The LD50 value was 3500 mg/kg bw. No further data were given.

 

The acute oral toxicity of the members of this category is low. All oral LD50 values in rats are >2000 mg/kg bw. Clinical signs observed in the available studies include lethargy and hunched posture, consistent with discomfort. Gross pathologial signs were consistent with the high pH of these materials (discoloration of the intestines and signs of hemorrhaging in the stomach). Value taken forward to CSR for acute oral toxicity of APD: LD50 >5000 mg/kg bw.

No data on acute inhalation toxicity are available. As a consequence of the relatively low vapour pressure of AMPD, inhalation is not considered to be a significant route of exposure. Furthermore, the particle size of AMPD is > 10 µM, indicating that most of the inhaled particles will remain in the upper airways and/or will be swallowed. Also, based on the particle size, it seems unlikely that particles of AMPD penetrate the pulmonary alveols.[Fri1] 

No data on acute dermal toxicity are available.

QSAR based dermal permeability regarding molecular weight, log Kow and water solubility, calculated a dermal absorption of 3 µg/cm2/h (DERMWIN, v.2.01, 2011, modified considering the Fick´s first law). This value is considered as indicator for a dermal absorption of 40%. Taking into account all data, dermal uptake of AMPD is considered as limited and the systemic toxicity via the dermal route is estimated to be low based on read-across within this chemical category AMPD belongs to.

According to the chemical structure of AMPD, it can be assumed that AMPD is not metabolised in-vivo and is excreted predominantly via urine. By calculating potential metabolites using the OECD QSAR toolbox v.2.0 (2010), this assumption is confirmed. No relevant metabolites were generated by the liver metabolism simulator, by the skin metabolism simulator or by the microbial metabolism simulator. Based on this information, it seems to be very unlikely that AMPD will be metabolised by cytochrome P450 enzymes in-vivo.

Moreover, studies on genetic toxicity via read-across based on a category approach (Ames test, gene mutation in mammalian cells in-vitro, chromosome aberration in-vitro) were all negative, indicating that there is no evidence of a reactivity of the test substance under the test conditions.

Since AMPD is a polar substance, highly water soluble and has a molecular weight lower than 500, its elimination mainly occurs non-metabolised by the kidneys.

Taking into account all available data, AMPD possesses a low acute toxicity und is expected to have only a low potential to accumulate in biological systems.