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Environmental fate & pathways

Hydrolysis

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Description of key information

Hydrolysis half-life: 2.2 days at pH 7 and 25°C (modified OECD 111); estimated half-life under standard OECD 111 conditions 2-4 days.

Key value for chemical safety assessment

Half-life for hydrolysis:
2.2 d
at the temperature of:
25 °C

Additional information

A hydrolysis half-life of 2.2 days at pH 7 and 25°C was determined for the substance in a study conducted according to OECD 111 but with significant modification: extra co-solvent was added because the substance has very low solubility in water (0.02 mg/l at 22°C). The result is considered to be reliable and was selected as key study. The study also measured the half-life of a reference substance, octamethyltrisiloxane (L3, CAS 107 -51 -7), for which a standard OECD 111 study is available. The half-lives for L3 at pH 7 and 25°C under standard and non-standard (20% acetonitrile co-solvent) conditions were 13.7 d and 8.6 d, respectively. This suggests that the half-life for the registration substance, 1,1,1,3,5,5,5-heptamethyltrisiloxane (H-L3), could be greater than that measured in the non-standard study. Therefore, a half-life of 2 to 4 days at pH 7 and 25°C under the standard conditions of the OECD 111 study is estimated. The chemical safety assessment is not sensitive to variations in the hydrolysis half-life within this range and the measured half-life of 2.2 days is used as the key value.

H-L3 can theoretically undergo two separate reactions in water: hydrolysis of the siloxane (Si-O-Si) group and reaction of the Si-H bond. The latter reaction would produce hydrogen gas as a co-product of hydrolysis. In the key study, the formation of hydrogen gas was monitored by head-space analysis. Hydrogen evolution occurred over the timescale of parent substance degradation but could not account for all the observed disappearance of parent substance. Therefore, it was concluded that degradation of parent substance was due to a combination of Si-O and Si-H bond hydrolysis.

The mechanism of the Si-H reaction is unknown; it may not be a true hydrolysis reaction. However, it is a chemical reaction with water and is referred to as hydrolysis in the remainder of this document.

The stated half-life is for removal of the parent substance due to hydrolysis. Rate constant information for the intermediate hydrolysis product of the structural analogue L3 is available from the standard OECD 111 study.

The following estimates of the rate constants for hydrolysis of L3 parent substance and intermediate hydrolysis product at pH 7 and 10°C, 25°C and 35°C were obtained:

 

10°C k1= 5E-04 h-1, 25°C k1= 2E-03 h-1, 35°C k1= 5E-03 h-1

10°C k2= 4E-04 h-1, 25°C k2= 2E-03 h-1, 35°C k2= 5E-03 h-1

 

k1

k2

Me3Si(OSiMe2)OSiMe3

Me3Si(OSiMe2)OH

HO(OSiMe2)OH

 

The rate of reaction of the intermediate hydrolysis product was as fast, or faster, than that of the L3 parent substance.

The same would be expected for H-L3.

 

Under laboratory conditions, the likely final hydrolysis products of H-L3 are methylsilanetriol and trimethylsilanol. Hydrogen is produced as a co-product of hydrolysis.

The key study is supported by a predicted hydrolysis rates for the Si-O cleavage. Hydrolysis half-lives of 0.7 h at pH 4, 26 h at pH 7 and 0.4 h at pH 9 and 20-25°C 7 were obtained for H-L3 using a validated QSAR method.

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.

kobs= k0+ kH3O+[H3O+] + kOH-[OH-] + ka[acid] + kb[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:

kobs≈kH3O+[H3O+]

 

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

 

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

t1/2(pH 2) = t1/2(pH 4) / 100

The calculated half-life of the substance at pH 2 and 20-25°C is therefore 0.007 hours (25 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, the hydrolysis half-life at 37.5ºC and pH 7 (relevant for lungs and blood) is approximately 19 hours. At 37.5ºC and pH 2 (relevant for conditions in the stomach following oral exposure), the half-life is approximately 9 seconds. 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 the submission substance at pH 2 and 37.5°C is approximately 5 seconds. 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 (i.e. 0.2 - 19 hours).

The hydrolysis half-lives of the substances used for read-across in other endpoint areas are hereby discussed.

Hydrolysis of the read-across substance octamethyltrisiloxane (L3, CAS 107-51-7)

Data for the substance octamethyltrisiloxane (L3, CAS 107-51-7) are read-across to the submission substance 1,1,1,3,5,5,5-heptamethyltrisiloxane for appropriate endpoints (see Section 1.4 of the CSR). The slow rate of hydrolysis is relevant to this read-across, as discussed in the appropriate Sections of the CSR for each endpoint.

For L3, hydrolysis half-lives at 25°C of 5.09 h at pH 5, 329 h at pH 7 and 9.76 h at pH 9 were determined in accordance with OECD 111 (Mosey 2007).  The measured half-lives are supported by predicted hydrolysis half-lives of 2.5 h at pH 4, 1.8 h at pH 5 and 3 h at pH 9 and 20-25°C.

The half-lives at pH 2 and 20-25°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 0.025 h (1.5 minutes) at pH 2 and 20-25°C, approximately 120 h at pH 7 and 37.5°C (relevant for lungs and blood) and 32 seconds at pH 2 and 37.5°C (relevant for conditions in the stomach following oral exposure).

The ultimate products of hydrolysis are dimethylsilanediol and trimethylsilanol. 

