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EC number: 252-161-3
CAS number: 34708-08-2
There are no in
vitro or in vivo data on the toxicokinetics of
No. 34708-08-2, EC No. 252-161-3).
The following summary
has therefore been prepared based on validated predictions of 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 other where appropriate, known or predicted
physicochemical properties of
triethoxy(3-thiocyanatopropyl)silane, reasonable predictions or
statements may be made about its potential ADME properties.
Human exposure to the
parent and hydrolysis products can occur via the oral route. When
oral exposure occurs, it is necessary to assume that, except for
the most extreme of insoluble substances, that uptake through
intestinal walls into the blood takes place. 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
predicted water solubility of 140 mg/L and a molecular
weight of 263.43. If oral exposure would occur, it is reasonable
to assume that systemic exposure will also occur, although the
molecular weight is above the ideal range.
The hydrolysis product
(3-thiocyanatopropyl)silanetriol with a water solubility of 2000
g/L and a molecular weight of 179.27 clearly meets both of these
criteria so should oral exposure occur then systemic exposure is
In the acute oral toxicity
study, clinical signs and mortality were observed which
confirm evidence of absorption from the gastrointestinal tract.
The fat solubility and
the 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 predicted log Kow
of 3.1 and a predicted water solubility of 140 mg/L,
absorption of triethoxy(3-thiocyanatopropyl)silane across the skin
is likely. The predicted water solubility (2000 g/L) of the
hydrolysis product, (3-thiocyanatopropyl)silanetriol,
is favourable for absorption across the skin although the log Kow
(-1.5) is less so. However, overall systemic exposure of (3-thiocyanatopropyl)silanetriol
via this route is considered likely. The available acute
dermal toxicity study with triethoxy(3-thiocyanatopropyl)silane,
showed clinical signs of toxicity and therefore, evidence for
After or during
deposition of a liquid on the skin, evaporation of the substance
and dermal absorption occur simultaneously which is why the vapour
pressure of a substance is also relevant. Triethoxy(3-thiocyanatopropyl)silane
and its hydrolysis product (3 -thiocyanatopropyl)silanetriol
are considered to be minimally volatile. Therefore,
evaporation from the skin surface is not considered a factor in
the extent of potential uptake from the skin.
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
Using these values for
triethoxy(3-thiocyanatopropyl)silane results in a blood:air
coefficient of 57000:1. Thereby, if lung exposure occurs, uptake
into the systemic circulation also would occur. The high water
solubility of the hydrolysis product, (3-thiocyanatopropyl)silanetriol,
results in a markedly higher blood:air partition coefficient.
Consequently, when hydrolysis has occurred (as expected in the
lungs), significant uptake would be expected into the systemic
circulation. However, the high water solubility of (3-thiocyanatopropyl)silanetriol
may lead to some of it being retained in the mucus of the lungs
and therefore, when hydrolysis has occurred, absorption is likely
to slow down.
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
triethoxy(3-thiocyanatopropyl)silane predicts that it will
distribute into the main body compartments as follows: fat >>
liver > brain ≈ muscle ≈ kidney with tissue:blood partition
coefficients of 104.4 for fat and 3.0 to 6.4 for the remaining
tissues. For the hydrolysis product, distribution would be minimal
with tissue:blood partition coefficients of less than 1 for all
tissues (zero for fat).
Table 1: tissue:blood
No data regarding the
metabolism of triethoxy(3-thiocyanatopropyl)silane is available.
Genetic toxicity tests in vitro showed no observable effect
differences with and without metabolic activation for
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.
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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