Registration Dossier

Administrative data

Description of key information

No reliable repeated-dose toxicity data are available for (3-chloropropyl)triethoxysilane, therefore good quality data for the analogous substance (3-chloropropyl)trimethoxysilane have been read-across.
In a 90-day inhalation study (DCC, 1993) in rats, conducted in accordance with OECD 413, the NOAEC was determined to be 100 ppm (813 mg/m3).
(3-Chloropropyl)trimethoxysilane was tested in an inhalation OECD 422 study (RCC, 2005), whole-body in rats, up to and including the highest concentration of 100 ppm. In this study there were no signs of general toxicity. Therefore based on these results the NOAEC was established to be at least 100 ppm (813 mg/m3).
A repeated application study via the dermal route is available for (3-chloropropyl)triethoxysilane. However, the purpose of this test was to determine irritation effects following repeated exposures, and did not meet the requirements for a repeated dose toxicity test.

Key value for chemical safety assessment

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEC
813 mg/m³

Additional information

No adequate repeated-dose 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 general systemic toxicity effects in rodents at the dose levels tested, it is considered that the observed toxicological effects are due to the action of the (3-chloropropyl)silyl moiety, although the specific toxicological mechanism cannot be determined from the available information. 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). No acute inhalation toxicity data are available for either substance, but acute oral and dermal LD50values for both substances in rats are >2000 mg/kg. It is therefore considered valid to read-across the results for the trimethoxy analogue to fill data gaps for the registered substance.

There are two reliability score 1 studies for repeated inhalation of (3-chloropropyl)trimethoxysilane. The 90-day study was selected as the key study as it tested over the longest duration.

In the key 90-day inhalation study, microscopic examinations did not reveal any adverse findings in females exposed to 0.5 or 5 ppm. Eight of 10 male animals in the 0.5 ppm exposure group were reported as normal. The two remaining male animals exhibited minimal chronic cystitis of the urinary bladder. Nine of 10 male animals were reported as normal in the 5.0 ppm exposure group. The remaining male animals exhibited minimal chronic cystitis of the urinary bladder. Treatment-related histopathological effects were observed in the 100 ppm group animals. Increased incidence of hyperplasia of the urinary bladder epithelium was noted in both sexes of this group.

It is not known whether the urinary bladder was inflated by a fixative before microscopic examination. Without inflation of the urinary bladder the relevance of the hyperplasia is questionable. Based onthe fact that the hyperplasia of the bladder was mild /minimal and in some cases associated with a minimal inflammation (cystitis) it can presumed that if the stimulus for the hyperplastic changes is removed the hyperplasia will resolve within a matter of weeks and the urinary bladder will return to a normal histologic appearance.A minimal/mild change of the urinary bladder not associated with any clinical symptoms or changes in urine parameters does not reflect a marked organ dysfunction. Therefore, the mild/minimal hyperplastic effects are not considered as adverse and the NOAEC is 100 ppm(813 mg/m3).

In a supporting study, (3-chloropropyl)trimethoxysilane was tested in an inhalation OECD 422 study (RCC, 2005), whole-body in rats, up to and including the highest concentration of 100 ppm. In this study there were no signs of general toxicity. Therefore based on these results the NOAEC was established to be at least 100 ppm (813 mg/m3).

Justification for classification or non-classification

Based on read-across from 3-chloropropyl(trimethoxysilane), there is no proposal to classify