Cyclohexyldimethoxymethylsilane

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2011-10-04 to 2011-12-12

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

The concentrations of the test substance were determined immediately after preparation (t=0) and at several sampling points after t=0. The samples taken were cooled to room temperature using running tap water. Immediately after cooling, 4 ml of each sample was added to 4 ml hexane for extraction of the test substance by shaking for 30 seconds. The extracts were subsequently analysed.

Samples have to be extracted with n-hexane as soon as possible to maximise accuracy and repeatability.

Buffers:

- pH: 4
- Type and final molarity of buffer: Acetate
- Composition of buffer: 0.1 M solution of 16.6% (v/v) 0.1 M sodium acetate and 83.4% (v/v) 0.1 M acetic acid. The buffer contains 0.0009% (w/v) sodium azide.

- pH: 7
- Type and final molarity of buffer: Phosphate
- Composition of buffer: Phosphate buffer pH 7, 0.1 M solution of 0.1 M potassium dihydrogenphosphate adjusted to pH 7 using 10 N sodium hydroxide. The buffer contains 0.0009% (w/v) sodium azide.

- pH: 9
- Type and final molarity of buffer: Borate
- Composition of buffer: 0.1 M solution of 0.1 M boric acid and 0.1 M potassium chloride adjusted to pH 9 using 10 N sodium hydroxide. The buffer contains 0.0009% (w/v) sodium azide.

Details on test conditions:

TEST SYSTEM (main study)
- Type, material and volume of test flasks, other equipment used: For each sampling time, duplicate sterile vessels under vacuum were filled with 6 ml test solution and placed in the dark in a temperature controlled environment.
- Sterilisation method: filtration
- Lighting: test conducted in the dark
- Measures to exclude oxygen: purged with N2 gas for 5 minutes
- Is there any indication of the test material adsorbing to the walls of the test apparatus? No

TEST MEDIUM
- Volume used/treatment: 6 ml
- Kind and purity of water: Tap water purified by a Milli-Q water purification system
- Identity and concentration of co-solvent: The test substance was spiked to the solutions at a target concentration of
2.5 mg/l using a spiking solution in acetone.

OTHER TEST CONDITIONS
- Adjustment of pH: refer to information on buffers.

Duration:

1.1 h

pH:

4

Initial conc. measured:

1.68 mg/L

Duration:

0.6 h

pH:

4

Initial conc. measured:

1.99 mg/L

Duration:

91.5 h

pH:

7

Initial conc. measured:

2.14 mg/L

Duration:

54.5 h

pH:

7

Initial conc. measured:

2.09 mg/L

Duration:

95.5 h

pH:

9

Initial conc. measured:

2.52 - 2.55 mg/L

Duration:

69.5 h

pH:

9

Initial conc. measured:

2.1 - 2.14 mg/L

Number of replicates:

two

Positive controls:

no

Negative controls:

no

Transformation products:

not measured

Key result

pH:

4

Temp.:

20 °C

Hydrolysis rate constant:

2.87 h-1

DT50:

0.24 h

Type:

(pseudo-)first order (= half-life)

Remarks on result:

other: Coefficient of correlation 0.998

Key result

pH:

4

Temp.:

25 °C

Hydrolysis rate constant:

4.15 h-1

DT50:

0.17 h

Type:

(pseudo-)first order (= half-life)

Remarks on result:

other: Coefficient of correlation 0.996

Key result

pH:

7

Temp.:

20 °C

Hydrolysis rate constant:

0.029 h-1

DT50:

24 h

Type:

(pseudo-)first order (= half-life)

Remarks on result:

other: Coefficient of correlation 0.98

Key result

pH:

7

Temp.:

25 °C

Hydrolysis rate constant:

0.031 h-1

DT50:

19 h

Type:

(pseudo-)first order (= half-life)

Remarks on result:

other: Interpolated conclusion

Key result

pH:

7

Temp.:

30 °C

Hydrolysis rate constant:

0.047 h-1

DT50:

15 h

Type:

(pseudo-)first order (= half-life)

Remarks on result:

other: Coefficient of correlation 0.98

Key result

pH:

7

Temp.:

50 °C

Hydrolysis rate constant:

0.149 h-1

DT50:

4.7 h

Type:

(pseudo-)first order (= half-life)

Remarks on result:

other: Coefficient of correlation 0.992

Key result

pH:

9

Temp.:

20 °C

Hydrolysis rate constant:

0.024 h-1

DT50:

29 h

Type:

(pseudo-)first order (= half-life)

Remarks on result:

other: Coefficient of correlation 0.97

Key result

pH:

9

Temp.:

25 °C

Hydrolysis rate constant:

0.031 h-1

DT50:

22 h

Type:

(pseudo-)first order (= half-life)

Key result

pH:

9

Temp.:

30 °C

Hydrolysis rate constant:

0.04 h-1

DT50:

18 h

Type:

(pseudo-)first order (= half-life)

Remarks on result:

other: Coefficient of correlation 0.98

Key result

pH:

9

Temp.:

50 °C

Hydrolysis rate constant:

0.15 h-1

DT50:

4.6 h

Type:

(pseudo-)first order (= half-life)

Remarks on result:

other: Coefficient of correlation 0.994

Other kinetic parameters:

A rate constant and half-life at 50°C at pH 4 could not be determined due to the very fast rate of reaction.

