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EC number: 225-805-6
CAS number: 5089-70-3
No reproductive toxicity data are available
for (3-chloropropyl)triethoxysilane, therefore good quality inhalation
data for the analogous substance (3-chloropropyl)trimethoxysilane have
been read-across. Both substances share a common hydrolysis product,
(3-chloropropyl) silanetriol, with the other hydrolysis products being
ethanol and methanol respectively. Since neither methanol nor ethanol
would contribute to reproductive toxicity effects in rodents at the dose
levels tested, it is considered that any observed toxicological effects
would be due to the action of the (3-chloropropyl) silyl moiety. Both
substances have log Kowin the range that is favourable for
absorption across the respiratory tract (ethoxy log Kow= 3.40
and methoxy log Kow= 1.97). It is therefore considered valid
to read-across the results for the trimethoxy analogue to fill data gaps
for the registered substance.
The OECD 422 study is the only study
available for the reproductive toxicity endpoint. In this study, (3-chloropropyl)trimethoxysilane
was tested whole-body in rats, up to and including the highest
concentration of 100 ppm. There were no signs of adverse effects on
reproduction and development.
There are two reliability score 1 studies for repeated inhalation
of (3-chloropropyl)-trimethoxysilane to fulfil the requirements of Annex
IX 8.6.2 which provide supporting information. The 90-day study was
selected as the key study as it was tested over the longest duration. In
this study, microscopic examinations did not reveal any adverse findings
in females exposed to 0.5 or 5 ppm. Treatment-related histopathologic
effects were observed in the 100 ppm group animals; however, these
effects were not considered adverse (see Section 5.6) and there were no
microscopic changes on reproductive organs/tissues at any dose
Based on the above mentioned studies
(3-chloropropyl)triethoxysilaneis not classifiedfor
reproductive toxicity. A NOAEC of 813 mg/m³ was determined for
reproductive and developmental toxicity for the most appropriate route
of exposure (inhalative).
An additional 2-generation reproductive toxicity study is not
considered necessary because:
- The available one-generation studies do not indicate
reproductive toxic effects at the highest dose tested.
- There is no particular concern with regard to exposure. Only
industrial uses are known and included in the dossier (production,
monomer, intermediate, non-metal surface treatment and laboratory
reagent). The risk characterization ratio for the worst case exposure
using ECETOC and ECHA defaults has been calculated as 4.3 x 10-2.
-Increasing evidence has been published that the 2-generation test
can be replaced by a one generation study or an even more reduced test.
At an OECD meeting on 21–23 October 2009 in Paris, Elizabeth Méndez, a
toxicologist at the US Environmental Protection Agency (EPA), presented
an analysis of 350 substances showing that only one would not have been
identified as dangerous had a second-generation study not been
performed. Another study (G. Janeret al. Reprod. Toxicol.24,97–102;
2007) found that in 176 multi-generation studies on 148 substances,
there were only three instances in which reproductive toxicity was not
identified until the second-generation test.
The registered substance (3-chloropropyl)triethoxysilane was tested in an oral OECD 414 developmental toxicity study (BSL, 2014) in which the maternal and foetal NOAELs were considered to be 300 mg /kg bw/day. Maternal effects at 1000 mg/kg bw/day included lower body weight, body weight gain and food consumption and were considered to be adverse. Foetal effects in the 1000 mg/kg bw/day group included skeletal variations such as delayed ossification and lower litter weight, which were considered to be attributable to the maternal effects. Other skeletal variations noted at this dose included wavy ribs and bent scapula. The increased incidence of skeletal variations noted together with the lower litter weight was considered to be adverse at 1000 mg/kg bw/day.
In the key developmental toxicity study (BSL,
2014) administration of (3 -chloropropyl)triethoxysilane at
doses of 0, 100, 300 or 1000 mg/kg bw/day by oral gavage to pregnant
female Wistar rats from gestation days 5 to 19 resulted in lower body
weight, body weight gain and food consumption at 1000 mg/kg bw/day and
were considered to be adverse. Lower terminal body weight, uterus weight
and mean total litter weight were also noted at this dose.
Increased incidences of skeletal findings such as delayed ossification
and lower litter weight recorded at 1000 mg/kg bw/day were considered to
be attributable to the maternal effects and not adverse. An increased
incidence of wavy ribs and bent scapula was also noted at this dose and
these findings are recognised as part of chondrodystrophy syndrome in
rats and have been demonstrated to be post-natally reversible and
therefore also not adverse (Carney and Kimmel (2007), De
Schaepdrijver et al. (2014), Mitchard and Stewart). However, the
increased incidence of skeletal variations noted together with the lower
litter weight was considered to be adverse at 1000 mg/kg bw/day.
Therefore the maternal and foetal No-Observed-Adverse-Effect-Levels
(NOAEL) were both considered to be 300 mg/kg bw/day.
In a supporting developmental screening study
conducted by the inhalation route with read-across substance (3-chloropropyl)
trimethoxysilane (RCC, 2005) no developmental effects were noted and the
foetal No-Observed-Adverse-Effect-Concentration (NOAEC) was considered
to be 813 mg/m3. Both the registered and read-across
substances share a common hydrolysis
product, (3-chloropropyl) silanetriol, with the other hydrolysis
products being ethanol and methanol respectively. Since neither methanol
nor ethanol would contribute to developmental toxicity effects in
rodents at the dose levels tested, it is considered that any observed
toxicological effects would be due to the action of the (3-chloropropyl)
silyl moiety. Both substances have log Kow in the range that
is favourable for absorption across the respiratory tract (ethoxy log Kow
of 3.40 and methoxy log Kow of 1.97). It is therefore
considered valid to read-across the results for the trimethoxy analogue
to provide additional screening developmental toxicity information.
Carney EW, Kimmel CA. Interpretation of skeletal variations for human
risk assessment: delayed ossification and wavy ribs. Birth Defects
Research (Part B) 80 (2007) 473–96.
Schaepdrjver L, Delille P, Geys H, Boehringer-Shahidi,Vanhove C. In vivo
longitudinal micro-CT study of bent long bones rat offspring.
Reproductive Toxicology 46 (2014) 91-97
T, Stewart J. Reduced post-natal versus pre-natal incidence of bent long
bones and scapulae in a preliminary investigation using the Han Wistar
rat. Toxicology 45 (2014) 39-44
Based on the available data 3 -chloropropyltriethoxysilane does not
require classification for for reproductive or developmental toxicity
according to Regulation (EC) 1272/2008.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
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