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EC number: 221-066-9
CAS number: 2996-92-1
Repeated dose toxicity:
Repeated dose toxicity: OECD TG 422 in rats: LOAEL = 100 mg/kg bw/day.
At all dose levels (100, 250 and 500 mg/kg bw/day) during the
histopathology examination, perivascular lymphoid cell infiltration and
transitional cell hyperplasia of the urinary bladder were observed in
males and females.
Repeated dose toxicity: OECD TG 412 in rats: NOAEC > 620 mg/m³.
No systemic toxicity was observed after repeated exposure to
concentrations up to 620 mg/m³.
Dermal toxicity: no measured data are available.
urea and cholesterol can both be indicative for kidney effects.
At all dose levels (100, 250 and 500 mg/kg
bw/day) during the histopathology examination, perivascular lymphoid
cell infiltration and transitional cell hyperplasia of the urinary
bladder were observed in males and females.Therefore, based on the
findings in urinary bladder noted in all test item-treated groups, a
general NOAEL could not be established.
Studies were chosen as key when the available study was of relevance and
of sufficient quality for classification, labelling and for risk
For the oral route, a reliable key OECD 422 combined repeated
dose/reproductive and developmental screening study is available for
trimethoxyphenylsilane. This study is a valid investigation of the
toxicological effects resulting from repeated oral-gavage administration
of the test item to male and female rats for at least 28 days. The test
item was administered in dried and deacidified corn oil as vehicle at
dosages of 100, 250, and 500 mg/kg body weight/day, and controls
received the vehicle only. At 250 mg/kg bw/day, treatment with the test
item caused an increase in the concentration of urea and bile acids.
Multifocular tubular degeneration/regeneration and transitional
hyperplasia of kidney were noted in males and females. During the
macroscopic examination, the urinary bladder was observed to be
thickened in males and females at all dose levels. This correlated with
the findings noted at the microscopic level. At all dose levels (100,
250 and 500 mg/kg bw/day) during the histopathology examination,
perivascular lymphoid cell infiltration and transitional cell
hyperplasia of the urinary bladder were observed in males and females.
Therefore, based on the findings in urinary bladder noted in all test
item-treated groups, a general NOAEL could not be established. The LOAEL
was 100 mg/kg bw/day (SEHSC, 2009).
For the structural analogue triethoxy(phenyl)silane (CAS 780 -69 -8), a
reliable combined repeated dose/reproductive and developmental screening
study according to OECD 422 by oral route is available (Eurofins, 2019).
The test substance was administered in corn oil as vehicle at dosages of
40, 120, and 360 mg/kg body weight/day, and controls received the
vehicle only. Two recovery groups were included which were treated with
vehicle only or 360 mg test substance/kg bw/day.
One rat from the high dose group with 360 mg/kg bw/day was sacrificed
moribund on day 15. As to histopathological evaluation, it is assumed
that the moribund condition of the animal was a consequence of backflow
nephrosis and considered to be treatment-related. There were no
treatment-related clinical signs throughout the treatment period up to
360 mg/kg bw/day. There were no treatment-related functional observation
changes at the end of the treatment and recovery periods.
Treatment-related adverse effects of the test item were found on male
and female body weight and food consumption mainly at 360 mg/kg bw/day.
Haematology and coagulation, clinical biochemistry, and urinalysis
parameters were not affected by the treatment in both genders. At
scheduled necropsy, treatment-related gross macroscopic findings were
noted in kidneys and urinary bladder. Changes in respective organ
weights are considered to be treatment related at 120 and 360 mg/kg
bw/day. Test item-related gross lesions consisted in the kidneys of
renal pelvis dilatation (in one decedent recovery male it was described
as enlarged kidney and abnormal consistency). Histologically, the
incidence of pelvic dilatation increased in males at 40 up to 360 mg/kg
bw/day, and tubular dilatation was noted in almost all males at 360
mg/kg bw/day. The findings at 120 and 360 mg/kg bw/day, degenerative and
inflammatory lesions consisted of increased incidences and/or severities
of tubular basophilia, pyelitis, and, at 360 mg/kg bw/day, of
interstitial inflammation, interstitial fibrosis and papillary necrosis.
