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EC number: 242-272-5
CAS number: 18395-30-7
There are no repeated dose toxicity data on trimethoxy(2-methylpropyl)silane or its hydrolysis product, (2-methylpropyl)silanetriol, so good quality data for the related substance triethoxyisobutylsilane (CAS 17980-47-1) have been used to assess the general systemic toxicity of trimethoxy(2-methylpropyl)silane. In a rat 28-day oral gavage study conducted using a protocol similar to OECD 407 and to GLP (Huntingdon Research Centre, 1988) the NOAEL for triethoxyisobutylsilane was at least 1000 mg/kg bw/day, as there were no adverse toxicological findings at this the only dose tested. In a repeated nose-only inhalation study, conducted to OECD 413 and to GLP (Safepharm Laboratories, Ltd., 1992a) the NOAEC for triethoxyisobutylsilane was at least 2.54 mg/l in rats. The key and supporting studies for triethoxyisobutylsilane show that this substance has a low potential to cause adverse health effects.
There are no repeated dose toxicity data on
trimethoxy(2-methylpropyl)silane or its hydrolysis product, (2-methylpropyl)silanetriol,
so good quality data for the related substance triethoxyisobutylsilane
(CAS 17980-47-1) have been used to assess the general systemic toxicity
of trimethoxy(2-methylpropyl)silane. (Isobutyl and 2-methylpropyl are
To reduce animal testing REACH recommends to
make use of a read-across approach where appropriate based on the high
accordance in properties relevant for the specific endpoint. In
the case of repeated dose toxicity and reproductive toxicity relevant
properties are structural similarity as well as physical-chemical and
basic toxicological parameters in the same range. In the following
paragraphs the read-across approach for trimethoxy(2-methylpropyl)silane
is evaluated point by point.
After oral application,
trimethoxy(2-methylpropyl)silane and triethoxy(2-methylpropyl)silane
both hydrolyse very rapidly (half-life in the order of a few seconds) to
a common silanol hydrolysis product, (2-methylpropyl)silanetriol, which
is thus the systemically relevant species after oral application. It is
concluded that both parent substances behave in a very similar way by
this route of exposure. After
inhalation exposure the parent substance is seen as most relevant for
the toxicological evaluation. Based on the physico-chemical parameters
the read-across substance is seen as the worst case. The non-silanol
hydrolysis products, methanol and ethanol, are not expected to
contribute to any adverse effects for systemic or reproductive toxicity
at the relevant dose levels. This is discussed further below.
Analogue approach justification
(a) Structural similarity
The registration and read-across substances
are structurally similar, containing a branched butyl chain bound to
silicon and three alkoxysilane (-SiOX) groups. They
share a common silanol hydrolysis product, (2-methylpropyl)silanetriol.
These substances are part of an analogue
group of alkoxysilane substances containing alkyl groups. The
read-across substance was selected as the most appropriate based on
(b) Similar physicochemical characteristics
A data matrix is attached in Section 13 of
the IUCLID dossier, and the key physicochemical parameters are
17980 -47 -1
Si hydrolysis product
log Kow (parent)
log Kow (silanol hydrolysis product)
Water sol (parent)
Water sol (silanol hydrolysis product))
Vapour pressure (parent)
Hydrolysis t1/2 at pH 7 and 25°C
Hydrolysis t1/2 at pH 2 and 37.5°C
ca. 5 seconds
Hydrolysis t1/2 at pH 7 and 37.5°C
The registered substance,
trimethoxy(2-methylpropyl)silane, hydrolyses in contact with water,
generating (2-methylpropyl)silanetriol and methanol. The calculated
half-life at pH 2 and 37.5°C is approximately 5 seconds (see Section
5.1.2). Compared to the typical gastric emptying half-life for liquids
in the order of 11 - 30 minutes for humans and 77 minutes in rats (RIVM,
http: //www. rivm.
nl/interspeciesinfo/intra/human/stomach/db_human_stomach. jsp), several
to many hydrolysis half-lives would therefore have occurred and
absorption in the intestine would almost exclusively relate to
For the triethoxy read-across substances, gut
pH hydrolysis will occur very rapidly, with a half-life of approximately
9 seconds, but due to the higher lipophilicity and lower water
solubility of the parent substance it is possible that some unhydrolysed
material is absorbed onto food present in the stomach and thus the true
rate of degradation in the stomach is difficult to predict.
