Hexamethylcyclotrisiloxane

Hydrolysis

Description of key information

Hydrolysis half-life (hexamethylcyclotrisiloxane): 23 min at pH 7, 2 min at pH 4, 0.4 min at pH 9 and 25°C

Additional information

Hydrolysis half-lives and rate constants at pH 4, 7 and 9 and 10, 25 and 35°C were determined in a reliable study conducted according to OECD 111, and in compliance with GLP (Dow Corning Corporation, 2004). Hydrolysis half-lives of 2 minutes at pH 4 and 25°C, 23 minutes at pH 7 and 25°C, and 0.4 minutes at pH 9 and 25°C were determined.

Hexamethylcyclotrisiloxane (D3) is a cyclic siloxane with three silicon atoms connected by three oxygen atoms, in which the Si-O bonds are susceptible to hydrolysis. All silicon atoms present are fully substituted with methyl groups. The stated half-lives are for removal of the registration substance due to hydrolysis. The products of this reaction are also unstable in water, and so further hydrolysis reactions will follow; the initial hydrolysis product is 1,1,3,3,5,5-hexamethyltrisiloxane-1,5-diol (CAS 3663-50 -1; L3-diol), with the final product being dimethylsilanediol (CAS 1066-42-8).

The supporting study (Spivack, 1994) determined that L3-diol hydrolyses to an equilibrium mixture in which dimethylsilanediol dominates. When dimethysilanediol, tetramethyldisiloxanediol (L2-diol) or L3-diol were dissolved in water at concentrations in the range of 1000 to 3000 ppm, a slow convergence over several days to an equilibrium position dominated by dimethylsilanediol was observed.

The following mechanism is suggested for the hydrolysis of D3:

	k1		k2		k3
D3	↔	HOSi(Me2)(OSiMe2)2OH L3-diol	↔	HOSi(Me2)(OSiMe2)OH L2-diol	↔	HOSi(Me2)OH DMSD	.

Information on the hydrolysis rate of the intermediate hydrolysis products of D3 (L3-diol and L2-diol) may be read-across from studies with octamethylcyclotetrasiloxane (D4) and decamethyltetrasiloxane (L4).

Half-lives for the hydrolysis reaction intermediates of the cyclic siloxane octamethylcyclotetrasiloxane (D4; CAS 556-67-2) were measured using radio-HPLC (Dow Corning Corporation 2005). The following mechanism was proposed for hydrolysis:

 

	k1and k2		k3		k4		k5
D4	↔	HO  Si(Me2)(OSiMe2)3 OH L4 -diol	→	HO  Si(Me2)(OSiMe2)2 OH L3 -diol	→	HOSi(Me2)(OSiMe2)OH L2 -diol	→	HOSi(Me2)OH DMSD

 

 

The first hydrolysis step is reversible; however the extent of reversibility under the dilute conditions of this study is minor. Non-linear regression analysis of the data was performed and the following rate constants at pH 7 and pH 9 for the individual reactions were estimated:

 

pH 7 k₁=8E-03 h^-1, k₂= 1E-03 h^-1, k₃= 4E-03 h^-1

pH 9 k₁=0.9 h^-1, k₂= 0.1 h^-1, k₃= 0.4 h^-1, k₄= 0.3 h^-1, k₅= 0.4 h^-1.

 

Using the rate constant k₃ at pH 7, a half-life value of 173 h at pH 7 and 25°C is calculated for octamethyltetrasiloxanediol (L4-diol).

The half-life for the hydrolysis of L3-diol and L2-diol at pH 7 and 25°C may be calculated from the rate constants k₄ and k₅ at pH 9 using the following algorithm to convert the rate at pH 9 to a rate at pH 7 (see attached QMRF for further details):

Log(T_1/2(pH9))= -1.63 + 0.84 * Log(T_1/2(pH7))

Half-life values of 240 h and 170 h at pH 7 and 25°C are calculated for the hydrolysis of L3-diol and L2-diol respectively. (Using the same algorithm to convert the half-life derived from the rate constant k₃ at pH 9 results in a half-life of 144 h for the hydrolysis of L4 -diol at pH 7, which is in reasonable agreement with the measured half-life of 173 h).

For the hydrolysis of decamethyltetrasiloxane (L4; CAS 141-62-8), the following mechanism was proposed (Dow Corning Corporation, 2009):

	k1		k2		k3
Me3Si(OSiMe2)2OSiMe3 L4	→	Me3Si(OSiMe2)2OH	→	HOSi(Me2)(OSiMe2)OH L2 -diol	→	HOSi(Me2)OH DMSD

 

Non-linear regression analysis of the data was performed, and the following rate constants at pH 7 and 10°C, 25°C and 35°C for the individual reactions were estimated:

 

10°C k₁= 1.8E-04 h^-1, 25°C k₁= 9.5E-04 h^-1, 35°C k₁= 3.2E-03 h^-1

10°C k₂= 2.3E-04 h^-1, 25°C k₂= 1.9E-03 h^-1, 35°C k₂= 5.2E-03 h^-1

10°C k₃= 5.3E-04 h^-1, 25°C k₃= 9.2E-03 h^-1, 35°C k₃= 27E-03 h^-1

 

Using the rate constant k3 and 25°C, a hydrolysis half-life of 75 h at pH 7 and 25°C is calculated for tetramethyldisiloxanediol (L2-diol).

From the evidence collated above, using a precautionary basis the half-life for the hydrolysis of the L2-diol and L3-diol is approximately 200 h at pH 7 and 25°C. Using the algorithms in Peter Fisk Associates (2014) to convert the rate at pH 7 to a rate at pH 9 and pH 4, half-lives for hydrolysis of L2-diol and L3-diol are expected to be approximately 2 h at pH 4 and 25°C and approximately 2 h at pH 9 and 25°C.

Hydrolysis under physiologically relevant conditions

The hydrolysis half-life of D3 at 35ºC and pH 7 (relevant for lungs and blood) is approximately 8.5 minutes. At 35°C and pH 5.5 (relevant for dermal exposure), the hydrolysis half-life is expected to be between the values for pH 4 (~45 seconds) and pH 7 (~8.5 minutes).

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 D3 at pH 2 and 35°C (relevant for conditions in the stomach following oral exposure) is therefore ≤5 seconds.

References:

Peter Fisk Associates (2014). Prediction of hydrolysis for Si-containing compounds at pH 4, 5 and 9. QSAR Model Reporting Format. Report no.: PFA.413.002.013. Owner company: Reconsile. Report date: 2014-04-15.