Hydrolysis of the read-across substance decamethyltetrasiloxane (L4, CAS 141-62-8)

Data for the substance decamethyltetrasiloxane (L4, CAS 141-62-8) are read-across to the submission substance 1,1,1,3,5,5,5-heptamethyltrisiloxane for appropriate endpoints (see Section 1.4 of the CSR).The slow rate of hydrolysis is relevant to this read-across, as discussed in the appropriate Sections of the CSR for each endpoint.

For L4, hydrolysis half-lives at 25°C of 14 h at pH 5, 728 h at pH 7 and 21.1 h at pH 9 were determined in accordance with OECD 111 (Mosey 2009). The measured half-lives are supported by predicted hydrolysis half-lives of 3.6 h at pH 4, 2.3 h at pH 5, 630 h at pH 7 and 5.3 h at pH 9 and 20-25°C.

The half-lives at pH 2 and 20-25°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 0.036 h (approximately 2.2 minutes) at pH 2 and 20-25°C, approximately 270 h at pH 7 and 37.5°C (relevant for lungs and blood) and approximately 50 seconds at pH 2 and 37.5°C (relevant for conditions in the stomach following oral exposure).

The ultimate products of hydrolysis are dimethylsilanediol and trimethylsilanol. 

Hydrolysis of the read-across substance 1,1,3,3-tetramethyldisiloxane (H2-L2, CAS 3277-26-7)

Data for the substance 1,1,3,3-tetramethyldisiloxane (H2-L2, CAS 3277-26-7) are read-across to the submission substance; 1,1,1,3,5,5,5-heptamethyltrisiloxane for appropriate endpoints (see Section 1.4 of the CSR).The slow rate of hydrolysis is relevant to this read-across, as discussed in the appropriate Sections of the CSR for each endpoint.

For H2-L2, a measured hydrolysis half-life at pH 7 and 25°C of 11.3 minutes was determined in a modified study conducted according to OECD 111, extra co-solvent was added to the study because H2-L2 has low water solubility in water (13 mg/l at 25°C). The half-life refers to the disappearance of parent H2-L2. The measured hydrolysis half-life was supported by a predicted hydrolysis half-lives of 0.1 h at pH 2, 0.2 h at pH 5, 1 h at pH 7 and 0.02 h at pH 9 and 20-25°C.

The half-lives at pH 2 and 20-25°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 0.001 h (3.6 seconds) at pH 2 and 20-25°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 for H2-L2 at pH 2 and 20-25°C is approximately 5 seconds. At pH 7 and 37.5°C (relevant for lungs and blood), the half-life is approximately 4 minutes, at pH 2 and 37.5°C (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 ultimate product of hydrolysis is dimethylsilanediol. 

Hydrolysis of the read-across substance trimethoxysilane (CAS 2487-90-3)

Data for the substance trimethoxysilane (CAS 2487-90-3) are read-across to the submission substance; 1,1,1,3,5,5,5-heptamethyltrisiloxane for appropriate endpoints (see Section 1.4 of the CSR).

Trimethoxysilane, HSi(OMe)3, is very unstable in the presence of water. The substance contains two reactive groups: Si-OMe and Si-H. The rate of Si-OMe hydrolysis has been measured in a reliable study conducted in accordance with OECD 111 and in compliance with GLP. Half-lives of ≤0.3 min at pH 4, 7 and 9 and 2°C were obtained for the substance. The result is considered to be reliable and selected as key study. Methanol is produced by this reaction. If Si-OMe is hydrolysed, but Si-H is not, silanetriol (HSi(OH)3) would be formed as an intermediate hydrolysis product.

The Si-H bond of silanetriol is expected to react in water, forming monosilicic acid, Si(OH)4 as the ultimate hydrolysis product. The rate of this reaction is uncertain. Neither silanetriol or monosilicic acid have been isolated; but only exist in dilute aqueous solution. They readily and rapidly (within minutes) condense to give insoluble polymeric species. Depending on the pH and concentration, solutions will contain varying proportions of monomeric silanol species, cyclic and linear oligomers and polymeric species of three-dimensional structure.

The half-lives at pH 2 and 20-25°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 less than 2 seconds pH 2 and 20-25°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 for trimethoxysilane at pH 2 and 20-25°C is approximately 5 seconds. At pH 7 and 37.5°C (relevant for lungs and blood), the half-life is approximately 4 minutes, at pH 2 and 37.5°C (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.

Under laboratory conditions, the ultimate hydrolysis products in this case are silicic acid and methanol. Hydrogen is a co-product of hydrolysis.

Hydrolysis of the read-across substance hexamethyldisiloxane (HMDS, CAS 107-46-0)

Data for the substance hexamethyldisiloxane (HMDS, CAS 107-46-0) are read-across to the submission substance octamethyltrisiloxane for appropriate endpoints (see Section 1.4 of the CSR). The silanol hydrolysis product of the two substances is relevant to this read-across, as discussed in the appropriate Sections of the CSR for each endpoint.

For hexamethyldisiloxane, hydrolysis half-lives at 25°C of 1.4 h at pH 5, 120 h at pH 7 and 12.4 h at pH 9 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 <0.014 h (<50 seconds) at pH 2 and 25°C, and 44 h at pH 7 and 37.5°C. At pH 2 and 37.5°C, the hydrolysis half-life is <18 seconds.

The ultimate hydrolysis product is trimethylsilanol.