3-(dimethoxymethylsilyl)propyl methacrylate

Endpoint summary

Description of key information

The key acute oral toxicity studies were read across from the analogous substances 3-(trimethoxysilylpropyl) methacrylate (CAS 2530-85-0) and [dimethoxy(methyl)silyl]methyl methacrylate (CAS 121177-93-3). The LD50 values were reported to be >2000 mg/kg for both substances (Dow Corning Corporation, 2001; Bioservice, 2003a).

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Study was conducted in accordance with an appropriate OECD guideline and in compliance with GLP.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The first acute oral toxicity study was read across from the analogous substance 3-(trimethoxysilylpropyl) methacrylate (CAS 2530-85-0). The study was conducted according to OECD 423, reporting an LD50 value of >2000 mg/kg, determined for male and female rats (Dow Corning Corporation, 2001).

Salivation was observed in all females immediately after dosing and noted for up to 1 hour. There were no clinical signs in males. Low bodyweight gain was recorded for one female on Day 15. No abnormalities were detected at necropsy.

The second acute oral toxicity study was read-across from [dimethoxy(methyl)silyl]methyl methacrylate. The study was conducted according to an appropriate OECD Test Guideline and in compliance with GLP, and reported an LD50 value greater than 2000 mg/kg bw for [dimethoxy(methyl)silyl]methyl methacrylate.

In the study 300 or 2000 mg/kg bw of test substance in corn oil was administered to 3 female rats per dose. The test animals were subject to a careful clinical examination performed several times on the day of dosing. Animals were observed once a day thereafter. No mortality or clinical signs of toxicity were observed in any of the test animals as well as no changes in body weight gain during a 14 -day observation period. No macroscopic abnormalities were observed in any of the test animals at necropsy.

Read-across justification

There are no available measured data for 3-[dimethoxy(methyl)silyl]propyl methacrylate (CAS 14513-34-9) for acute toxicity. This document describes the analogue approach for fulfilling this endpoint by read-across from two source substances, 3-trimethoxysilylpropyl methacrylate (CAS 2530-85-0) and [dimethoxy(methyl)silyl]methyl methacrylate (CAS 121177-93-3), according to the Read-across Assessment Framework (RAAF).

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 1) 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 first source substance, 3-trimethoxysilylpropyl methacrylate (CAS 2530-85-0), has a silicon atom bound to three methoxy groups, and one propyl methacrylate group. Its measured hydrolysis half-lives are 0.018 h at pH 4, 1.87 h at pH 7 and 0.068 h at pH 9 and 20°C.

At pH 2 (the known pH of the stomach), the hydrolysis rate is approximately 5 seconds. The products of hydrolysis are 3-(trihydroxysilyl)propyl methacrylate (1 mole) and methanol (3 moles).

The source substance has log Kow of 2.1 at 20°C (QSAR), water solubility of 2200 mg/l at 20°C (QSAR) and vapour pressure of 2.3 Pa at 25°C (QSAR).

The second source substance [dimethoxy(methyl)silyl]methyl methacrylate (CAS 121177-93-3), has a silicon atom bound to two methoxy groups, one methyl group and one methyl methacrylate group. Its predicted hydrolysis half-lives are 1.8 h at pH 7, 0.2 h at pH 4, 0.04 h at pH 9 and 25°C.

The hydrolysis products in this case are [dihydroxy(methyl)silyl]methyl methacrylate (1 mole) and methanol (2 moles). The source substance has a log Kow of 2.4 at 20°C, vapour pressure of 37 Pa at 25°C and water solubility of 2500 mg/l.

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

The registration and the first read-across substance, 3-trimethoxysilylpropyl methacrylate (CAS 2530-85-0), are structurally similar and are members of an analogue group of alkoxysilanes and silanols containing a methacrylate group. Both substances have a propyl methacrylate side-chain attached to the silicon atom.

