Dichlorocyclohexylmethylsilane

Hydrolysis

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

2012-05-07 to 2012-05-11

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

The study conducted according to a generally accepted scientific principles, but was not in compliance with GLP.

Qualifier:

according to guideline

Guideline:

EU Method C.7 (Degradation: Abiotic Degradation: Hydrolysis as a Function of pH)

Principles of method if other than guideline:

Screening method based on 1H-NMR spectroscopy.

GLP compliance:

no

Analytical monitoring:

not specified

Buffers:

pH 4: citrate buffer, pH 7: phosphate buffer and pH 9: borate buffer
- pH: 4
- Type and final molarity of buffer:
- Composition of buffer: Citric acid / sodiumhydroxide / chlorhydrogen, company Merck


- pH: 7
- Type and final molarity of buffer:
- Composition of buffer: Potassium dihydrogen phosphate / disodiumhydrogen phosphate; company Merck


- pH: 9
- Type and final molarity of buffer:
- Composition of buffer: CertiPur, Boron acid / potassium chloride / NaOH, company Merck

Duration:

27 min

pH:

4

Temp.:

27

Duration:

27 min

pH:

7

Temp.:

27

Duration:

27 min

pH:

9

Temp.:

27

Preliminary study:

The hydrolysis was observed to have been completed when the first NMR spectrum of each pH series were measured.

Transformation products:

no

pH:

4

Temp.:

27 °C

DT50:

< 27 min

Remarks on result:

other: Preliminary result

pH:

7

Temp.:

27 °C

DT50:

< 27 min

Remarks on result:

other: Preliminary result

pH:

9

Temp.:

27 °C

DT50:

< 27 min

Remarks on result:

other: Preliminary result

Other kinetic parameters:

None determined.

Details on results:

Due to the rapid hydrolysis during the preliminary study, the main study was not conducted.

Conclusions:

Hydrolysis half-lives of <<27 min at pH 4, pH 7 and pH 9 were determined at 27°C in a non-guideline study conducted according to generally accepted scientific principles. The result is considered reliable.

Reference 2

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

2001

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

The study was conducted according to a test protocol that is comparable to the appropriate OECD test guideline method. It was not compliant with GLP.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Deviations:

yes

Remarks:

Studies were conducted at 1.5±0.5 °C to slow the hydrolysis reaction rate.

GLP compliance:

no

Analytical monitoring:

no

Details on sampling:

Not applicable

Buffers:

Buffers were selected because they had a very low or non-detectable chloride ion concentration. Buffers were prepared by titration of acetic acid, sodium phosphate monobasic or boric acid with sodium hydroxide. Constant ionic strength of 0.50 M was maintained by addition of appropriate volumes of 5 M sodium nitrate solution. Buffer solutions were made to known final volumes in polypropylene volumetric flasks with deionized water. Final pH adjustments were made by dropwise addition of a 2M sodium hydroxide solution using a calibrate pH meter. Prior to use, all buffer solutions were sparged with argon for at least 15 minutes to exclude oxygen and carbon dioxide. The buffers were not sterilized. The pH of each buffer solution was measured just prior to the kinetic experiment for which it was used.

- pH: Target: 4.0; Measured: 4.00
- Type and final molarity of buffer: Acetic Acid/Sodium Hydroxide, 0.20M
- Composition of buffer: 100mL 1.00 M Acetic Acid solution, 20 mL 1M Sodium Hydroxide solution, 46 mL 5M Sodium Nitrate solution. Total volume 500 mL.

- pH: Target: 7.0; Measured: 7.01
- Type and final molarity of buffer: Sodium Phosphate, monobasic/Soidum Hydroxide, 0.20M
- Composition of buffer: 100mL 1.00 M Sodium Phosphate, monobasic solution, 61.5 mL 1M Sodium Hydroxide solution, 5.4 mL 5M Sodium Nitrate solution. Total volume 500 mL.

- pH: Target: 9.0; Measured: 8.99
- Type and final molarity of buffer: Boric acid/Sodium hydroxide, 0.30M
- Composition of buffer: 9.27 g boric acid (neat reagent), 53 mL 1M Sodium Hydroxide solution, 39.5 mL 5M Sodium Nitrate solution. Total volume 500 mL.

