1-(N,N-bis(2-hydroxyethyl)amino)propan-2-ol

Endpoint summary

Description of key information

In the absence of specific data on the ADME of DEIPA, it’s physicochemical properties and relevant toxicity data (where available) were assessed for insights into likely ADME characteristics. DEIPA has a MW >100 and <500 and a log Pow >-1 and < 4, characteristics considered favourable for oral and dermal absorption. Signs of systemic toxicity observed following repeated oral administration in rats confirm that absorption can occur via this route. Due to DEIPA’s low volatility, inhalation of DEIPA vapours is not expected. However, ready absorption would be expected following inhalation of DEIPA aerosols. Wide tissue distribution of absorbed DEIPA could occur (due to its low MW). However, metabolism (probably involving oxidation of the two ethanol groups), excretion, a low MW and low Log Pow mean that bioaccumulation is unlikely. Urinary excretion is the most likely elimination pathway of absorbed DEIPA.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

100

Absorption rate - dermal (%):

100

Absorption rate - inhalation (%):

100

Additional information

Assessment of toxicokinetics based on the physicochemical properties of DEIPA, based on:

Molecular weight: 163 Daltons

Water solubility: Miscible in all proportions

Partition coefficient Log Pow: -1.0

Vapour pressure: 0.0084 Pa

Surface tension: 61.2 mN/m at 20.3 °C

Boiling point: 325°C

ABSORPTION

Oral

The molecular weight (MW) of the substance (163) and the Log Pow (-1.0) (Butler, 2012) favour absorption from the gastro-intestinal tract following ingestion (ECHA, 2012a). DEIPA is miscible with water in all proportions i.e. soluble without limit (Butler, 2012) and thus will readily dissolve in the gastrointestinal fluid (ECHA, 2012a). As the MW is below 200, it has the potential to pass through aqueous pores or be carried through the epithelial barrier by the bulk passage of water (ECHA, 2012a). Signs of systemic toxicity observed in a repeated dose (28-day) oral gavage study in rats (Stebbins and Zablotny, 1999) support the expectation that DEIPA is absorbed orally. Therefore, a value of 100% oral absorption is proposed.

 

Inhalation

According to an expert report, and based on a low estimated vapour pressure of 7 x10^-7 kPa, inhalation of DEIPA vapours is not expected (NICNAS, 2009). A recent guideline study established a comparable vapour pressure of 8.4 x 10^-6 kPa for DEIPA (Atwal, 2012a); both values are below the 0.5 kPa threshold considered by ECHA (2012b) to display low volatility. Considering the low vapour pressure and high boiling point (325°C), the opportunity for exposure by inhalation is likely to be low.

However, absorption would be expected if inhalation of a DEIPA aerosol occurred. Since DEIPA is miscible, it will readily diffuse into the mucous lining the respiratory tract and the low Log Pow value favours absorption directly across the respiratory tract epithelium by passive diffusion. Evidence of absorption following oral exposure (signs of systemic toxicity) also suggest that the substance will be absorbed following inhalation exposure. A default value of 100% inhalation absorption is usually applied in these circumstances (ECHA, 2012a).

Dermal

The MW and Log Pow are within ranges that favour dermal absorption. ECHA recommends a default value of 100% skin absorption for such substances (MW below 500 and Log Pow between -1 and 4) (ECHA, 2012a). The liquid state and miscibility of DEIPA are thought to assist penetration into the stratum corneum and subsequently the epidermis, also favouring absorption.

DISTRIBUTION and METABOLISM

No test data are available regarding the distribution and metabolism of DEIPA. As a small molecule, a wide tissue distribution is possible (ECHA, 2012a) but the structure suggests that DEIPA will either be metabolised by oxidation of the two ethanol groups to carboxylic acids, with subsequent conjugate formation (e. g. glucuronidation or sulfation) or be directly conjugated, in phase-II reactions.

ELIMINATION

The low MW and probable ready oxidation/conjugation are indicative of ready excretion, presumably via the urine. Based on that and on the low Log Pow, bioaccumulation is not expected. Biliary excretion tends to be limited to compounds of higher molecular weights (around 300 in the rat, approx. >500 in humans) (ECHA, 2012a; OECD, 2011) and is likely not a significant excretion route for DEIPA.

 

 

References

ECHA (2012a). European Chemicals Agency. Guidance on information requirements and chemical safety assessment. Chapter R.7c: Endpoint specific guidance. November 2012 (version 1.1).

OECD (2011). Manual for the assessment of chemicals. Chapter 4. Initial assessment of data. Available at:http://www.oecd.org/env/ehs/risk-assessment/49188998.pdf.

 

NICNAS (2009). Australian National Industrial Chemicals Notification and Assessment Scheme. Full Public Report. DEIPA. File No: STD/1344. December 2009.http://www.nicnas.gov.au/publications/CAR/new/Std/StdFULLR/std1000FR/std1344FR.pdf