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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 these 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 the
log of the n-octanol:water partition coefficient (log Kow).
by using this parameter and others, as known or predicted for
triethoxy(3-thiocyanatopropyl)silane, reasonable predictions or
statements may be made about its potential absorption,
distribution, metabolism, and elimination (ADME) properties.
Human exposure to the
parent and hydrolysis products can occur via the oral route. When
oral exposure occurs, uptake
through intestinal walls into the blood is likely to take place.
Uptake from intestines is
assumed 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 g/mol) through
aqueous pores or carriage of such molecules across membranes with
the bulk passage of water (Renwick, 1993).
predicted water solubility of 140 mg/L at
20°C and a molecular
weight of 263.43 g/mol. Thus if
oral exposure occurs, systemic exposure also will occur,
although the molecular weight is above the ideal range.
hydrolysis product (3-thiocyanatopropyl)silanetriol with a
predicted water solubility of 1E+06 mg/l at 20°C and a molecular
weight of 179.27 g/mol clearly meets both of the above criteria.
So should oral exposure occur, then systemic exposure is very
In the acute oral toxicity
Pharma AG, 1987), clinical
signs and mortality were observed which confirm evidence of
absorption from the gastrointestinal tract.
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 at 20°C, absorption of
triethoxy(3-thiocyanatopropyl)silane across the skin is likely.
The predicted water solubility of the hydrolysis product,
(3-thiocyanatopropyl)silanetriol (1E+06 at 20°C), 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 the dermal route is
considered likely. The available acute dermal toxicity study with
triethoxy(3-thiocyanatopropyl)silane (Harlan Laboratories Ltd,
2011) showed clinical signs of toxicity and therefore, evidence
for dermal absorption.
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,
with vapour pressures of <100 Pa at 20°C (measured; Value for CSA:
0.38 Pa at 25°C, predicted) and 2E-06 Pa at 25°C (predicted),
respectively. Therefore, evaporation from the skin surface is not
considered a factor in the extent of potential uptake of either
substance from the skin..
is a quantitative structure–property relationship (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; Collectively calculated for this assessment based on
molecular weight (see oral absorption above), and on water
solubility, log Kow, and vapour pressure (see dermal
as estimated for 37.5°C.
these values for triethoxy(3-thiocyanatopropyl)silane results in a
blood:air coefficient of 951: 1. Thereby, if lung exposure occurs,
some uptake into the systemic circulation would occur. In
comparison, the high water solubility and low vapour pressure of
the hydrolysis product (3-thiocyanatopropyl)silanetriol results in
a markedly higher blood:air partition coefficient of 1.8E+12: 1.
Consequently, when hydrolysis has occurred (as expected in the
lungs), significant uptake of this hydrolysis product 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, likely slowing down
its systemic absorption.
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 value for 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
(3-Thiocyanatopropyl)silanetriol (silanol hydrolysis product)
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 assuming that human blood contains 0.7% lipids.
this algorithm, the soluble fraction of
triethoxy(3-thiocyanatopropyl)silane in blood is approximately 10%
and for (3-thiocyanatopropyl)silanetriol is >99%. The low
molecular weight, high water solubility, and low log Kowof
the hydrolysis product (3-thiocyanatopropyl)silanetriol suggest
that it is likely to be effectively eliminated via the kidneys in
urine. Any unhydrolysed parent substance (higher molecular weight,
lower water solubility, and higher log Kow) would be
predicted to be not as readily eliminated from the body. However,
since the parent substance is expected to be hydrolysed in the
body, the hydrolysis product will be excreted via urine and its
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.
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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