Octamethyltrisiloxane

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2007-10-18 to 2008-05-05

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to an appropriate OECD test guideline, and in compliance with GLP.

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

GLP compliance:

yes

Radiolabelling:

yes

Analytical monitoring:

yes

Details on sampling:

- Sampling intervals for the parent/transformation products: sampling was done at an appropriately spaced interval, based on the expected half-life, to obtain data in the desired range between 10 and 90% hydrolysis of the test substance. Reactions were usually followed for 2-3 half-lives.

Buffers:

- pH: 5
- Type and final molarity of buffer: 0.005M
- Composition of buffer: acetic acid with lithium hydroxide


- pH: 7
- Type and final molarity of buffer: 0.005M
- Composition of buffer: imidazole with hydrochloric acid


- pH: 9
- Type and final molarity of buffer: 0.005M
- Composition of buffer: boric acid with lithium hydroxide

Details on test conditions:

TEST SYSTEM
- Type, material and volume of test flasks, other equipment used: thin-wall KG-51 borosilicate glass tubes (5 mm o.d., 4.2 mm i.d., 200 mm length; Wilmad LabGlass, Buena, NJ, USA)

- Sterilisation method: Nalgene sterile filtration unit with a 0.20 um cellulose nitrate (CN) membrane used

- Measures taken to avoid photolytic effects: Samples were aged in dark incubator

- Measures to exclude oxygen: buffer solutions were sparged with helium gas for a minimum of 15 min to exclude oxygen and carbon dioxide

- If no traps were used, is the test system closed/open: closed

TEST MEDIUM
- Volume used/treatment:

- Kind and purity of water: deionized water from a Millipore Milli-Q Integral 5

- Preparation of test medium: The test medium was characterised prior to dilution. Primary stock solution was prepared by diluting the radiolabelled sample in acetonitrile.

Temp.:

25

Positive controls:

no

Negative controls:

no

Preliminary study:

The preliminary test at 50C was not conducted since the substance was expected to be hydrolytically unstable (t1/2 < 1 year). The definitive kinetic experiments were conducted for pH 5, 7, and 9 at each of the three temperatures 10, 25, and 35C.

Transformation products:

yes

No.:

#1

No.:

#2

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

The following mechanism is proposed for hydrolytic degradation of MDM to HODOH in dilute aqueous solution:

MDM→MDOH→HODOH

where HODOH refers to dimethylsilanediol. Production of trimethylsilanol as a co-product in the consecutive hydrolysis steps is implied, as well as co-reactant H2O for all steps; these are omitted from the scheme for clarity.

% Recovery:

89.5 - 100.5

pH:

5.01

Temp.:

25 °C

% Recovery:

65.3 - 82.2

pH:

6.98

Temp.:

25 °C

% Recovery:

85.8 - 92.9

pH:

9

Temp.:

25 °C

pH:

7

Temp.:

25 °C

Hydrolysis rate constant:

2.11 h-1

DT50:

13.7 d

pH:

5

Temp.:

25 °C

Hydrolysis rate constant:

0.136 h-1

DT50:

5.09 h

pH:

9

Temp.:

25 °C

Hydrolysis rate constant:

0.071 h-1

DT50:

9.76 h

Other kinetic parameters:

Due to the partitioning of the substance to the headspace of the test vessel, a non-linear regression that explicitly accounts for the partitioning process was used to analyse the pH 7 kinetic data. Data from the pH 5 and 9 experiments was also analysed by non-linear regression to allow k2 to be estimated.

k1 values obtained by the two methods were qualitatively consistent with the expectation that decreasing recovery produces an overestimate of k1 by linear regression analysis.

The rate constant for L3 (K1) and MDOH (k2) for the non-linear regression at neutral pH (pH 7) and 10°C, 25°C and 35°C are:

10°C- k1 = 5E-04 h-1, 25°C - k1 = 2E-03 h-1, 35°C- k1 = 5E-03 h-1
10°C- k2= 4E-04 h-1, 25°C - k2 = 2E-03 h-1, 35°C- k2 = 5E-03 h-1

Data for the pH 5 and 9 experiments were also analysed using non-linear regression to estimate k2, obs which cannot be obtained by linear regression analysis. In these cases, the rate of transfer of L3 from solution to the headspace was negligible compared to rate of hydrolysis.

