4,4,7,7-tetraethoxy-3,8-dioxa-4,7-disiladecane

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

(Q)SAR

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification

Justification for type of information:

See attached QMRFs/QPRFs

Principles of method if other than guideline:

The result was obtained using an appropriate QSAR method (see attached QMRF and QPRF for details).

The model for hydrolysis at pH 7 has been developed for, and applies specifically to di- and tri-alkoxysilanes. It is a multiple linear regression based model with descriptors representing (i) steric effects of the alkoxy group, (ii) steric effects of the side-chain(s), and (iii) electronic effects of the side-chain(s).

The models for hydrolysis at pH 4, 5 and 9 have been developed for, and apply specifically to organosilicon compounds. They are linear regression based models where the descriptor is the half-life at pH 7.

Transformation products:

yes

No.:

#1

No.:

#2

Key result

pH:

4

DT50:

0.8 h

Remarks on result:

other: 20 - 25°C

Key result

pH:

5

DT50:

0.7 h

Remarks on result:

other: 20 - 25°C

Key result

pH:

7

DT50:

36 h

Remarks on result:

other: 20 -25°C

Key result

pH:

9

DT50:

0.5 h

Remarks on result:

other: 20 - 25°C

Conclusions:

A hydrolysis half lives of 0.8 hours at pH 4, 36.0 hours at pH 7 and 0.5 hours at pH 9 and 20 - 25°C were obtained using an accepted calculation method. The result is considered to be reliable.

Description of key information

Hydrolysis half-life: 36 h at pH 7, 0.8 h at pH 4, 0.7 h at pH 5 and 0.5 h at pH 9 and 20-25°C (QSAR)

Key value for chemical safety assessment

Half-life for hydrolysis:

36 h

at the temperature of:

25 °C

Additional information

The hydrolysis half-lives of 4,4,7,7-tetraethoxy-3,8-dioxa-4,7-disiladecane have been predicted using a validated QSAR estimation method to be 0.8 h at pH 4, 0.7 h at pH 5, 36 h at pH 7, and 0.5 h at pH 9 and 20-25°C.

Hydrolysis reactions of alkoxysilanes can be catalysed by both acid and base. The rate of hydrolysis is slowest close to pH 7 and increases 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. This is supported by studies for various organosilicon compounds in which calculation of k_H3O+ and k_OH- from the experimental results at pH 4 and 9, respectively, resulted in reasonable estimates of the half-life at pH 7. 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 4,4,7,7-tetraethoxy-3,8-dioxa-4,7-disiladecane at pH 2 and 20 - 25°C is therefore 0.008 hours (approximately 29 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 4,4,7,7-tetraethoxy-3,8-dioxa-4,7-disiladecane the hydrolysis half-life at 37.5ºC and pH 7 (relevant for lungs and blood) is approximately 13 hours. At 37.5ºC and pH 2 (relevant for conditions in the stomach following oral exposure), the hydrolysis half -life is approximately 11 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 (0.3 - 13 h).

The ultimate product of the hydrolysis reaction under dilute condition is 1,1,1,4,4,4-hexahydroxy-1,4-silabutane. The other hydrolysis product is ethanol.

The hydrolysis half-lives of substances used for read-across in other areas are discussed below:

Hydrolysis of the read-across substance, triethoxyisobutylsilane (CAS No. 17980-47-1)

Data for the substance, triethoxyisobutylsilane (CAS No. 17980-47-1) are read-across to the submission substance 4,4,7,7-tetraethoxy-3,8-dioxa-4,7-disiladecane for appropriate endpoints (see Section 1.4 of the CSR). The hydrolysis half-lives of the two substances is relevant to this read-across, as discussed in the appropriate sections of the CSR for each endpoint.

Hydrolysis half-lives at 50°C of <0.5 h at pH 4, 1.7 h at pH 9 and <1 h at pH 6.2 were determined in a study conducted according to an appropriate test protocol. At pH 7, no degradation was observed over 72 hours. However, the study was not conducted according to GLP, only the preliminary study was carried out and limited validation of the analytical method is presented (Gorlitz 1988). Therefore, it is not possible to assign this result as reliable and half-lives have been predicted using two estimation methods. Half-lives of 0.7 h at pH 4, 0.7 h at pH 5, 30 h at pH 7 and 0.4 h at pH 9 and 20-25°C were calculated using a validated QSAR estimation method (Peter Fisk Associates 2014a). These results are used for assessment purposes. In Pohl 2008, hydrolysis half-lives of 4.9 minutes at pH 4, approximately 27 h at pH 7 and 24.5 minutes at pH 9 and 25°C were calculated using a valid calculation method.

The hydrolysis products are (isobutyl)silanetriol and methanol.