In addition to the propylmethacrylate side-chain, the target substance has two methoxy groups and one methyl group bound to silicon. The source substance has three methoxy groups bound to silicon. Therefore, the difference between the two structures is that one of the three methoxy groups in the source substance is replaced by a methyl group in the target substance. The silanol hydrolysis products are 3-[dihydroxy(methyl)silyl]propyl methacrylate and 3-(trihydroxysilyl)propyl methacrylate for the registered substance and read-across substance, respectively. The common non silanol hydrolysis product is methanol.

These two substances both hydrolyse in similar rate to a disilanol (1 mole) or a trisilanol (1 mole) and methanol (2 or 3 moles). The hydrolysis products of these two substances are structurally similar in the same way as the parent substances. They both have a propyl methacrylate side-chain. The difference is that the registered substance has a methyl group attached to the silicon atom.

The source substance, [dimethoxy(methyl)silyl]methyl methacrylate (CAS 121177-93-3), and the target substance, 3-[dimethoxy(methyl)silyl]propyl methacrylate (CAS 14513-34-9), are structurally similar. They are both dimethoxy silanes with one methyl group. The difference is that the source substance has a methyl methacrylate side-chain attached to the silicon atom, while the target substance has a propyl methacrylate side-chain instead.

These two substances both hydrolyse in similar rate to a disilanol (1 mole) and methanol (2 moles). The hydrolysis products of these two substances are structurally similar in the same way. They are both disilanols with one methyl side-chain. The difference is that the source substance has a methyl methacrylate side-chain, whereas the target substance has propyl methacrylate side-chain (see Table 1).

Table 2: Physico-chemical properties  

Property		Target substance		Source substance		Source substance
Substance name		3-[Dimethoxy(methyl)silyl]propyl methacrylate		3-trimethoxysilylpropyl methacrylate (CAS 2530-85-0)		[dimethoxy(methyl)silyl]methyl methacrylate
CAS number		14513-34-9		2530-85-0		121177-93-3
Hydrolysis half-life		5 seconds at pH 2 and 25ºC		5 seconds at pH 2 and 25ºC		7 seconds at pH 2 and 25ºC
Silanol hydrolysis product		3-[dihydroxy(methyl)silyl]propyl methacrylate		3-(trihydroxysilyl)propyl methacrylate		[dihydroxy(methyl)silyl]methyl methacrylate
Non-Si hydrolysis product		methanol		methanol		methanol
LogKow value		3.4 at 20°C (QSAR)		2.1 at 20°C (QSAR)		2.4 at 20°C (QSAR)
Vapour pressure		1.3 Pa at 25°C (QSAR)		2.3 Pa at 25°C (QSAR)		37 Pa at 25°C (QSAR)
Water solubility		240 mg/L at 20°C (QSAR)		2200 mg/l at 20°C (QSAR)		2500 mg/l

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

The first acute oral toxicity study on 3-(trimethoxysilylpropyl) methacrylate (CAS 2530-85-0) was conducted according to OECD 423 and in compliance with GLP. An LD50 value of >2000 mg/kg was determined for male and female rats (Dow Corning Corporation, 2001).

Salivation was observed in all females immediately after dosing and noted for up to 1 hour. There were no clinical signs in males. Low bodyweight gain was recorded for one female on Day 15. No abnormalities were detected at necropsy.

The second acute oral toxicity study on [dimethoxy(methyl)silyl]methyl methacrylate (CAS 121177-93-3) was conducted according to an appropriate OECD Test Guideline and in compliance with GLP (Bioservice, 2003a). An LD50 value greater than 2000 mg/kg bw for [dimethoxy(methyl)silyl]methyl methacrylate was reported.

In the study 300 or 2000 mg/kg bw of test substance in corn oil was administered to 3 female rats per dose. The test animals were subject to a careful clinical examination performed several times on the day of dosing. Animals were observed once a day thereafter. No mortality or clinical signs of toxicity were observed in any of the test animals as well as no changes in body weight gain during a 14 -day observation period. No macroscopic abnormalities were observed in any of the test animals at necropsy.

