3,6,9,12-tetraoxahexadecan-1-ol

Endpoint summary

Description of key information

Half life: elimination expected to be quite rapid, with a half life of around 4 -6 hours.

The substance is expected to show a low rate of absorption through skin, with a permeability constant <20 ug/cm2/hr.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - dermal (%):

10

Additional information

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-butoxyethoxy)ethoxy)ethanol (TEGBE), a closely related substance adjacent to this one in the butyl glycol ethers homologous series, 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. TetraEGBE is expected to exhibit similar metabolism.

An in vitro study determined that the permeability of TEGBE to human skin is quite low. The permeability co-efficient was determined to be 22 +/-8.6ug/cm2/hr. Exposure to the substance also caused no significant deterioration of skin barrier properties. This is confirmed by QSAR data which predicts that it will have a dermal penetration rate of 0.26mg/cm2/hr. In comparison, TetraEGBE is predicted to have a penetration rate of 0.1mg/cm2/hr and a lag time of 3 hours, more than double that of TEGBE. Total uptake of a high dose equivalent to the acute toxicity limit dose of 2000 mg/kgbw is predicted to be only 3% of the applied dose.