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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

In vitro: Gene mutation (Bacterial reverse mutation assay / Ames test): negative with and without metabolic activation in Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537 or TA 102 (OECD TG 471) (BSL, 2015).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The read-across substance tris(isopropenyloxy)(vinyl)silane (CAS 15332-99-7) has been tested for mutagenicity to bacteria, in a study which was conducted according to the OECD TG 471, compliant with GLP (BSL, 2015). No evidence of a test-substance related increase in the number of revertants was observed with or without metabolic activation in Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537 or TA 102 in the initial plate incorporation assay or the repeat experiment using the pre-incubation method, up to limit concentrations. Appropriate positive, solvent and negative (water) controls were included and gave the expected results. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test.

Read-across justification

There are no available measured data fortri(isopropoxy)(vinyl)silane (CAS 18023-33-1)for genetic toxicity. Therefore, the Annex requirements are not fulfilled. This document describes the analogue approach for fulfilling this endpoint by read-across from the source substance,tris(isopropenyloxy)(vinyl)silane (CAS 15332-99-7),according to the Read-across Assessment Framework (RAAF)[1].

Read-across is proposed in accordance with RAAF Scenario 2: “This scenario covers the analogue approach for which the read-across hypothesis is based on different compounds which have the same type of effect(s). For the REACH information requirement under consideration, the effects obtained in a study conducted with one source substance are used to predict the effects that would be observed in a study with the target substance if it were to be conducted. The same type of effect(s) or absence of effect is predicted. The predicted strength of the effects may be similar or based on a worst case.”

The read-across justification is presented (Table 5.6.4) according to RAAF scenario 2 assessment elements (AE) as outlined in Table B1 of the RAAF1:

Table 1: RAAF scenario 2 assessment elements (AE) as given in Appendix B (Table B1) of the RAAF1

AE A.1

Characterisation of source substance

AE A.2

Link of structural similarity and differences with the proposed Prediction

AE A.3

Reliability and adequacy of the source study

AE 2.1

Compounds the test organism is exposed to

AE 2.2

Common underlying mechanism, qualitative aspects

AE 2.3

Common underlying mechanism, quantitative aspects

AE 2.4

Exposure to other compounds than to those linked to the prediction

AE 2.5

Occurrence of other effects than covered by the hypothesis and Justification

AE A.4

Bias that influences the prediction

 

1.  AE A.1 Identity and characterisation of the source substance

The source substance,tris(isopropenyloxy)(vinyl)silane (CAS 15332-99-7), has one vinyl functional silane with three isopropenyloxy groups. Its hydrolysis half-lives were estimated to be 0.3 h at pH 4, 0.4 h at pH 5, 6.6 h at pH 7 and 0.1 h at pH 9 and 20-25°C. These values are indicative of the upper limit for the hydrolysis half-lives of the submission substance because:

- The carbon-carbon double bond in the isopropenyloxy side-chain could weaken the Si-O bond electronically

- In addition, the carbon atom of the isopropenyloxy side-chain is sterically less hindering compared to isopropyloxy group.

Both of these effects are expected to speed up the hydrolysis rates of the source substance. 

Therefore, the result is reliable, sufficient to justify that the hydrolysis half-lives of the substance is <12 hours and are used for assessment purposes.

As the hydrolysis reaction may be acid or base-catalysed, the rate of reaction is expected to be slowest at around pH 7 and increase as the pH is raised or lowered. The calculated half-life of the substance at pH 2 and 20-25°C is therefore ≤0.003 h (approximately ≤11 seconds). Reaction rate increases with temperature therefore hydrolysis will be faster at physiologically relevant temperatures compared to standard laboratory conditions. Thus, for tris(isopropenyloxy)(vinyl)silane the hydrolysis half-life at 37.5ºC and pH 7 (relevant for lungs and blood) is approximately ≤2.4 hours. At 37.5ºC and pH 2 (relevant for conditions in the stomach following oral exposure), the half-life is approximately ≤4 seconds. However, it is not appropriate or necessary to attempt to predict accurately when the half-life is less than 5-10 seconds. As a worst-case it can therefore be considered that the half-life of the substance at pH 2 and 37.5°C is approximately 5 seconds. The hydrolysis products in this case are vinylsilanetriol andpropen-2-ol/acetone.

