Choline hydroxide

Dissociation constant

Link to relevant study record(s)

Reference

Endpoint:

dissociation constant

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

2013-03-06 to 2013-03-07

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well documented guideline study (OECD 112) without restrictions.

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

OECD Guideline 112 (Dissociation Constants in Water)

Deviations:

no

GLP compliance:

no

Dissociating properties:

yes

No.:

#1

pKa:

11.2

Temp.:

21.5 °C

Results (0.5M sulphuric acid)

 

As often happens when titrating hydroxides, two end points were detected with a small difference between the two. For the purpose of determination of the dissociation constant, a single equivalence point, to be used to determine the appropriate bracketing measurements, was used, at the mid-point of the curve between the two end points.

 

Table 1. End Point Titre

Wt. of test substance (g)	Titre (mL)
0.9918	3.7355
1.6384	6.1741
2.4684	9.3115

 

Calculation of pKa

The pKa was given by the pH value corresponding to half the volume of titre required to attain the equivalence point. This was calculated in triplicate from the titre/pH value tables generated by the auto-titrator by using the pH of the volumes bracketing the half volume of the end point (4 data points) to prepare a graph and then using the graph to determine the pH at half volume.

 

Table 2. Raw data for calculation of pKa

Test	End Point Volume (mL)	Half Volume (mL)	Bracketing Volume (mL)	pH
1	3.7355	1.8677	1.1170	12.532
			1.7070	12.419
			2.2230	12.281
			2.6430	12.131
2	6.1741	3.0870	1.7960	12.668
			2.4660	12.585
			3.0880	12.506
			3.7030	12.396
3	9.3115	4.6557	3.9480	12.739
			4.6270	12.675
			5.2830	12.606
			5.9260	12.519

 

Calculation of pKa for Test 1: Y= -0.2606 x 1.8677 + 12.842 = 12.36

Calculation of pKa for Test 2: Y= -0.1409 x 3.0870 + 12.928 = 12.49

Calculation of pKa for Test 3: Y= -0.1105 x 4.6557 + 13.181 = 12.67

 

Table 3. calculated pKa values

Test	Weight sample (g)	pKa measured
1	0.9918	12.36
2	1.6384	12.49
3	2.4684	12.67

 

To calculate the pKa at ideal (zero) weight, a graph is plotted of the pKa values determined versus the weight of test substance and extrapolated to the intercept on the x-axis: extrapolated to zero weight = 12.15, reported as 12.2.

The individual results do vary considerably in accordance with the weight taken indicating a significant concentration dependence. Because of this, it was decided to perform a further triplicate test using lower weights of test substance and using a titrant of 0.1M hydrochloric acid.

 

 

Results (0.1M hydrochloric acid)

 

Again two end points were detected with a small difference between the two. For the purpose of determination of the dissociation constant, a single equivalence point, to be used to determine the appropriate bracketing measurements, was used, at the mid-point of the curve between the two end points.

 

Table 4: End Point Titre

Wt. of test substance (g)	Titre (mL)
0.0760	2.7602
0.1600	5.8044
0.2934	10.5923

 

 

Calculation of pKa

 

The pKa was given by the pH value corresponding to half the volume of titre required to attain the equivalence point. This was calculated in triplicate from the titre/pH value tables generated by the auto-titrator by using the pH of the volumes bracketing the half volume of the end point (4 data points) to prepare a graph and then using the graph to determine the pH at half volume.

 

Table 5. Raw data for calculation of pKa

Test	End Point Volume (mL)	Half Volume (mL)	Bracketing Volume (mL)	pH
1	2.7602	1.3801	0.7380	11.493
			1.2800	11.358
			1.7740	11.178
			2.0920	10.998
2	5.8044	2.9022	2.0660	11.756
			2.7270	11.641
			3.2000	11.569
			3.7770	11.472
3	10.5923	5.2961	3.9580	11.919
			4.6620	11.867
			5.3540	11.811
			6.0310	11.746

 

Calculation of pKa for Test 1: Y= -0.3573 x 1.3801 + 11.782 = 11.29

Calculation of pKa for Test 2: Y= -0.1651 x 2.9022 + 12.095 = 11.62

Calculation of pKa for Test 3: Y= -0.0832 x 5.2961 + 12.252 = 11.81

 

Table 6: calculated pKa values

Test	Weight sample (g)	pKa measured
1	0.0760	11.29
2	0.1600	11.62
3	0.2934	11.81

 

Result extrapolated to zero weight = 11.17, reported as 11.2.