Estimation method (if used):

Not applicable.

Details on test conditions:

TEST SYSTEM
- Type, material and volume of test flasks, other equipment used: The vessels used for the individual hydrolysis experiments were wide mouth low-density polyethylene bottles (Cole-Parmer/Bel-Art, 90 mL, 52 x 69 mm) with screw caps. Plastic, instead of glass containers were used since it is
known that the SiOH layer on glass will react with SiCl compounds (Smith, A.L., The Analytical Chemistry of Silicones (1991) 112, 29.). One screw cap was fitted with a rubber grommet to hold the chloride electrode securely in place and a rubber septa (Aldrich, Suba-Seal, i.d. 9.5 mm) to allow injection of the chlorosilane solution using a microliter syringe. The modified screw cap w as used with a new vessel for each pH and chlorosilane hydrolysis experiment after replacing the rubber septa and cleaning the chloride electrode with deionized water.
- Sterilisation method: The vessels were not sterilized.
- Lighting: No details given.
- Measures taken to avoid photolytic effects: No photolytic effects expected.
- Measures to exclude oxygen: Stock solutions of the test substance were prepared in a nitrogen-purged glove bag. Buffer solutions were purged with argon for 15 minutes before use.
- Details on test procedure for unstable compounds: The test substance is very unstable in contact with moisture. Acetonitrile was used to make up the stock solutions; it is considered a suitable solvent for chlorosilanes. Solutions of the test substance were prepared inside a nitrogen-purged glove bag and stored in 22-mL plastic vials having septum lined open-top caps (oven dried to remove trace moisture). When not in use, the kinetic solutions were stored in a secondary airtight container filled with Drierite.
- Details of traps for volatile, if any: None.
- If no traps were used, is the test system closed/open: Closed
- Is there any indication of the test material adsorbing to the walls of the test apparatus?: No (see comments above on selection of test vessels)

TEST MEDIUM
- Volume used: 450 µL of the test substance in acetonitrile was injected into 50 mL of the buffer solution.
- Preparation of test medium: A 0.1M stock solution of the test substance in acetonitrile was prepared. This was injected directly into the buffer solution at the start of the hydrolysis experiment.
- Renewal of test solution: Not applicable.
- Identity and concentration of co-solvent: Acetonitrile (99.93% purity), 0.9% in final test solution.

OTHER TEST CONDITIONS
- Adjustment of pH: No pH adjustment was carried out during the test.
- Dissolved oxygen: No details given.

Duration:

2.3 min

pH:

4

Initial conc. measured:

0.001 mol/L

Duration:

4 min

pH:

7

Initial conc. measured:

0.001 mol/L

Duration:

2.7 min

pH:

9

Initial conc. measured:

0.001 mol/L

Number of replicates:

Replicates:  One at pH 4, 7, and 9

Positive controls:

not specified

Negative controls:

not specified

Statistical methods:

Since the hydrolysis was so rapid, there was insufficient data to use statistical methods to interpret the results.

Preliminary study:

The substance is known to be unstable at environmentally relevant temperatures, therefore, no preliminary study was required.

Test performance:

There were a few instances where higher than expected [Cl-] readings (called spikes hereafter) were observed. The definitive reason for the spikes is unknown, however, possible causes were: (a) hydrolysis product precipitate physcially striking the sensing membrane, or (b) the chlorosilane solution was injected into the buffer too fast causing a disturbance to the sensing membrane, or (c) the chloride ion concentration was temporarily concentrated near the sensing membrane prior to achieving a homogeneous solution. The spikes had no effect on the hydrolysis results.

Transformation products:

yes

No.:

#1

No.:

#2

Details on hydrolysis and appearance of transformation product(s):

- Formation and decline of each transformation product during test: Increase in chloride ion concentration was measured during the test.  For given solution conditions,the degradation product hydrogen chloride was observed to be stable during data collection.  Consequently, HCl was considered stable. The total concentrations of chloride ion as a percentage of the theoretical concentration at the end of the tests were 99%, 105% and 95% at pH 4, 7 and 9, respectively.
The stability of silanol was not measured, however silanols will undergo condensation reactions to form siloxanes (Smith, A. L., The Analytical Chemistry of Silicones 1991, 112, 12).
- Pathways for transformation: Due to the limitation imposed by the response time of the ion selective electrode, only the total hydrolysis could be studies potentiomaterically. It was not possible to differentiate between first, second and third chloride ion replacement by a hydroxyl group from the aqueous buffer, producing a silanol.

