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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Link to relevant study record(s)

Description of key information

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

An in vitro study established that the half life of ethoxypropyl acetate hydrolysis to ethoxypropanol in rat plasma is around 48 mins (SD=7). An in vivo study was carried out to determine the toxicokinetic parameters of propylene glycol ethyl ether acetate following intravenous dosing to male Sprague-Dawley rats and its metabolite propylene glycol ethyl ether. In addition, the toxicokinetic parameters of propylene glycol ethyl ether were determined. The test substance was dosed iv at dose levels of 10 and 100 body weight with analysis of the blood samples by GC-MS analysis using a method developed and validated in terms of selectivity, calibration, accuracy/recovery, repeatability and limit of quantification. The PGEEA data in blood showed a rapid decline. The half-life of PGEEA in blood for the low and high dose group was ~3 -4.5 and 1.98 minutes, respectively in the low and high dose animals. This rapid decline is most likely caused by fast hydrolysis into PGEE considering the measured PGEE concentrations in blood, which were much higher (~20x) than those of PGEEA. This is consistent with data on other glycol ethers that show in vivo hydrolysis is much faster than in vitro. The data does establish a strong case that hydrolysis is fast and that of the resultant parent ethoxypropanol is much slower, which in turns provides a strong justification for using data on ethoxypropanol to predict the systemic toxicological properties of ethoxypropyl acetate.

General considerations related to the metabolism of glycol ethers are well documented (Casarett & Doull’s Toxicology, 2001; ECETOC Technical Report).  Glycol ethers follow two main oxidative pathways of metabolism, either via alcohol dehydrogenase (ADH) or the microsomal CYP mixed function oxidase (MFO) (O‑demethylation or O‑dealkylation). The first pathway gives rise to the formation and excretion of alkoxyacetic acids. The second mainly leads to the production and exhalation of carbon dioxide (CO2) via ethylene glycol (MEG) or propylene glycol, which enter intermediary metabolism via the tricarboxylic acid (TCA) cycle.  Glycol ethers may also be conjugated with glucuronide or sulfate, but this is thought to occur mainly after saturation of the other metabolic pathways.

According to their pathways of metabolism, the glycol ethers may be divided into three groups:

·        ethylene glycol mono- and di-alkyl ethers and their acetates;

·        diethylene glycol mono- and di-alkyl ethers and their acetates;

·        propylene glycol ethers.

Monoethylene glycol ethers bearing a primary OH-group (alkoxyethanols) are primary alcohols that are oxidised via ADH and aldehyde dehydrogenase (ALDH) to their corresponding alkoxyacetic acids. Monopropylene glycol mono-alkyl ethers with a primary OH function (n-alkoxypropanols) follow similar pathways yielding alkoxypropionic acid.  In addition to ADH-mediated oxidation of glycol ethers bearing a primary alcohol function, microsomal oxidation (catalysed by CYP MFO: O-demethylation or O-dealkylation) may also occur, but this pathway has relatively lower capacity.

Monopropylene glycol mono-alkyl ethers etherified at the primary carbon (sec-alkoxypropanols) are secondary alcohols that cannot be metabolised to alkoxypropionic acids. These compounds are either renally excreted after conjugation or, to some extent may form ketones that may enter the intermediary metabolism via the TCA cycle and eventually expired as CO2.  Monopropylene glycol mono-alkyl ethers etherified at the seconday carbon (n‑alkoxypropanols) are primary alcohols, that can be oxidised via ADH to their corresponding alkoxypropionic acids.

The metabolism of glycol ethers is considered a pre-requisite for their toxicity, as the alkoxyacetic acids and perhaps their acetaldehyde precursors are regarded as the ultimate toxicants.  Evidence of this comes from: protection of toxicity afforded by inhibition of alcohol and aldehyde dehydrogenases; similar toxicity profiles of ethylene glycol ethers and their alkoxyacetic acid metabolites; and the differential toxicities of those glycol ethers metabolized via the oxidative and O-dealkylase pathways (Miller et al, 1984; Ghanayem et al, 1987).

All acetate esters are rapidly hydrolysed in vitro and Glycol ether acetates are no exception, being rapidly hydrolysed in vivo to the parent glycol ethers by plasma esterases and are thus likely to exhibit the same systemic toxicity profile as the parent glycol ether.

