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EC number: 208-762-8
CAS number: 540-97-6
A well reported study (Dow Corning Corporation, 2004) conducted
according to an EPA guideline and in compliance with GLP found that a
single oral dose of labelled D6 (1000 mg/kg bw/day) given to male and
female rats was largely excreted as D6 in the faeces within 48 hours,
with less than 12% having been absorbed. Radioactivity recovered in the
urine (0.3-0.4% of the administered dose) was present exclusively as
polar metabolites; two major metabolites were identified
(methylsilanetriol (50-70%) and dimethylsilanediol (30-50%); females
tended to show more of the latter). Whole body autoradiography and mass
balance data indicate that the majority of the administered dose
remained in the gastrointestinal tract. Low levels of radioactivity were
present in organs and tissues (liver, fat, bone marrow) indicating some
absorption. Some metabolites were present in the blood. However,
considerable variability was seen in radioactivity levels in expired
volatiles (from 3.86% to 25.28% of administered dose) may be due to off
gassing from the faecal pellets that were not collected as intended but
remained inside the cage. This phenomenon could potentially give some
false high values for expired volatiles and absorption due to
partitioning from the faecal matter into the air. The entire
radioactivity in the expired volatiles was attributed to parent D6.
Metabolic profile evaluation of urine and faeces showed that the entire
radioactivity in the urine consisted of polar metabolites, whereas in
the faeces the majority was parent D6 with a trace non-polar metabolite.
A well conducted guideline in vitro study (Dow Corning Corporation,
2003) found no penetration by D6 through samples of human skin following
24-hour semi-occluded contact. Of the applied dose, 46.4% of D6 was
found on the skin; 40% was volatilised; 3% was found in the skin;
virtually none (0.003%) penetrated the skin. A further wash at 24 hours
indicated that D6 present in the skin did not penetrate the skin but
continued to evaporate.
There are no data regarding the absorption of D6 following inhalation;
however, inhalation is likely to be a minor route of exposure due to the
low vapour pressure (4.7 Pa at 25°C) of D6. This highly lipophilic
substance (log Kow= 8.87) might be taken up by micellar solubilisation,
particularly as it has poor water solubility (0.005 mg/l). Based on the
available sub-acute and sub-chronic toxicity studies for D6, it can be
concluded that D6 has no tendency to accumulate after repeated dosing.
While D6 is very lipophilic (log Kow= 8.87), it is readily eliminated by
biotransformation to polar metabolites. No genotoxicity was detected in
any of the in vitro mutagenicity tests in the absence or presence of
metabolising enzymes or in any in vivo tests, so no indication of the
importance of the metabolism of the registered substance was obtained
from these studies. Overall, it can be concluded that D6 has a low
In a single oral dose (450 mg/kg bw) kinetically-derived maximum dose
(KMD) study conducted via gavage, administered to groups of female
rabbits, absorption, metabolism, and excretion of 14C-D6 was
investigated (The Dow Chemical Company, 2018). The Group A rabbit was
administered 12C-D6 (non-radiolabelled; cold dose) on Gestation day (GD)
19 to determine the time point for maximum concentration (Cmax) in
plasma and to give preliminary information for analytical method
validation. The second group of animals (Group 1, n=2) was administered
14C-D6 (radiolabeled) on GD 26 to obtain samples for the definitive
portion of the study. Only one of the two rabbits was confirmed to be
pregnant as the other rabbit showed no signs of implantation (received
non-pregnant from the supplier). The Group 2 rabbit (received
non-pregnant from the supplier) was cold-dosed with 12C-D6 on GD 26. The
samples collected from this animal were stored as contingency samples
but were not analysed.
D6 derived-radioactivity was: 1) slowly absorbed and Cmax was at 48
hours (last blood collection), 2) metabolised (based on comparison of
14C-activity and parent plasma AUCs and 2% of the dose in urine) and 3)
eliminated in the feces with 56% of the administered dose recovered
within 48 hours post-dosing. Absorption and elimination rates could not
be calculated from this study and plasma profiling of metabolites was
not possible due to low levels of radioactivity in plasma samples.
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