Key result

pH:

4

Temp.:

1.5 °C

DT50:

ca. 0.2 min

Type:

not specified

Remarks on result:

other: This value represents an estimated upper limit of the hydrolysis half-life. It refers to disappearance of the test material (based on chloride ion concentration) assuming the first hydrolysis step is rate limiting.

Key result

pH:

7

Temp.:

1.5 °C

DT50:

ca. 0.3 min

Type:

not specified

Remarks on result:

other: This value represents an estimated upper limit of the hydrolysis half-life. It refers to disappearance of the test material (based on chloride ion concentration) assuming the first hydrolysis step is rate limiting.

Key result

pH:

9

Temp.:

1.5 °C

DT50:

ca. 0.1 min

Type:

not specified

Remarks on result:

other: This value represents an estimated upper limit of the hydrolysis half-life. It refers to disappearance of the test material (based on chloride ion concentration) assuming the first hydrolysis step is rate limiting.

Other kinetic parameters:

None determined.

Details on results:

TEST CONDITIONS
- pH, sterility, temperature, and other experimental conditions maintained throughout the study: Yes

MAJOR TRANSFORMATION PRODUCTS
The chloride ion concentration was measured over the course of the hydrolysis. Measured concentrations are given in Tables 1-3.

INDICATION OF UNSTABLE TRANSFORMATION PRODUCTS:
- The silanol hydrolysis product is known to undergo condensation to siloxanes, however, the test report does not indicate that this was observed during the hydrolysis test.

PATHWAYS OF HYDROLYSIS
- Description of pathways: Hydrolysis is thought to proceed via consecutive replacement of Si-Cl with Si-OH. Due to the rapidity of the hydrolysis
further study of reaction pathways was not possible.
- Figures of chemical structures attached: No

Since the hydrolysis was so rapid, there was insufficient data to determine rate constants for the hydrolysis reactions by regression modelling. First order or pseudo-first order behaviour could not be confirmed because: (a) sparse nature of the data during the critical portion of the process (20 -70%) hydrolyzed), b) the inherent limitation associated with measuring co-product concentration for consecutive reactions, and (c) the relationship between k1, k2 and k3 is not known. Although rate constants and half-lives could not be determined quantitatively, the data was adequate for estimating the upper limit of t1/2.

Tables 1 - 3 show the results of the chloride ion measurements during the hydrolysis experiments. Table 4 illustrates the calculation of the hydrolysis half-lives at each pH.

Table 1. Results at pH 4

Time (sec)		[Cl-] (mM)	Blank Corrected [Cl-] (mM)*	% of Theoretical [Cl-]
10		0.699	0.667	33
20		0.748	0.716	35
30		1.08	1.05	52
40		1.22	1.19	59
50		1.43	1.40	69
60		1.59	1.56	77
70		1.78	1.75	87
80		1.95	1.92	95
90		2.02	1.99	99
100		2.03	2.00	99
110		2.03	2.00	99
120		2.03	2.00	99
130		2.03	2.00	99
140		2.03	2.00	99

* Subtracted chloride ion concentration measured in buffer blank = 0.0325 mM.

Table 2. Results at pH 7

Time (sec)		[Cl-] (mM)	Blank Corrected [Cl-] (mM)*	% of Theoretical [Cl-]
10		0.134	0.107	5
20		0.665	0.638	32
30		0.844	0.817	41
40		1.04	1.01	50
50		1.21	1.18	59
60		1.34	1.31	65
70		1.44	1.41	70
80		1.54	1.51	75
90		1.63	1.60	79
100		1.73	1.70	84
110		1.82	1.79	89
120		1.87	1.84	91
130		1.92	1.89	94
140		1.97	1.94	96
150		2.02	1.99	99
160		2.07	2.04	101
170		2.10	2.07	103
180		2.12	2.09	104
190		2.14	2.11	105
200		2.14	2.11	105
210		2.14	2.11	105
220		2.14	2.11	105
230		2.15	2.12	105
240		2.15	2.12	105

* Subtracted chloride ion concentration measured in buffer blank = 0.0275 mM.

