Reaction mass of 4,4,13,13-tetraethoxy-3,14-dioxa-8,9-dithia-4,13-disilahexadecane and 4,4,14,14-tetraethoxy-3,15-dioxa-8,9,10-trithia-4,14-disilaheptadecane

Hydrolysis

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

hydrolysis

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the substance is highly insoluble in water

Reference 2

Endpoint:

hydrolysis

Type of information:

(Q)SAR

Adequacy of study:

supporting 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:

Please refer to the attached QM(P)RF documents

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.

pH:

4

DT50:

0.8 - 1.2 h

Remarks on result:

other: pH 4 result for S2 at 20-25°C

pH:

4

DT50:

0.8 - 1.4 h

Remarks on result:

other: pH 4 result for S3 at 20-25°C

pH:

5

DT50:

0.8 - 1 h

Remarks on result:

other: pH 5 result for S2 at 20-25°C

pH:

5

DT50:

0.8 - 1.1 h

Remarks on result:

other: pH 5 result for S3 at 20-25°C

pH:

7

DT50:

40 - 90 h

Remarks on result:

other: pH 7 result for S2 at 20-25°C

pH:

7

DT50:

40 - 110 h

Remarks on result:

other: pH 7 result for S3 at 20-25°C

pH:

9

DT50:

0.5 - 1 h

Remarks on result:

other: pH 9 result for S2 at 20-25°C

pH:

9

DT50:

0.5 - 1.1 h

Remarks on result:

other: pH 9 result for S3 at 20-25°C

The predicted half-lives for the constituents of the substance are shown below:

 

Constituent name	Abbreviation	Hydrolysis half-lives
		pH 4	pH 5	pH 7	pH 9
4,4,13,13-tetraethoxy-3,14-dioxa-8,9-dithia-4,13-disilahexadecane	S2	0.8 - 1.2	0.8 - 1.0	40-90	0.5 - 1.0
4,4,14,14-tetraethoxy-3,15-dioxa-8,9,10-trithia-4,14-disilaheptadecane	S3	0.8 - 1.4	0.8 - 1.1	40-110	0.5 - 1.1

Conclusions:

Hydrolysis half-life values at 20-25°C pH 4, pH 5, pH 7 and pH 9 were obtained for the constituents of the substance using an accepted calculation method. The result is considered to be reliable.

Description of key information

Hydrolysis half-lives at 20-25°C for S2 are 0.8-1.2 h at pH 4; 0.5 – 1.0 h at pH 5, approximately 40 – 90 h at pH 7 and 0.5 – 1.0 h at pH 9 (20-25°C). The corresponding values for S3 are 0.8 – 1.4 h at pH 4, 0.5 – 1.1 h at pH 6, approximately 40 – 110 h at pH 7 and 0.5 – 1.1 h at pH 9.  (QSAR).

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. The constituents of the substance have water solubility values of <1 mg/l.

Predicted hydrolysis half-lives for S2 are 0.8-1.2 h at pH 4; 0.5 – 1.0 h at pH 5, approximately 40 – 90 h at pH 7 and 0.5 – 1.0 h at pH 9 (20-25°C). The corresponding values for S3 are 0.8 – 1.4 h at pH 4, 0.5 – 1.1 h at pH 6, approximately 40 – 110 h at pH 7 and 0.5 – 1.1 h at pH 9. These values were determined for the constituents of the substance using a validated QSAR estimation 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 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_obsat pH 2 should be approximately 100 times greater than k_obsat 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-lives of the constituents at pH 2 and 25°C are therefore, 0.008 - 0.012 h (approximately 30 – 43 seconds) for S2 and 0.008 - 0.014 h (approximately 30 – 50 seconds) for S3.

 

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.

 

The half-lives at 37.5ºC and pH 7 (relevant for lungs and blood) and pH 2 (relevant for conditions in the stomach following oral exposure) are calculated as showin in the table below. 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 4 and pH 7. The hydrolysis half-lives for the constituents are summarised in the table below.

