3-(chlorodimethylsilyl)propyl methacrylate

Hydrolysis

Description of key information

Hydrolysis: Half-life <1 min at 25°C and pH 4, 7 and 9 (analogue read-across) (for the chlorosilane group).

Additional information

The registration substance 3-(chlorodimethylsilyl)propyl methacrylate contains two types of hydrolysable groups: one chlorosilane group (which reacts to the corresponding silanols plus hydrochloric acid) and one methacrylate ester group (which has the potential to react to the corresponding alcohol plus methacrylic acid). The chemical safety assessment of the substance assumes that these reaction processes will proceed independently based on their rates under the relevant conditions.

Hydrolysis of the chlorosilane group:

No hydrolysis study is available for the submission substance. However, a reliable study according to OECD 111 is available for the related substance chlorotrimethylsilane. This substance is fully hydrolysed within a few minutes at pH 4, 7 and 9 and 1.5°C.

The read-across is made in the context of evidence from other available data for chlorosilane structural analogues, as illustrated in Table 1 below.

Table 1: Hydrolysis half-lives at pH 4, 7 and 9 for chlorosilanes

CAS No	Name	Result – half-life at pH 4 (seconds)	Result – half-life at pH 7 (seconds)	Result – half-life at pH 9 (seconds)	Temperature	Klimisch
75-77-4	Chlorotrimethylsilane	7	11	8	1.5 ± 0.5˚C	2
75-78-5	Dichloro(dimethyl) silane	10	17	7	1.5 ± 0.5˚C	2
75-79-6	Trichloro(methyl) silane	7	9	6	1.5 ± 0.5˚C	2
80-10-4	Dichloro(diphenyl) silane	6	10	8	1.5 ± 0.5˚C	2
675-62-7	Dichloromethyl(3,3,3-trifluoropropyl) silane	8	12	9	1.5 ± 0.5˚C	2
5578-42-7	Dichlorocyclohexylmethylsilane	<<27 min[1]	<<27 min[2]	<<27 min[3]	27°C	2
18379-25-4	Trichloro(2,4,4-trimethylpentyl)silane	<<2 min[7]	<<2 min[7]	<<2 min[7]	27°C	2
4518-98-3	1,1,2,2-tetrachloro-1,2-dimethyldisilane	8	7	7	1.5 ± 0.5˚C	2
13154-25-1	Chlorotri(3-methyl-propyl) silane	Not quantified[4]	Not quantified[5]	Not quantified[6]	50˚C	1

[1]No parent substance was detected when the first measurement was taken.

[2]No parent substance was detected when the first measurement was taken.

[3]No parent substance was detected when the first measurement was taken.

[4]In this test the t₀ analysis (50˚C) showed a recovery <LOD, suggestive of an extremely rapid reaction.

[5]In this test the t₀ analysis (50˚C) showed a recovery <LOD, suggestive of an extremely rapid reaction.

[6]In this test the t₀ analysis (50˚C) showed a recovery <LOD, suggestive of an extremely rapid reaction.

[7]determination of hydrolysis kinetics was not possible, very fast hydrolysis and precipitation of solids was observed.

For six substances, quantitative half-life data at 1.5ºC are available; one study at 27°C gave a limit half-life, one study with one further substance at 50ºC found no parent substance to be present at t0, indicating extremely rapid hydrolysis. The measured half-lives at pH 4, 7 and 9 and 1.5ºC are all ≤17 s.

Hydrolysis half-lives of 7 seconds at pH 4, 11 seconds at pH 7 and 8 seconds at pH 9 and 1.5°C were determined for chlorotrimethylsilane in accordance with OECD 111 (Dow Corning Corporation 2001).

Since the hydrolysis was so rapid relative to the timescale of the analytical measurement, there was insufficient data to determine rate constants for the hydrolysis reactions of these chlorosilanes using regression modelling. However, the data was adequate for estimating the upper limit of t_1/2. Half-lives were estimated as 0.1 t, where t=time for complete hydrolysis.

In a preliminary study for another monochlorosilane, chlorotri(3-methyl-propyl)silane, the study was conducted at 50°C for 2.4 hours at pH 4, pH 7 and pH 9. The measured concentration of the test substance at t0 and 50°C, indicate a recovery that is less than the limit of determination of the analytical instrument used (GC). However, the authors (White and Mullee 2002) of the study used a limit value that is twice the baseline noise of the instrument to estimate the concentration of the test sample. This suggests that the test substance was rapidly hydrolysed in aqueous media. In addition, a degradant peak was observed in the chromatogram at approximately 3.6 minutes. The result from this study is used as supporting data.

Given the very rapid hydrolysis rates in water observed for all tested chlorosilanes, and the lack of significant variation in the half-lives for the different substances, it is considered appropriate to read-across this result to 3-(chlorodimethylsilyl)propyl methacrylate.