Table 3. Results at pH 9

Time (sec)		[Cl-] (mM)	Blank Corrected [Cl-] (mM)*	% of Theoretical [Cl-]
10		1.68	1.64	81
20		1.21	1.17	58
30		1.45	1.41	70
40		1.64	1.60	79
50		1.81	1.77	88
60		1.87	1.83	91
70		1.89	1.85	92
80		1.91	1.87	93
90		1.92	1.88	94
100		1.93	1.89	94
110		1.93	1.89	94
120		1.93	1.89	94
130		1.95	1.91	95
140		1.94	1.91	94
150		1.95	1.91	95
160		1.95	1.91	95

* Subtracted chloride ion concentration measured in buffer blank = 0.0405 mM.

Table 4. Overall results

pH		Time to total hydrolysis	% Theoretical [Cl-] at this temperature	t1/2 / s*
4		100	99	10
7		170	102	17
9		70	92	7

* Time to total hydrolysis / 10

Validity criteria fulfilled:

yes

Conclusions:

A hydrolysis half-life of ca. 0.3 minutes at pH 7 and 1.5°C was determined in a reliable study conducted according to an appropriate test protocol. It was not conducted according to GLP.

Reference 3

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

The study was conducted according to an appropriate OECD test guideline, and in compliance with GLP, and was considered to be reliability 1 (reliable without restrictions). Read across to the registered substance is considered scientifically justified; the read across is considered to be reliability 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Deviations:

yes

Remarks:

The study was conducted at 1.5 °C ± 0.5 °C to slow the hydrolysis reaction rate.

GLP compliance:

no

Radiolabelling:

no

Analytical monitoring:

yes

Buffers:

Buffer solutions of known pH and concentration were prepared by titration of acetic acid, sodium phosphate monobasic and boric acid solution with sodium hydroxide solution. Constant ionic strength of 0.5 M was maintained for buffers by the addition of volumes of 5 M sodium nitrate solution.

Number of replicates:

One replicate per pH level

Transformation products:

yes

No.:

#1

No.:

#2

Details on hydrolysis and appearance of transformation product(s):

pH 4: t1/2= 6s, pH 7: t1/2= 10s, pH 9: t1/2= 8s

Key result

pH:

4

Temp.:

1.5 °C

DT50:

0.1 min

Key result

pH:

7

Temp.:

1.5 °C

DT50:

0.167 min

Key result

pH:

9

Temp.:

1.5 °C

DT50:

0.133 min

No rate constant or definative t1/2 determined due to rapidity of hydrolysis (sparse data points for 20-70% hydrolysed). Upper limit t1/2 estimated (assuming first hydrolysis step is rate-limiting). Observation of stable[Cl-] was used to estimate t1/2; assumed 10 half-lives = exhaustive hydrolysis.

Conclusions:

The half life of the test substance was reported to be 6 seconds at pH 4, 10 seconds at pH 7 and 8 seconds at pH 9.

Reference 4

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

The study was conducted according to an appropriate OECD test guideline, and in compliance with GLP, and was considered to be reliability 1 (reliable without restrictions). Read across to the registered substance is considered scientifically justified; the read across is considered to be reliability 2.

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Deviations:

yes

Remarks:

The study was conducted at 1.5 °C ± 0.5 °C to slow the hydrolysis reaction rate.

GLP compliance:

no

Radiolabelling:

no

Analytical monitoring:

yes

Buffers:

Buffer solutions of known pH and concentration were prepared by titration of acetic acid, sodium phosphate monobasic and boric acid solution with sodium hydroxide solution. Constant ionic strength of 0.5 M was maintained for buffers by the addition of volumes of 5 M sodium nitrate solution.

