Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via inhalation route
Dose descriptor:
NOAEC
813 mg/m³
Additional information

No reproductive 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 reproductive toxicity effects in rodents at the dose levels tested, it is considered that any observed toxicological effects would be due to the action of the (3-chloropropyl) silyl moiety. 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). It is therefore considered valid to read-across the results for the trimethoxy analogue to fill data gaps for the registered substance.

The OECD 422 study is the only study available for the reproductive toxicity endpoint. In this study, (3-chloropropyl)trimethoxysilane was tested whole-body in rats, up to and including the highest concentration of 100 ppm. There were no signs of adverse effects on reproduction and development.

There are two reliability score 1 studies for repeated inhalation of (3-chloropropyl)-trimethoxysilane to fulfil the requirements of Annex IX 8.6.2 which provide supporting information. The 90-day study was selected as the key study as it was tested over the longest duration. In this study, microscopic examinations did not reveal any adverse findings in females exposed to 0.5 or 5 ppm. Treatment-related histopathologic effects were observed in the 100 ppm group animals; however, these effects were not considered adverse (see Section 5.6) and there were no microscopic changes on reproductive organs/tissues at any dose concentration.

Based on the above mentioned studies (3-chloropropyl)triethoxysilaneis not classifiedfor reproductive toxicity. A NOAEC of 813 mg/m³ was determined for reproductive and developmental toxicity for the most appropriate route of exposure (inhalative).

An additional 2-generation reproductive toxicity study is not considered necessary because:

- The available one-generation studies do not indicate reproductive toxic effects at the highest dose tested.

- There is no particular concern with regard to exposure. Only industrial uses are known and included in the dossier (production, monomer, intermediate, non-metal surface treatment and laboratory reagent). The risk characterization ratio for the worst case exposure using ECETOC and ECHA defaults has been calculated as 4.3 x 10-2.

-Increasing evidence has been published that the 2-generation test can be replaced by a one generation study or an even more reduced test. At an OECD meeting on 21–23 October 2009 in Paris, Elizabeth Méndez, a toxicologist at the US Environmental Protection Agency (EPA), presented an analysis of 350 substances showing that only one would not have been identified as dangerous had a second-generation study not been performed. Another study (G. Janeret al. Reprod. Toxicol.24,97–102; 2007) found that in 176 multi-generation studies on 148 substances, there were only three instances in which reproductive toxicity was not identified until the second-generation test.

- Two generation tests demand sacrificing a significant amount of test animals which appears disproportionate considering the hazard profile of this substance as demonstrated by the existing data.

Short description of key information:
No reproductive toxicity data are available for (3-chloropropyl)triethoxysilane; therefore good quality data for the analogous substance (3-chloropropyl)trimethoxysilane have been read across.

(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 adverse effects on reproduction. Therefore based on these results the NOAEC was established to be at least 100 ppm (813 mg/m3).

Effects on developmental toxicity

Description of key information
The registered substance (3-chloropropyl)triethoxysilane was tested in an oral OECD 414 developmental toxicity study (BSL, 2014) in which the maternal and foetal NOAELs were considered to be 300 mg /kg bw/day. Maternal effects at 1000 mg/kg bw/day included lower body weight, body weight gain and food consumption and were considered to be adverse. Foetal effects in the 1000 mg/kg bw/day group included skeletal variations such as delayed ossification and lower litter weight, which were considered to be attributable to the maternal effects. Other skeletal variations noted at this dose included wavy ribs and bent scapula. The increased incidence of skeletal variations noted together with the lower litter weight was considered to be adverse at 1000 mg/kg bw/day.
Effect on developmental toxicity: via oral route
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
300 mg/kg bw/day
Study duration:
subacute
Species:
rat
Effect on developmental toxicity: via inhalation route
Additional information

In the key developmental toxicity study (BSL, 2014) administration of (3 -chloropropyl)triethoxysilane at doses of 0, 100, 300 or 1000 mg/kg bw/day by oral gavage to pregnant female Wistar rats from gestation days 5 to 19 resulted in lower body weight, body weight gain and food consumption at 1000 mg/kg bw/day and were considered to be adverse. Lower terminal body weight, uterus weight and mean total litter weight were also noted at this dose.

 

Increased incidences of skeletal findings such as delayed ossification and lower litter weight recorded at 1000 mg/kg bw/day were considered to be attributable to the maternal effects and not adverse. An increased incidence of wavy ribs and bent scapula was also noted at this dose and these findings are recognised as part of chondrodystrophy syndrome in rats and have been demonstrated to be post-natally reversible and therefore also not adverse (Carney and Kimmel (2007), De Schaepdrijver et al. (2014), Mitchard and Stewart). However, the increased incidence of skeletal variations noted together with the lower litter weight was considered to be adverse at 1000 mg/kg bw/day. Therefore the maternal and foetal No-Observed-Adverse-Effect-Levels (NOAEL) were both considered to be 300 mg/kg bw/day.

In a supporting developmental screening study conducted by the inhalation route with read-across substance (3-chloropropyl) trimethoxysilane (RCC, 2005) no developmental effects were noted and the foetal No-Observed-Adverse-Effect-Concentration (NOAEC) was considered to be 813 mg/m3. Both the registered and read-across 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 developmental toxicity effects in rodents at the dose levels tested, it is considered that any observed toxicological effects would be due to the action of the (3-chloropropyl) silyl moiety. Both substances have log Kow in the range that is favourable for absorption across the respiratory tract (ethoxy log Kow of 3.40 and methoxy log Kow of 1.97). It is therefore considered valid to read-across the results for the trimethoxy analogue to provide additional screening developmental toxicity information.

Carney EW, Kimmel CA. Interpretation of skeletal variations for human risk assessment: delayed ossification and wavy ribs. Birth Defects Research (Part B) 80 (2007) 473–96.

De Schaepdrjver L, Delille P, Geys H, Boehringer-Shahidi,Vanhove C. In vivo longitudinal micro-CT study of bent long bones rat offspring. Reproductive Toxicology 46 (2014) 91-97

Mitchard T, Stewart J. Reduced post-natal versus pre-natal incidence of bent long bones and scapulae in a preliminary investigation using the Han Wistar rat. Toxicology 45 (2014) 39-44


Justification for selection of Effect on developmental toxicity: via oral route:
Study was conducted according to an appropriate guideline and in compliance with GLP.

Justification for classification or non-classification

Based on the available data 3 -chloropropyltriethoxysilane does not require classification for for reproductive or developmental toxicity according to Regulation (EC) 1272/2008.