The hydrolysis of [tris(isopropenyloxy)(vinyl)silane] produces vinylsilanetriol and 3 molecules of propen-2-ol. Propen-2-ol is an enol type structure, which is in equilibrium with its keto tautomer, propanone (commonly called acetone). The equilibrium heavily favours the keto form at room temperature. Therefore, the hydrolysis products of [tris(isopropenyloxy)(vinyl)silane] are acetone (3 moles) and vinylsilanetriol (1 mole).

The source substance has LogKow of 3.8 at 20°C and vapour pressure of 5.3 Pa at 25°C.

 

2.  AE A.2 Link of structural similarities and differences with the proposed prediction

The target and source substance have similar physico-chemical properties as well as hydrolysis rates (Table 2). The target substancetri(isopropoxy)(vinyl)silane (CAS 18023-33-1), has a vinyl functional silane with three isopropoxy groups, while the source substancetris(isopropenyloxy)(vinyl)silane (CAS 15332-99-7)hasone vinyl functional silane with three isopropenylox groups. The hydrolysis half-lives for both substances have been predicted using a validated QSAR estimation method. Hydrolysis half-lives are estimated to be 0.3 h at pH 4, 0.4 h at pH 5, 6.6 h at pH 7 and 0.1 h at pH 9 and 20-25°C. These values are indicative of the upper limit for the hydrolysis half-lives of the source substance because:

- The carbon-carbon double bond in the isopropenyloxy side-chain could weaken the Si-O bond electronically

- In addition, the carbon atom of the isopropenyloxy side-chain is sterically less hindering compared to isopropyloxy group.

 Both of these effects are expected to speed up the hydrolysis rates of the source substance.

Therefore, the result is considered to be reliable, sufficient to justify that the hydrolysis half-lives of both substances is <12 hours and are used for assessment purposes.

The calculated half-life of both substances at pH 2 and 20-25°C is therefore ≤0.003 h (approximately ≤11 seconds). Thus, for tri(isopropoxy)(vinyl)silane and tris(isopropenyloxy)(vinyl)silane the hydrolysis half-life at 37.5ºC and pH 7 (relevant for lungs and blood) is approximately ≤2.4 hours. At 37.5ºC and pH 2 (relevant for conditions in the stomach following oral exposure), the half-life is approximately ≤4 seconds. However, it is not appropriate or necessary to attempt to predict accurately when the half-life is less than 5-10 seconds. As a worst-case it can therefore be considered that the half-life of the substances at pH 2 and 37.5°C is approximately 5 seconds.

The silicon-containing hydrolysis product for both the target and source substance is vinylsilanetriol. The non-Si hydrolysis products are isopropanol and acetone, respectively.

Reaction rate increases with temperature therefore hydrolysis will be faster at physiologically relevant temperatures compared to standard laboratory conditions.

As the hydrolysis reaction may be acid or base-catalysed, the rate of reaction is expected to be slowest at around pH 7 and increase as the pH is raised or lowered.

Table 2:Physico-chemical properties

Property

Target substance

Source substance

Substance name

tri(isopropoxy)(vinyl)silane

tris(isopropenyloxy)(vinyl)silane

CAS number

18023-33-1

15332-99-7

Hydrolysis half-life

≤2.4 hours at 37.5ºC and pH 7

≤2.4 hours at 37.5ºC and pH 7

Silanol hydrolysis product

vinylsilanetriol

vinylsilanetriol

Non-Si hydrolysis product

isopropanol

acetone

LogKow value

3.8 at 20°C (QSAR)

3.8 at 20°C (QSAR)

Vapour pressure

64 Pa at 25°C (QSAR)

5.3 Pa at 25°C (QSAR)

 

3.  AE A.3 Reliability and adequacy of the source study

Tris(isopropenyloxy)(vinyl)silane (CAS 15332 -99 -7) has been tested for mutagenicity to bacteria, in a study which was conducted according to the OECD TG 471, compliant with GLP (BSL, 2015). No evidence of a test-substance related increase in the number of revertants was observed with or without metabolic activation in Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537 or TA 102 in the initial plate incorporation assay or the repeat experiment using the pre-incubation method, up to limit concentrations. Appropriate positive, solvent and negative (water) controls were included and gave the expected results. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test.

