2-(2-butoxyethoxy)ethyl acetate

Endpoint summary

Description of key information

Short description of key information on bioaccumulation potential result: 
Half life for hydrolysis of ester to parent glycol ether: 3 minutes
>90% elimination in urine, primarily as metabolites 2-(2-butoxyethoxy)acetic acid and diethylene glycol, within 24hours.  Elimination time and routes independent of dose.

Additional information

In an in vitro study to establish the rate of in vitro metabolism of 2 -(2 -butoxyethoxy)ethyl acetate in the blood of rats to the parent glycol ether 2-(2-butoxyethoxy)ethanol, hydrolysis was found to be very rapid with a half life of approximately 3 minutes.

An in vivo study was conducted to determine the metabolic fate and disposition of 2 -(2 -butoxyethoxy)ethyl acetate following a single oral gavage dose. Urinary metabolites were analysed and all other possible routes of elimination were also examined. The substance was rapidly and completely absorbed from the gastrointestinal tract and subsequently nearly all eliminated within 24hours, primarily in the urine. Dose level had little effect on the pattern of metabolites or relative importance of the potential elimination routes available. The main metabolite observed was 2 -(2 -butoxyethoxy)acetic acid. No butoxyacetic acid was detected nor any unchanged parent compound.

In a study to examine the absorption and elimination of radio-labelled 2 -(2 -butoxyethoxy)ethyl acetate in rats following 24hr dermal occluded exposure, it was established that the main route of elimination is overwhelmingly via the urine and that this is eliminated mainly within 24 hours. The glucoronidate conjugate was also found at significant levels (5 -8%). Males and females showed similar absorption rates and the dermal absorption rate was estimated to be 1.58 and 1.28mg/cm2/hr for males and females respectively. Washing studies showed that 90%+ of externally applied substance could be removed after 5 minutes exposure by skin washing.

In an in vitro skin permeation study, the rate of 2 -(2 -butoxyethoxy)ethyl acetate penetration in vitro through human skin was determined. The rate of flux of neat substance was measured at 59 ± 36ug/cm2/hr. The rate of flux of substance was approximately 2.5x faster when present as a saturated aqueous solution (6.65% v/v) but the lag time increased by a factor of 2.

Overall the data shows that 2-(2-butoxyethoxy)ethyl acetate is very rapidly hydrolysed in vivo to the parent glycol ether 2-(2-butoxyethoxy)ethanol, which suggests that data for the latter is likely to be a very good surrogate for the systemic toxicity of the former. The data also show that the subsequent metabolites are primarily 2-(2-butoxyethoxy)acetic acid and diethylene glycol, which are overwhelmingly eliminated in the urine within 24 hours of dosing.