 

Reaction rate increases with temperature, and therefore hydrolysis will be faster at 25ºC and at physiologically-relevant temperatures. Under ideal conditions, hydrolysis rate can be recalculated according to the equation:

DT₅₀(XºC) = DT₅₀(T°C) *e^(0.08.(T-X))

Where T = temperature for which data are available and X = target temperature.

Using the half-life that is quantitatively derived for chlorotrimethylsilane at 1.5ºC and pH 7 (11 seconds) the calculated hydrolysis half-life at 25ºC and pH 7 is approximately 2 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 submission substance at pH 7 and 25°C is approximately 5 seconds.

The calculated hydrolysis half-life at 37.5ºC and pH 7 (relevant for lungs and blood and in vitro and in vivo (intraperitoneal administration) assays) is approximately 5 seconds.

Using the half-life that is quantitatively derived for chlorotrimethylsilane at 1.5ºC and pH 4 (7 seconds) the calculated hydrolysis half-life at 25ºC and pH 4 is approximately 1 second. As a worst-case the half-life at pH 4 and 25°C is approximately 5 seconds.

As the hydrolysis reaction may be acid or base catalysed, the rate of reaction is expected to be slowest at pH 7 and increase as the pH is raised or lowered (this is consistent with the data presented above). The half-life at pH 4 and 37.5°C is approximately 5 seconds, therefore, the half-life at pH 2 and 37.5°C (relevant for oral exposure) is also estimated as 5 seconds as a worst-case. At 37.5°C and pH 5.5 (relevant for dermal exposure), the hydrolysis half-life is estimated to be in between the half-lives at pH 4 and pH 7 and 37.5°C, and thus also approximately 5 seconds as a worst-case.

Hydrolysis in air

The above hydrolysis studies were carried out with the substance dissolved in water.

Consideration of the rates of reaction with moisture in air is relevant for inhalation exposure assessment. Experience in handling and use, as well as the extremely rapid rates observed in the available water-based studies, would suggest that rates of reaction in moist air will also be rapid. If any unreacted chlorosilane were to reach the airways, it would rapidly hydrolyse in this very moist environment.

In a study of the acute toxicity to rats via the inhalation route (Dow Corning Corporation 1997), dichloro(dimethyl)silane was quantified in the exposure chamber using Thermal Conductivity Detection and identification was confirmed using GC/MS. The relative humidity (RH) in the exposure chamber was 30-35%. The mean measured concentrations in the exposure chambers during exposure (1 hour) was only about 15% of the nominal concentration of dichloro(dimethyl)silane. The test atmosphere contained an amount of chloride consistent with the nominal concentration of test article as determined via electrochemical detection. Thus, the majority of parent had hydrolysed in the test atmosphere at only 30-35% relative humidity.

Similarly, in a study to assess stability of dichloro(dimethyl)silane vapour in air using gas-sampling FTIR (Dow Corning 2009), dichloro(dimethyl) silane was observed to be extremely unstable in high relative humidity atmospheres. At 75% relative humidity (RH) level, a stable test atmosphere of the substance could not be generated. In dry air (<5% RH), the substance had achieved 28% loss after 1 hour and 71% loss after 3.2 hours.

A simulated nose-only exposure study (Dow Corning Corporation 2013) has been conducted to determine hydrolytic stability of dichloro(dimethyl) silane under conditions typical of nose-only vapour inhalation exposures. The vapour generation was on 1 day for 3 hrs 14 minutes; concentrations of parent material were measured at 30 minute intervals using gas chromatography (GC). The nominal concentration was 50 ppm. The mean temperature was 21.6°C and the relative humidity (RH) was 57%. 24% parent concentration remaining in the test atmosphere relative to nominal concentration was measured by GC. This indicates 76% hydrolysis of the parent substance had taken place by the time the test atmosphere reached the GC. It was concluded that at least 20-29% of the parent test article would be present in the breathing zone relative to the nominal concentration under typical conditions used for nose-only inhalation exposure of rats. It is therefore possible to expose rats in a nose-only study to parent chlorosilane, because the transit time from the substance reservoir to the nose is very rapid (<1 second), however, this is not considered to be representative of human exposure conditions.

The authors of this summary have used the information from this study to estimate a half-life for dichloro(dimethyl) silane in air of approximately 7 seconds (95% confidence limit = 3-11 seconds), which is comparable to the half-life in water.

