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EC number: 239-311-3
CAS number: 15267-95-5
No studies are available. Based on molecular structure, molecular
weight, water solubility, and octanol-water partition coefficient it can
be expected that (chloromethyl)triethoxysilane is likely to be absorbed.
However, hydrolysis is expected to occur rapidly, and data from the
silanol containing degradation product indicate a less favourable
absorption. Due to the high water solubility, distribution in the body
is likely, and a fast excretion via the renal route can be expected. The
bioaccumulation potential is expected to be negligible.
There are no studies available in which the
toxicokinetic properties of (chloromethyl)triethoxysilane have been
investigated. Therefore, the toxicokinetic behaviour assessment of the
substance and its hydrolysis product was estimated by its
physico-chemical properties and the available toxicology studies on the
(Chloromethyl)triethoxysilane hydrolyses in
contact with water (predicted
half-life 2.5 h at pH 7), generating (chloromethyl)silanetriol
and ethanol. Acid environment is hereby known to catalyse this abiotic
and enzyme-independent reaction and enhance the reaction rate, further
increased by the body temperature of approximately 37°C present in
mammals (predicted half-life 5 s at pH 2 and 37.5°C). This suggests that
systemic exposure to both the parent, (chloromethyl)triethoxysilane, and
to the hydrolysis product, (chloromethyl)silanetriol, is possible.
Hence, this toxicokinetic behaviour assessment will try to predict the
behaviour of both these substances. The toxicokinetic of ethanol is
discussed elsewhere and is not included in this summary.
The molecular weight and the predicted water
solubility of (chloromethyl)triethoxysilane are 212.75 g/mol and 1100
mg/l at 20°C, respectively. In contrast, the molecular weight and
predicted water solubility of the hydrolysis product,
(chloromethyl)silanetriol, are 128 g/mol and 1E+06 mg/L at 20°C. The
hydrolysis product is smaller in size and more water soluble, and
thereby suggests that it will have greater potential to be absorbed
through biological membranes than the parent substance. Furthermore, the
predicted moderate log Kow of 2.5 for the parent substance indicates
that this substance is lipophilic enough to efficiently pass through
biological membranes by passive diffusion. However, the hydrolysis
product chloromethylsilanetriol is less lipophilic (log Kow of -2.1) and
therefore, passing of biological membranes by passive diffusion is less
likely, but due to its low molecular weight and its high water
solubility, it still has the potential to pass through aqueous pores or
be carried through the epithelial barrier by the bulk passage of water.
Oral: An acute oral toxicity study in
rats with (chloromethyl)triethoxysilane given by gavage did show signs
of systemic toxicity (dragging of limbs, decreased activity, hunched
posture, ruffled fur and/or swaying gait on test day 1 which persisted
up to test day 3) and reported an LD50 between 2000 and 5000 mg/kg body
weight. Therefore, indicating that absorption via the oral route is
possible. If ingestion occurs, the parent substance hydrolyses in the
low pH of the stomach and absorption of the parent substance is expected
to be low. It is more likely to be the hydrolysis product that is
The predicted water solubility of the parent
(1100 mg/L) and hydrolysis products (1E+06 mg/L) suggest that both
substances will readily dissolve in the gastrointestinal fluids.
Additionally, the low molecular weight (≤212 g/mol) of the substances
suggests they will have the potential to pass through aqueous pores or
be carried through the epithelial barrier by the bulk passage of water.
Furthermore, the moderate log Kow of 2.5 for the parent substance
suggests that it is lipophilic enough to be absorbed by passive
Inhalation: The vapour pressure of
the parent substance (6.5 Pa) indicates that inhalation of the
registered substance as a vapour is not likely to occur. Additionally,
an acute inhalation toxicity limit test (rats, vapour, whole body
exposure, LD50>4.7 mg/L was conducted, which did not result in any signs
of systemic toxicity. The predicted moderate water solubility (1100
mg/L) and log Kow (2.5) of the parent substance suggest that absorption
from the respiratory tract epithelium by passive diffusion is likely.
However, the very high water solubility (1E+06 mg/L) and the high
hydrophilicity (log Kow and -2.1) of the hydrolysis product,
chloromethylsilanetriol, might cause retention in the mucous of the
lungs. Therefore, once hydrolysis has occurred, absorption is likely to
slow down. Particles deposited on the mucociliary blanket will be
elevated into the laryngeal region and ultimately be swallowed
(ingestion). Since inhalation exposure did result in systemic toxicity,
absorption via the respiratory tract may therefore be a possibility.
