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EC number: 242-272-5
CAS number: 18395-30-7
There are no in vivo data on the
toxicokinetics of trimethoxy(2-methylpropyl)silane.
The following summary has therefore been
prepared based on validated predictions of the physicochemical
properties of the substance itself and its silanol hydrolysis productand
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 Kowso by using this, and other where appropriate, known
or predicted physicochemical properties oftrimethoxy(2-methylpropyl)silane
or its hydrolysis products, reasonable predictions or
statements may be made about their potential absorption, distribution,
metabolism and excretion (ADME) properties.
Trimethoxy(2-methylpropyl)silane is a
moisture-sensitive liquid that hydrolyses rapidly in contact with water (half-lifeapproximately
4.1 hours at pH 7,0.2 hours at pH 4, 0.3 hours at pH 5, 0.1 hours
at pH 9 and 20 - 25°C),
generating methanol and (2-methylpropyl) silanetriol.
Human exposure can occur via the inhalation
or dermal routes. Relevant inhalation exposure would be to the parent
and hydrolysis products.
The toxicokinetics of methanol have been reviewed in other major
reviews and are not considered further here.
Significant oral exposure is not expected for
However, oral exposure to humans via the environment may be
relevant for the hydrolysis product,(2-methylpropyl)
silanetriol.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 can 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).
very water soluble and has a molecular weight of approximately 136 so
fulfils both criteria. Therefore, it is considered that should
oral exposure take place it is reasonable to assume that resulting
systemic exposure will occur also.
The fat solubility and therefore potential dermal penetration of a
substance can be estimated by using the water solubility and log Kowvalues.
Substances with log Kowvalues between 1 and 4 favour dermal
absorption (values between 2 and 3 are optimal) particularly if water
solubility is high. With a log Kowof 2.1 and water solubility
of 4900 mg/l, absorption oftrimethoxy(2-methylpropyl)silaneacross
the skin is likely to occur. 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
is volatile this may limit the potential for dermal absorption.
The high water solubility of the hydrolysis product,(2-methylpropyl)
silanetriol, is favourable for absorption across the skin
but the log Kowof -1.0 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 stratum corneum.Therefore
once hydrolysis has occurred on the skin, absorption is likely to be
substantially decreased. The available reliable skin irritation study
did not report systemic effects. There are no other dermal studies to
check for signs of systemic availability.
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,trimethoxy(2-methylpropyl)silane,
results in a blood:air partition coefficient of approximately 170:1
meaning that if lung exposure occurred there would be uptake into the
systemic circulation.The high water solubility of the hydrolysis
product, (2-methylpropyl) silanetriol,
results in a markedly higher blood:air partition coefficient
(approximately 2.9E+06:1, if a water solubility of 1000 mg/L is used) 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 (2-methylpropyl)
silanetriol may lead to some of it being retained in the
mucus of the lungs so once hydrolysis has occurred, absorption is likely
to slow down.
The acute inhalation study showed signs of
narcosis during exposure, indicating uptake had occurred.
For blood:tissue partitioning a QSPR algorithm has been developed
by De Jonghet 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)
Using this value fortrimethoxy(2-methylpropyl)silanepredicts
that, should systemic exposure occur, distribution would primarily be
into fat, with potential slight distribution into liver, muscle, brain
For the hydrolysis product,(2-methylpropyl)
silanetriol,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 1: tissue:blood partition coefficients
There are no data regarding the metabolism of
trimethoxy(2-methylpropyl)silane. Genetic toxicity tests in vitro showed
no observable differences in effects with and without metabolic
activation for trimethoxy(2-methylpropyl)silane.
In a 28-day ready biodegradation test there was no evidence for
biodegradation other than could be accounted for by biodegradation of
the non-silanol hydrolysis product, ethanol, which is readily
biodegradable (see Section 4). This suggests that the substance
and its silanol hydrolysis product are not recognised by biological
systems containing all the mammalian enzymes and metabolic systems.
A determinant of the extent of urinary excretion is the soluble fraction
in blood. QPSR’s as developed by De Jongh et al. (1997)
using log Kowas an input parameter, calculate the solubility
in blood based on lipid fractions in the blood assuming that human blood
contains 0.7% lipids.
Using this algorithm, the soluble fraction of
blood is approximately 53% while the corresponding value for the
hydrolysis product, (2-methylpropyl) silanetriol, 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 unlikely.
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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