Choline hydroxide

pH

Administrative data

Endpoint:

pH

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2013-03-11

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: well-documented study, data were gained within the water solubility determination of the test item according the preliminary test from the OECD 105 guideline

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Reference

Endpoint:

melting point/freezing point

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2013-03-06 to 2013-03-07

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well documented guideline study in accordance with OECD 102

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 102 (Melting point / Melting Range)

Deviations:

no

GLP compliance:

yes

Type of method:

method to determine freezing temperature

Melting / freezing pt.:

< -20 °C

Atm. press.:

ca. 100 kPa

Remarks on result:

other: The test substance was not frozen, after overnight storage at -20 °C.

Conclusions:

The freezing point of a 45 % solution of choline hydroxide was determined in an OECD 102 guideline study and consideration of guidance given in ECHA Guidance on Information Requirements and Chemical Safety Assessment Chapter R.7a: Endpoint Specific Guidance December 2016 Section R.7.1.2.1., classified as reliable without restrictions. On removal from the freezer, a visual assessment of the physical state of the test substance was performed and an observation that the test substance was not frozen was recorded. A full study does not need to be conducted below a lower limit of -20 °C. Hence the freezing point of the test item was determined to be < -20 °C in this study. The outcome of this study is considered reasonable and within the scientifically expected ranges.

Executive summary:

The freezing point of a 45 % aqueous solution of choline hydroxide was determined according to OECD Guideline 102 (Melting point / Melting Range). The freezing point of the test item was determined to be < -20 °C in this study.The study was classified as Klimisch 1 (reliable without restriction) and fully satisfies the requirements of OECD 102.

Cross-reference 2

Reason / purpose for cross-reference:

reference to same study

Reference

Endpoint:

relative density

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2013-03-18

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well documented guideline study (OECD 109) 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 109 (Density of Liquids and Solids)

Deviations:

no

GLP compliance:

no

Type of method:

pycnometer method

Type:

relative density

Density:

1.08

Temp.:

20 °C

Remarks on result:

other: The relative density was determined to be 1.08 ± 0.01

Determination of the relative density

Measurements

Density of water at 20°C = 0.99821 g/mL (X); Density of water at 4°C = 1g/mL (Y)

	Test 1	Test 2
Weight of pycnometer (A) g	20.4521	22.9409
Weight of pycnometer + water (B) g	44.9200	47.8684
Weight of pycnometer (A1) g	20.4518	22.9407
Weight of pycnometer + test substance (C) g	46.9254	49.8688

Calculations Used to Determine Relative Density

 

Volume of pycnometer (mL)           V = (B - A) / X

 

Density of test substance (g/mL)    D1 = (C - A1) / V

Relative density                 D (20/4) = D1 / Y

Results

Using the values and equations above, the relative density for Tests 1 and 2 were calculated. 

	Test1	Test2
Volume of pycnometer (mL) (V)	24.5118	24.9722
Density of test substance (D1)	1.0800	1.0783
Relative Density   (D1/Y)	1.0800	1.0783

Mean relative density reported as 1.08 ± 0.01 at 20°C ± 0.5°C.

Conclusions:

The density of a 45% solution of choline hydroxide was determined in an OECD 109 guideline study, classified as reliable without restrictions. Hence, the results in general are considered as reliable and can be used for further risk assessment. Although the salt choline hydroxide is a solid compound, it is very hygroscopic and cannot be kept water-free under normal environmental conditions. Furthermore, it is marketed as an 45 % aqueous solution and is therefore the predominantly available form. Hence, it is justified out of scientific reasons and exposure considerations to regard choline hydroxide as aqueous solution. The outcome of this study is considered reasonable and within the scientifically expected ranges, the results are considered as valid because of their reproducibility.

Executive summary:

The relative density D(20/4) of a 45 % aqueous solution of choline hydroxide was determined according to OECD Guideline 109 (Density of Liquids and Solids / pycnometer method) to be 1.08 ± 0.001 at 20 °C ± 0.9 °C. D(20/4) describes the density of the substance at 20 °C in proportion to the density of water at 4 °C. The determination of the density of the aqueous solution of choline hydroxide is justified out of scientific reasons and exposure considerations and the results are within the scientifically expected range. The study was classified as Klimisch 1 and meets fully the OECD 109 guideline requirements.