Details on results:

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

Based on the number of components, their order of appearance through the course of hydrolysis, and their decreasing retention times (i.e. increasing polarity), the results were consistent with assignment of parent octamethyltrisiloxane (L3), followed by the expected intermediate, pentamethyldisiloxanol (MDOH), and final product, dimethylsilanediol. The co-product trimethylsilanol, Me3Si(OH), was not observed due to the selective placement of the 14C label on the Me2SiO2/2 unit during synthesis.

pH 7 experiments displayed a highly systemic recovery profile, in sharp contrast to the typically non-systemic variation observed in the non-neutral pH experiments. The systemic changes observed in the pH 7 systems were explained by exchange of L3 between the solution and the vapor phase in the vessel headspace, which was significant during these longer experiments. Consequently, non-linear regression analysis was required to obtain unbiased estimates of the L3 hydrolysis rate constants for the neutral pH experiments, as well as to obtain rate constants for hydrolysis of the MDOH intermediate whose concentration varied non-linearly with
time in all experiments.

Table 1: Average Percent ¹⁴C Recoveries Within Each Experiment

 

			Fitted Data Points			All Data Points
Date Initiated	Measured pH	Temp °C	Average Solution Recovery	High Recovery	Low Recovery	Average Solution Recovery	High Recovery	Low Recovery
10/25/07	5.01	25.0	94.1%	100.5%	89.5%	94.3%	100.5%	86.8%
10/30/07	7.02	10.0	62.8%	76.6%	53.8%	64.6%	89.1%	53.8%
10/30/07	6.98	25.0	71.4%	82.2%	65.3%	74.6%	94.5%	65.3%
11/5/07	7.01	35.0	59.8%	78.7%	47.4%	61.7%	96.7%	46.9%
11/20/07	4.95	35.0	90.7%	92.6%	87.8%	91.5%	99.2%	86.6%
11/27/07	4.98	10.0	93.9%	97.8%	88.2%	94.5%	109.3%	88.2%
12/4/07	8.99	10.1	87.3%	91.2%	80.1%	87.5%	91.2%	80.1%
12/4/07	9.00	25.0	89.1%	92.9%	85.8%	89.0%	92.9%	85.8%
12/12/07	8.99	35.0	90.3%	95.0%	79.3%	90.4%	95.0%	79.3%
12/20/07	8.97	34.9	87.7%	92.7%	83.0%	87.7%	92.7%	83.0%

Recovery:

The average solution recovery at pH 5 and 9 for all data point ranged from 88 - 95% for all experiment with a grand average of 91%. In most cases, the difference between the minimum and maximum recovery was <16% and the standard deviation within-experiment recovery ranged from 2 - 5%. For example, at pH 9 and 10°C experiment, a recovery profile spanning ~ three half-lives with an average recovery of 88% with a minor variation (4% RSD) was obtained. Solvent rinses minimally contributed to the total recovery, suggesting little or no physical adsorption of the test substance or hydrolysis products to the wall of the sample vessels.

The range of average recovery at pH 7 experiment was 62 - 75%. The low recovery data obtained at pH7 suggest that partitioning to the small (estimated 5% of the total volume) but unavoidable headspace volume in each tube was responsible for the systematic decrease in recovery. The losses to volatilization were modelled by non-linear regression using a two-box model to account for this loss mechanism and to avoid overestimating kobs.

Table 2: Summary of Kinetic Results Based on Linear Regression Analysis

 

Initiation Date	pH	Temp (°C)	Kinetic Range	Number of Points	k1(h^-1)	SE, k1   (h^-1)	r^2	t1/2(h)
11/27/2007	5	10	87-8%	10	4.54E-02	2.45E-04	0.9998	1.53E+01
10/25/2007	5	25	85-6%	9	1.36E-01	1.05E-03	0.9996	5.09E+00
11/20/2007	5	35	90-7%	9	2.87E-01	5.02E-03	0.9979	2.41E+00
12/04/2007	9	10	84-15%	11	1.01E-02	2.73E-04	0.9935	6.86E+01
12/04/2007	9	25	92-11%	10	7.11E-02	4.81E-04	0.9996	9.76E+00
12/12/2007	9	35	85-12%	11	2.46E-01	8.29E-03	0.9899	2.82E+00
12/20/2007	9	35	84-16%	9	2.41E-01	5.17E-03	0.9968	2.88E+00

