Methyl [3-(trimethoxysilyl)propyl]carbamate

Hydrolysis

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

hydrolysis

Type of information:

(Q)SAR

Adequacy of study:

key 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

Principles of method if other than guideline:

The result was obtained using an appropriate QSAR method (see attached QMRF and QPRF for details).

GLP compliance:

no

Estimation method (if used):

The result was obtained using an appropriate QSAR method (see attached QMRF and QPRF for details).

Transformation products:

yes

No.:

#1

No.:

#2

pH:

7

DT50:

3 h

Type:

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

Remarks on result:

other: 20-25°C

pH:

4

DT50:

0.2 h

Type:

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

Remarks on result:

other: 20-25°C

pH:

5

DT50:

0.3 h

Type:

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

Remarks on result:

other: 20-25°C

pH:

9

DT50:

0.1 h

Type:

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

Remarks on result:

other: 20-25°C

The result was obtained using an appropriate QSAR method (see attached QMRF and QPRF for details).

Validity criteria fulfilled:

not applicable

Conclusions:

A hydrolysis half life of approximately 3 h at 20-25°C and pH 7 was obtained using an accepted calculation method. The result is considered to be reliable.

Reference 2

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

16 Nov 2016 - 19 Sep 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Reason / purpose for cross-reference:

reference to same study

Qualifier:

no guideline followed

Principles of method if other than guideline:

- The hydrolysis test was conducted as a preliminary test within the purposes of an adsorption study according to OECD 106 (see cross reference). Soil samples from 5 different soil types (neutral pH) were weighed into test vessels with 0.01 M CaCl2-solution. After agitation overnight the aqueous phase was filtrated and fortified with the test item. Samples were shaken and at defined sampling points, samples were analyzed to determine hydrolysis of the test item.

GLP compliance:

yes (incl. QA statement)

Remarks:

Staatliches Gewerbeaufsichtsamt Hildesheim, Germany

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

- Concentrations tested: 1 mg/L
- Samples: Soils were weighed into the test vessels and an appropriate volume of 0.01 M CaCl2-solution was added. After agitation overnight (12 h minimum), the samples were used for experiments.. Afterwards, the aqueous phase was filtered and fortified with the test item. Samples were shaken on an overhead shaker. At defined sampling points, samples were stabilized with acetonitrile (factor 1.1)and subsequently analyzed to determine hydrolysis of the test item by analysing the concentration of Methyl-[3-trimethoxysilyl)propyl]carbamateby LC-MS/MS.

Estimation method (if used):

The response of the test item was determined as a function of time. The ln responses were plotted against time and the slope of the resulting regression graph gives the rate constant k [1/unit of time]:
K = - slope

The half-life (T½) [unit of time] of the reaction is given by:
T1/2= (0.693/kobs)

Details on test conditions:

TEST SYSTEM
- Type of test flasks: 20 mL headspace vials
- Sterilisation method: none
- Lighting: not specified
- Details on test procedure for unstable compounds: see details on sampling
- 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
- other: soil samples from 5 different soil types were weighed into the test vessels and an appropriate volume of 0.01 M CaCl2-solution was added

OTHER TEST CONDITIONS
- Adjustment of pH: no

Duration:

24 h

Temp.:

20 °C

Remarks:

Hydrolysis was measured in 5 different soils with pH between 5.5 and 7.2

Number of replicates:

two per soil

Transformation products:

not measured

pH:

7.1

Hydrolysis rate constant:

0.001 s-1

DT50:

1.8 h

Remarks on result:

other: Eurosoil 2

pH:

5.5

Hydrolysis rate constant:

0 s-1

DT50:

4.3 h

Remarks on result:

other: Eurosoil 3

pH:

6.7

Hydrolysis rate constant:

0 s-1

DT50:

2.2 h

Remarks on result:

other: Eurosoil 4

pH:

7.2

Hydrolysis rate constant:

0 s-1

DT50:

1 h

Remarks on result:

other: LUFA 2.4

pH:

7.2

Hydrolysis rate constant:

0 s-1

DT50:

