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EC number: 219-784-2
CAS number: 2530-83-8
There are no reliable in vivo data on the toxicokinetics of [3-(2,3-epoxypropoxy)propyl]trimethoxysilane.
The following summary has therefore been prepared based on the
physicochemical properties of the substance itself and its hydrolysis
products and using this data in algorithms that are the basis of many
computer-based physiologically based pharmacokinetic or toxicokinetic
(PBTK) prediction models. The main input variable for the majority of
these algorithms is log Kow so by using this, and where
appropriate, other known or predicted physicochemical properties of [3-(2,3-epoxypropoxy)propyl]trimethoxysilane,
reasonable predictions or statements may be made about its potential
absorption, distribution, metabolism and excretion (ADME) properties.
[3-(2,3-epoxypropoxy)propyl]trimethoxysilane is a
moisture-sensitive liquid that has a measured hydrolysis half-life of
6.5 hours at pH 7 and 25°C, generating
3-(2,3-epoxypropoxy)propylsilanetriol and methanol. Hydrolysis of the
alkoxy and epoxy groups occur independently. Human exposure can occur
via the inhalation or dermal routes. Relevant inhalation and dermal
exposure would be predominantly to the parent substance.
The toxicokinetics of methanol have been reviewed in other major
reviews and are not considered further here.
Significant oral exposure is not expected for this substance.
However, oral exposure to humans via the environment may be
relevant for the hydrolysis product,
3-(2,3-epoxypropoxy)propylsilanetriol. When oral exposure takes
place it can be assumed, except for the most extreme of insoluble
substances, that uptake through intestinal walls into the blood occurs.
Uptake from intestines must be assumed to be possible for all substances
that have appreciable solubility in water or lipid. Other mechanisms by
which substances can be absorbed in the gastrointestinal tract include
the passage of small water-soluble molecules (molecular weight up to
around 200) through aqueous pores or carriage of such molecules across
membranes with the bulk passage of water (Renwick, 1993).
3-(2,3 -Epoxypropoxy)propylsilanetriol is highly water soluble
(1E+06 mg/l) and has a molecular weight of 194.26 in
the favourable range. Should oral exposure occur, based on its known
properties it is reasonable to assume that systemic exposure is
likely. However, an available toxicokinetic study (WIL, 2000) reports
little or no absorption of the test article 30 minutes following oral
administration. This is likely to be due to
“limited by condensation” solubility properties of the hydrolysis
the high dose in the study would had led to the formation of a siloxane
wax upon hydrolysis. This behaviour might not be expected at lower
concentrations, so it is possible that oral exposure to low doses will
result in uptake.
The fat solubility and therefore potential dermal penetration of a
substance can be estimated by using the water solubility and log Kow
values. Substances with log Kow values between 1 and 4
favour dermal absorption (values between 2 and 3 are optimal)
particularly if water solubility is high. With a log Kow of
0.5 and water solubility of 1.1 E+05 mg/l, absorption of [3-(2,3-epoxypropoxy)propyl]trimethoxysilane
across the skin is unlikely. After or during deposition of a liquid on
the skin, evaporation of the substance and dermal absorption occur
simultaneously so the vapour pressure of a substance is also relevant
but as [3-(2,3-epoxypropoxy)propyl]trimethoxysilane has a
low vapour pressure evaporation is not likely to be a factor.
