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Dissociation constant

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Endpoint:
dissociation constant
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 112 (Dissociation Constants in Water)
Deviations:
no
Remarks:
The study was conducted according to the test guidelines in effect at the time of study conduct.
GLP compliance:
yes
Dissociating properties:
no

The temperature of all the test solutions remained within the acceptable range of 24 ± 1°C during all titrations. The pH of the test substance solutions was approximately 10 to 11 at the end of the titration with 0.1N sodium hydroxide.

 

The authors acknowledge that phenols typically have pKa values of approximately 10 to 11. In an attempt to measure pKa values in this range, a test was performed using a 0.1 N sodium hydroxide titrant since titration with 0.01 N sodium hydroxide did not yield solutions with pH values in that range. While the maximum pH of these solutions was >12, these titrations using 0.1 N sodium hydroxide did not yield any additional pKa values. This is likely due to the limited water solubility of the material (25.1 mg/L) and the relatively high titrant concentration required to achieve solutions with pH >10. Employing methods described in this report, it was not possible to determine the pKa values for the test substance.

Conclusions:
Employing methods described in this report, it was not possible to determine the pKa values for the test substance.
Executive summary:

Potentiometric titration with a glass, hydrogen selective electrode was used for the determination of the acid dissociation constant (pKa) of the test substance at 24 ± 1°C. Test solutions of approximately 125 mg a.i./L were prepared in purified reagent water employing acetone at approximately 1% as a co-solvent to enhance test substance solubility. The solutions were titrated with 0.1 N sodium hydroxide over a pH range of approximately 8 to 11.

Phenols typically have a pKa in the range of 10 to 11 depending on the ring substituents. Testing was conducted at 24 ±°C with the test substance at a concentration of 125 mg a.i./L. Samples were titrated with 0.1 N sodium hydroxide and did not result in a definable endpoint typical for a phenol. This is due, in part, to the low water solubility (25.1 mg/L) of the test material and the inherent difficulties of determining pKa values in the pKa 10 range using potentiometric methodologies. Triplicate titrations showed no definable endpoint.

Endpoint:
dissociation constant
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a (Q)SAR model, with limited documentation / justification, but validity of model and reliability of prediction considered adequate based on a generally acknowledged source
Justification for type of information:
QSAR prediction
Principles of method if other than guideline:
Four different approaches to generate a pKa for the test substance were used. These were ACD Labs v12.0, SPARC v4.5, Pipeline Pilot v12.0, and a substituent fragment method.
GLP compliance:
no
Dissociating properties:
no
pKa:
10
Temp.:
25 °C
Remarks on result:
other: Four approaches give comparable pKa values, and are in agreement with what a pKa would be expected for a phenol (phenol pKa measured value of 9.99). Accordingly, a pKa for the test substance would be expected to be on the order of 10.
pKa:
10.02 - 11.3
Temp.:
25 °C
Remarks on result:
other: ACD Labs v12.0; temperature not reported in models, so standard temperature of 25°C is assumed.
pKa:
9.99 - 10.29
Temp.:
25 °C
Remarks on result:
other: SPARC v4.5; temperature not reported in models, so standard temperature of 25°C is assumed.
pKa:
9 - 11.16
Temp.:
25 °C
Remarks on result:
other: Pipeline Pilot v12.0; temperature not reported in models, so standard temperature of 25°C is assumed.
pKa:
10.21
Temp.:
25 °C
Remarks on result:
other: Substituent fragment method; temperature not reported in models, so standard temperature of 25°C is assumed.

 

Derived pKa estimates

ACD Labs v12.0

SPARC

Pipeline Pilot

Perrin

10.02

9.99

9

10.21

10.79

10.14

10.08

 

11.30

10.29

11.16

 

 

The four approaches give comparable results for the pKa for the test substance, which are all in good agreement with what a pKa would be expected for a phenol. As part of a weight of evidence approach, the estimated pKa values derived are in good agreement with that for phenol itself, which has a measured value of 9.99. Accordingly, a pKa of the test substance would be expected to be of the order of 10.

 

Phenol:

pKa =9.99 at 25°C (Lide DR (ed.) (2002-2003). CRC Handbook of Chemistry and Physics, 83rded., p. 8-49, CRC Press, Inc., Boca Raton, FL.

Conclusions:
The pKa of the test substance would be expected to be of the order of 10.
Executive summary:

Four different approaches to generate a pKa for the test substance were used. These were ACD Labs v12.0, SPARC v4.5, Pipeline Pilot v12.0, and a substituent fragment method as reported in Perrin DD, Dempsey B, and Serjeant EP (1981). pKa prediction for organic acids and bases. Chapman and Hall, London and New York. The four approaches give comparable results for the pKa for the test substance, which are all in good agreement with what a pKa would be expected for a phenol. As part of a weight of evidence approach, the estimated pKa values derived are in good agreement with that for phenol itself, which has a measured value of 9.99. Accordingly, a pKa of the test substance would be expected to be of the order of 10.

Description of key information

Weight of evidence

Key value for chemical safety assessment

pKa at 20°C:
10

Additional information

A pKa for the test substance would be expected to be on the order of 10.