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EC number: 219-787-9
CAS number: 2530-87-2
There are no in vivo or in vitro data on the
toxicokinetics of (3-chloropropyl)trimethoxysilane.
The following summary has therefore been prepared based on the
physicochemical properties of the substance itself and its hydrolysis
products, using this data in algorithms that are the basis of many
computer-based physiologically based pharmacokinetic or toxicokinetic
(PBTK) prediction models. Although these algorithms provide a numerical
value, for the purposes of this summary only qualitative statements or
comparisons will be made. 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-chloropropyl)trimethoxysilane or its hydrolysis products, reasonable
predictions or statements may be made about their potential absorption,
distribution, metabolism and excretion (ADME) properties.
(3-Chloropropyl)trimethoxysilane is a moisture-sensitive, volatile
liquid that hydrolyses in contact with water with a hydrolysis half-life
of <0.083 hour at pH 4, 3.1 hours at pH 7 and <0.1 hour at pH 9 and
25oC, generating methanol and (3-chloropropyl)silanetriol.
Human exposure can occur via the inhalation or dermal routes. Relevant
inhalation and dermal exposure would be to the parent substance and
hydrolysis products. The toxicokinetics of methanol is discussed
elsewhere and is not included in this summary.
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-chloropropyl)silanetriol. When oral exposure
takes place it can be assumed that, except for the most extreme of
insoluble substances, uptake through intestinal walls into the blood
takes place. 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,
As (3-chloropropyl)silanetriol is very water soluble (1.0E+06 mg/L at
20°C (QSAR)) and has a molecular weight of approximately 156.64 it meets
both of these criteria, so should oral exposure occur it is reasonable
to assume systemic exposure will also occur.
In an acute oral toxicity study, there was no evidence of systemic
toxicity, and therefore no evidence of absorption.
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. Due to the likelihood that hydrolysis of
(3-chloropropyl)trimethoxysilane might occur during contact with skin,
exposure via this route is predicted to be to the parent and hydrolysis
products. 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. However, both
(3-chloropropyl)trimethoxysilane and its hydrolysis product
(3-chloropropyl)silanetriol have low vapour pressure, so it is
considered that volatilisation would be minimal therefore it would not
limit dermal absorption potential.
The predicted log Kow (2.0) of (3-chloropropyl)trimethoxysilane suggest
that the parent substance could be absorbed very effectively through the
The very high predicted water solubility (1E+06 mg/L) and low predicted
log Kow (-1.1) of the hydrolysis product, (3-chloropropyl)silanetriol,
suggest that it is too hydrophilic to cross the lipid rich stratum
corneum. Therefore, dermal uptake is likely to be low.
Therefore, absorption of the test substance might be expected to be
significantly reduced once hydrolysis has occurred.
In an acute dermal toxicity study, there was no evidence of systemic
toxicity, and therefore no evidence of absorption.
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 variables.
Using these values for the parent substance
(3-chloropropyl)trimethoxysilane, the QSPR predicts a blood:air
partition coefficient of approximately 2.3E+02:1 meaning that, if lung
exposure occurred there would be some uptake into the systemic
circulation. For the hydrolysis product (3-chloropropyl)silanetriol the
predicted blood:air partition coefficient is very high (approximately
1.66E+10:1) 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
(3-chloropropyl)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.
Repeated dose studies on (3-chloropropyl)trimethoxysilane showed signs
of systemic toxicity, and therefore were evidence of absorption via the
inhalation route. It must also be considered that some of the absorbed
effects could be a result of oral exposure resulting from transport of
mucus out of the respiratory tract.
The absorbed material may be in the form of the parent and hydrolysis
products. The log Kow of the parent substance means that it is likely to
distribute into cells and the intracellular concentration might be
higher than the extracellular concentration, particularly in fatty
tissues. The hydrophilic nature of (3-chloropropyl)silanetriol will
limit its diffusion across membranes (including the blood-brain and
blood-testes barriers) and its accumulation in fatty tissues.
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 the parent substance and the silanol
hydrolysis product predicts that distribution of the parent substance is
likely to occur while distribution of the hydrolysis product would be
Toxicity studies provide evidence for distribution to the bladder and
Table 1 Tissue:blood partition coefficients
There are no data on the metabolism of (3-chloropropyl)trimethoxysilane.
However, it will hydrolyse to form methanol and
(3-chloropropyl)silanetriol once absorbed into the body. There were no
observable differences in effects with and without metabolic activation
in bacterial mutagenicity tests, which were positive; however in vitro
mammalian mutagenicity tests gave positive results with metabolic
activation, but negative results without metabolic activation,
indicating possible potential for metabolism by hepatic enzymes in vivo.
The potential for genetic toxicity observed in vitro was not confirmed
when the substance was tested in an in vivo micronucleus assay.
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% lipids.
Using this algorithm, the soluble fraction of
(3-chloropropyl)trimethoxysilane in blood is approximately 58%
suggesting it is likely that some of it will be effectively eliminated
via the kidneys in urine while accumulation is also likely to occur. The
soluble fraction of the hydrolysis product, (3-chloropropyl)silanetriol,
in blood is approximately 99% suggesting it is likely to be effectively
eliminated via the kidneys in urine and accumulation is very 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.
DeJongh, 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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