Number of replicates:

One replicate per pH level

Transformation products:

yes

No.:

#1

No.:

#2

Details on hydrolysis and appearance of transformation product(s):

pH 4: t1/2= 8s, pH 7: t1/2= 12s, pH 9: t1/2= 9s

Key result

pH:

4

Temp.:

1.5 °C

DT50:

0.133 min

Key result

pH:

7

Temp.:

1.5 °C

DT50:

0.2 min

Key result

pH:

9

Temp.:

1.5 °C

DT50:

0.15 min

No rate constant or definative t1/2 determined due to rapidity of hydrolysis (sparse data points for 20-70% hydrolysed). Upper limit t1/2 estimated (assuming first hydrolysis step is rate-limiting). Observation of stable[Cl-] was used to estimate t1/2; assumed 10 half-lives = exhaustive hydrolysis.

Conclusions:

The half life of dichloromethyl(3,3,3-trifluoropropyl)silane was reported to be 8 seconds at pH 4, 12 seconds at pH 7 and 9 seconds at pH 9.

Description of key information

Half-life <1 minute at 25°C and pH 4, pH 7 and pH 9 (analogue read-across).

Additional information

Measured hydrolysis half-lives of <<27 mins at pH 4, pH 7 and pH 9 and 27°C were determined for the substance in a study conducted according to generally acceptable scientific principles. Only a preliminary study was carried out and a more precise knowledge of the half-life is needed for use in the chemical safety assessment. Therefore, data are read-across from other dichlorosilanes.

Reliable studies according to OECD 111 are available for other related dichlorosilane substances: dichloro(dimethyl)silane, dichloromethyl(3,3,3-trifluoropropyl)silane and dichloro(diphenyl)silane. These substances are fully hydrolysed within a few minutes at pH 4, pH 7 and pH 9 and 1.5°C. This read-across is made in the context of evidence from other available data for chlorosilane structural analogues, as shown in the table below.

 

Dichloro(cyclohexyl)methylsilane contains the reactive group Si-Cl. Strong evidence based on read-across within the category of chlorosilanes is available to indicate that the Si-Cl bonds will rapidly hydrolyse to Si-OH with a half-life of ≤17 seconds at pH 4, pH 7 and pH 9 and 1.5°C (see below). The hydrolysis products are cyclohexyl(methyl)silanediol and hydrogen chloride.

 

For six substances, quantitative half-life data at 1.5ºC are available; a study with one further substance at 50ºC found no parent substance to be present at t₀, indicating extremely rapid hydrolysis. The measured half-lives at pH 4, 7 and 9 and 1.5ºC are all ≤17 s.

Table4.1.2: Hydrolysis data for chlorosilanes

CAS	Name	Result – half-life at pH 4 (seconds)	Result – half-life at pH 7 (seconds)	Result – half-life at pH 9 (seconds)	Temperature	Klimisch
75-77-4	Chlorotrimethylsilane	7	11	8	1.5 ± 0.5˚C	2
75-78-5	Dichloro(dimethyl)silane	10	17	7	1.5 ± 0.5˚C	2
75-79-6	Trichloro(methyl)silane	7	9	6	1.5 ± 0.5˚C	2
80-10-4	Dichloro(diphenyl)silane	6	10	8	1.5 ± 0.5˚C	2
675-62-7	Dichloromethyl(3,3,3-trifluoropropyl)silane	8	12	9	1.5 ± 0.5˚C	2
4518-98-3	1,1,2,2-tetrachloro-1,2-dimethyldisilane	8	7	7	1.5 ± 0.5˚C	2
5578-42-7	Dichloro(cyclohexyl)methylsilane	<<27 min	<<27 min	<<27 min	27°C	2
13154-25-1	Chlorotri(3-methyl-propyl)silane	Not quantified*	Not quantified*	Not quantified*	50˚C	1

*In this test the t₀analysis (50˚C) showed a recovery <LOD, suggestive of an extremely rapid reaction.

Hydrolysis half-lives of 10 seconds at pH 4, 17 seconds at pH 7 and 7 seconds at pH 9 and 1.5°C were determined for dichloro(dimethyl)silane in accordance with OECD 111 (Dow Corning Corporation 2001).

Hydrolysis half-lives of 8 seconds at pH 4, 12 seconds at pH 7 and 9 seconds at pH 9 and 1.5°C were determined for dichloromethyl(3,3,3-trifluoropropyl)silane in accordance with OECD 111 (Dow Corning Corporation 2001).