Details on results:

TEST CONDITIONS
- pH, sterility, temperature, and other experimental conditions maintained throughout the study: Yes
- Anomalies or problems encountered (if yes): none

Table 1: Hydrolysis of dicyclopentyldimethoxysilane, expressed as percentage of the applied substance based on GC-FID analysis, at pH 7 and 20˚C

Compound	Sampling times (hours)
	0	0.5	1	19.5	22	27	43	46.3	50	72	91.5
Parent compound (mg.L)	2.14 2.14	2.05 1.99	2.01 2.11	0.958 0.864	0.912 1.01	0.759 0.901	0.500 0.539	0.382 0.396	0.284 0.388	0.231 0.263	0.168 0.168
Total % recovery	100 100	96 93	94 98	45 40	43 47	35 42	23 25	18 18	13 18	11 12	7.9 7.8

Table 2: Hydrolysis of dicyclopentyldimethoxysilane, expressed as percentage of the applied substance based on GC-FID analysis, at pH 7 and 30˚C

Compound	Sampling times (hours)
	0	3.5	5	7	23	25.5	28.75	30.75	47.25	54.5
Parent compound (mg.L)	2.09 2.09	1.73 1.81	1.44 1.49	1.27 1.30	0.499 0.488	0.574 0.559	0.431 0.424	0.414 0.411	0.244 0.272	0.186 0.157
Total % recovery	100 100	83 87	69 71	61 62	24 23	27 27	21 20	20 20	12 13	8.9 7.5

 

Table 3: Hydrolysis of dicyclopentyldimethoxysilane, expressed as percentage of the applied substance based on GC-FID analysis, at pH 4 and 20˚C

Compound	Sampling times (hours)
	0	0.083	0.17	0.25	0.33	0.42	0.50	0.58	0.67	0.75	1.1*
Parent compound (mg.L)	1.68 1.73	1.32 1.33	1.04 1.09	0.770 0.811	0.625 0.674	0.504 0.452	0.392 0.382	0.326 0.328	0.252 0.267	0.199 0.194	0.0711 0.0755
Total % recovery	99 102	78 78	61 64	45 48	37 40	30 27	23 22	19 19	15 16	12 11	4.2 4.4

* extrapolated results

 

Table 4: Hydrolysis of dicyclopentyldimethoxysilane, expressed as percentage of the applied substance based on GC-FID analysis, at pH 4 and 25˚C

Compound	Sampling times (hours)
	0	0.067	0.13	0.20	0.27	0.33	0.40	0.47	0.53	0.60
Parent compound (mg.L)	1.99 1.91	1.26 1.26	0.942 0.901	0.672 0.764	0.614 0.633	0.427 0.472	0.326 0.345	0.263 0.257	0.172 0.194	0.148 0.149
Total % recovery	102 98	65 65	48 46	35 39	32 33	22 24	17 18	14 13	8.8 10	7.6 7.7

 

 

Table 5: Hydrolysis of dicyclopentyldimethoxysilane, expressed as percentage of the applied substance based on GC-FID analysis, at pH 9 and 20˚C

Comp-ound	Sampling times (hours)
	0	0.3	0.7	1	1.3	2	4.5	23.5	31	47	54.5	76	95.5
Parent comp-ound (mg.L)	2.55 2.52	2.23*	2.14 2.21	2.12 2.16	2.17 2.18	2.07 2.13	1.82 2.03	0.886 0.85	0.932 0.816	0.626 0.53	0.447 0.467	0.515 0.389	0.288 0.213
Total % recovery	101 99	88	84 87	84 85	85 86	82 84	72 80	35 33	37 32	25 21	18 18	20 15	11 8.4

* misinjection

 

Table 6: Hydrolysis of dicyclopentyldimethoxysilane, expressed as percentage of the applied substance based on GC-FID analysis, at pH 9 and 30˚C

Compound	Sampling times (hours)
	0	3	4.5	6	21.5	24	26.3	29	46	53	69.5
Parent compound (mg.L)	2.14 2.10	1.75 1.85	1.80 1.73	1.60 1.59	0.657 0.649	0.559 0.547	0.530 0.519	0.462 0.430	0.326 0.315	0.212 0.217	0.150 0.151
Total % recovery	101 99	83 87	85 82	75 75	31 31	26 26	25 24	22 20	15 15	10 10	7.1 7.1

 

Validity criteria fulfilled:

yes

Conclusions:

A half-life of 19 h for hydrolysis of dicyclopentyldimethoxysilane at pH7 at 25ºC was determined in a reliable study, conducted according to an appropriate test protocol, and in compliance with GLP.