1.9 h

Remarks on result:

other: LUFA 5M

Table 1: Determination of Hydrolysis in Aqueous Phase

Time [h]	Eurosoil 2		Eurosoil 3		Eurosoil 4		LUFA 2.4		LUFA 5M
	Mean c [mg/L]	%	Mean c [mg/L]	%	Mean c [mg/L]	%	Mean c [mg/L]	%	Mean c [mg/L]	%
0.00	0.991	-	0.990	-	0.977	-	0.991	-	0.991	-
0.25	0.759	77	0.836	84	0.829	85	0.674	68	0.786	79
0.5	0.614	62	0.743	75	0.718	74	0.530	53	0.644	65
1	0.476	48	0.631	64	0.613	63	0.403	41	0.530	53
2	0.278	28	0.509	51	0.445	46	0.203	21	0.342	35
4	0.127	13	0.401	41	0.299	31	0.0662	7	0.171	17
6	0.0491	5	0.285	29	0.166	17	0.0148	1	0.0794	8
24	0.0000632	0.006	0.0181	2	0.000387	0.040	-	-	0.000108	0.011

Mean c= mean concentration of two test item replicates, internal standard taken into account

% = percent of initially measured concentration, t0 set to 100%

Validity criteria fulfilled:

not applicable

Conclusions:

The test item is prone to fast hydrolysis. Therefore a Tier 1 test (preliminary study) in order to determine the hydrolysis half-lives of the substance in soil eluates was performed within the purposes of an adsorption study according to OECD guidance 106. The hydrolysis rate and a hydrolytic half-life were determined in soil-conditioned 0.01 M CaCl2 solution for each soil and spiked with the test item. Half-lives between 1 - 4.3 h were determined for the substance depending on the soil.

Description of key information

Hydrolysis: half-life ca. 3.0 h at 20-25°C and pH7 

Additional information

Methyl-N-[3 (trimethoxysilyl)propyl]carbamate hydrolysis rapidly when released in water. The substance has a two-step hydrolysis. The rate of formation of the first hydrolysis products, methyl-N-[3 (trihydroxysilyl)propyl]carbamate and methanol is relatively fast (half-life 3 h at room temperature and pH 7, QSAR - Peter Fisk Associates 2014, see below). However, the rate of formation of the ultimate hydrolysis products, (3-aminopropyl)silanetriol plus methanol and CO2, is extremely slow. Hydrolysis rates (half-life, 25’C, pH 7) of carbamates is reported to vary from a few seconds to 105 years; for a primary carbamate with two alkyl substituents (as is the case for this substance), the rate is likely to be towards the upper end of this range. For example, the hydrolysis half-life of O-ethyl-N-methylcarbamate is reported as being 40,000 years (Mabey & Mill, 1978).

A QSAR developed by Peter Fisk Associates (2014) predicts half-lives at 20-25°C of 0.2 h at pH 4, 0.3 h at pH 5, 3.0 h at pH 7 and 0.1 h at pH 9. 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.

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. This is supported by studies for various organosilicon compounds in which calculation of k_H3O+and k_OH-from the experimental results at pH 4 and 9, respectively, resulted in reasonable estimates of the half-life at pH 7.

Therefore, at low pH:

k_obs≈k_H3O+[H₃O⁺]

At pH 4 [H₃O⁺]=10^-4mol dm^-3and at pH2 [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

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.

Furthermore a hydrolysis study conducted as a preliminary test within the purposes of an adsorption study according to OECD 106, verifies experimentally the fast hydrolysis of the substance. The half-life of the substance was determined in soil eluates of 5 different soil types having neutral pH values (5.5 - 7.2). The parent substance was analytically monitored via LC-MS at time points 0, 0.25, 0.5, 1, 2, 4, 6 and 24 h. The hydrolysis half-lives were between 1 - 4.3 h, indicating rapid hydrolysis of the substance in soils of neutral pH.

The initial hydrolysis products are methyl-N-[3-(trihydroxysilyl)propyl]carbamate and methanol. Based on the experimental and calculated data it is concluded that the substance will hydrolyse rapidly under environmentally relevant conditions.

Reference:

Mabey W. & Mill T. (1978). Critical review of hydrolysis of organic compounds in water under environmental conditions. J Phys Chem Ref Data. 7(2): 383-415.