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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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

Short description of key information on absorption rate: 
A QSAR-derived permeability coefficient (Kp) for the substance is available (0.0835 cm/hour) which is used for calculation of the percentage absorption.

Key value for chemical safety assessment

Absorption rate - dermal (%):

Additional information

No data on the toxicokinetics of TAEE (2-ethoxy-2-methylbutane) are available. However, Article 13 of the REACH legislation states that, in case no appropriate animal studies are available for assessment, information should be generated whenever possible by means other than vertebrate animal tests, i. e. applying alternative methods such as in vitro tests, QSARs, grouping and read-across. 

For the structural analogues of the substance, TAME (2-methoxy-2-methylbutane) and ETBE (2-ethoxy-2-methylpropane), toxicokinetic data are available (analogue approach). The three tertiary ethers TAEE, TAME and ETBE are structural homologues of each other, with an ether bond as a common functionality for all three substances, and differing only in the carbon chain length of alkyl substituents. Thus, ETBE contains ethyl and butyl groups, while TAME contains methyl and tert-amyl groups. TAEE can be considered as a superposition of the two latter substances, as it contains tert-amyl and ethyl substituents.

The molecular weights of the substances are also very close to each other, with MW of 102 g/mol for TAME and ETBE and 116 g/mol for TAEE. Available toxicokinetic data on TAME and ETBE indicate that the substances are rapidly absorbed after inhalation and oral exposure and are distributed evenly in the body, the distribution governed mainly by their solubility. They are metabolised primarily via hydrolysis of the ether bond, leading to the formation of the respective alcohols which are either excreted or metabolised further. The route of administration appeared not to have an influence on metabolism, with urine representing the main route of excretion.

Human data on TAME and ETBE are available based on which the percentage uptake after inhalation exposure can be assessed.Eight healthy male volunteers were exposed to ETBE vapour (0, 5, 25, and 50 ppm) during 2 hoursof light physical exercise(Nihlén, Löf and Johanson, 1998a).ETBE was rapidly absorbed and distributed into the blood after inhalation exposure.The respiratory uptake of ETBE was 32-34%. In the study with TAME, six men per group were exposed in a 15 m3exposure chamber to 0, 15 or 50 ppm TAME for 4 hours(Pekari, 1997a).The physical activity of the exposed subjects corresponded to light deskwork.The respiration uptake was approximately 50%.

Based on these data of TAME and ETBE, uptake after inhalation was estimated to be 50% for TAEE.


Dermal absorption was estimated using a QSAR model which considers dermal absorption as a two stage process (permeation of the stratum corneum followed by transfer from the stratum corneum to the epidermis, with the epidermis considered not to form a barrier to further permeation). The model was validated by estimating skin absorption rates for substances where experimental measurements were available, with predicted values generally within one order of magnitude of the measured value. The model predicted a permeability coefficient (aqueous Kp) of 0.0835 cm/hour, with a calculated initial absorption rate for neat TAEE of 3.91 mg/cm2/hour. Based on the REACH Guidance appendix R14.1, it was calculated that the evaporation rate of TAEE is 219 mg/cm2/hour. The dermal absorption of neat TAEE was calculated to be 1.8% (3.91/219). For the calculation of the dermal DNEL, an absorption percentage of 2% is used (as a worst case figure).

Information used for DNEL derivation

The inhalation and dermal absorption percentages used for DNEL derivation (in case of applying route-to-route extrapolation) are 50% (based on data for TAME and ETBE) and 2%, respectively.