2,11-Dioxa-3,10-disiladodecane, 3,3,10,10-tetramethoxy-

Endpoint summary

Description of key information

A limited acute oral study conducted to GLP but without the required duration or extent of observation is supported by two good quality (guideline and GLP) repeated dose oral studies. The acute oral toxicity study (Dow Corning Corporation, 2009d) found no mortality or adverse effects in very restricted examinations 5 hours following administration of up to 2000 mg/kg bw of the test substance to rats.
A good quality (guideline and GLP) acute inhalation study found the LC50 of 1,6-bis(trimethoxysilyl)hexane in the rat to be in excess of the highest vapour concentration that could be generated under the conditions of this study, 0.042 mg/l (Dow Corning Corporation, 1993). This concentration, which was nominal and based on weight measurements, was not associated with any clear treatment-related effects.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

1 000 mg/kg bw

Quality of whole database:

The only acute oral study on 1,6-bis(triemethoxysilyl)hexane is a gavage study in rats, the aim of which was to determine the systemic availability of this material and/or its derivatives. This study, limited as an acute oral toxicity study, found no mortality or adverse effects in restricted examinations 5 hours following administration of up to 2000 mg/kg bw (Dow Corning Corporation, 2009d). No post-mortem examination was made.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

42 mg/m³ air

Quality of whole database:

A single generally well conducted guideline study found no deaths at the highest concentration of 1,6-bis(trimethoxysilyl)hexane that could be generated (0.042 mg/l, nominal).

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The animals in the available oral study all survived until their designated post dose blood collection time point (2h and 5 h) at all dose levels: 500 mg/kg (low dose), 1000 mg/kg (mid dose), and 2000 mg/kg (high dose) (Dow Corning Corporation, 2009). The study was designed for the purpose of systemic availability rather than as a definitive acute oral toxicity study. However, the lack of mortality in this study is supported by the key repeated dose oral study (Hita Laboratories, 1996, Dow Corning Corporation, 2010b)(see Section 5.6), in which no treatment-related deaths occurred. In a third available repeated dose oral toxicity study (WIL, 2015), two of ten animals died at 1000 mg/kg bw. On the basis of the available information it is possible to conclude that the acute oral LD₅₀is >1000 mg/kg bw.

 

The measured plasma concentrations of test material support the lack of acute toxicity effects (Dow Corning Corporation, 2009). The plasma concentrations of the test material were drastically reduced between the 2 and 5 hour time points, showing that the substance was being cleared effectively to this point. Since no adverse clinical effects or deaths occurred at the peak plasma concentrations or during several hours of reducing plasma levels, it is unlikely that they would occur later. Delayed effects cannot be ruled out, but they are less likely in the absence of absolutely no other effects.

 

It is not possible to derive a definitive LD₅₀ from the acute oral toxicity data that are available, but based on the weight of evidence it is considered unlikely that the substance would meet the criteria for classification for this endpoint.

In the case of the inhalation route, the highest vapour concentration that could be generated (0.042 mg/l, nominal) did not result in any deaths. The test material would not be classified based on these data.

Justification for selection of acute toxicity – oral endpoint
The only acute oral toxicity study identified (Dow Corning Corporation, 2009d) is limited in respect of the duration and extent of observations.

Justification for selection of acute toxicity – inhalation endpoint
The only acute inhalation study identified is a good quality study involving 4-hour exposure of rats to the highest concentration of 1,6-bis(trimethoxysilyl)hexane that could be generated under the test conditions, 0.042 mg/l, nominal (Dow Corning Corporation, 1993).

Justification for classification or non-classification

Based on the available information on the registered substance, no classification for acute toxicity is required in accordance with Regulation (EC) No 1272/2008.