Dodecamethylpentasiloxane

Hydrolysis

Description of key information

Hydrolysis half-life: 30.3 d (728 h) at pH 7, 14 h at pH 5 and 21.1 h at pH 9 and 25°C (Category read-across). The stated half-life is for removal of parent. Complete reaction to the ultimate end products will take longer.

Key value for chemical safety assessment

Half-life for hydrolysis:

30.3 d

at the temperature of:

25 °C

Additional information

No hydrolysis study is available for the submission substance (L5, CAS 141-63-9). However, a reliable study conducted in accordance with OECD 111 is available for a structurally related substance L4 (CAS 141-62-8). Hydrolysis half-lives at 25°C of 30.3 d (728 h) at pH 7, 14 h at pH 5, and 21.1 h at pH 9 were determined at room temperature for L4. These results are read-across to L5. The results are considered to be reliable and are assigned as key study.

L4 is a linear siloxane chain with four 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. L5 is a structurally related linear siloxane, with five silicon atoms and four oxygen atoms.

As well as being structural analogues, both siloxanes have consistent physicochemical properties including high molecular weight (310 and 384 g/mol respectively), very high log K_ow (above 8 for both substances) and very low solubility in water (7E-03 mg/l for L4 and 7E-05 mg/l for L5). The substances generally possess similar physicochemical properties. There are no significant steric differences between the Si centres in the two structures. Therefore, the rate of reaction at pH 7 is expected to be approximately the same. The ultimate end products of the hydrolytic reaction, dimethylsilanediol and trimethylsilanol, will be the same for both structures. The stated half-life is for removal of the registration substance due to hydrolysis.

A half-life value of approximately 2000 h at 20-25°C and pH 7 was obtained using an accepted validated QSAR method (Peter Fisk Associates 2014b). Similarly, predicted half-lives at 20-25°C of approximately 6.6 h at pH 4, 3.6 h at pH 5 and approximately 14 h at pH 9 were obtained for the submission substance (Peter Fisk Associates 2014a).

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^-4mol dm^-3and at pH 2 [H₃O⁺] =10^-2mol 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 is therefore 0.07 hours (4 minutes). 

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) * e^(0.08.(T-X))

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

Thus, for L5 the hydrolysis half-life at 37.5ºC and pH 7 (relevant for lungs and blood) is approximately 270 hours. At 37.5ºC and pH 2 (relevant for conditions in the stomach following oral exposure), the hydrolysis half-life is calculated as 90 seconds. At 37.5°C and pH 5.5 (relevant for dermal exposure), the hydrolysis half-life is expected to be between the values for pH 5 (5 h) and pH 7 (270 h).

The ultimate products of hydrolysis are dimethylsilanediol and trimethylsilanol. 

The experiments at pH 7 were more susceptible to recovery decreases by partitioning of the submission substance into vapour phase due to the extended durations of the study. Therefore, to explicitly account for this process, the pH 7 experiments were analysed using non-linear regression. Similarly, non-linear regression was applied to the data at pH 5 and pH 9 experiments as confirmation of the linear regression results (k₁,_obs) and to obtain estimate for k₂,_obsand k₃,_obs.

 

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

 

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

 

	k1		k2		k3
Me3Si(OSiMe2)2OSiMe3	→	Me3Si(OSiMe2)2OH	→	HO(OSiMe2)2OH	→	HO(OSiMe2)OH

 

The rate of reaction of the intermediate hydrolysis products was faster than that of the parent substance.

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

Data for the substance, octamethyltrisiloxane (CAS 107-51-7) are read-across to the submission substance, dodecamethylpentasiloxane for appropriate endpoints (see Section 1.4 of the CSR). The structural similarity and the siloxane hydrolysis half-life of the two substances is relevant to this read-across, as discussed in the appropriate Sections of the CSR for each endpoint.

For octamethyltrisiloxane, hydrolysis half-lives at 25°C of 5.09 h at pH 5, 329 h (13.7 days) at pH 7 and 9.76 h at pH 9 were determined in accordance with OECD 111 (Dow Corning Corporation, 2007).

The ultimate products of hydrolysis are dimethylsilanediol and trimethylsilanol.

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

Data for the substance, decamethyltetrasiloxane (CAS 141-62-8) are read-across to the submission substance, dodecamethylpentasiloxane for appropriate endpoints (see Section 1.4 of the CSR).The structural similarity and the siloxane hydrolysis half-life of the two substances is relevant to this read-across, as discussed in the appropriate Sections of the CSR for each endpoint.

Both substances are siloxanes belonging to the same analogue group and the hydrolysis rates are discussed above.

The ultimate products of hydrolysis are dimethylsilanediol and trimethylsilanol.