Furthermore, there was urothelial hyperplasia in two males at 120 mg/kg
bw/day, and in all males and four females at 360 mg/kg bw/day. Males
were more affected than females. The findings were still present after
the recovery period.
Pelvic dilatation is common in rats, as are the single incidences of
tubular basophilia at minor severity degrees. Therefore, findings at 40
mg/kg bw/day are not considered to be test item-related. There were also
ureter dilatation and thickening of the urinary bladder wall noted at
necropsy. Histologically, these alterations correlated with the ureters
of one male at 120 mg/kg bw/day, and with all males and three females at
360 mg/kg bw/day to dilatation, associated in some cases at 360 mg/kg
bw/day with mucosal and/or muscularis hyperplasia, and/or inflammation.
The highest degree of mucosal hyperplasia was noted at the most distal
portions of the ureters.
In the urinary bladder, there was diffuse urothelial hyperplasia in both
sexes at 120 and 360 mg/kg bw/day. This finding was associated with an
increased incidence and severity of mononuclear cell foci. In one male,
the urethra was found in its full length and diameter within the
prostate tissue. The urothelium showed moderate hyperplasia accompanied
by a minimal subacute inflammation. At some locations, in mucosal folds,
precipitation of an unknown material was seen. The precipitation was
noted by chance only due to the unusual circumstances of observing the
urethra within the prostate gland. This finding explains the higher
grading of urothelial hyperplasia at more distal parts of the urinary
system. Precipitation is deemed to cause irritative effects to the
urothelium that causes backflow nephrosis with dilatation of the renal
pelvis (hydronephrosis) and tubular dilatation (nephrohydrosis).
Stress-related lesions were noted in the adrenals by cortical
hypertrophy and in the thymus by increased thymic atrophy.
Based on the findings in the urinary tract, the NOAEL for
triethoxy(phenyl)silane in this study for general toxicity is considered
to be 40 mg/kg bw/day.
Comparing the findings in the screening study with both substances it
can be seen that their target organ is the same and their toxicity is in
the same range. Thus, read across between both substances can be
In a key study, an acceptable repeated inhalation toxicity study similar
or equivalent to the OECD TG 412, but not in compliance with GLP, the
test item was administered to Sprague-Dawley rats (10 per sex and dose)
by whole body exposure at concentrations of 9.5, 52.4, and 76.5 ppm,
corresponding to 0.077, 0.425, and 0.620 mg/l for 6.5 hours per day, 5
days/week for a total of 28 days.
There were no compound related effects in mortality, clinical signs,
body weight, food consumption, haematology, clinical chemistry, organ
weights, or gross and histologic pathology.
Based on no systemic toxicity after repeated exposure to concentrations
up to 0.62 mg/l, the NOAEC was set at > 620 mg/m³, which was the highest
dose tested (Bio-Research Laboratories, 1980).
oral exposure there were signs of adverse effects in the urinary bladder
of rats at all doses and therefore it is proposed that
trimethoxyphenylsilane has to be classified for STOT-RE Cat 2, with the
hazard statement 'H373: May cause damage to organs according to
Regulation (EC) 1272/2008.
available data on repeated dose toxicity of the registered substance by
the inhalation route do not meet the criteria for classification
according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and is
therefore conclusive but not sufficient for classification of the
data are available for the dermal route. However, dermal absorption of
the submission substance is expected to be low 0.004 mg/cm²/h (DERMWIN
V2.00.2009). Generally, absorption of xenobiotica via the inhalation
route is higher than via the dermal route, as the skin is known to have
a barrier function and the lung is an exchange organ. Since no specific
target organ toxicity was observed after inhalation exposure, a hazard
via the dermal route can be excluded.
conclusion, the hazard statement "H373: May cause damage to urinary
bladder after prolonged or repeated oral exposure" will be applied.
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