2,4,6,8-tetramethyl-2,4,6,8-tetravinylcyclotetrasiloxane

Hydrolysis

Description of key information

Hydrolysis half-life: 1.1 h at pH 4, 0.9 h at pH 5, approximately 63 hour at pH 7 and 0.8 pH 9 at 20 - 25°C (QSAR)

Key value for chemical safety assessment

Half-life for hydrolysis:

63 h

at the temperature of:

20 °C

Additional information

 The requirement to conduct a hydrolysis study for the substance is waived in accordance with column 2 of REACH Annex VIII because the substance is insoluble in water (measured solubility is 7.3-8.8 ppb at 23°C).

The registration substance has an average purity of >70% 2,4,6,8-tetramethyl-2,4,6,8-tetravinylcyclotetrasiloxane (Vi4-D4), with <20% 2,4,6,8,10-pentamethyl-2,4,6,8,10-pentavinylcyclopentasiloxane Vi5-D5 (CAS 17704-22-2; Impurity 1) and <10% 2,4,6-trimethyl-2,4,6-trivinylcyclotrisiloxane Vi3-D3 (CAS 3901-77-7; Impurity 2) present as impurities.

For each component, the half-lives have been determined using a validated QSAR method. The results are supported by read-across from the fully methylated cyclic siloxane of the appropriate ring-size.

Hydrolysis half-lives of 1.1 h at pH 4, approximately 63 h at pH 7 and 0.8 h at pH 9 and at 20-25°C were obtained for 2,4,6,8-tetramethyl-2,4,6,8-tetravinylcyclotetrasiloxane (Vi4-D4) using a validated QSAR estimation method. The result is considered to be reliable and has been used for assessment purposes. The QSAR applies to siloxanes and allows predictions of hydrolysis half-life at pH 7 based on the number of silicon-oxygen atoms in the ring, the ring-strain and the number of Si-H bonds.

This result is supported by measured hydrolysis half-lives of 1.8 h at pH 4, 69 – 144 h at pH 7 and 0.9 – 1 h at pH 9 and 24.6°C (Dow Corning Corporation 2005) which was determined for octamethylcyclotetrasiloxane (CAS no: 556-67-2, D4), in accordance with OECD 111. Similarly, in Dow Corning Corporation 2004, hydrolysis half-lives of 33 h at pH 5, 69 h at pH 7 and 0.56 h at pH 9 and 25°C were obtained for D4 in accordance with OECD 111. D4 is a cyclic siloxane chain with four silicon atoms, connected by four oxygen atoms, in which the Si-O bonds are susceptible to hydrolysis. All silicon atoms present are fully substituted with methyl groups. Similarly, the submission substance is a cyclic siloxane chain with four silicon atoms, connected by four oxygen atoms, in which the Si-O bonds are susceptible to hydrolysis. All silicon atoms present are substituted with one methyl group and one vinyl group. As well as being structural analogues, both siloxanes have consistent chemical properties including high molecular weight (297 and 345 g/mol for D4 and Vi4-D4 respectively), high log K_ow (6.5 for both substances) and very low solubility in water (0.056 mg/l and 0.0073 - 0.0088 mg/l for D4 and Vi4-D4 respectively).

 

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 uncatalyzed 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 pH2 [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 the substance at pH 2 and 20-25°C is therefore 0.011 hours (approximately 40 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 Vi4-D4 the hydrolysis half-life at 37.5ºC and pH 7 (relevant for lungs and blood) is approximately 23 hours. At 37.5ºC and pH 2 (relevant for conditions in the stomach following oral exposure), hydrolysis half-life is approximately 15 seconds. At 37.5°C and pH 5 (relevant for dermal exposure), the hydrolysis half-life is expected to be between the values for pH 4 (0.4 h) and pH 7 (23 h).

The hydrolysis half-lives of the impurities have been determined using a validated QSAR estimation method. Predicted half-lives of approximately 5.8 h at pH 4, approximately 1600 h at pH 7 and approximately 11 h at pH 9 and 20 - 25°C were determined for impurity 1. This results in a half-life of 0.06 h (3.5 min) at pH 2 and 25°C, 1.3 min at pH 2 and 37.5°C and 600 h at pH 7 and 37.5°C, calculated as above. Similarly, half-lives of 0.1 h at pH 4, 0.6 h at pH 7 and 0.02 h at pH 9 and 20 - 25°C were determined for impurity 2. This results in a half-life of 5 seconds at pH 2 and 25°C, 5 seconds at pH 2 and 37.5°C and 600 h at pH 7 and 37.5°C. These values were calculated as above but with a lower limit of 5 seconds imposed becauseit is likely that factors such as diffusion become rate-determining when the half-life is less than 5-10 seconds. The hydrolysis half-lives of D3 and D5 were also read-across to Vi3-D3 (Impurity 2) and Vi5-D5 (Impurity 1), respectively. Half-lives of 2 minutes, 23 minutes and 0.4 minutes at pH 4, 7 and 9 and 25°C respectively were determined for D3. Also, half-lives of 9.3 h, 1590 h and 24.8 - 31.6 h at pH 4, 7 and 9 and 25°C were respectively determined for D5.

