Tetrapropyl orthosilicate

Endpoint summary

Additional information

Data are available from a bacterial mutagenicity study on tetrapropyl orthosilicate. No further information is available for the registered substance, however, reliable data are available for the closely related substance, tetraethyl orthosilicate (CAS 78-10-4). Tetrapropyl orthosilicate and tetraethyl orthosilicate both hydrolyse to silicic acid. Tetrapropyl orthosilicate hydrolyses rapidly (hydrolysis half-life 6.7 h at pH 7 (measured); tetraethyl orthosilicate also hydrolyses rapidly (hydrolysis half-life 4.4 h at pH 7 (measured). The non-silicon containing hydrolysis products are propanol and ethanol, respectively. Neither of these substances is known to be genotoxic; ethanol is not associated with genetic toxicity (OECD 2004); negative results are reported for in vitro bacterial and mammalian mutagenicity and for in vitro cytogenicity in the disseminated IUCLID for propan-1-ol. It is therefore considered that read-across between these substances is scientifically justified. Additional information is given in a supporting report (PFA (2013aa)) attached in Section 13 of the IUCLID 5 dossier.

Tetraethyl orthosilicate was chosen as read-across substance as it has the same hydrolysis product as registered substance and neither substance has any functional groups that are associated with genetic toxicity.

Tetrapropyl orthosilicate has been tested according to OECD 471 and under GLP conditions (Leuschner (2002). The study is considered to be reliability 1. No increase in the number of revertants was observed when the substance was tested to limit concentration in Salmonella typhimurium strains TA 98, TA 100, TA 102, TA 1535 and TA1537 in an initial plate incorporation test, with and without metabolic activation. A repeat assay using the preincubation method reproduced the result. Appropriate positive and solvent controls were included and gave expected results. It is concluded that the test substance is not mutagenic to bacteria under the conditions of the test. A supporting study also found no evidence of mutagenicity to bacteria (DCC 1984). The most reliable study was selected as key.

The analogue substance tetraethyl orthosilicate has been tested in a reliable study according to OECD 473 under conditions of GLP (Gudi, R., Brown, C. (2002). No test-substance related increase in the number of structural or numerical chromosome aberrations in CHO cells was observed with or without metabolic activation when tested up to cytotoxic concentrations. Appropriate solvent and positive controls were concluded and gave expected results. It is concluded that the test substance is negative for the induction of chromosome aberrations under the conditions of the test.

Data are also available for tetraethylorthosilicate for mutagenicity to Chinese hamster ovary cells from a reliable study according to a protocol that is similar to OECD TG 476 (Slesinski (1981)). Weak responses (increase in the number of revertants relative to the solvent control) were obtained at the 1.4 and 1.1 µg/ml concentrations tested without activation. The biological significance of these results was doubtful because the effects were produced at non-consecutive doses and were within the range of variations observed in historical negative control data. It is therefore considered that the test substance is negative for the induction of mutations in mammalian cells under the conditions of this test.

Testing in vivo is not indicated as all the in vitro results were negative.

Justification for selection of genetic toxicity endpoint
The bacterial mutagenicity key study was selected on the basis of reliability. It was conducted in accordance with an appropriate OECD guideline and with GLP. The key studies for mammalian mutagenicity and cytogenicity endpoints were the available studies for these endpoints for the surrogate substance which was selected on the basis of structural similarity to the registered substance. They were conducted in accordance with an appropriate OECD guideline, or similar protocol. The cytogenicity study was conducted in accordance with GLP.

Short description of key information:
Information is available from a bacterial mutagenicity study on tetrapropyl orthosilicate. No further information is available for the registered substance, however, reliable data are available for the closely related substance, tetraethylorthosilicate (CAS 78-10-4).

In vitro:
Gene mutation (Bacterial reverse mutation assay / Ames test): negative with and without activation in Salmonella typhimurium strains TA 98, TA 100, TA 102, TA 1535 and TA1537 (OECD TG 471).
Cytogenicity in mammalian cells: read-across from analogous substance tetraethylorthosilicate (CAS 78-10-4): negative in Chinese hamster ovary cells (OECD TG 473).
Mutagenicity in mammalian cells: read-across from analogous substance tetraethylorthosilicate (CAS 78-10-4): negative in Chinese hamster ovary cells (similar to OECD TG 476).

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the available in vitro genotoxicity data, tetrapropyl orthosilicate is not classified for mutagenicity according to Regulation (EC)1272/2008.