Table 3: Final Parameter Values from Curve Fitting of Experimental Data Using a Two-Box Model

 

Initiation Date	Nominal pH	Temp. (ºC)	Kinetic Range	Number of Points	k1(h^-1)	k2(h^-1)	νiw     (cm h^-1)	Kia/w
10/30/2007	7	10	91-7%	14	4.74E-04	3.85E-04	1.12E-02	53.1
10/30/2007	7	25	82-8%	13	2.11E-03	1.86E-03	2.68E-02	30.6
11/05/2007	7	35	88-11%	9	4.92E-03	5.30E-03	1.06E-01	128
11/27/2007	5	10	87-8%	10	4.56E-02	2.06E-02
10/25/2007	5	25	85-6%	9	1.43E-01	6.22E-02
11/20/2007	5	35	90-7%	9	2.66E-01	1.30E-01
12/04/2007	9	10	84-15%	11	1.09E-02	2.00E-02
12/04/2007	9	25	92-11%	10	7.17E-02	1.35E-01
12/12/2007	9	35	85-12%	11	2.41E-01	4.68E-01
12/20/2007	9	35	84-16%	9	2.39E-01	4.60E-01

Note: The parameters,, and A were treated as constants during non-linear regression analyses and held at 2.2 cm³, 0.14 cm³, and 0.14 cm², respectively, for all experiments

Table 4: Estimated Catalytic Constants and Predicted Half-Life for Hydrolysis of MDM

 

	Nominal Temp (± 0.2 °C)
	10	25	35
kH3O+, 10^3M^-1h^-1	4.54	13.6	28.7
kOH-, 10^3M^-1h^-1	1.01	7.11	24.3
kOH- /kH3O+	0.22	0.52	0.85
k1, pH7, 10^-3h^-1	0.470	2.11	4.92
k2, pH7, 10^-3h^-1	0.378	1.86	5.30

Validity criteria fulfilled:

yes

Conclusions:

A hydrolysis half-life of 13.7 d (329 h) at pH 7 and 25°C was determined for the substance using an appropriate method. The result is considered reliable.

Description of key information

Hydrolysis half-life: 329 h (13.7 d) at pH 7, 9.76 h at pH 9, 5.09 h at pH 5 and 25°C (measured data). The stated half-life is for removal of parent. Complete reaction to the ultimate end products will take longer.

Key value for chemical safety assessment

Half-life for hydrolysis:

13.7 d

at the temperature of:

25 °C

Additional information

Hydrolysis half-lives of 329 h (13.7 d) at pH 7, 9.76 h at pH 9, and 5.09 h at pH 5 and 25°C were determined for the substance using a method in accordance with OECD 111 and in compliance with GLP. The result is considered to be reliable and was selected as key study.

Octamethyltrisiloxane (L3) is a linear siloxane chain with three silicon atoms, connected by two oxygen atoms, in which the Si-O bonds are susceptible to hydrolysis. All silicon atoms present are fully substituted with methyl groups. The stated half-life is for removal of the registration substance due to hydrolysis. The products of this reaction are also unstable in water, and so further hydrolysis reactions will follow, the ultimate products being dimethylsilanediol (1 mole) and trimethylsilanol (2 moles) per mole of parent substance. The reaction pathway reported is:

	k1		k2
Me3Si(OSiMe2)OSiMe3	→	Me3Si(OSiMe2)OH	→	H(OSiMe2)OH

Regression analysis (concentration versus reaction time) was performed on the experimental data. The experiments conducted at pH 7 were more susceptible to recovery decreases by partitioning of L3 into vapour phase due to the extended durations of the study. Therefore, to explicitly account for this process, the pH 7 experiments were analysed using non-linear regression. Similarly, non-linear regression was applied to the data at pH 5 and pH 9, the rate of transfer of L3 from solution to the headspace was negligible compared to rate of hydrolysis.