Cross-reference 3

Reason / purpose for cross-reference:

reference to same study

Reference

Endpoint:

vapour pressure

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: Scientifically accepted calculation method

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:

other: REACH guidance on QSAR R.6, May 2008

Deviations:

not applicable

Principles of method if other than guideline:

MPBPWIN program (v 1.43): scientifically accepted calculation method for organic chemicals

GLP compliance:

no

Remarks:

not applicable

Type of method:

other: estimated by calculation

Key result

Temp.:

25 °C

Vapour pressure:

0 Pa

Remarks on result:

other: Modified Grain Method (MPBPWIN v1.43), calculated for pure choline hydroxide

Temp.:

25 °C

Vapour pressure:

2 828.4 Pa

Remarks on result:

other: Modified Grain Method (MPBPWIN v1.43), calculated for 45 % aqueous solution of choline hydroxide

Results

 

Running Choline Hydroxide (CAS: 123-41-1) through the EPISUITEMPBPWINtool gave the following:

 

Predicted BP = 415.48 °C (Adapted Stein and Brown method)

Predicted MP = 160.24 °C (Weighted method derived from 285.48 for Adapted Joback method and 128.93 for Gold and Ogle method)

Predicted VP = 1.43x10^-7 Pa at 25 °C (Modified Grain method using the predicted BP and MP).

 

The EPISUITEMPBPWINdata file is given in Figure 1.

 

As the Choline base is a 45 % solution of Choline Hydroxide in water, the individual vapour pressure values for each of the components was used to estimate the vapour pressure of the mixture by multiplying the predicted value by the mole fraction for each of the components and then summing together, with a vapour pressure value used for water of 3172.5 Pa at 25 °C.

 

moles choline hydroxide = 45/121.18 = 0.3713

moles water = 55/18.02 = 3.0522

 

total moles = 3.4235

 

mole fraction choline hydroxide = 0.3713/3.4235 = 0.1085

mole fraction water = 3.0522/3.4235 = 0.8915

 

VPmix = 0.1085*1.43x10^-7+ 0.8915*3172.5 = 2828.4 Pa at 25 °C.

Conclusions:

The vapour pressure of the pure choline hydroxide was calculated to be 1.43 * E-7 Pa at 25 °C using the Modified Grain method of MPBPWIN program v1.43. For the calculation an estimated boiling point of 415.48 °C (Adapted Stein and Brown method) was used.
As the substance is marketed as an 45 % aqueous solution, the vapour pressure was calculated using Raoult´s law and an experimental vapor pressure value for water of 3172.5 Pa at 25 °C, resulting in a calculated vapour pressure of 2828.4 Pa at 25 °C which is in the scientifically expected range as it is close to the vapour pressure of water.

Executive summary:

Intertek estimated the Vapour presure (as well as melting and boiling point) of Choline hydroxide in 2013 (Intertek, 2013) using MPBPWIN program (v 1.43) made available by the U.S. Environmental Protection Agency. This program requires just the input of the chemical structure of the desired compound by SMILES notation. The calculation is done by three different methods: Antoine, Modified Grain and Mackay, whereby the Modified Grain method is preferentially utilized. By taking this method into account and using an estimated boiling point of 415.48 °C, pure choline hydroxide has a vapour pressure of 1.43 * E-7 Pa at 25 °C.

Using Raoult´s law and an experimental vapor pressure value for water of 3172.5 Pa at 25 °C, the vapour pressure of a 45 % solution of choline hydroxide can be calculated to 2828.4 Pa at 25 °C. The result was gained by a scientifically accepted calculation method.

Cross-reference 4

Reason / purpose for cross-reference:

reference to same study

Reference

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2013-03-21 to 2013-03-22

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well-documented guideline study according to OECD 107. The fact that Choline hydroxide was tested as 45 % aqueous solution is not expected to influence the outcome of the partition coefficient testing.

