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Administrative data

Link to relevant study record(s)

Description of key information

No toxicokinetic data are available for 2-[[2-(dimethylamino)ethyl]methylamino]ethanol. Studies are not required under REACH and a theoretical assessment of the toxicokinetic properties is provided, based on relevant data from the existing toxicity studies and taking into account the structure of the substance.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential
Absorption rate - oral (%):
50
Absorption rate - dermal (%):
50
Absorption rate - inhalation (%):
100

Additional information

Absorption

The substance is of relatively low molecular weight (Mw 146.2) and high water solubility, which would tend to favour oral absorption. The substance is predicted to be orally bioavailable according to Lipinski Rules (Oasis). Signs of toxicity including sedation, curved body position, ruffled fur, somnolence, ataxia and tremors were observed at all dose levels (2000, 3200 and 5000 mg/kg bw) in the acute oral toxicity study. The signs of toxicity may indicate systemic exposure; however it is also possible that signs may reflect local discomfort following gavage dosing with a corrosive substance. In the 14-day range-finding study, clinical signs (including laboured breathing, arched back and piloerection) were observed at gavage dose levels of 500, 700 and 1000 mg/kg bw/d. There were no clear effects on haematological or clinical chemistry parameters in this study which would indicate systemic exposure. Increased liver weight was reported for females, which is consistent with absorption from gastrointestinal tract; histopathology was not performed in this study. An OECD 422 screening study performed at gavage dose levels of 25, 100 or 400 (250) mg/kg bw/d.

The low molecular weight and high water solubility of the substance will favour dermal absorption; however this may be limited by the low lipid solubility (LogP =-0.584). For the purposes of the REACH risk assessment, dermal absorption is assumed to be equivalent to oral absorption (default assumption).

The substance is a non-volatile liquid; therefore inhalation exposure is likely to be limited unless it is used in a manner which generates inhalable particles. For the purposes of the REACH risk assessment and in the absence of specific data, inhalation absorption of 100% is assumed (default value; equivalent to twice the level of oral absorption).

Metabolism

Metabolism simulators (in vivorat metabolism, rat liver S9 metabolism (OECD QSAR Toolbox v4.0)) indicates extensive metabolism for 2-[[2-(dimethylamino)ethyl]methylamino]ethanol. There is some evidence from thein vitrogenotoxicity studies of different toxicity in the absence and presence of metabolic activation, which also indicate that the substance is metabolised. Metabolism is predicted to proceed via oxidation of the terminal hydroxyl group, N-demethylation and/or amide hydrolysis, resulting in a large number of low molecular weight metabolites.

Excretion

The low molecular weight and very high water solubility of 2-[[2-(dimethylamino)ethyl]methylamino]ethanol indicates that urinary excretion will be extensive and that biliary excretion will not occur.

Distribution

There is no definitive evidence for post-hepatic absorption of the substance or its metabolites; however, based on the molecular weight and water solubility of the substance and its postulated metabolites, extensive distribution is likely.

Bioaccumulation potential

Based on the assessment above (including predicted extensive metabolism and excretion), bioaccumulation is considered to be unlikely. Metabolism simulators include low molecular weight metabolites which may be incorporated into normal metabolic pathways; this does not represent bioaccumulation.