Table: Hydrolysis half-lives for constituents of the submission substance

 

Constituent name	Abbreviation	Half-lives at 20-25°C (h)				Half-lives at 25°C (h)	Half-lives at 37.5°C
		pH 4	pH 5	pH 7	pH 9	pH 2	pH 2	pH 7
4,4,13,13-tetraethoxy-3,14-dioxa-8,9-dithia-4,13-disilahexadecane	S2	0.8 - 1.2	0.8 - 1.0	40-90	0.5 - 1.0	0.012	Ca. 11 - 16 s	Ca. 15 - 33 h
4,4,14,14-tetraethoxy-3,15-dioxa-8,9,10-trithia-4,14-disilaheptadecane	S3	0.8 - 1.4	0.8 - 1.1	40-110	0.5 - 1.0	0.014	Ca. 11 - 19 s	Ca. 15 - 40 h

 

The products of hydrolysis are: ethanol and (3-{[3-(trihydroxysilyl)propyl]disulfanyl}propyl)silanetriol and(3-{[3-(trihydroxysilyl)propyl]trisulfanyl}propyl)silanetriol for S2 and S3, respectively.

The hydrolysis data for substances used in this dossier for read-across purposes for other endpoints are now discussed.

Hydrolysis of the read-across substance Polysulfides, bis[3-(triethoxysilyl)propyl] (CAS Number: 211519-85-6)

Data for the substance polysulfides, bis[3-(triethoxysilyl)propyl] (CAS 211519-85-6) are read-across to the submission substance 4,4,13,13-tetraethoxy-3,14-dioxa-8,9-dithia-4,13-disilahexadecane for appropriate endpoints (see Section 1.4 of the CSR).

The properties of both substances and the rate of hydrolysis of the two substances are relevant to this read-across, as discussed in the appropriate Sections of the CSR for each endpoint. Polysulfides, bis[3-(triethoxysilyl)propyl] (CAS No: 211519-85-6) is also known as Reaction mass of 4,4,15,15-tetraethoxy-3,16-dioxa-8,9,10,11-tetrathia-4,15-disilaoctadecane and 4,4,14,14-tetraethoxy-3,15-dioxa-8,9,10-trithia-4,14-disilaheptadecane and 4,4,13,13-tetraethoxy-3,14-dioxa-8,9-dithia-4,13-disilahexadecane. It is a multiconstituent substance with three constituents. Each constituent is a bis[3-triethoxysilyl)propyl)polysulfide, where the number of sulfur atoms is 2 to 4. The constituents may be denoted as S2, S3 and S4 respectively.

For the three constituents S2, S3 and S4, hydrolysis half-lives at 20 - 25°C of S2 and S3 are discussed above for the registration substance. For S4, the hydrolysis half-lives are: 0.8 – 1.5 h at pH 4, 40 - 130 h at pH 7 and 0.5 – 1.4 h at pH 9.

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 submission substance above. This gives half-lives of 0.008 – 0.012 h (approximately 30 - 40 seconds), 0.008 – 0.014 h (approximately 30 - 50 seconds) and 0.008 – 0.015 h (approximately 30 - 54 seconds) at pH 2 and 20 - 25°C for S2, S3 and S4 respectively. At pH 2 and 37.5°C, half-lives of S2, S3 and S4 are approximately 11 – 14 seconds, 11 – 18 seconds and 11 – 20 seconds respectively. Similarly, at pH 7 and 37.5°C, half-lives of S2, S3 and S4 are approximately 15- 30 h, 15- 40 h and 15 – 50 h respectively.

The hydrolysis products for S2, S3 and S4 respectively are (3-{[3-(trihydroxysilyl)propyl]disulfanyl}propyl)silanetriol, (3-{[3-(trihydroxysilyl)propyl]trisulfanyl}propyl)silanetriol, [3-({[3-(trihydroxysilyl)propyl]disulfanyl}disulfanyl)propyl]silanetriol and ethanol.