The following estimates of the rate constants for hydrolysis of parent substance and intermediate hydrolysis product at pH 7 and 10°C, 25°C and 35°C were obtained by non-linear regression of the measured results:

10°C k₁= 4.7E-04 h^-1,           25°C k₁= 2.1E-03 h^-1,           35°C k₁= 4.9E-03 h^-1

10°C k₂= 3.9E-04 h^-1,           25°C k₂= 1.9E-03 h^-1,           35°C k₂= 5.3E-03 h^-1

Predicted rates of hydrolysis for pH 7 based on these rate constants agreed with measured values to within 13%. This suggested that catalysis by hydronium and hydroxide accounts for the observed rates at neutral pH, with catalysis by hydronium dominating at lower temperature.

The rate of reaction of the intermediate hydrolysis product was as fast, or faster, than that of the parent substance.

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 5 [H₃O⁺] = 10^-5mol dm^-3and at pH 2 [H₃O⁺] = 10^-2mol dm^-3; therefore, k_obsat pH 2 should be approximately 1000 times greater than k_obsat pH 5.

The half-life of a substance at pH 2 is calculated based on:

t_1/2(pH 2) = t_1/2(pH 5) / 1000

The calculated half-life of the substance at pH 2 is therefore 0.0014 hours.

Reaction rate increases with temperature therefore hydrolysis will be faster at physiologically relevant temperatures compared to standard laboratory conditions. For L3 the hydrolysis half-life at 37.5ºC and pH 7 (relevant for lungs and blood) is calculated as 106 hours. At 37.5ºC and pH 2 (relevant for conditions in the stomach following oral exposure), the hydrolysis half- life is calculated as 7.5 seconds. At 37.5°C and pH 5.5 (relevant for dermal exposure), the hydrolysis half-life is calculated as 6.6 hours.

In a further study report (Dow Corning Corporation 2016), hydrolysis half-lives over a range of pH at 25°C, 12°C and 9°C were calculated using data from the key study (Dow Corning Corporation 2007). 12°C and 9°C are considered broadly representative of freshwater and marine environments, respectively. The Arrhenius parameters were derived by linear regression analysis of the original experimental data, and subsequently rate constants were calculated for temperatures and pH range of interest.

	Half-life at 9°C (days)	Half-life at 12°C (days)	Half-life at 25°C (days)
pH 6	7	5.5	2.1
pH 7	58	44.1	13.5
pH 8	31.9	21	3.9

 For the environmental exposures assessment, the parent will be considered as the half-life for hydrolysis of the parent is greater than 12 hours at pH 7.

 

Hydrolysis of the read-across substance decamethyltetrasiloxane (CAS 141-62-8)

Data for the substance decamethyltetrasiloxane (CAS 141-62-8)are read-across to the submission substance octamethyltrisiloxane for appropriate endpoints (see Section 1.4 of the CSR).The silanol hydrolysis product of the two substances is relevant to this read-across, as discussed in the appropriate Sections of the CSR for each endpoint.

For decamethyltetrasiloxane, hydrolysis half-lives at 25°C of 14 h at pH 5, 728 h (30.3 days) at pH 7 and 21.1 h at pH 9 were determined in accordance with OECD 111 (Dow Corning Corporation, 2009).

The half-lives at pH 4 and 25°C, 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 3.6 h at pH 4 and 25°C, 0.036 h at pH 2 and 25°C, 19 seconds at pH 2 and 37.5°C and 270 h at pH 7 and 37.5°C.

The ultimate products of hydrolysis are dimethylsilanediol and trimethylsilanol. 

Hydrolysis of the read-across substance hexamethyldisiloxane (CAS 107-46-0)

Data for the substance hexamethyldisiloxane(CAS 107-46-0) are read-across to the submission substance octamethyltrisiloxane for appropriate endpoints (see Section 1.4 of the CSR).The silanol hydrolysis product of the two substances is relevant to this read-across, as discussed in the appropriate Sections of the CSR for each endpoint.

For hexamethyldisiloxane, hydrolysis half-lives at 25°C of 1.4 h at pH 5, 120 h at pH 7 and 12.4 h at pH 9 were determined in accordance with OECD 111 (Dow Corning Corporation, 2006b).

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 <0.014 h (<50 seconds) at pH 2 and 25°C, and 44 h at pH 7 and 37.5°C. At pH 2 and 37.5°C, the hydrolysis half-life is <18 seconds.

The ultimate hydrolysis product is trimethylsilanol.