4,4,13,13-tetraethoxy-3,14-dioxa-8,9-dithia-4,13-disilahexadecane

Hydrolysis

Link to relevant study record(s)

Reference

Reference 1

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, but not (completely) 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

pH:

4

DT50:

>= 0.8 - <= 1.2 h

Remarks on result:

other: Temperatures; 20-25°C

pH:

7

DT50:

>= 40 - <= 80 h

Remarks on result:

other: Temperatures; 20-25°C

pH:

9

DT50:

>= 0.5 - <= 1 h

Remarks on result:

other: Temperatures; 20-25°C

Conclusions:

Hydrolysis half-life values of 0.8-1.2 h at pH 4, 40-80 h at pH 7 and 0.5-1.0 h at pH 9 and 20-25°C were obtained for the substance using an accepted calculation method. The result is considered to be reliable.

Reference 2

Endpoint:

hydrolysis

Data waiving:

study technically not feasible

Justification for data waiving:

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

Description of key information

Hydrolysis half-lives: 40 - 80 h at pH 7, 0.8 - 1.2 h at pH 4 and 0.5 - 1 h at pH 9 and 20-25°C (QSAR)

Key value for chemical safety assessment

Half-life for hydrolysis:

80 h

at the temperature of:

20 °C

Additional information

A hydrolysis study is considered not technically feasible because the water solubility of the substance is low (≤ 1 mg/l) and analytical method of sufficient sensitivity is not available. Clariant 1998, reported that the substance has a very low water solubility; therefore, at concentrations required for the hydrolysis study, no suitable analytical method is available.

 

The hydrolysis half-lives of the substance has been calculated using validated QSAR estimation methods to be 0.8 - 1.2 h at pH 4, 0.8 - 1.0 h at pH 5, 40 - 80 h at pH 7 and 0.5 – 1.0 h at pH 9 and 20-25°C. The result is considered to be reliable.

 

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^-4 mol 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 and 20-25°C is therefore 0.008-0.012 hours (approximately 30-40 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 substance, hydrolysis half-life at 37.5ºC and pH 7 (relevant for lungs and blood) is approximately 15-30 hours. At 37.5ºC and pH 2 (relevant for conditions in the stomach following oral exposure), the hydrolysis half-life is approximately 11-14 seconds.

 

The hydrolysis products are (3-{[3-(trihydroxysilyl)propyl]disulfanyl}propyl)silanetriol and ethanol.

 

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, bis[3-(triethoxysilyl)propyl]polysulfides (CAS 211519-85-6, EC No. 915-673-4)

 

Data for the substance, bis[3-(triethoxysilyl)propyl]polysulfides  (EC name: 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 and 4,4,15,15-tetraethoxy-3,16-dioxa-8,9,10,11-tetrathia-4,15-disilaoctadecane, 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 the following endpoints: toxicity to aquatic algae; toxicity to microorganisms; acute toxicity: inhalation; skin sensitisation; mammalian mutagenicity; reproductive and developmental toxicity. For the short-term toxicity to aquatic invertebrates, acute toxicity: oral, acute toxicity: dermal and repeated dose toxicity: oral, available studies are used as supporting studies. 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 section for each endpoint.

 

Reaction Mass of 4,4,13,13-tetraethoxy-3,14-dioxa-8,9-dithia-4,13-disilahexadecane (S2) and 4,4,14,14-tetraethoxy-3,15-dioxa-8,9,10-trithia-4,14-disilaheptadecane (S3) and 4,4,15,15-tetraethoxy-3,16-dioxa-8,9,10,11-tetrathia-4,15-disilaoctadecane (S4) (CAS 211519-85-6) is a multi-constituent substance with three constituents and a named impurity, 4,4,16,16-tetraethoxy-3,17-dioxa-8,9,10,11,12-pentathia-4,16-disilanonadecane (S5). Each constituent and the named impurity is a bis[3-triethoxysilyl)propyl)polysulfide, where the number of sulfur atoms is 2 to 5. The constituents may be denoted as S2, S3 and S4, and the impurity as S5. The constituent S2 is the main constituent of the registered substance, and S3 is a named impurity.

 

For the three constituents S2, S3 and S4, and S5 impurity, hydrolysis half-lives at 20 -25°C of 40 - 80 h (S2), 40 - 100 h (S3), 40 - 120 h (S4) and 40 – 140 h (S5) at pH 7 were estimated by QSAR estimation methods. At pH 4 and 20-25°C, half-lives are 0.8–1.2 h (S2), 0.8–1.3 h (S3), 0.8–1.4 h (S4) and 0.8 - 1.6 h (S5); similarly, at pH 9, half-lives are 0.5–1 h (S2), 0.5–1.1 h (S3), 0.5–1.2 h (S4) and 0.5 - 1.5 h (S5).

 

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.

 

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 shown 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.

 

Table 4.1.2: Hydrolysis half-lives for the constituents of the read across substance (bis[3-(triethoxysilyl)propyl]polysulfides). The constituents include the submission substance (S2) and the named impurity of the submission substance (S3).

Substance name	Abbreviation	Half-lives at 20-25°C (h)				Half-lives at 20-25°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	40-80	0.5 - 1.0	0.012	ca. 16 s	ca. 28 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	0.013	ca. 17 s	ca. 34 h
4,4,15,15-Tetraethoxy-3,16-dioxa-8,9,10,11-tetrathia-4,15-disilaoctadecane	S4	0.8 - 1.5	0.8 -1.2	40-130	0.5 - 1.4	0.014	ca. 19 s	ca. 42 h
4,4,16,16-Tetraethoxy-3,17-dioxa-8,9,10,11,12-pentathia-4,16-disilanonadecane	S5	0.8 - 1.6	0.8 - 1.2	40 - 140	0.5 - 1.5	0.016	ca. 21 s	ca. 51 h

 

The products of hydrolysis are ethanol, and (3-{ [3-(trihydroxysilyl)propyl]disulfanyl} propyl)silanetriol, (3-{ [3-(trihydroxysilyl)propyl]trisulfanyl} propyl)silanetriol, [3-({ [3-(trihydroxysilyl)propyl]disulfanyl} disulfanyl)propyl]silanetriol and (3-{[3-(trihydroxysilyl)propyl]pentasulfanyl}propyl)silanetriol for S2, S3, S4 and S5, respectively.