Hydrolysis half-lives of 6 seconds at pH 4, 10 seconds at pH 7 and 8 seconds at pH 9 and 1.5°C were determined for dichloro(diphenyl)silane in accordance with OECD 111 (Dow Corning Corporation 2001).

Since the hydrolysis was so rapid relative to the timescale of the analytical measurement, there was insufficient data to determine rate constants for the hydrolysis reactions of these chlorosilanes using regression modelling. However, the data was adequate for estimating the upper limit of t_1/2. Half-lives were estimated as 0.1t, where t=time for complete hydrolysis.

All of the tested substances have smaller alkyl side-chains than the registration substance. Based on consideration of the likely reaction mechanisms and comparison with the related group of alkoxysilane substances (cyclohexyldimethoxymethylsilane is predicted to hydrolyse about 6 times slower thandichloro(dimethyl)silane), this might result in the registration substance hydrolysing more slowly than the tested substances.

However, it is reasonable to conclude that the half-life of this substance at pH 4, pH 7 and pH 9 and 25ºC is <1 minute. This is based on (i) the extremely short half-lives for all substances where this has been measured; (ii) the lack of significant variation in the measured half-lives for different structures; (iii) the expected increase in reaction rate at 25ºC versus 1.5ºC; (iv) the extremely rapid hydrolysis at 50ºC of the sterically hindered chlorotri(3-methyl-propyl)silane; and (v) experience in handling and use.

Given the very rapid hydrolysis rates in water (≤17 seconds at 1.5°C and pH 4, pH 7 and pH 9) observed for all tested dichlorosilanes, and the lack of significant variation in the half-lives for the different substances, it is considered appropriate to read-across this result to dichloro(cyclohexyl)methylsilane.

Reaction rate increases with temperature, and therefore hydrolysis will be faster at 25ºCand at physiologically-relevant temperatures. Under ideal conditions, hydrolysis rate can be recalculated according to the equation:

DT₅₀(XºC) = DT₅₀(T°C) *e^(0.08.(T-X))

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

Using the longest half-life measured for the dichlorosilanes at 1.5ºC and pH 7 (17 seconds) the estimated hydrolysis half-life at 25ºC and pH 7 is 2.6 seconds. However, it is not appropriate or necessary to attempt to predict accurately when the half-life is less than 5-10 seconds. As a worst-case it can therefore be considered that the half-life of the substance at pH 7 and 25°C is approximately 5 seconds.

The estimated hydrolysis half-life at 37.5ºC and pH 7 (relevant for lungs and blood and in vitro and in vivo (intraperitoneal administration) assays) is 1 second, so worst-case approximately 5 seconds.

Using the longest half-life measured for the dichlorosilanes at 1.5ºC and pH 4 (10 seconds), the estimated hydrolysis half-life at 37.5ºC and pH 4 is 0.6 second, so worst-case approximately 5 seconds.

As the hydrolysis reaction may be acid or base catalysed, the rate of reaction is expected to be slowest at pH 7 and increase as the pH is raised or lowered (this is consistent with the data presented above). The half-life at pH 4 and 37.5°C is estimated to be around 5 s, therefore, the half-life at pH 2 and 37.5°C (relevant for oral exposure) is also estimated as 5 s as a worst-case. At 37.5ºC and pH 5.5 (relevant for dermal exposure), the hydrolysis half -life is estimated to be in between the half-lives at pH 4 and pH 7 at 37.5ºC, and thus also approximately 5 seconds as a worst case.

Hydrolysis in air

The above hydrolysis studies were carried out with the substance dissolved in water. Consideration of the rates of reaction with moisture in air is relevant for inhalation exposure assessment. Experience in handling and use, as well as the extremely rapid rates observed in the available water-based studies, would suggest that rates of reaction in moist air will also be rapid. If any unreacted chlorosilane were to reach the airways, it would rapidly hydrolyse in this very moist environment.

