Registration Dossier

Administrative data

Description of key information

In an acute inhalation study conducted using a protocol similar to OECD 403 and to GLP (Dow Corning Corporation, 1982), the LC50 for tetramethyl orthosilicate in Sprague-Dawley rats was 63 ppm (equivalent to 392 mg/m3). The main clinical sign observed in the post-exposure period (14 days) was gasping and coughing. Animals at the two higher exposure concentrations experienced loss of body weight. No deaths occurred at 31 ppm, there were three deaths at 50 ppm, and nine deaths at 88 ppm. All deaths occurred in the first week after exposure. The main macroscopic abnormality was lung damage and this was present in all animals. The extent of the damage ranged from small discrete foci to areas covering entire lobes of the lungs.
There are no oral data on tetramethyl orthosilicate, so good quality data on the structurally-related substance, tetraethyl orthosilicate have been read-across.The study reports an oral LD50 value of >2500 mg/kg which was determined in a reliable study conducted according to OECD guideline 423, and in compliance with GLP (Bayer AG, 2001). There were no clinical signs or test substance related deaths.
There are no reliable dermal data available.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 500 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
392 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

There is only one reliable inhalation study (Dow Corning Corporation, 1992), and no reliable dermal data regarding the acute toxicity of tetramethyl orthosilicate.

There are no oral data on tetramethyl orthosilicate, so good quality data on the structurally-related substance, tetraethyl orthosilicate (CAS No. 78-10-4) have been used for read-across for the oral route (Bayer AG, 2001). In the absence of measured data for tetramethyl orthosilicate, it is considered appropriate to use this result in support of the acute oral toxicity endpoint. The registered substance and tetraethyl orthosilicate are hydrolysed rapidly in the presence of moisture, with half-lives at pH 7 and 25 °C of <3 minutes and 4.4 hours respectively, generating silicic acid and methanol or ethanol. At the low pH of the stomach, hydrolysis will be very rapid for both substances, estimated to be approximately 5 seconds in both cases (see Section 4.1.1.1). Neither of the non-silicon containing hydrolysis products, methanol and ethanol, is acutely harmful to rats at the relevant dose levels (OECD 2004a and OECD 2004b), with reported LD50 values of at least 5628 and 15010 mg/kg respectively. Since the two substances share the common hydrolysis product, silicic acid, and no enhanced toxity would thus be expected from hydrolysis to methanol rather than ethanol at test concentrations relevant to current guideline limit values, it is considered appropriate to read-across the available acute oral result.


Justification for selection of acute toxicity – oral endpoint
The selected study is the most recent, reliable acute oral toxicity study available for the most relevant surrogate substance. It was conducted in accordance with an appropriate OECD test guideline and in compliance with GLP.

Justification for selection of acute toxicity – inhalation endpoint
The selected study is the most recent, reliable acute inhalation study available for the registration substance. It was conducted in accordance with an appropriate OECD test guideline and in compliance with GLP.

Justification for classification or non-classification

According to the available acute inhalation data tetramethyl orthosilicate is classified as 'Acute Toxic 1 (vapour)' with the hazard statement 'H330: Fatal if inhaled' according to Regulation (EC) No 1272/2008. It is not classified for the oral or dermal routes.