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EC number: 217-496-1
CAS number: 1873-88-7
There are no in vivo data on the
toxicokinetics of 1,1,1,3,5,5,5-heptamethyltrisiloxane (H-L3).
The following summary has therefore been prepared based on in vitro data
for a structurally-related substance decamethyltetrasiloxane (L4, CAS
141 -62 -8), and the physicochemical properties of H-L3
itself 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 H-L3
reasonable predictions or statements may be made about its potential
absorption, distribution, metabolism and excretion (ADME) properties.
In contact with water, the substance reacts moderately (half-life of
2.15 days at pH 7 and 25°C). The
likely final hydrolysis products are methylsilanetriol and
Relevant human exposure to H-L3 can occur via the oral, inhalation
or dermal routes.
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).
The molecular weight of H-L3 (approximately 223) is close to the
favourable range for absorption but due to its highly lipophilic nature
and low water solubility the only means by which absorption from the
gastrointestinal tract is likely to occur is via micellar solubilisation.
Oral exposure to the hydrolysis products methylsilanetriol
and trimethylsilanol is potentially possible via the
environment. As they are both highly water soluble and have molecular
weights below 200 they therefore possess favourable characteristics for
absorption so should oral exposure occur then systemic exposure is
There was evidence of oral absorption in the repeated dose
toxicity study in rats for H-L3.
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. Therefore, with a log Kow of
6.2 and water solubility of 0.02 mg/l, dermal absorption is unlikely to
occur as H-L3 is not sufficiently soluble in water to partition from the stratum
corneum into the epidermis. Furthermore, 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.H-L3 is volatile so this would further reduce the
potential for dermal absorption.
There are no dermal toxicity studies available on H-L3 to check
for signs of dermal absorption.
However, there is a dermal absorption study for the structurally
related substance, L4, which has similar physicochemical properties to
H-L3 In this in vitro dermal penetration study (Dow
Corning Corporation, 2006) using human skin, conducted using a study
comparable to OECD 428 and to GLP almost all (99.9%) of the recovered14C-L4
volatilised from the skin surface and was captured in the charcoal
baskets placed above the exposure site. Only a small amount of applied
dose (0.06%) was found on the skin surface after 24 hours exposure or
remained in the skin after washing and tape stripping (0.03%). Little,
if any (0.001%), of the applied dose penetrated through the skin into
the receptor fluid. The total amount of dose absorbed was estimated to
be 0.03% of applied dose with virtually all of the absorbed test
substance retained in 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 independent
Using these values for H-L3results
in an extremely low blood:air partition coefficient (approximately
2.0E-04:1) so absorption across the respiratory tract
epithelium is likely to be restricted to micellar solubilisation. There
are no inhalation toxicity studies to check for signs of absorption.
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)
Using this for H-L3 predicts
that should systemic exposure occurit will distribute into the
main body compartments as follows: fat >> brain > liver ≈ kidney >
Table 1: tissue:blood partition coefficients
The repeated dose toxicity study showed effects in the liver and
kidney H-L3-related material must have distributed to these organs.
However, there were no reported effects in the brain.
There are no data regarding the metabolism of H-L3. Genetic
toxicity tests in vitro showed no observable
differences in effects with and without metabolic activation for H-L3.
There was no observable biodegradation in a ready biodegradation test.
A determinant of the extent of urinary excretion is the soluble fraction
in blood. QPSR’s as developed by DeJongh 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 ofH-L3 in blood is
<1E-04%. Therefore, H-L3 would not
be eliminated via the urine.
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