A simulated nose-only exposure study (Houghton 2013) has been conducted to determine hydrolytic stability of dichloro(dimethyl)silane under conditions typical of nose-only vapour inhalation exposures. The vapour generation was on 1 day for 3 hrs 14 minutes; concentrations of parent material were measured at 30 minute intervals using gas chromatography (GC). The nominal concentration was 50 ppm. The mean temperature was 21.6°C and the relative humidity (RH) was 57%. 24% parent concentration remaining in the test atmosphere relative to nominal concentration was measured by GC. This indicates 76% hydrolysis of the parent substance had taken place by the time the test atmosphere reached the GC. It was concluded that at least 20-29% of the parent test article would be present in the breathing zone relative to the nominal concentration under typical conditions used for nose-only inhalation exposure of rats. It is therefore possible to expose rats in a nose-only study to parent chlorosilane, because the transit time from the substance reservoir to the nose is very rapid (<1 second), however, this is not considered to be representative of human exposure conditions.

This represents extremely rapid hydrolysis because the time taken for the test substance to reach the GC was very short (13-15 seconds).The authors of this summary have used the information from this study to estimate a half-life for dichloro(dimethyl)silane in air of approximately 7 seconds (95% confidence limit = 3 -11 seconds), which is comparable to the half-life in water.

In a study of the acute toxicity to rats via the inhalation route (Dow Corning Corporation 1997), dichloro(dimethyl)silane was quantified in the exposure chamber using Thermal Conductivity Detection and identification was confirmed using GC/MS. The relative humidity (RH) in the exposure chamber was 30 -35%. The mean measured concentrations in the exposure chambers during exposure (1 hour) was only about 15% of the nominal concentration of dichloro(dimethyl)silane. The test atmosphere contained an amount of chloride consistent with the nominal concentration of test article as determined via electrochemical detection. Thus, the majority of parent had hydrolysed in the test atmosphere at only 30-35% relative humidity.

Similarly, in a study to assess stability of dichloro(dimethyl)silane vapour in air using gas-sampling FTIR (Dow Corning 2009), dichloro(dimethyl)silane was observed to be extremely unstable in high relative humidity atmospheres. At 75% relative humidity (RH)level, a stable test atmosphere of the substance could not be generated. In dry air (<5% RH), the substance had achieved 28% loss after 1 hour and 71% loss after 3.2 hours.

The significant extent of chlorosilane hydrolysis demonstrated in the studies with dichloro(dimethyl)silane is in good agreement with the theoretical capacity for hydrolysis in air under conditions typical of a rat repeated exposure test.

Theoretically, air at 20°C and 50% relative humidity would have more than 100 times the amount of water necessary for complete hydrolysis of dichloro(cyclohexyl)methylsilane:

Water content of air at 20°C = 17.3 g/m³  (100% humidity)

Assuming a 50% humidity = 8.65g water/m³= 8.65 mg water/l

Molecular weight of water = 18 g/mole; So 8.65 mg water/l = 0.48 mmol water/l

50 ppm HCl is the estimated upper exposure limit based on HCl corrosivity for a repeated exposure test

As dichloro(cyclohexyl)methylsilane has 2 Cl groups this would be equivalent to 25 ppm

Molecular weight of dichloro(methyl)(phenyl)silane = 197.18 g/mol

25 ppm dichloro(cyclohexyl)methylsilane is equivalent to 202 mg/m³ or 0.001 mmol/l

Therefore, it can be concluded that the registered substance will hydrolyse very rapidly under conditions relevant for environmental and human health risk assessment and no further testing is necessary. It is not possible or necessary to attempt a quantitative prediction of rate or half-life because the chemical safety assessment is not sensitive to this uncertainty within this range. Additional information is given in a supporting report (PFA 2013ab) attached in Section 13.

The hydrolysis products for the present substance are cyclohexyl(methyl)silanediol and hydrochloric acid.

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

Hydrolysis of the read-across substance cyclohexyldimethoxymethylsilane (CAS 17865-32-6)

Data for the related substance, cyclohexyldimethoxymethylsilane (CAS 17865-32-6) are read-across to the submission substance dichloro(cyclohexyl)methylsilane for appropriate endpoints, e.g. biodegradation in water, short-term toxicity to fish, short-term toxicity to aquatic invertebrates, toxicity to algae, repeated dose toxicity - oral, in vitro cytogenicity and genetic toxicity in vivo. The silanol hydrolysis product of these substances are relevant to this read-across as discussed in the relevant sections for each endpoint.