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 107 (Partition Coefficient (n-octanol / water), Shake Flask Method)

Deviations:

no

GLP compliance:

no

Type of method:

shake-flask method to: flask method

Partition coefficient type:

octanol-water

Analytical method:

other: potentiometric titration

Type:

log Pow

Partition coefficient:

-2.25

Temp.:

25 °C

pH:

11.3

Remarks on result:

other: average out of 6 determinations

Type:

log Pow

Partition coefficient:

-2.301

Temp.:

25 °C

pH:

11.61

Remarks on result:

other: Weight of sample: 18.039 mg, ratio n-octanol:water (ml:ml) = 18:18

Type:

log Pow

Partition coefficient:

-2.523

Temp.:

25 °C

pH:

11.6

Remarks on result:

other: Weight of sample: 18.039 mg, ratio n-octanol:water (ml:ml) = 18:18

Type:

log Pow

Partition coefficient:

-2.222

Temp.:

25 °C

pH:

11.38

Remarks on result:

other: Weight of sample: 12.026 mg, ratio n-octanol:water (ml:ml) = 24:12

Type:

log Pow

Partition coefficient:

-2.097

Temp.:

25 °C

pH:

11.39

Remarks on result:

other: Weight of sample: 12.026 mg, ratio n-octanol:water (ml:ml) = 24:12

Type:

log Pow

Partition coefficient:

-2.097

Temp.:

25 °C

pH:

10.81

Remarks on result:

other: Weight of sample: 3.006 mg, ratio n-octanol:water (ml:ml) = 12:24

Type:

log Pow

Partition coefficient:

-2.398

Temp.:

25 °C

pH:

10.92

Remarks on result:

other: Weight of sample: 3.006 mg, ratio n-octanol:water (ml:ml) = 12:24

The stability of Stock Solutions 1, 2, and 3 from which the test solutions were prepared was checked alongside the sample analysis. These solutions were analysed at the end of the partition coefficient test experimental work and the concentration of test substance present was determined. These values were then compared with the theoretical concentrations of the solutions.

 

A value of 1036 mg/L was determined for Stock Solution 1. Comparison of this value with the theoretical concentration of the solution (1002.15 mg/L) indicates a 103.4 % recovery.

A value of 520 mg/L was determined for Stock Solution 2. Comparison of this value with the theoretical concentration of the solution (501.08 mg/L) indicates a 103.8 % recovery.

A value of 260 mg/L was determined for Stock Solution 3. Comparison of this value with the theoretical concentration of the solution (250.54 mg/L) indicates a 103.8 % recovery.

 

These values were deemed to show that there has been no significant degradation of the stock solutions in terms of concentration over the test period and therefore the solutions used in the test were considered to have been stable for the duration of the test. 

 

The pH of the water layers and the presaturated water blank was measured on completion of the partition coefficient shake flask test period, using a Sirius GLpH automatic pH meter which was calibrated prior to measurements being performed.

 

Table 1: Summary of Results

Calculation of Partition Coefficient (SOP 049.02)
	TEST 1A	TEST 1B	TEST 2A	TEST 2B	TEST 3A	TEST 3B
Weight of Sample mg	18.039	18.039	12.026	12.026	3.006	3.006
Volume of n-Octanol Saturated Water mLs	18	18	24	24	12	12
Volume of Water Saturated n-Octanol mLs	18	18	12	12	24	24
Dilution of n-Octanol Layers (If examined neat enter 1)	1	1	1	1	1	1
Concentration in n-Octanol phase mg/L	5	3	3	4	2	1
Concentration in n-Octanol phase x dilution mg/L	5	3	3	4	2	1
Number of mg in n-Octanol phase	0.090	0.054	0.036	0.048	0.048	0.024
Dilution of Water Layers (If examined neat enter 1)	1	1	1	1	1	1
Concentration in Water phase mg/L	1058.000	1064.000	522.000	526.000	264.000	268.000
Concentration in Water phase x dilution mg/L	1058.000	1064.000	522.000	526.000	264.000	268.000
Number of mg in Water phase	19.044	19.152	12.528	12.624	3.168	3.216
Total Number of mg recovered	19.134	19.206	12.564	12.672	3.216	3.240
p = conc in octanol/conc in water	0.005	0.003	0.006	0.008	0.008	0.004
Mean P for each test condition	0.004		0.007		0.006
Mean P for all determinations	0.006
Standard deviation of individual P from mean P	0.002
Log P	-2.301	-2.523	-2.222	-2.097	-2.097	-2.398
Log mean P for all determinations (2dp)	-2.25
pH of aqueous layer	11.61	11.66	11.38	11.39	10.81	10.92

