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EC number: 252-029-5
CAS number: 34443-12-4
absorption/excretion, toxicokinetics, metabolism and distribution data
of TBEC were evaluated from the available toxicological data and the
physicochemical properties as suggested by the REACH Guidance Chapter
is a clear colorless liquid at room temperature with a molecular weight
of 246.3 g/mol. The substance is only very slightly soluble in water
(5.39 mg/L). The logKow of TBEC was measured to be 5.2. Based on this
log Kow a logBCF of 3.1 was calculated. TBEC (without its impurities)
has a very low vapor pressure of 4 10e-7 Pa at 20 °C.
is at least partially degraded hydrolytically to 2-ethylhexanol at 25
°C, with half-live of 19.4, 83.0, 131.3 and 98.0 h at pH 9, 8, 7 and 4,
respectively. Tert-butanol was not detected during the hydrolysis tests.
The half-life of TBEC hydrolysis decreases when increasing the
temperature at pH 9: t1/2 is 19.4 h at 25 °C, 4.7 h at 37 °C, and 1.4 h
at 50 °C. In addition, hydrolysis occurs at pH 4 (rat stomach pH), with
a half-life of 12.9 hours at 37°C. Regarding these data, it can be
expected that hydrolysis at pH 1.2 (human stomach pH) and 37 °C is
possible but relatively limited.
means that following oral exposure, mainly TBEC (and not its possible
hydrolysis by products) will be absorbed both in human and in rats.
absorption is favored for molecular weights below 500 g/mol. Based on
the high logKow of 5.2 and the water solubility, TBEC may be taken up by
micellular solubilisation. When administered orally TBEC may hydrolyze
to 2-ethylhexanol but in a relatively small extent. Acute and subacute
oral toxicity of TBEC are low.
a model to predict either high or low fraction absorbed for an orally
administered, passively transported substance, the rates of absorption
of TBEC were 100 and 90% for doses of 1 and 1000 mg, respectively
(Danish QSAR database). According
to the pkCSM method (Pires et al., 2015) for predicting small-molecule
pharmacokinetic properties, TBEC is also expected to be readily absorbed
(91%) by the oral route. Therefore, for human risk assessment, a default
absorption rate of 100% will be used.
on physico–chemical properties of TBEC the substance is not likely to
penetrate skin to a large extent as the high logKow value and the low
water solubility do not favor dermal penetration.
dermal absorption of TBEC was estimated with IH SkinPerm v2.04 model
(AIHA, 2018). Compared to in vitro data from OECD 428 studies, IH
skinPerm allowed the estimation of the dermal absorption rate with a
good confidence and a low frequency (ca. 2%) of underestimation for
liquids (Arkema’s internal validation study, 2018). According to the
data input, IH SkinPerm v2.04 model leads to the following results:
Deposition over time
End time observation 8 hr
Total deposition (mg) or deposition rate (mg/cm²/hr
Fraction absorbed (%)
Amount absorbed (mg)
Lag time stratum corneum (min)
Max. derm. abs. (mg/cm²/h)
across the epidermis is expected to be low (2.94%). This was confirmed
in an acute dermal toxicity study resulting in an LD0 value of more than
2000 mg/kg bw (with no associated clinical signs). In addition, TBEC was
not shown to be a skin sensitizer and is only slightly to moderately
irritating for skin. The
skin absorption rate is therefore limited and considered at 10% for risk
on the low vapour pressure of 4 10e-7 Pa, inhalation exposure is very
unlikely. Nevertheless, if the substance reaches the lung, TBEC may be
absorbed by micellular solubilisation. The low water solubility may
enhance penetration to the lower respiratory tract.
Once absorbed via the gastrointestinal
tract it is likely that TBEC will be distributed systemically into cells
due to its lipophilic properties and the intracellular concentration may
be higher than extracellular concentration particularly in fatty tissues.
According to the pkCSM method (Pires et
al., 2015) for predicting small-molecule pharmacokinetic properties,
TBEC is expected to have a high steady state volume of distribution, a
low fraction unbound to serum proteins, and to readily cross the
blood-brain barrier and penetrate the CNS.
metabolism of TBEC by cytP450 was evaluated by the Xenosite P450
Metabolism 1.0 software. XenoSite is able to predict the site of
metabolism (SOM) of a molecule for cytP4501A2, 2A6, 2B6, 2C8, 2C9, 2C19,
2D6, 2E1, 3A4 CYP isoforms (Pires et al., 2015). Xenosite computes a
probability score varying between 0 and 1 (a high probability to be a
SOM is characterized by a high score), which reflects both the
confidence of the model that a particular atom is metabolised and the
statistical likelihood that its prediction for that atom is correct, but
they do not explicit model selectivity (which molecules are substrates
of a given CYP enzyme). According to the cyt P450 isoforms and the
substance isomers, TBEC is preferentially metabolized by cytP4502C9 on
the hexyl radical.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
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