The hydrolysis half-lives of cyclohexyldimethoxymethylsilane (CAS 17865-32-6, CHMS) were read-across from the hydrolysis study of the analogous substance, dicyclopentyldimethoxysilane (CAS 126990-35-0, DCPMS). For dicyclopentyldimethoxysilane (CAS 126990-35-0), hydrolysis half-lives at 25°C of 0.17 h at pH 4, 19 hours at pH 7 and 22 h at pH 9 were obtained using a suitable method (Method C.7) and in compliance with GLP (Brekelmans, M 2012). For cyclohexyldimethoxymethylsilane (CAS 17865-32-6), two preliminary studies reported hydrolysis half-lives of <1 day at 50°C and pH 4, pH 7 and pH 9 (Berding 1989) and <2.4 hours at 50°C at pH 4, pH 7 and pH 9 (Hogg 1995) were reported for the substance.

Both substances, CHMS and DCPMS have two methoxy groups which undergo the hydrolysis reaction. The substances have similar affinity with water (demonstrated by log K_ow values of 4.3 and 5.5 respectively). While the alkyl substituents differ, the two substances have a similar overall molecular weight, which can be an indicator of steric factors affecting the rate of reaction (188 g/mol and 196 g/mol respectively).

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-life ofdicyclopentyldimethoxysilaneat pH 2 and 25°C is therefore 0.0017 hours (6 seconds).However, it is not appropriate or necessary to attempt to predict accurately when the half-life is less than 5-10 seconds. As a worst-case it can therefore be considered that the half-life of the substance at pH 2 and 25°C is approximately 5 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) * e^(0.08.(T-X))

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

Thus, fordicyclopentyldimethoxysilanethe hydrolysis half-life at 37.5ºC and pH 7 (relevant for lungs and blood) is 7 hours. At 37.5ºC and pH 2 (relevant for conditions in the stomach following oral exposure), it is not appropriate to apply any further correction for temperature to the limit value and the hydrolysis half-life is therefore approximately 5 seconds.

The hydrolysis products are cyclohexyl(methyl)silanediol and methanol.

Hydrolysis of the read-across substance dichloro(dimethyl)silane (CAS 75-78-5)

Data for the substance dichloro(dimethyl)silane (CAS 75-78-5) are read-across to the submission substance dichloro(cyclohexyl)methylsilane for repeated dose toxicity- inhalation endpoint. The hydrolysis product of the two substances are relevant to this read-across, as discussed in each endpoint.

For dichloro(dimethyl)silane, hydrolysis half-lives at 1.5°C of <1 minute at pH 4, pH 7 and pH 9 were obtained for the substance.

The half-lives at pH 2 and 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 registration substance above. This gives a half-life of approximately 5 seconds.

The hydrolysis products are dimethylsilanediol and hydrochloric acid.

Hydrolysis of the read-across substance trichloro(methyl)silane (CAS 75-79-6)

Data for the substance trichloro(methyl)silane (CAS 75-79-6) are read-across to the submission substance dichloro(cyclohexyl)methylsilane for repeated dose toxicity- inhalation endpoint. The hydrolysis product of the two substances are relevant to this read-across, as discussed in each endpoint.

For trichloro(methyl)silane, hydrolysis half-lives at 1.5°C of <1 minute at pH 4, pH 7 and pH 9 were obtained for the substance.

The half-lives at pH 2 and 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 registration substance above. This gives a half-life of approximately 5 seconds.

The hydrolysis products are methylsilanetriol and hydrochloric acid.

Hydrolysis of the read-across substance dicyclopentyldichlorosilane (CAS 139147-73-2)

Data for related substance dicyclopentyldichlorosilane (CAS 139147-73-2) is read-across to the submission substance dichloro(cyclohexyl)methylsilane for appropriate endpoint e.g. toxicity to microorganisms. The silanol hydrolysis product of this substance is relevant to this read-across, as discussed in the appropriate sections of the endpoint.

For dicyclopentyldichlorosilane, hydrolysis half-lives at 25°C of <1 minutes at pH 4, pH 7 and pH 9 were read-across from other dichlorosilanes.