Description of key information

Hydrolysis: 0.17 hours at pH 4, 19 hours at pH 7 and 22 hours at pH 9 and 25°C (EU Method C.7) read across from a structural analogue.

Key value for chemical safety assessment

Half-life for hydrolysis:

19 h

at the temperature of:

25 °C

Additional information

Two preliminary hydrolysis studies are available for the submission substance. In Hogg 1995, hydrolysis half-lives of <2.4 hours at pH 4, pH 7 and pH 9 and 50°C were obtained for the submission substance in accordance with EU Method C.7. Similarly, in Berding 1989, hydrolysis half-lives of <1 day at pH 4, pH 7 and pH 9 and 50°C were also obtained for the substance according to OECD 111. Since the available studies on the submission substance are preliminary results, hydrolysis study from analogous substance, dicyclopentyl(dimethoxy)silane (DCPMS, CAS 126990-35-0) has been read-across.

For dicyclopentyl(dimethoxy)silane, hydrolysis half-lives reported below are obtained in a study conducted in accordance with EU Method C.7 and in compliance with GLP (Brekelmans 2012).

pH 4: 0.24 h at 20°C and 0.17 hours at 25°C

pH 7: 24 hours at 20°C, 19 hours at 25°C, 15 hours at 30°C and 4.7 hours at 50°C

pH 9: 29 hours at 20°C, 22 hours at 25°C, 18 hours at 30°C and 4.6 hours at 50°C

Both the submission substance, cyclohexyl(dimethoxy)methylsilane (CAS 17865-32-6) and the analogue substance, dicyclopentyl(dimethoxy)silane (CAS 126990-35-0) have two methoxy groups [Si(OCH₃)₂] which undergo 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 (188.34 and 228.41 g/mol respectively).

Analysis of parent substance in test media by gas chromatography was undertaken as part of the fish, invertebrates and algal inhibition studies performed using this substance (SafePharm Laboratories Ltd. 1996c, 1996d and 1996e respectively). The studies suggest that the half-life of the cyclohexyl(dimethoxy)methylsilane is approximately 24 hours at 14⁰C and pH 7 in the fish study and approximately 24 hours at 21⁰C and pH 7-8 in the freshwater invertebrate study. The hydrolysis rate appears to be faster in the algal study where the parent substance could not be traced in solution after 72 hours. The temperature of the algal study was 24⁰C and the pH range was 8 to 10. This is limited evidence for understanding of the half-life, but may be indicative of the potential for the submission substance to undergoes hydrolyses in contact with water.

The hydrolysis reactions of alkoxysilanes typically acid or base catalysed. 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^-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 the substance at pH 2 is therefore 0.0017 hours (approximately 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, for cyclohexyl(dimethoxy)methylsilane the hydrolysis half-life at 37.5ºC and pH 7 (relevant for lungs and blood) is approximately 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. At pH 5.5 and 37.5°C relevant for dermal absorption, the half-life will be between that of pH 4 and pH 7 (0.06 hours to 7 hours).

The hydrolysis products are cyclohexylmethylsilanediol and methanol.

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 dicyclopentyl(dimethoxy)silane (CAS 126990-35-0)

Data for the substance, dicyclopentyl(dimethoxy)silane (CAS 126990-35-0) are read-across to the submission substance cyclohexyl(dimethoxy)methylsilane (CAS 17865-32-6) for hydrolysis and toxicity to microorganisms endpoints. The silanol hydrolysis products and the rate of hydrolysis of the two substances are relevant to this read-across, as discussed in the appropriate sections for the endpoints.

For dicyclopentyl(dimethoxy)silane, the hydrolysis half-lives are discussed above.

The hydrolysis products are dicyclopentylsilanediol and methanol.

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

Data for the substance, dicyclopentyldichlorosilane, CAS 139147-73-2 are read-across to the submission substance cyclohexyl(dimethoxy)methylsilane (CAS 17865-32-6) for the toxicity to microorganisms endpoint. The silanol hydrolysis products and the rate of hydrolysis of the two substances are relevant to this read-across, as discussed in the appropriate sections for the endpoints.

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

The hydrolysis products are dicyclopentylsilanedioland methanol.