The significant extent of chlorosilane hydrolysis demonstrated in the study with dichloro(dimethyl)silane is in good agreement with the theoretical capacity for hydrolysis in air under conditions typical of a rat repeated exposure test. Theoretically, air at 20°C at 50% relative humidity would have more than 100 times the amount of water necessary for complete hydrolysis of 3-(chlorodimethylsilyl)propyl methacrylate:

 

Water content of air at 20°C = 17.3 g/m³ (100% humidity)

Assuming a 50% humidity = 8.65g water/m³ = 8.65 mg water/l

Molecular weight of water = 18 g/mole; So 8.65 mg water/l = 0.48 mmol water/l

50 ppm HCl is the estimated upper exposure limit based on HCl corrosivity for a repeated exposure test

As 3-(chlorodimethylsilyl)propyl methacrylate has 1 Cl group this would be equivalent to 50 ppm

Molecular weight of 3-(chlorodimethylsilyl)propyl methacrylate = 220.77 g/mol

50 ppm 3-(chlorodimethylsilyl)propyl methacrylate is equivalent to 451.47 mg/m³ or 0.002 mmol/l.

Therefore, it can be concluded that the registered substance will hydrolyse very rapidly under conditions relevant for environmental and human health risk assessment and no further testing is necessary. It is not possible or necessary to attempt a quantitative prediction of rate or half-life because the chemical safety assessment is not sensitive to this uncertainty within this range. Additional information is given in a supporting report (PFA 2013ab) attached in Section 13.

The hydrolysis products for the submission substance are 3-[hydroxy(dimethyl)silyl]propyl methacrylate and hydrochloric acid.

Note on hydrolysis of the methacrylate ester group:

Very limited evidence of the hydrolysis of the methacrylate ester group is available. The hydrolysis half-life of methyl methacrylate (a much more soluble substance) is reported to be >1 year at 25°C and pH 7 and 14.4 days at 25°C and pH 9 (WHO CICAD summary citing Howard, 1989). In the case of the registration substance 3-(chlorodimethylsilyl)propyl methacrylate, the reaction is expected to be slower due to the steric effects of the 3-(chlorodimethylsilyl)propyl group (Mabey and Mill 1978). For the purposes of the chemical safety assessment, in the absence of clear evidence it is considered that the hydrolysis of the methacrylate ester group is not significant for the chemical safety assessment at any relevant pH. Therefore, where the chemical safety assessment considers hydrolysis products, these are identified as 3-[hydroxy(dimethyl)silyl]propyl methacrylate and hydrochloric acid. The same assumptions are made for read-across substances containing methacrylate groups. This is a conservative position in the absence of clear evidence, as the methacrylate structural feature is likely to be more toxic than the corresponding alcohol.

The hydrolysis data for substances used in this dossier for read-across purposes for other endpoints are now discussed.

Hydrolysis of the read-across substance 3-trimethoxysilylpropyl methacrylate CAS No. 2530-85-0

Data for the substance, 3-trimethoxysilylpropyl methacrylate (CAS No. 2530-85-0) are read-across to the submission substance 3-(chlorodimethylsilyl)propyl methacrylate for appropriate endpoints. The silanol hydrolysis product and the rate of hydrolysis of the two substances are relevant to this read-across, as discussed in the appropriate Sections for each endpoint.

The hydrolysis of 3-trimethoxysilylpropyl methacrylate has been determined in accordance with OECD 111 Test Guideline and in compliance with GLP (Lange, 2016). Hydrolysis half-life values are:

pH 4: 0.0165 h at 16.5°C, 0.018 h at 20°C, 0.0155 h at 25°C

pH 7: 2.52 h at 16.5°C, 1.87 h at 20°C, 1.7 h at 25°C

pH 9: 0.0883 h at 16.5°C, 0.068 h at 20°C, 0.0491 h at 25°C

In addition, hydrolysis half-lives at 20 - 25°C of 0.3 h at pH 4, 0.3 h at pH 5, 4.4 h at pH 7 and 0.1 h at pH 9 were predicted for the substance using a validated QSAR estimation method. Similarly, hydrolysis half-lives of 3 h at 25°C and pH 7 and 4 h at 20°C and pH 7 were determined in a preliminary study conducted in accordance with OECD 111 and in compliance with GLP. At pH 4 and pH 9, the test substance was observed to undergo rapid hydrolysis and as such half-lives at these pHs was estimated to be < 1 hour. In a secondary source to which reliability could not be assigned, a hydrolysis half-life of 121.6 mins (approximately 2 hours) at pH 4.5 and 25°C was reported for the substance. The available data are in agreement that 3-trimethoxysilylpropyl methacrylate undergoes rapid hydrolytic degradation.

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. For an acid-base catalysed reaction in buffered solution, the measured rate constant is a linear combination of terms describing contributions from the uncatalysed reaction as well as catalysis by hydronium, hydroxide, and general acids or bases.

k_obs= k₀+ k_H3O+[H3O⁺] + k_OH-[OH-] + k_a[acid] + k_b[base]

At extremes of pH and under standard hydrolysis test conditions, it is reasonable to suggest that the rate of hydrolysis is dominated by either the hydronium or hydroxide catalysed mechanism.