The high water solubility 1.0E+06 mg/l of the hydrolysis product,
3-(2,3-epoxypropoxy)propylsilanetriol, is favourable for absorption
across the skin but the log Kow of -2.6 is not. Therefore
absorption across the skin is not likely to occur as the substance is
likely to be too hydrophilic to cross the lipid-rich environment of the
Therefore absorption might be expected to be significantly reduced
once hydrolysis has occurred. The available acute dermal toxicity
studies (Mellon, 1962, Dow Corning Corporation, 1963) suggest that
absorption and systemic exposure does occur via the dermal route, with
death and gross pathology recorded in animals exposed to the test
There is a QSPR to estimate the blood:air partition coefficient
for human subjects as published by Meulenberg and Vijverberg (2000). The
resulting algorithm uses the dimensionless Henry coefficient and the
octanol:air partition coefficient (Koct:air) as independent
Using these values for the parent substance [3-(2,3-epoxypropoxy)propyl]trimethoxysilane,
results in a blood:air partition coefficient of approximately 2.2E+05:1
meaning that if lung exposure occurred there would be uptake into the
systemic circulation, though the high water solubility of the parent
substance may lead to some of the substance being retained in the mucus
of the lungs. The high difference in log Kow between the
parent substance and hydrolysis product,
3-(2,3-epoxypropoxy)propylsilanetriol, results in a markedly higher
blood:air partition coefficient (approximately 21.5E+11:1) of the
hydrolysis product so once hydrolysis has occurred, as it would be
expected to in the lungs, then significant uptake would be expected into
the systemic circulation. However, the high water solubility of the
hydrolysis product 3-(2,3-epoxypropoxy)propylsilanetriol may lead to
this substance being retained in the mucus of the lungs so absorption
may be lower than the blood:air partition coefficient would suggest.
There available inhalation studies (Allied Corporation, 1982, Dow
Corning Corporation, 1982) show evidence of absorption, including dose
related toxicity and body weight changes, indicating systemic exposure.
For blood:tissue partitioning a QSPR algorithm has been developed
by DeJongh et al. (1997) in which the distribution of compounds
between blood and human body tissues as a function of water and lipid
content of tissues and the n-octanol:water partition coefficient (Kow)
is described. Using this value for [3-(2,3-epoxypropoxy)propyl]trimethoxysilane
predicts that, should systemic exposure occur, distribution would be
slight into fat, liver, muscle, brain and kidney.
For the hydrolysis product, distribution into the main body
compartments would be minimal with tissue:blood partition coefficients
of less than 1 for all major tissues (zero for fat).
Table 5.1.2: Tissue:blood partition coefficients
An in vivo bioavailability study for another trialkoxysilane,
4-((triethoxysilyl)methyl)morpholine (CAS 21743-27-1) shows evidence for
systemic exposure following IP administration (Harlan 2009). This study
is included to support the need for more data on genetic toxicity.
There are no data on the metabolism of [3-(2,3-epoxypropoxy)propyl]trimethoxysilane.
However, it will hydrolyse to form 3-(2,3-epoxypropoxy)propylsilanetriol
and methanol once absorbed into the body. Genetic toxicity tests in
vitro showed no observable differences in effects with and without
A determinant of the extent of urinary excretion is the soluble fraction
in blood. QPSRs as developed by DeJongh et al. (1997) using log Kow
as an input parameter, calculate the solubility in blood based on
lipid fractions in the blood assuming that human blood contains 0.7%
Using this algorithm, the soluble fraction of [3-(2,3-epoxypropoxy)propyl]trimethoxysilane
in blood is approximately 98% while
the corresponding value for the hydrolysis product, 3-(2,3-epoxypropoxy)propylsilanetriol,
is > 99%. Therefore these figures suggest that both the parent and the hydrolysis
product are likely to be effectively eliminated via the kidneys in urine
and accumulation is therefore unlikely.
Renwick A. G. (1993) Data-derived safety factors for the evaluation of
food additives and environmental contaminants. Fd. Addit. Contam.10:
Meulenberg, C.J. and H.P. Vijverberg, Empirical relations predicting
human and rat tissue:air partition coefficients of volatile organic
compounds. Toxicol Appl Pharmacol, 2000. 165(3): p. 206-16.
De Jongh, J., H.J. Verhaar, and J.L. Hermens, A quantitative
property-property relationship (QPPR) approach to estimate in vitro
tissue-blood partition coefficients of organic chemicals in rats and
humans. Arch Toxicol, 1997.72(1): p. 17-25.
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