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Dissociation constant

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Endpoint:
dissociation constant
Type of information:
calculation (if not (Q)SAR)
Remarks:
estimated by calculation
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The result was obtained by the valid application of a well-established appropriate predictive method.
Principles of method if other than guideline:
The pKa of the amine group was obtained using the SPARC on-line property calculator.
GLP compliance:
no
Dissociating properties:
yes
No.:
#1
pKa:
17.48
Temp.:
22 °C
Conclusions:
A first pKa of 17.48 was determined for the substance using an appropriate predictive method.
Endpoint:
dissociation constant
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2008
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The study was well documented and meets generally accepted scientific principles, and conducted 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.
Justification for type of information:
The requirement to test the substance for dissociation constant is waived because in contact with water the substance rapidly hydrolyses to form methyl-N-[3(trihydroxysilyl)propyl]carbamate and methanol. There are no reliable measured data for the dissociation constant of methyl-N-[3(trihydroxysilyl)propyl]carbamate. The typical dissociation constants for the hydroxyl protons of silanetriols are available from studies in other silanetriols. It is appropriate to read-across dissociation constant data for methyl-N-[3(trihydroxysilyl)propyl]carbamate from phenylsilanetriol. This suggests that silanols are not expected to undergo significant dissociation within the range of pH relevant in the environment or in vivo. Phenylsilanetriol has a measured first dissociation constant of approximately 10 in a reliable study using a relevant test method (reliability 1; read across conclusion is given reliability 2).
Principles of method if other than guideline:
No determination of the dissociation constants in water was possible using OECD Method 112. The test material did not demonstrate pH sensitive spectral profiles in the ultraviolet region of the electromagnetic spectrum. In addition, the weakly acidic nature of the anticipated dissociating groups was not suitable for investigation by either the titration of conductometric methods. An estimation of the first dissociation constant was made using a procedure based on OECD Method 107 (partition coefficient by the shake flask method) and the relationship between partition coefficient, aqueous phase pH and dissociation constant.
GLP compliance:
yes (incl. certificate)
Dissociating properties:
yes
No.:
#1
pKa:
9.6
Temp.:
22 °C
Remarks on result:
other: ±0.3
No.:
#2
pKa:
> 11
Temp.:
22 °C
Remarks on result:
other: Estimate
No.:
#3
pKa:
> 11
Temp.:
22 °C
Remarks on result:
other: Estimate

The results of each determination are shown in the following table:

Nominal test pH

Sample Number

Aqueous Phase pH

Partition coefficient (P’ow)

Dissociation constant (pKa)

8.0

1

7.99

0.874

8.7*

8.0

2

8.03

0.941

8.9*

8.5

3

8.58

0.883

9.3

8.5

4

8.58

0.883

9.3

9.0

5

9.08

0.879

9.8

9.0

6

9.08

0.837

9.7

9.5

1

9.21

0.563

9.3

9.5

2

9.26

0.648

9.5

10.0

3

9.78

0.408

9.6

10.0

4

9.91

0.404

9.7

10.5

5

10.48

0.182

9.8

10.5

6

10.49

0.178

9.8

* The results at pH 8 were excluded from the determination of the final pKa mean and range on the basis that the accuracy of the estimation method decreased as the distance between the dissociation constant and the aqueous phase pH increased, pH 8.0 being >1.5 units from the final estimation value. This is consistent with the approach used in the titration method in OECD method 112.

Conclusions:
A first dissociation constant of 9.6 for phenylsilanetriol was determined in a reliable study conducted in compliance with GLP.
Endpoint:
dissociation constant
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
The requirement to test the substance for dissociation constant is waived because in contact with water the substance rapidly hydrolyses to form methyl-N-[3(trihydroxysilyl)propyl]carbamate and methanol. There are no reliable measured data for the dissociation constant of methyl-N-[3(trihydroxysilyl)propyl]carbamate. The typical dissociation constants for the hydroxyl protons of silanetriols are available from studies in other silanetriols. It is appropriate to read-across dissociation constant data for methyl-N-[3(trihydroxysilyl)propyl]carbamate from phenylsilanetriol. This suggests that silanols are not expected to undergo significant dissociation within the range of pH relevant in the environment or in vivo. Phenylsilanetriol has a measured first dissociation constant of approximately 10 in a reliable study using a relevant test method (reliability 1; read across conclusion is given reliability 2).
Reason / purpose:
read-across source
Principles of method if other than guideline:
No determination of the dissociation constants in water was possible using OECD Method 112. The test material did not demonstrate pH sensitive spectral profiles in the ultraviolet region of the electromagnetic spectrum. In addition, the weakly acidic nature of the anticipated dissociating groups was not suitable for investigation by either the titration of conductometric methods. An estimation of the first dissociation constant was made using a procedure based on OECD Method 107 (partition coefficient by the shake flask method) and the relationship between partition coefficient, aqueous phase pH and dissociation constant.
GLP compliance:
yes (incl. certificate)
Dissociating properties:
yes
No.:
#1
pKa:
9.6
Temp.:
22 °C
Remarks on result:
other: ±0.3
No.:
#2
pKa:
> 11
Temp.:
22 °C
Remarks on result:
other: Estimate
No.:
#3
pKa:
> 11
Temp.:
22 °C
Remarks on result:
other: Estimate

The results of each determination are shown in the following table:

Nominal test pH

Sample Number

Aqueous Phase pH

Partition coefficient (P’ow)

Dissociation constant (pKa)

8.0

1

7.99

0.874

8.7*

8.0

2

8.03

0.941

8.9*

8.5

3

8.58

0.883

9.3

8.5

4

8.58

0.883

9.3

9.0

5

9.08

0.879

9.8

9.0

6

9.08

0.837

9.7

9.5

1

9.21

0.563

9.3

9.5

2

9.26

0.648

9.5

10.0

3

9.78

0.408

9.6

10.0

4

9.91

0.404

9.7

10.5

5

10.48

0.182

9.8

10.5

6

10.49

0.178

9.8

* The results at pH 8 were excluded from the determination of the final pKa mean and range on the basis that the accuracy of the estimation method decreased as the distance between the dissociation constant and the aqueous phase pH increased, pH 8.0 being >1.5 units from the final estimation value. This is consistent with the approach used in the titration method in OECD method 112.

Conclusions:
A first dissociation constant of 9.6 for the source substance phenylsilanetriol was determined in a reliable study conducted in compliance with GLP.

Description of key information

Dissociation constant (substance): 17.48 (QSAR)
Dissociation constant (silanol hydrolysis product): pKa approximately 10

Key value for chemical safety assessment

Additional information

The requirement to test the substance for dissociation constant is waived because in contact with water the substance rapidly hydrolyses to form methyl [3-(trihydroxysilyl)propyl]carbamate and methanol. However, the dissociation constant of the parent compound has been calculated using an appropriate predictive method to be 17.48. Silanols are not expected to undergo significant dissociation within an environmental relevant range. This is supported by measured data for another silanetriol (phenylsilanetriol) which has a first dissociation constant, pKa = 9.6.