Therefore, at low pH:

k_obs≈k_H3O+[H3O⁺]

At pH 4 [H₃O⁺] = 10^-4 mol dm^-3 and at pH 2 [H₃O⁺] = 10^-2 mol dm^-3; therefore, k_obs at pH 2 should be approximately 100 times greater than k_obs at pH 4.

The half-life of a substance at pH 2 is calculated based on:

t_1/2(pH 2) = t_1/2(pH 4) / 100

 

The calculated half-life of 3-trimethoxysilylpropyl methacrylate at pH 2 and 20°C is therefore 0.0018 hours (approximately 1 second). 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 be considered that the half-life for the substance at pH 2 and 20°C is approximately 5 seconds.

 

Reaction rate increases with temperature therefore hydrolysis will be faster at physiologically relevant temperatures compared to standard laboratory conditions. Under ideal conditions, hydrolysis rate can be recalculated according to the equation:

 

DT₅₀(XºC) = DT₅₀(T) x e^(0.08.(T-X))

Where T = temperature for which data are available and X = target temperature.

Thus, for the submission substance, at pH 7 and 37.5°C (relevant for lungs and blood); the half-life is 0.46 hours.

The hydrolysis products in this case are 3-(trihydroxysilyl)propyl methacrylate and methanol.

Hydrolysis of the read-across substance 3-[dimethoxy(methyl)silyl]propyl acrylate CAS No. 13732-00-8)

Data for the substance 3-[dimethoxy(methyl)silyl]propyl acrylate (CAS No. 13732-00-8) are read-across to the registration substance 3-(chlorodimethylsilyl)propyl methacrylate for appropriate endpoints. The silanol hydrolysis product and the rate of hydrolysis of the two substances are relevant to this read-across, as discussed in the appropriate Sections for each endpoint.

Hydrolysis half-lives of 0.2 h at pH 4, 0.2 h at pH 5, 1.7 h at pH 7 and 0.04 h at pH 9 and 20-25°C were predicted for the substance using a validated QSAR estimation method.

The half-lives at pH 2 and 25°C, at pH 7 and 37.5°C and at pH 2 and 37.5°C may be calculated in the same way as for the CAS No. 2530-85-0 above. This gives a half-life of 0.002 h (approximately 7 seconds) at pH 2 and 25°C. 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 be considered that the half-life for the substance at pH 2 and 25°C is approximately 5 seconds. At pH 7 and 37.5°C, the half-life is 0.63 hours and at pH 2 and 37.5°C, the half-life is approximately 5 seconds as a worst-case. At 37.5ºC and pH 5.5 (relevant for dermal exposure), the hydrolysis half -life will be in between the half-lives at pH 5 and pH 7 at 37.5ºC (0.07 - 0.63 hours).

The hydrolysis products in this case are 3-[dihydroxy(methyl)silyl]propyl acrylate and methanol.

Hydrolysis of the read-across substance [dimethoxy(methyl)silyl]methyl methacrylate CAS no. 121177-93-3

Data for the substance [dimethoxy(methyl)silyl]methyl methacrylate (CAS 121177-93-3) are read-across to the registration substance, 3-(chlorodimethylsilyl)propyl methacrylate for appropriate endpoints. The silanol hydrolysis product and the rate of hydrolysis of the two substances are relevant to this read-across, as discussed in the appropriate sections for each endpoint.

Hydrolysis half-lives of 1.8 h at pH 7, 0.2 h at pH 4, 0.04 h at pH 9 and 20-25°C were predicted for the substance using a validated QSAR estimation method.

The half-lives at pH 2 and 25°C, at pH 7 and 37.5°C and at pH 2 and 37.5°C may be calculated in the same way as for the CAS No. 2530-85-0 above. This gives a half-life of 0.002 h (approximately 7 seconds) at pH 2 and 25°C. 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 be considered that the half-life for the substance at pH 2 and 25°C is approximately 5 seconds. At pH 7 and 37.5°C, the half-life is 0.66 hours and at pH 2 and 37.5°C, the half-life is approximately 5 seconds as a worst-case. At 37.5ºC and pH 5.5 (relevant for dermal exposure), the hydrolysis half-life will be in between the half-lives at pH 4 and pH 7 at 37.5ºC (0.07 - 0.66 hours).

The hydrolysis products in this case are [dihydroxy(methyl)silyl]methyl methacrylate and methanol.

Reference:

Mabey W, Mill T (1978). Critical review of hydrolysis of organic compounds in water under environmental conditions. Journal of Physical and Chemical reference data. Washington D.C, American Chemical Society, vol. 7, pages 383-415.