Registration Dossier

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

No experimental data are available regarding the toxicokinetic behavior and metabolism of di-n-butyl ether. The appearance of systemic toxicity after oral and inhalative exposure shows the bioavailability of dibutyl ether via these routes. Given the Log Kow of 3.35 and Molecular Weight of approximately 130, di-n-butyl ether is likely to penetrate the skin based on the EPA DERMWIN QSAR program that predicts the log Kp to be -1.135 The EPA DERMWIN QSAR uses the calculation Log Kp = -2.72 + 0.71*(Log Kow) - 0.0061(MW).

It should be noted that this substances is also volatile (vapour pressure of 4.6hPa) and so it will easily volatalise, therefore dermal exposures in unnocluded circumstances will be less likely to lead to significant systemic exposure. Occluded or semi-occluded exposures would however likely lead to systemic exposure. No data is available regarding metabolism, however liver enzyme induction observed in the 4 week repeated dose oral study indicates this substance is metabolised to some extent prior to excretion, potentially involving breaking of the ether bond and/or glucuronic acid conjugation. Breaking of the ether bond will release n-butanol which can be subsequently metabolised to the butanoic acid or excreted as is via exhalation or urniary excretion. Based on the physicochemical properties of this substance it is likely that this substance is excreted via the urinary route and potentially exhalation (given the volatilty). The metabolism of the ether bond is known to happen with the glycol ethers via O-dealkylation, where the ether bond is metabolised releasing the glycol and the alcohol. For example, the glycol ether phenoxy propanol is metabolised to some extent to release phenol and propylene glycol (Saghir et al, 2003 - xenobiotica, vol. 33, no. 10, 1059–1071). Given the potential for this metabolism of the ether bond it is considered plausible to utilise repeated dose toxicity data on butanol in conjunction with the available data on n-butyl ether to characterise the repeated dose toxicity of this substance. Additional support for this metabolic pathway comes from the various publications on the human metabolism of methyl tert butyl ether, where o-dealkylation removes the methyl group, leaving a tertiary butanol group: Amberg et al 1999 (Tox.Sci. 51, 1 -8).