The toxicity of the propylene glycol ethers with the alkoxy group at the primary position is quite different from that of the ethylene glycol ethers, presumably because these propylene glycol ethers are not metabolised to their corresponding alkoxypropionic acids.  Miller et al (1984) reported remarkable differences in the toxicological properties of ethylene glycol monomethyl ether (EGME, 2-methoxyethanol, a primary alcohol), and propylene glycol monomethyl ether (PGME, 1-methoxy-2-propanol, a secondary alcohol).  The differences in toxicity were attributed to differences in metabolism, characterized by EGME being primarily oxidized to methoxyacetic acid, and PGME undergoing O-demethylation to form propylene glycol. In the case of propylene glycol methyl ether, developmental effects have been reported when the primary position is occupied by a hydroxyl group.

Casarett & Doull’s Toxicology.  Edited by Custis D. Klaassen.  6th Edition (2001).  Pp 898-899.  McGraw-Hill Companies, Inc.

Miller RR, Hermann EA, Young JT, et al. (1984) Ethylene glycol monomethyl ether and propylene glycol monomethyl ether: Metabolism, disposition, and subchronic inhalation toxicity studies.  Environ Health Perspect 57:233-39.

Ghanayem BI, Burka LT, Matthews HB. (1987) Metabolic basis of ethylene glycol monobutyl ether (2-butoxyethanol) toxicity: Role of alcohol and aldehyde dehydrogenases. J Pharmacol Exp Ther 242:222-31.

Domoradzki JY, Brzak KA, Thornton CM. (2003) Hydrolysis kinetics of propylene glycol monomethyl ether acetate in rats in vivo and in rat and human tissues in vitro. Toxicol Sci 75:31-39.

Stott WT and McKenna MJ. (1985) Hydrolysis of several glycol ether acetates and acrylate esters by nasal mucosal carboxylesterase in vitro. Fundam Appl Toxicol 5:399-404.

Discussion on absorption rate:

There is no data available on ethoxypropyl acetate itself. However, dermal Absorption is an important exposure route for glycol ethers in general.  Dugard et al. (1984) studied the absorption of eight glycol ethers through human skin in vitro.  2-methoxyethanol was most readily absorbed (mean steady rate of 2.82 mg/cm2/hr), followed by 1-methoxypropan-2-ol (1.17 mg/cm2/hr).  There was a trend of reducing absorption rate with increasing molecular weight for monoethylene glycol ethers (2-methoxyethanol, 2.82 mg/cm2/hr; 2-ethoxyethanol, 0.796 mg/cm2/hr; 2-butoxyethanol, 0.198 mg/cm2/hr).  The rate of absorption of 2-ethoxyethanol was similar to that of the parent acetate.

Dermal uptake studies of 1-methoxypropan-2-ol have also been conducted in human volunteers.  Brooke et al (1998) exposed subjects at rest to 100 ppm 1-methoxypropan-2-ol vapour with and without fresh-air fed half masks to compare skin-only and whole-body exposure, respectively, and measured uptake in blood, breath and urine samples.  Dermal uptake was calculated to be 9.6 ± 6.5% based on breath samples, 8.0 ± 5.7% based on blood samples, and 4.2 ± 1.7% based on urine samples.  In a similar study, Devanthéry et al, 2002 measured total and conjugated 1-methoxypropan-2-ol levels in urine, exhaled air, and blood of human volunteers exposed to 1-methoxypropan-2-ol vapour, with and without respiratory protection, at levels up to 95 ppm for 6 hours.  These investigators reported that 1-methoxypropan-2-ol was not detected in breath, blood or urine following dermal-only exposure.

Dugard PH, Walker M, Mawdsley SJ, and Scott RC. (1984) Absorption of some glycol ethers through human skin in vitro.  Environ Health Perspect 57:193-7.

Brooke I, Cocker J, Delic JI, Payne M, Jones K, Gregg NC, Dyne D. 1998. Dermal uptake of solvents from the vapour phase: an experimental study in humans. Ann Occup Hyg 42:531-540. 

Devanthéry A, Berode M, Droz PO. 2002. Propylene glycol monomethyl ether (PGME) occupational exposure 1, biomonitoring by analysis of PGME occupational exposure. Int Arch Environ Health 73:311-315.