4. AE A.4 Bias that influences the prediction

Data on the source substances 3-trimethoxysilylpropyl methacrylate (CAS 2530-85-0) and [dimethoxy(methyl)silyl]methyl methacrylate (CAS 121177-93-3) were read-across to the registered (target) substance 3-[dimethoxy(methyl)silyl]propyl methacrylate (CAS 14513-34-9). The source substances and the target substance have similar chemical structure and physico-chemical properties. All three substances hydrolyse at similar rate, and produce 3-[dihydroxy(methyl)silyl]propyl methacrylate, 3-(trihydroxysilyl)propyl methacrylate or [dihydroxy(methyl)silyl]methyl methacrylate, as the silicon-containing hydrolysis products. They share a common non-silanol hydrolysis product, methanol. Therefore, their toxicological properties are expected to be similar, with similar acute toxicity. No other data for relevant substances were available. These substances are the closest structural analogues to the target substance; other alkoxysilanes with methacrylate side-chains show consistent results.

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

The source substances as well as the target substance hydrolyse very rapidly in contact with water under conditions relevant for oral exposure. Therefore, the test organism is mainly exposed to their hydrolysis products, 3-[dihydroxy(methyl)silyl]propyl methacrylate, 3-(trihydroxysilyl)propyl methacrylate or [dihydroxy(methyl)silyl]methyl methacrylate and methanol.  The source and target substances have been profiled using the OECD QSAR Toolbox v. 4.1. The three substances and their silanol hydrolysis products show similar profiles for all toxicological endpoints. No alert for acute toxicity was detected by OECD QSAR Toolbox v.4.1.

The acute toxicity of methanol is well established. Opthalmologic changes and acidosis are described as typical primary effects in humans, in which 300 - 1000 mg/kg methanol is considered to result in death (OECD 2004). At the doses of parent substance, the methanol toxicity is not expected to be relevant.

Methanol is classified as Acute Tox. Category 3 via oral, inhalation and dermal routes in Annex VI of Regulation (EC) No 1272/2008.

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 3-[dimethoxy(methyl)silyl]propyl methacrylate, therefore data are read-across from the structurally analogous substances 3-trimethoxysilylpropyl methacrylate (CAS 2530-85-0) and [dimethoxy(methyl)silyl]methyl methacrylate (CAS 121177-93-3). These three substances hydrolyse at similar rate to a disilanol (1 mole) or a trisilanol (1 mole) and methanol (2 or 3 moles). The non-silanol hydrolysis product, methanol, is not expected to be relevant for this endpoint. Moreover, they have similar physico-chemical properties. Thus, all three 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, 3-[dimethoxy(methyl)silyl]propyl methacrylate, nor the source substances, 3-trimethoxysilylpropyl methacrylate (CAS 2530-85-0) and [dimethoxy(methyl)silyl]methyl methacrylate (CAS 121177-93-3), have impurities of toxicological concern.

Purity of test substance in the study with the source substance, 3-trimethoxysilylpropyl methacrylate (CAS 2530-85-0), was not reported. However, the Substance Identity Profile for the REACH Registration of this substance indicates that it has a purity of >98% and no impurities are present at >1%.

The test substance in the study with the second source substance, [dimethoxy(methyl)silyl]methyl methacrylate (CAS 121177-93-3), has a purity of 98.6%.

The target substance, 3-[dimethoxy(methyl)silyl]propyl methacrylate (CAS 14513-34-9), has a purity of >98% and no impurities are present at >1%.

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.

OECD (2004b): SIDS Initial Assessment Report for SIAM 19, Berlin, Germany, 18-20 October 2004, Methanol, CAS 67-56-1.

 

Justification for classification or non-classification

Based on the available data on the analogous substance 3-(trimethoxysilylpropyl) methacrylate (CAS 2530-85-0) no classification is required for acute toxicity according to Regulation (EC) No. 1272/2008.