Dermal: The moderate water solubility
(1100 mg/lL, log Kow (2.5) and molecular weight (212 g/mol) of the
parent substance suggest that absorption via the dermal route is
possible. Hydrolysis is considered to be of minor importance due to the
low presence of water on the skin surface. Additionally, for the
hydrolysis product, chloromethylsilanetriol, the high water solubility
of 1E+06 mg/L and a log Kow<-1 (-2.1) suggest that the substance would
be too hydrophilic to cross the lipid rich environment of the stratum
corneum. Since skin sensitising study using
(chloromethyl)triethoxysilane showed sensitising potential, some dermal
absorption of the substance must have occurred.
The low molecular weight (<128.6 g/mol) and
very high water solubility (1E+06 mg/L) of the hydrolysis product
suggests it will diffuse through aqueous channels and pores and will be
widely distributed. The log Kow of -2.1 indicates it is unlikely to be
distributed into cells and therefore the extracellular concentration
will be higher than the intracellular concentration. However, the parent
substance with the moderate water solubility (1100 mg/L) and log Kow
(2.5) is lipophilic and therefore likely to distribute into cells and
the intracellular concentration may be higher than extracellular
concentration. Accumulation in the body is not favourable for both
There are no data regarding a in vivo
transformation of (chloromethyl)triethoxysilane except via abiotic
hydrolysis. The predicted hydrolysis half-life at pH 7 (20°C) is 4.6 h.
At physiological temperature (37°C), this half-life will be
substantially shortened. Likewise, under gastric conditions (pH 2), the
hydrolysis is predicted to be quantitative within a few minutes. Gastric
transit half-life in the rat is about 2 h, so that there is little
likelihood that appreciable amounts of parent enter the duodenum (Enck
et al., 1989).
The hydrolysis product could
theoretically be subject to further metabolism, e.g., via
monooxygenases. However, after the initial hydrolysis step has occurred,
the reaction product, (chloromethyl)triethoxysilane, already possesses
an appreciable water solubility of 1E+06 mg/L at 20°C (predicted by
QSAR) which qualifies the molecule for immediate urinary excretion.
Thus, further enzymatic oxidation of (chloromethyl)silanetriol is rather
unlikely to occur. It is therefore assumed that abiotic hydrolysis is
the only significant route of metabolism. Phase-II metabolism by
conjugation with glucuronic acid or sulphate is often seen in molecules
bearing hydroxyl groups. However, these conjugates are either not formed
at all or very short-lived, because such conjugates could not be
detected in ADME studies with the siloxanes D4, D5, and HMDS. In all
cases, non-conjugated silanol metabolites were detected in urine. It is
therefore concluded that the primary hydrolysis product,
(chloromethyl)silanetriol, is the only significant metabolite of
The reactivity of
(chloromethyl)triethoxysilane towards water suggests high reactivity to
other biological nucleophils like protein-bound amino acids with
hydroxyl groups. (Chloromethyl)silanetriol lacks this reactivity and has
a much lower tendency to be taken up into potential target tissues in
the first place, judged by the reduced tissue-blood partition
coefficients (see table below). Therefore, hydrolysis is considered a
very efficient detoxification step.
Tissue:blood partition coefficients
This has direct implications for human
risk assessment since assessment factors for toxicokinetic interspecies
differences are per default set as the allometric scaling (AS) factor
which in turn reflects the different caloric demand of different
species. However, abiotic hydrolysis is clearly independent of caloric
demand. It is a quasi-first order reaction since the reaction partner,
water, is available in great excess. The hydrolysis rate therefore
depends only on the concentration of the parent molecule. Hence, the
metabolism of the parent does not underlie the AS principle when
extrapolating dose descriptors from rodent studies to DNELs.
(Chloromethyl)triethoxysilane is known to
undergo hydrolysis with a predicted half-life of 5 s (pH 2) to 2.5
h (pH 7). The hydrolysis product named above is far more water
soluble than the parent chemical and has a molecular weight lower than
300 g/mol. Therefore, it is expected to be excreted predominantly via
the renal route.
P. et al. (1989) Stress effects on gastrointestinal transit times in the
rat. Gut 30, 455-459
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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