Nevertheless, reading across from ethoxy to methoxy can be considered as
worst case since uptake in the intestine would be higher for the ethoxy
compared to either methoxy or silanol species.
With respect to the inhalation route, the log
Kowof both substances is favourable for absorption across the
respiratory tract. Following uptake, rapid hydrolysis of the
registration substance followed by excretion via urine will occur
(calculated half-life 1.5 hours, as discussed in Section 5.1.2). For the
read-across substance, hydrolysis at blood temperature and pH is slower
(half-life 11 hours) therefore the potential for systemic distribution
is greater and can be considered a worst case i.e. hydrolysis is a
The existing 90-day repeated inhalation study
with triethoxy(2-methylpropyl)silane was performed at the highest
achievable vapour concentration for the substance. Although the more
volatile registration substance could achieve higher concentrations in
air than this value, additional testing at higher concentrations are not
considered to be appropriate since the available data clearly
demonstrate no adverse effects at a concentration that is in excess of
classification cut-offs for repeated inhalation toxicity according to
Regulation (EC) No 1272/2008. The low toxicity of the substance is also
demonstrated by the absence of effects in a repeated oral study.
(d) Similar acute toxicity
Acute oral and inhalation toxicity studies
are available for the registered substance and the read-across
substance. Clinical signs were observed at high dose levels indicating
systemic availability. In addition, an acute dermal toxicity study is
available for the read-across substance. In all cases, the test data
demonstrated that the substances were not acutely hazardous by any
The available data are summarised in the
Acute oral toxicity LD50(mg/kg bw)
>2000 (Hüls, 1993a)
>5000 (Huntingdon Research Centre, 1987a)
Acute dermal toxicity LD50(mg/kg bw)
>2000 (Huntingdon Research Centre, 1987b)
Acute inhalation toxicity LC50(mg/l)
>11 (Dow Corning Corporation, 1984)
>5.9 (Huntingdon Research Centre, 1990)
Additional information is given in a
supporting report attached in Section 13 of the IUCLID 5 dossier (PFA,
(e) Discussion of repeated
systemic toxicity of the non-silanol hydrolysis products
The repeated dose toxicity of the non-silanol
hydrolysis products, methanol and ethanol, has been extensively studied.
It is beyond the scope of this assessment to review all of the available
data in detail. However, the key findings from the disseminated REACH
dossiers and OECD SIAR reports (OECD 2004a and OECD 2004b) are reported
here to support read-across arguments.
The majority of repeated dose toxicity
information for methanol comes from inhalation studies in rats and
Generally effects noted include nasal
irritation in rats (but not monkeys), CNS depression, effects on body
and organ weight and in some cases effects on clinical chemistry
parameters. Studies were conducted up to significant doses and generally
effects when noted, are considered adverse only at upper end of the dose
ranges studied e. g 650 mg/m3in monkeys, 13000 mg/m3in
Methanol is not classified for repeated dose
toxicity in Annex VI of Regulation (EC) No 1272/2008.
Generally in repeat dose studies in animals
with ethanol very large doses are used, and often specific endpoints
relating to known effects in humans are the primary focus of such
studies. However, adverse effects on the liver have been noted in
animals but only at very high doses >8 g/kg/day.
Ethanol is not classified for repeated dose
toxicity in Annex VI of Regulation (EC) No 1272/2008.
Based on the similar chemical structure,
toxicokinetics and acute toxicity properties, it is considered
appropriate to read-across existing data from
triethoxy(2-methylpropyl)silane to trimethoxy(2-methylpropyl)silane. The
non-silanol hydrolysis products would not contribute toxic effects in
rats at the dose levels tested.
Based on the available oral and inhalation read-across repeated dose
toxicity studies, trimethoxy(2-methylpropyl)silane is not classified for
specific target organ toxicity following repeated exposure according to
Regulation (EC) No 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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