The quality criterion in Guideline 107 for repeatability of results states that the determined values of the partition coefficient expressed as their common logarithms should fall within a range of ± 0.3 log units. All six replicates reported above meet this criterion.

Conclusions:

The partition coefficient of a 45 % aqueous solution of choline hydroxide was determined according to OECD 107 without restrictions to be -2.25 at 25 °C ± 1 °C. The quality criterion is fulfilled, i.e. the determined values of the partition coefficient of all six replicates expressed as their common logarithms fall within a range of ± 0.3 log units. Due to the ionic structure and rather small molecular weight of the substance, this result is in the scientifically expected range and can be used for further risk assessment.
In addition, the only difference between the test item and the registered substance is an additional amount of 55 % water. This addition is not considered relevant as i.a. the distribution of the compound in water is measured after the establishment of the equilibrium, and hence the logPow of the test item and pure Choline hydroxide are considered be identical (-2.25).

Executive summary:

The water/octanol partition coefficient of a 45 % aqueous solution of choline hydroxide was determined according to OECD 107, shake flask method, without restrictions to be -2.25 at 25 °C ± 1 °C.

The only difference between the test item and the registered substance is an additional amount of 55 % water. This addition is not considered relevant as i.a. the distribution of the compound in water is measured after the establishment of the equilibrium, and hence the logPow of the test item and pure Choline hydroxide are considered be identical (-2.25).

As such, the study was classified as Klimisch 1, fulfills the guideline requirements and the results meet the quality criterion therein.

Cross-reference 5

Reason / purpose for cross-reference:

reference to same study

Reference

Endpoint:

water solubility

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2013-03-11

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: well-documented study (preliminary test / OECD 105 guideline) without deviations

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 105 (Water Solubility)

Deviations:

no

GLP compliance:

no

Type of method:

other: visual inspections

Water solubility:

> 90 vol%

Temp.:

22 °C

pH:

14.2

Remarks on result:

other: Referring to a 45 % aqueous solution of choline hydroxide; the test item was confirmed as fully miscible

Water solubility:

> 486 g/L

Temp.:

22 °C

pH:

> 14.2

Remarks on result:

other: recalculated via the density of the 45 % solution, which was possible because the test item did not reveal any precipitation from visual inspection

Table 1: All test solution weighings, measurements and observations  

Wt sample (g)	Soluble?	% w/w	Miscible?	pH
1.0019	9.0145	10.00	Yes	13.10
2.0218	8.0179	20.14	Yes	13.35
3.0082	7.0246	29.98	Yes	13.51
4.0043	6.0252	39.93	Yes	13.62
5.0325	5.0037	50.14	Yes	13.73
6.0116	4.0157	59.95	Yes	13.83
7.0120	3.0171	69.92	Yes	13.94
8.0046	2.0251	79.81	Yes	14.06
9.0044	1.0001	90.00	Yes	14.20

 

pH of distilled water blank = 7.72

 

In addition the test substance and all test solutions were observed to contain no precipitate.

 

The water solubility oftest substance Choline Base was confirmed as miscible in all proportions as a 45 weight % solution in water. It is therefore reasonable to calculate the water solubility of Choline Base assuming that the test substance is fully soluble in water as a 45 weight % solution in water:

 

45 weight % is equivalent to 450 g/kg x 1.08 kg/L (Density of Test Solution) = 486 g/Litre.

 

This will be reported as a minimum solubility value of >486 g/Litre.

Conclusions:

Interpretation of results: very soluble (> 10000 mg/L)
The test substance and all test solutions were observed to contain no precipitate.

