2-(2-(2-ethoxyethoxy)ethoxy)ethanol

Endpoint summary

Description of key information

Short description of key information on absorption rate:

Permeability co-efficient: 24 +/-0.9ug/cm2/hr

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

No metabolism data is available for this substance. There is data on a large number of other glycol ethers in the family of ethylene oxide derived members that allows a good insight into the way TEGEE is likely to behave in vivo.

The main metabolic pathway for metabolism of ethylene glycol monoalkyl ethers is oxidation via alcohol and aldehyde dehydrogenases (ALD/ADH) that leads to the formation of an alkoxy acid. Alkoxy acids are the only toxicologically significant metabolites of glycol ethers that have been detected in vivo. Methoxy acetic acid, a metabolite of ethylene glycol methyl ether, is a known testicular toxicant in rats, and butoxyacetic acid, a metabolite of ethylene glycol butyl ether, causes hemolysis of rodent red blood cells.

In a study to examine the metabolism 2 -(2 -(2-methoxyethoxy)ethoxy)ethanol, SD rats were given a single oral dose of 1000 and the urine collected over two 24 hour periods for analysis for a number of expected metabolites. The dominant metabolite was 2 -(2 -(2-methoxyethoxy)ethoxy)acetic acid, which accounted for 81% of the original dose. Unmetabolised 2 -(2 -(2-methoxyethoxy)ethoxy)ethanol and its glucoronide conjugate, triethylene glycol, methoxyethoxyethoxyacetic acid were also found at levels of 1 -5% . In addition, the metabolite methoxyacetic acid was found, the amount accounting for 0.5% of the dose of 2 -(2 -(2-methoxyethoxy)ethoxy)ethanol given. This demonstrates that oxidation of the hydroxyl function is the dominant metabolic pathway but small amounts of the substance are metabolised by cleavage of the ether linkage. The study also showed that 100% of the dose of 2 -(2 -(2-methoxyethoxy)ethoxy)ethanol was eliminated within 24 hours in the urine.

In a study to examine the metabolism 2 -(2 -butoxyethoxy)ethanol, SD rats were given a single oral dose of 1000mg/kgbw and the urine collected over two 24 hour periods for analysis for a number of expected metabolites. The main metabolite was 2 -(2 -(2 -butoxyethoxy)ethoxy)acetic acid (BEEAA), which accounted for 43% of the original dose. The metabolite butoxyacetic acid was found, the amount accounting for ~4% of the dose of 2 -(2 -(2 -butoxyethoxy)ethoxy)ethanol given. This demonstrates that oxidation of the hydroxyl function is the main metabolic pathway but lesser amounts of the substance are metabolised by cleavage of the ether linkages and also through oxidation of the butyl chain, although metabolites from the latter route could also be due to further oxidation of BEEAA as the secondary metabolites from these two routes are the same. The study also showed that >98% of the dose of 2 -(2 -(2 -butoxyethoxy)ethoxy)ethanol was eliminated within 24 hours demonstrating rapid metabolism (half life ~4 -5 hours) and no potential for bioaccumulation. Around 85% of the dose was collected in the urine within 48 hours, which is considered within the boundaries of what can be considered complete recovery.

These two studies on TEGME and TEGBE allow interpolation to predict the behaviour of TEGEE. The principal metabolite of 2-(2-(2-ethoxyethoxy)ethoxy)ethanol will certainly be 2-[2-(2- ethoxyethoxy)ethoxy] acetic acid. The onlly other metabolite of consideration would be the monoalkoxyacetic acid. TEGME produces an insigificant 0.5% of methoxyacetic acid whereas TEGBE produces 4% of butoxyacetic acid. Whilst this is not a concern for this substance, the question remains would TEGEE behave more like TEGME or TEGBE? TEGEE is closer to TEGME than TEGBE in the homologous series and there is no evidence of alkyl chain metabolism in either the methyl or ethyl series compared to the butyl series. There is no evidence of DEGEE forming ethoxyacetic acid as a metabolite. Therefore, it can de deduced that TEGEE is likely to be closer to TEGME than TEGBE and it is assumed that TEGEE will produce less than 1% ethoxyacetic acid as a metabolite.

An in vitro study determined that the permeability of 2-(2-(2 -ethoxyethoxy)ethoxy)ethanol to human skin is quite low. The permeability co-efficient was determined to be 24 +/-0.9ug/cm2/hr, which is around 1% of the skin penetration rate of the shorter chain glycol ether ethylene glycol methyl ether. Exposure to the substance also caused no significant deterioration of skin barrier properties.