2-(2-aminoethoxy)ethanol

Endpoint summary

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

Assessment of the toxicokinetic behavior of 2-(2-aminoethoxy)ethanol

 

Since no toxicokinetic studies are available for 2-(2-aminoethoxy)ethanol (CAS 929-06-0), the following assessment is based on the available physicochemical properties and results from other toxicological studies.

 

Physical chemical properties

2-(2-aminoethoxy)ethanol is a colorless, slightly viscous liquid at 20 °C and 1013.25 hPa and has a molecular weight of 105.14 g/mol. The test item has a high water solubility of at least 1000 g/L at 20.0°C. The log Pow was determined to be -1.89 at 25°C and the dissociation constant of the test substance (pKa) is 9.62 at 23 °C. Due to the low vapour pressure of the test substance (0.01423 hPa at 20°C, 0.02429 hPa at 25°C and 0.25023 hPa at 50°C) and the relatively high boiling point ( 222.5 °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. Based on chemical structure, no surface activity is predicted.

 

Adsorption

Gastrointestinal absorption:

The test item contains ionizable groups and has a high water solubility of at least 1000 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 makes the test item favourable for absorption in the GI tract. However, the very low Log Pow of -1.89 might prevent the test item from uptake by micellular solubilization or passive diffusion. No clear conclusion on gastrointestinal absorption can be drawn from the available oral acute toxicity studies. In these studies, toxic effects were only observed at doses above 2000 mg/kg bw and it remains unclear if the effects were caused by the corrosivity of the substance rather than gastrointestinal absorption. Regarding oral repeated dose toxicity, prenatal developmental toxicity studies in rat and rabbit as well as an extended one-generation reproduction study in rat are available. The oral administration of the test substance to pregnant Wistar rats from implantation to one day prior to the expected day of parturition (GD 6-19) provided evidence of maternal toxicity, such as a nonregenerative, normocytic, normochromic anemia, a disturbance of platelet homeostasis and a decrease in ALP activities, at the highest dose level of 1000 mg/kg bw/d. These effects indicate that gastrointestinal absorption of the test substance took place. On the contrary, the oral administration of the test substance to pregnant New Zealand White rabbits from implantation to one day prior to the expected day of parturition (GD 6-28) at doses as high as 200 mg/kg bw/d caused neither evidence of maternal nor developmental toxicity. However, this might be attributed to the lower top dose or to a potential insensitivity of the rabbit compared to rat rather than an effect of hindered gastro-intestinal uptake. In an oral extended one-generation reproduction toxicity study, clinical signs of toxicity and mortality during lactation were observed in the F0 parental animals as well as adolescent and adult F1 offspring, suggesting  gastrointestinal absorption. All in all, based on the effects of the prenatal development study and the extended one-generation reproduction toxicity study in rats, gastrointestinal absorption of the test substance has to be expected.

 

Respiratory absorption:

Due to the low vapour pressure of the test substance (0.01423 hPa at 20°C, 0.02429 hPa at 25°C and 0.25023 hPa at 50°C) and high boiling point (222.5°C), the volatility of the substance is rather low and inhalation exposure to vapors is hence considered to be also low. Due to the low Log Pow and high water solubility, vapours of the very hydrophilic test substances may be retained within the mucus. Experimental toxicity data also suggest, that respiratory absorption of the test substance might be low. The inhalation of a saturated vapor-air mixture for 8 hours caused no mortality, clinical signs or indications at necropsy in two inhalation risk tests. No clinical signs or indications at necropsy were observed. In line with that, no signs of systemic toxicity as well as adverse effects on reproductive performance, fertility and developmental toxicity were observed following inhalative exposure of up to 40 mg/m³ in a combined repeated dose toxicity study with the reproduction/developmental toxicity screening test. However, local signs of toxicity to the respiratory tract were observed at 16 mg/m³.

 

 

Dermal absorption:

Liquids and substances in solution are taken up more readily than dry particulates. With a very low vapour pressure, the test substance will not evaporate in significant amounts from the skin and will be available for absorption. Moreover, the molecular weight of < 500 g/mol favours dermal absorption. However, the very high water solubility (1000 g/l) and low Log Pow value (-1.89) indicate, that the substance may be too hydrophilic to cross the lipid rich environment of the stratum corneum. Therefore, dermal uptake is expected to be low. However, since the substance is a skin corrosive, damage to the skin surface may enhance penetration of the test substance. In an acute dermal toxicity study, no mortalities were observed at the highest test dose level of 3000 mg/kg bw. Clinical signs observed were transient and included decreased activity, poor grooming, diarrhoea, abnormal gait and stance and dyspnoea. A clear mucous anal discharge and a yellow discolouration of fur, with necrosis and skin sloughing surrounding the application site were observed. Terminal necropsy of animals revealed severe irritation and/or yellow discolouration of the underlying muscle tissue at the application site and also necrotic or discoloured fascia. Mottled lungs and pale kidneys were observed. All in all, dermal absorption cannot conclusively be assessed based on this study, since it remains unclear, whether the effects were caused by the corrosivity of the substance rather than its systemic toxicity. In line with that, dermal irritation was noted at the lowest dose tested (17 mg/kg/day) in a subchronic dermal study (OECD test guideline 411), whereas the NOAEL for systemic toxicity was determined to be 175 mg/kg/day (highest dose tested). Moreover, the substance has been tested negative for skin sensitization in a Buehler test. Thus, dermal uptake cannot be verified based on this study. Conclusively, experimental data did not suggest dermal absorption of the test substance.

 

Distribution and Accumulation

No data available.

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. Due to the low Log Pow of -1.89, the test substance is unlikely to accumulate in adipose tissue.

 

Metabolism

Using the OECD toolbox v.4.4, the in vivo Rat metabolism simulator provided four potential metabolites, as well as four simulated skin metabolites. Studies assessing genotoxicity (Ames test; BASF, 2019; HPRT test, BASF, 2019; in vivo MNT, BASF, 2001) 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 low molecular weight of the parent compound and its water solubility, it is conjectured that the test substance would probably primarily undergo a renal elimination.