The water solubility of test substance Choline Base (as a 45 % aqueous solution) was confirmed as miscible in all proportions. It is therefore reasonable to calculate the water solubility of Choline Base assuming that the test substance is fully soluble in water as a 45 weight % solution in water:

45 weight % is equivalent to 450 g/kg x 1.08 g/L (Density of Test Solution) = 486 g/Litre.

This will be reported as a minimum solubility value of >486 g/Litre.

Executive summary:

The water solubility of a 45 % choline hydroxide (CB) solution was determined in a OECD 105 guideline study by visual inspection. All tested proportions ranging from 1:9 to 9:1 were reported fully miscible and no phase separation occured. Also, choline base as a 45 % solution did not exhibit any visual precipitation. This allows the conclusion that the water solubility of choline hydroxide is > 486 g CB / 1L water, so choline hydroxide is very soluble.

Cross-reference 6

Reason / purpose for cross-reference:

reference to same study

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.

Cross-reference 7

Reason / purpose for cross-reference:

reference to same study

Reference

Endpoint:

viscosity

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2013-03-06

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well documented guideline study (OECD 114) 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 Test Guideline 114 (Viscosity of Liquids)

Deviations:

no

GLP compliance:

no

Type of method:

other: rotational rheometer

Temp.:

20°C

Parameter:

dynamic viscosity (in mPa s)

Value:

25.3

Remarks on result:

other: At 20 °C, the behaviour of the test substance was found to be Newtonian over the measured shear range of 10 to 200 1/s.

Temp.:

40°C

Parameter:

dynamic viscosity (in mPa s)

Value:

10.6

Remarks on result:

other: At 40 °C, the behaviour of the test substance was found to be Newtonian over the measured shear range of 10 to 200 1/s.

Raw data of the individual tests

 

Table 1. Test 1 at 20 °C, Individual Test Result = 25.20 mPa.s

1329003 10468749 T1 @ 20 °C
Time s	Temperature °C	Shear Stress Pa	Shear Rate 1/s	Viscosity Pas	Target Shear Rate 1/s
50.0	20.0	0.2498	9.955	0.02510	10.00
100.1	20.0	0.3189	12.16	0.02623	12.21
150.1	20.0	0.3726	14.84	0.02511	14.91
200.2	20.0	0.4550	18.12	0.02511	18.21
250.3	20.0	0.5562	22.13	0.02513	22.23
300.4	20.0	0.6794	27.02	0.02514	27.14
350.5	20.0	0.8303	33.00	0.02516	33.14
400.6	20.0	1.007	40.29	0.02499	40.47
450.6	20.0	1.239	49.20	0.02518	49.42
500.7	20.0	1.517	60.07	0.02525	60.34
550.8	20.0	1.847	73.35	0.02518	73.68
600.9	20.0	2.256	89.57	0.02519	89.97
651.0	20.0	2.757	109.4	0.02521	109.9
701.1	20.0	3.365	133.5	0.02520	134.1
751.2	20.0	4.105	163.1	0.02518	163.8
801.3	20.0	5.024	199.1	0.02523	200.0

 

 

Table 2. Test 2 at 20 °C, Individual Test Result = 25.43 mPa.s

1329003 10468749 T2 @ 20 °C
Time s	Temperature °C	Shear Stress Pa	Shear Rate 1/s	Viscosity Pas	Target Shear Rate 1/s
50.02	20.0	0.2518	9.955	0.02529	10.00
100.1	20.0	0.319	12.16	0.02624	12.21
150.2	20.1	0.3757	14.84	0.02531	14.91
200.3	20.0	0.4585	18.12	0.02530	18.21
250.4	20.0	0.5596	22.13	0.02528	22.23
300.5	20.0	0.6838	27.02	0.02531	27.14
350.6	20.0	0.8353	33.00	0.02531	33.14
400.6	20.0	1.024	40.29	0.02542	40.47
450.7	20.0	1.247	49.20	0.02535	49.42
500.8	20.0	1.528	60.07	0.02544	60.34
550.9	20.0	1.864	73.35	0.02541	73.68
601	20.0	2.276	89.57	0.02541	89.97
651.1	20.0	2.78	109.4	0.02542	109.9
701.2	20.0	3.399	133.5	0.02545	134.1
751.3	20.0	4.153	163.1	0.02547	163.8
801.4	20.0	5.071	199.1	0.02547	200.0