 

Summary of Results

 

The results obtained show a strong concentration dependence causing significant variation in the individual pKa results obtained and therefore the calculation of the ideal pKa by extrapolation to zero concentration. As the true pKa value assumes infinite dilution i.e. is a measure of the activity of hydrogen ions, and therefore should not be influenced by surrounding ions, the pKa value to be reported will be that obtained using 0.1M HCl and therefore calculated using the lowest concentrations.

 

Dissociation constant:11.2 at 21.5 °C

Conclusions:

The dissociation constant of Choline hydroxide was determined in a OECD 112 guideline study without deviations by titration to be pKa = 11.2 at 21.5 °C. So in general, the results are considered as reliable. However, the results obtained show a strong concentration dependence causing significant variation in the individual pKa results obtained and therefore the calculation of the ideal pKa by extrapolation to zero concentration was performed. As the true pKa value assumes infinite dilution i.e. is a measure of the activity of hydrogen ions, and therefore should not be influenced by surrounding ions, the pKa value to be reported will be that obtained using 0.1M HCl and therefore calculated using the lowest concentrations.
Since due to the alkaline properties of choline base (pH = 14.9 of a 45 % solution), the pKb value is the more relevant one and can be assumed to be pKb = 14.1 – pKa = 2.9, indicating dissociating properties.

Executive summary:

The dissociation constant of Choline hydroxide was determined in a OECD 112 guideline study by titration to be pKa = 11.2 at 21.5 °C.

Description of key information

In accordance with section 1 of REACH Annex XI, the dissociation constant study does not need to be conducted as the substance is a salt. Salts are reaction products of acids and bases that retain their ionic character. So salts are never undissociated. The dissociation constant is only relevant for substances with a acid or basic character.

The dissociation constant of a 45 % aqueous solution has been determined: 11.2 at 21.5 °C (OECD Guideline 112 (Dissociation Constants in Water))

Key value for chemical safety assessment

pKa at 20°C:

11.2

Additional information

First of all the dissociation constant study does not need to be conducted as the substance is a salt. Salts are reaction products of acids and bases that retain their ionic character. So salts are never undissociated. The dissociation constant is only relevant for substances with a acid or basic character.

Nevertheless choline hydroxide has an ionic substance and one of the ions contains an alcohol group which typically is able to dissociate. Choline hydroxide is a quaternary amine salt, it can be easily concluded that it dissociates in water into the corresponding positively charged quaternary hydroxyl alkylammonium ion and the negatively charged respective anion (OH-).

This is because typically salts (ionic bonding) are electrovalent substance. Electrovalent substances are made up of ions in the solid state. The oppositely charged ions are held together by strong electrostatic (coulombic) force of attraction. Due to these forces the ions cannot move. When these substances are dissolved in water, the ions free themselves from this binding. Thus the break up of an electrovalent compound into free mobile ions when dissolved in water or when melted, is called electrolytic dissociation. This is a 100 % dissociation. Nevertheless the quaternary ammonium salt has an alcohol group which is from a chemically point of view able to dissociate. This dissociation from to alcohol into a proton and the hydroxyl-molecule is calculated as mentioned above and can be considered as the dissociation constant beside the electrolytic dissociation.

The available determination of the dissociation constant of choline hydroxide (45 % aqueous solution) according to OECD 112 Guideline study without deviations by titration will be used for the purpose a PNEC calculation according to the equilibrium partitioning method. The pKa value was reported to be pKa = 11.2 at 21.5 °C. In general, the results are considered as reliable. However, the results obtained show a strong concentration dependence causing significant variation in the individual pKa results obtained and therefore the calculation of the ideal pKa by extrapolation to zero concentration was performed. As the true pKa value assumes infinite dilution i.e. is a measure of the activity of hydrogen ions, and therefore should not be influenced by surrounding ions, the pKa value to be reported will be that obtained using 0.1M HCl and therefore calculated using the lowest concentrations. Since due to the alkaline properties of choline base (pH = 14.9 of a 45 % solution), the pKb value is the more relevant one and can be assumed to be pKb = 14.1 – pKa = 2.9, indicating dissociating properties.