The half-lives refer to degradation of parent substance by ring-opening of the siloxane. Full hydrolysis will take longer. The intermediate hydrolysis products are linear siloxanediols. The ultimate hydrolysis product is methylvinylsilanediol.

The hydrolysis half-lives of substances used for read-across purposes in other endpoints are hereby discussed below.

Hydrolysis of the read-across substance octamethylcyclotetrasiloxane, D4 (CAS No. 556-67-2)

Data for the substance octamethylcyclotetrasiloxane (CAS 556-67-2) are read-across to the submission substance 2,4,6,8-tetramethyl-2,4,6,8-tetravinylcyclotetrasiloxane for appropriate endpoints (see Section 1.4 of the CSR). The structural similarity and similar physicochemical and environmental fate properties of the two substances is relevant to this read-across.

For D4, hydrolysis half-lives of 1.8 h at pH 4, 69-144 h at pH 7 and 0.9-1 h at pH 9 and 24.6°C were determined in accordance with OECD 111 ( Dow Corning Corporation 2006b).

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 registration substance above. This gives a half-life of 0.018 h (65 seconds) at pH 2 and 24.6°C, and 25-51 h at pH 7 and 37.5°C. At pH 2 and 37.5°C, the hydrolysis half-life is 23 seconds.

The ultimate hydrolysis product is dimethylsilanediol.  

Hydrolysis of the read-across substance decamethylcyclopentasiloxane (CAS 541-02-6)

Data for the substance decamethylcyclopentasiloxane (CAS 541-02-6) are read-across to the registration substance for appropriate endpoints (see Section 1.4). The structural similarity and similar physicochemical and environmental fate properties of the two substances is relevant to this read-across.

For decamethylcyclopentasiloxane, hydrolysis half-lives at 25°C are described above. 

Hydrolysis of the read-across substance hexamethylcyclotrisiloxane (CAS 541-05-9)

Data for the substance hexamethylcyclotrisiloxane (CAS 541-05-9) are read-across to the registration substance for appropriate endpoints (see Section 1.4). The structural similarity and similar physicochemical and environmental fate properties of the two substances is relevant to this read-across.

For hexamethylcyclotrisiloxane, hydrolysis half-lives at 25°C are described above. 

Hydrolysis of the read-across substance trimethoxy(vinyl)silane (CAS No: 2768-02-7)

Data for the substance trimethoxy(vinyl)silane (CAS No. 2768-02-7) are read-across to the submission substance 2,4,6,8-tetramethyl-2,4,6,8-tetravinylcyclotetrasiloxane for appropriate endpoints (see Section 1.4 of the CSR). The presence of similar side chain (vinyl) in the two substances is relevant to this read-across.

Trimethoxy(vinyl)silane has measured half-lives of <10 minutes, <2.4 h and <10 minutes at pH 4, pH 7 and pH 9 and 50°C in a preliminary study according to OECD 111. Also, it has predicted half-lives at 20-25ºC of 0.04 h (2 minutes) at pH 4, 0.1 h at pH 7, and 0.004 h (14 seconds) at pH 9. In a secondary source to which reliability could not be assigned, half-lives of 0.24 h at pH 7 and 0.58 h at pH 4 and 23°C were reported for trimethoxyvinylsialne.

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 based on the predicted half-lives in the same way as for the registration substance above. This gives a half-life of 0.0004 h (approximately 1 second) at pH 2 and 25°C. However, it is likely that factors such as diffusion become rate-determining when the half-life is less than 5-10 seconds. As a worst-case it can therefore be considered that the half-life of trimethoxy(vinyl)silane at pH 2 and room temperature is approximately 5 seconds.

At pH 7 and 37.5°C (relevant for lungs and blood) and at 37.5ºC and pH 5.5 (relevant for dermal exposure), the half-life is approximately 0.04 hours (2 minutes), at 37.5ºC and pH 2 (relevant for conditions in the stomach following oral exposure), it is not appropriate to apply any further correction for temperature to the limit value and the hydrolysis half -life is therefore approximately 5 seconds

The hydrolysis products are vinylsilanetriol and methanol.