 

 

Table 3. Test 1 at 40 °C, Individual Test Result = 10.57 mPa.s

1329003 10468749 T1 @ 40 °C
Time s	Temperature °C	Shear Stress Pa	Shear Rate 1/s	Viscosity Pas	Target Shear Rate 1/s
50.0	40.0	0.1047	9.955	0.01052	10.00
100.1	40.0	0.1129	12.16	0.009289	12.21
150.1	40.0	0.156	14.84	0.01051	14.91
200.2	40.0	0.1899	18.12	0.01047	18.21
250.3	40.0	0.2316	22.13	0.01047	22.23
300.4	40.0	0.2843	27.02	0.01052	27.14
350.5	40.0	0.3467	33.00	0.01051	33.14
400.6	40.0	0.4352	40.29	0.01080	40.47
450.7	40.0	0.5181	49.20	0.01053	49.42
500.8	40.0	0.6374	60.07	0.01061	60.34
550.9	40.0	0.7769	73.35	0.01059	73.68
601.0	40.0	0.9473	89.57	0.01058	89.97
651.1	40.0	1.158	109.4	0.01059	109.9
701.2	40.0	1.413	133.5	0.01058	134.1
751.3	40.0	1.722	163.1	0.01056	163.8
801.4	40.0	2.111	199.1	0.01060	200.0

 

 

Table 4. Test 2 at 40 °C, Individual Test Result = 10.56 mPa.s

1329003 10468749 T2 @ 40 °C
Time s	Temperature °C	Shear Stress Pa	Shear Rate 1/s	Viscosity Pas	Target Shear Rate 1/s
50.02	40.0	0.1035	9.955	0.01039	10.00
100.1	40.0	0.1399	12.16	0.01151	12.21
150.1	40.0	0.1549	14.84	0.01043	14.91
200.2	40.0	0.1898	18.12	0.01047	18.21
250.3	40.0	0.2321	22.13	0.01049	22.23
300.4	40.0	0.2828	27.02	0.01047	27.14
350.5	40.0	0.3451	33.00	0.01046	33.14
400.6	40.0	0.4308	40.29	0.01069	40.47
450.7	40.0	0.5161	49.20	0.01049	49.42
500.8	40.0	0.6367	60.07	0.0106	60.34
550.9	40.0	0.7745	73.35	0.01056	73.68
601	40.0	0.9434	89.57	0.01053	89.97
651	40.0	1.152	109.4	0.01054	109.9
701.1	40.0	1.408	133.5	0.01054	134.1
751.2	40.0	1.723	163.1	0.01057	163.8
801.3	40.0	2.103	199.1	0.01056	200.0

 

Conclusions:

The viscosity of a 45 % solution of choline hydroxide was determined in an OECD 114 guideline study, classified as reliable without restrictions. Hence, the results in general are considered as reliable and can be used for further risk assessment. Although the salt choline hydroxide is a solid compound, it is very hygroscopic and cannot be kept water-free under normal environmental conditions. Furthermore, it is marketed as an 45 % aqueous solution and is therefore the predominantly available form. Hence, it is justified out of scientific reasons and exposure considerations to regard choline hydroxide as aqueous solution, which requires to perform the testing for viscosity instead of a particle size distribution. The outcome of this study is considered reasonable and within the scientifically expected ranges.

Executive summary:

The viscosity of a 45 % aqueous solution of Choline hydroxide was determined according to OECD Test Guideline 114 (Viscosity of Liquids / rotational viscometer) to be 25.3 mPa.s at 20 °C and 10.6 mPa.s at 40 °C. The determination of the viscosity is justified out of scientific reasons and exposure considerations and the results are within the scientifically expected range. The study was classified as Klimisch 1 and meets fully the OECD 114 guideline requirements. 