 

4.  AE A.4 Bias that influences the prediction

Data on the source substance tris(isopropenyloxy)(vinyl)silane (CAS 15332-99-7) were read-across to the registered (target) substance tri(isopropoxy)(vinyl)silane (CAS 18023-33-1). The source substance and the target substance have similar chemical structure and physico-chemical properties. Both substances hydrolyse at the same rate, and produce vinylsilanetriol as the silicon-containing hydrolysis product. The non-silanol hydrolysis products are similar, therefore their toxicological properties are expected to be similar, with similar genotoxic effects. No other data for relevant substances were available.

5.  AE A.2.1 Compounds the test organism is exposed to

The source substance as well as the target substance hydrolyse very rapidly in contact with water. Therefore, the test organism is mainly exposed to their hydrolysis products,vinylsilanetriol and isopropanol or vinylsilanetriol and propen-2-ol, which will be predominantly in the keto form, acetone. Vinylsilanetriolhas been profiled using the OECD QSAR Toolbox and it does not contain any structural alerts for toxicity.

The toxicity of isopropanol has been evaluated in rats and mice by repeated inhalation and oral exposures. The only adverse effects - in addition to clinical signs - identified from these studies were to the kidney and included accumulation of hyaline (protein) droplets in kidney proximal tubule cells (males only, subchronic exposure) and an exacerbation of chronic progressive nephropathy, a spontaneous disease of unknown etiology common in aged rats (males and females, chronic exposure). In the mouse, minimal to mild effects to the kidney including renal tubular proteinosis and tubular dilation were observed following chronic exposure. Generally, these effects were only noted at high doses (> 500 ppm).

Data show that only high concentrations of acetone are required to cause death of animals via inhalation route. Acetone is not classified for acute oral, dermal or inhalation toxicity. No studies were located regarding death of animals after intermediate- or chronic-duration inhalation exposure to acetone. The only effect on the respiratory system observed in humans exposed to acetone vapours is irritation of the nose, throat, trachea, and lungs. The irritating properties of acetone in humans have been noted both in workers who were exposed to acetone occupationally and in volunteers under controlled laboratory conditions. Exposure of animals to much higher concentrations of acetone than those reported in humans has resulted in respiratory effects. The irritancy potential of acetone has been investigated in a number of studies. Published data indicates that the substance is irritating to eyes but not skin. Acetone has also been shown not to have any skin sensitisation or target organ toxicity properties. Moreover, acetone does not have any genotoxic potential. There is no indication of adverse reproductive effects in absence of generalized toxicity. Indications of developmental toxicity in mice and rats (reduction of foetal weights, increase of late resorptions) were only observed at exposure concentrations that induced significant maternal toxicity. Therefore, acetone is not considered to have adverse effects on reproduction or development.

6.  AE A.2.2 and A.2.3 Common underlying mechanism, qualitative and quantitative aspects

No toxicity data are available for the target substance tri(isopropoxy)(vinyl)silane (CAS 18023-33-1), therefore data are read-across from the structurally analogous substance tris(isopropenyloxy)(vinyl)silane (CAS 15332-99-7). Both substances hydrolyse at the same rate, and produce vinylsilanetriol as the silicon-containing hydrolysis product. The non-silanol hydrolysis products are similar, isopropanol for the target substance andpropen-2-ol/acetone for the source substance, and they have similar toxicity profiles.Following hydrolysis both the target and source substances produce one mole of vinylsilanetriol and one mole of isopropanol orpropen-2-ol/acetone, respectively. Moreover, they have similar physico-chemical properties. Thus, both substances are expected to have similar toxicity profiles.

7.  AE 2.4 Exposure to other compounds than to those linked to the prediction

Neither the target substance, tri(isopropoxy)(vinyl)silane (CAS 18023-33-1), nor the source substance, tris(isopropenyloxy)(vinyl)silane (CAS 15332-99-7), have impurities of toxicological concern.

8.  AE 2.5 Occurrence of Other Effects than Covered by the Hypothesis and Justification

Not relevant

 


[1]European Chemicals Agency (ECHA) (2015) Read-across Assessment Framework. Appendix B, Scenario 2.



Justification for classification or non-classification

Based on the available bacterial mutagenicity data, tris(isopropoxy)(vinyl)silane does not require classification according to Regulation (EC) No 1272/2008.