2,2,4,4,6,6-hexamethylcyclotrisilazane

Hydrolysis

Description of key information

Hydrolysis: Half-life << 1 min at 25°C and pH 4, 7 and 9 (OECD 111) (read-across from an analogous organosilazane)

Additional information

No measured hydrolysis data are available for the registration substance. Si-N bonds are known to be energetically unfavourable compared to the much more stable Si-O, as a consequence of the much greater bond formation energy of Si-O (89 kCal/mol = 372 kJ/mol) compared to Si-N (77 kCal/mol = 322 kJ/mol), which leads to the ready exchange of oxygen for nitrogen in many Si-N containing compounds (Rochow, 1966). Bond dissociation energies of the Si-N bonds in the molecules Me₃Si-NHMe, Me3Si-NMe₂and Me₃Si-N(SiMe₃)₂lie in the range 98 -109 kCal/mol (=410-456 kJ/mol). The average bond dissociation energy for Si-O is 111 kCal/mol (464 kJ/mol) and that for Si-O in Me₃Si-OH is even more stable at 133 kCal/mol (556 kJ/mol) (all values taken from Gelest, undated). For substances with Si-N-Si bond, experience in handling and use indicates very rapid hydrolysis.

It is therefore relevant to refer to available hydrolysis evidence for other structures containing the structural feature Si-N-Si. A good example is 1,1,1,3,3,3-hexamethyldisilazane (CAS 999-97-3, HMDZ), for which reliable data on hydrolysis rate are available. The hydrolysis of hexamethyldisilazane to form ammonium ion and trimethylsilanol is well established. Hydrolysis of the Si-N bond results in the formation of amines/ammonia and silanols as co-products (Bazantet al1965).

Measured hydrolysis half-lives of ≤0.04 min, ≤0.5 min, and ≤0.1 at pH 4, 7 and 9 and 1.5°C respectively were determined for 1,1,1,3,3,3 -hexamethyldisilazane (CAS 999-97-3), in accordance with OECD 111 and in compliance with GLP. The read-across result is considered to be reliable and is selected as key study.

 

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 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

The calculated half-life of the registration substance at pH 2 and 1.5°C is therefore <0.0004 minutes (0.02 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 for 2,2,4,4,6,6-hexamethylcyclotrisilazane at pH 2 and 1.5°C is <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 2,2,4,4,6,6-hexamethylcyclotrisilazane, the predicted hydrolysis half-life at 37.5ºC and pH 7 (relevant for lungs and blood) is <2 seconds. As discussed above, it is appropriate to consider that the half-life at pH 7 and 37.5 ºC is <5 seconds. 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 <5 seconds.

The hydrolysis products of the registration substance are dimethylsilanediol and ammonia.

The hydrolysis products of the read-across substance 1,1,1,3,3,3-hexamethyldisilazane are trimethylsilanol and ammonia.

Ammonia (NH₃) exists in the aquatic environment in equilibrium with the ammonium ion. (NH₄⁺). Under normal environmental conditions of pH, ammonium ions (NH₄⁺) predominate.

 

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 dimethoxydimethylsilane (CAS 1112-39-6)

Data for the substance dimethoxydimethylsilane (CAS 1112-39-6) are read-across to the submission substance 2,2,4,4,6,6-hexamethylcyclotrisilazane for appropriate endpoints. The silanol hydrolysis product and the rate of hydrolysis of the two substances are relevant to this read-across, as discussed in the appropriate sections for each endpoint.

 

For dimethoxydimethylsilane (CAS 1112-39-6), hydrolysis half-lives at 20 -25°C of 0.7 h at pH 7, 0.1 h at pH 4 and 0.02 h at pH 9 were predicted for the substance using a validated QSAR estimation method. The predicted result is supported by a measured half-life of <0.6 h at pH 7 and pH 9 at 25°C (SEHSC 2008). 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 0.3 h at pH 7 and 37.5°C. The half-life for the substance at pH 2 and 37.5°C and pH 2 and 25°C is approximately 5 seconds.

The hydrolysis products in this case are dimethylsilanediol and methanol.

 

Hydrolysis of the read-across substance Dimethylsilanediol (CAS 1066-42-8)

Dimethylsilanediol is not susceptible to hydrolysis under conditions expectedin vivoand in the environment; it is one of the ultimate products of hydrolysis of the registration substance.

 

References:

Rochow, E.G. (1966): Polymeric methylsilazanes, Pure and Applied Chemistry, IUPAC, vol 13, issue 1, pp 247 -262

Walsh, R. (undated): Bond dissociation energies in organosilicon compounds. Department of Chemistry, University of Reading, UK, available online through Gelest Technical Library at http://www.gelest.com/gelest/forms/GeneralPages/technology_library.aspx

Bazant,V; Chvalovsky,V (1965). In Chemistry of Organosilicon Compounds; Organosilicon Compounds Volume 1; Academic Press Inc.:New York, 1965; pp. 85-86.