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: OECD 105 water solubility

Deviations:

not applicable

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Choline hydroxide

EC Number:

204-625-1

EC Name:

Choline hydroxide

Cas Number:

123-41-1

Molecular formula:

C5H14NO.HO

IUPAC Name:

choline hydroxide

Test material form:

other: liquid

Details on test material:

- Name of test material (as cited in study report): Choline Base / Ethanaminium, 2-hydroxy-N,N,N-trimethyl-, hydroxide
- Substance type: Aqueous solution of the pure substance
- Physical state: liquid solution

Results and discussion

pH value

pH value 1

pH value:

13.1

Temp.:

21.5 °C

Concentration:

10 other: %(w/w)

Remarks on result:

other: %(w/w) referring to a 45 % solution of choline base

pH value 2

pH value:

13.35

Temp.:

21.5 °C

Concentration:

20 other: %(w/w)

Remarks on result:

other: %(w/w) referring to a 45 % solution of choline base

pH value 3

pH value:

13.51

Temp.:

21.5 °C

Concentration:

30 other: %(w/w)

Remarks on result:

other: %(w/w) referring to a 45 % solution of choline base

pH value 4

pH value:

13.62

Temp.:

21.5 °C

Concentration:

40 other: %(w/w)

Remarks on result:

other: %(w/w) referring to a 45 % solution of choline base

pH value 5

pH value:

13.73

Temp.:

21.5 °C

Concentration:

50 other: %(w/w)

Remarks on result:

other: %(w/w) referring to a 45 % solution of choline base

pH value 6

pH value:

13.83

Temp.:

21.5 °C

Concentration:

60 other: %(w/w)

Remarks on result:

other: %(w/w) referring to a 45 % solution of choline base

pH value 7

pH value:

13.94

Temp.:

21.5 °C

Concentration:

70 other: %(w/w)

Remarks on result:

other: %(w/w) referring to a 45 % solution of choline base

pH value 8

pH value:

14.06

Temp.:

21.5 °C

Concentration:

80 other: %(w/w)

Remarks on result:

other: %(w/w) referring to a 45 % solution of choline base

pH value 9

pH value:

14.2

Temp.:

21.5 °C

Concentration:

90 other: %(w/w)

Remarks on result:

other: %(w/w) referring to a 45 % solution of choline base; this value corresponds to approx. 486 g/L choline base.

Any other information on results incl. tables

Table 1: All test solution weighings, measurements and observations 

Wt sample (g)	Wt water	% w/w	Miscible?	pH
1.0019	9.0145	10.00	Yes	13.10
2.0218	8.0179	20.14	Yes	13.35
3.0082	7.0246	29.98	Yes	13.51
4.0043	6.0252	39.93	Yes	13.62
5.0325	5.0037	50.14	Yes	13.73
6.0116	4.0157	59.95	Yes	13.83
7.0120	3.0171	69.92	Yes	13.94
8.0046	2.0251	79.81	Yes	14.06
9.0044	1.0001	90.00	Yes	14.20

 

pH of distilled water blank = 7.72

Applicant's summary and conclusion

Conclusions:

The pH value of various choline hydroxide solutions, i.e. different ratios of a 45 % aqueous Choline hydroxide (CB) solution and water, was determined within the water solubility determination of the test item according the preliminary test from the OECD 105 guideline. Although the exact concentrations of choline hydroxide are not known, they can be approximated, for example for the highest concentration tested: A mixture of 90 % of a 45 % choline base solution contains approx. 440 g/L Choline base, which revealed a pH of 14.2.
Consequently, choline base solutions, especially the 45 % Choline hydroxide solution, which is the form placed on the market, are expected to have a very high pH value and can be classified as corrosive without further testing, which has various impacts on risk assessment and necessity of the performance of various testings, which will be individually discussed.

Executive summary:

The pH value of various Choline hydroxide solutions, i.e. different ratios of a 45 % aqueous Choline hydroxide (CB) solution and water, was determined within the water solubility determination of the test item according the preliminary test from the OECD 105 guideline. The exact concentrations of choline hydroxide could be approximated, a mixture of 90 % of a 45 % choline base solution contains approx. 440 g/L choline base, which revealed a pH of 14.2.

The determined pH values are ranging from 13.10 (10 %(w/w) of a 45 % CB solution) to 14.20 (90 %(w/w) of a 45 % CB solution, corresponding to approx. 440 g/L).