Trimethyl[2-(phosphonooxy)ethyl]ammonium chloride, calcium salt (1:1)

Partition coefficient

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

partition coefficient

Type of information:

calculation (if not (Q)SAR)

Adequacy of study:

weight of evidence

Study period:

April 27, 2017 - September 22, 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method A.8 (Partition Coefficient - Shake Flask Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of method:

estimation method (solubility ratio)

Partition coefficient type:

octanol-water

Analytical method:

titration method

Key result

Type:

log Pow

Partition coefficient:

< -2.3

Temp.:

20 °C

Remarks on result:

not determinable because of methodological limitations

Details on results:

According to information contained in the section 1.1 of test EEC A.8 the determination of partition coefficient using shake flask is not applicable, when log Pow values in the range between -2 and 4. For such substance, the value of partition coefficient log Pow should be calculated using the individual measured in 1 -octanol and in water.
The concentration of 2 -trimethylazaniumylethyl phosphate chloride, tetrahydrate couldn't be determinated in octanol phase using potenciometric titration.

Approximate solubility of 2-Trimethylazaniumylethyl phosphate chloride, tetrahydrate in 1-octanol is <1g/L.
Thus the only method that can be applied for evaluation partition coefficient log Pow value is an preliminary estimation from the ratio approximate solubilities of the test substance in the pure solvents.
Pow estimate = C1-octanol approximate/ Cwoda approximate
Estimate form the ratio approximate solubility of the 2-Trimethylazaniumylethyl phosphate chloride, tetrahydrate in the pure solvents value of logarithm to base 10 of test item partition coefficient 1-octanol/water (log Pow) at 20.0 ºC is <-2.3.

The test item stock solution was prepared in water pre-saturated with 1 -octanol. The measured of the 2 -trimethylazaniumylethyl phosphate chloride, tetrahydrate concentration in stock solution (water) was 4.683 g/kg (4.683 g/L). Density of 1 -octanol (supplier data) is 0.825 g/L.

Determination of the 2 -trimethylazaniumylethyl phosphate chloride, tetrahydrate content in water phase.

Table 1. Calibration solution

No. of the sample131702/wz	Weight of the sample  [g]	Volume of titrant  [ml]	Content [%]	Content [g/kg]	Average
1/1	0.1010	3.15	102.744	1 027.4	1 027.52
1/2	0.1020	3.20	103.542	1 035.4
1/3	0.1010	3.12	101.971	1 019.7

 

Table 2. Study solution

No. of the sample	Weight of the sample  [g]	Volume of titrant [ml]	Content [%]	Content [g/kg]	Average
1W	3.5124	1.020	0.096	0.984	0.978
1W	3.5563	1.021	0.095	0.973
2W	3.5217	1.024	0.096	0.985	0.982
2W	3.5299	1.020	0.095	0.979
3W	4.4012	1.020	0.076	0.785	0.774
3W	4.6232	1.042	0.074	0.763
4W	4.5810	1.020	0.073	0.754	0.756
4W	4.5662	1.022	0.074	0.758
5W	2.2045	1.040	0.156	1.598	1.566
5W	2.2531	1.020	0.149	1.534
6W	2.2814	1.022	0.148	1.517	1.540
6W	2.2143	1.021	0.152	1.563
podst1-1	0.5001	7.07	0.466	4.793	4.683
podst1-2	0.5156	6.96	0.445	4.574

Table 3. Results of measurements at 20.0°C

 

Vial number	1	2	3	4	5	6
Temperature                                 [°C]	19.9		20.1		20.1
Volume of added stock solution  [mL]	1	1	1	1	1	1
Volume of water                          [mL]	4	4	5.7	5.7	2.3	2.3
Volume of 1-octanol                    [mL]	5	5	3.3	3.3	6.7	6.7
Volume 1-octanol phase/ volume of water phase	1:1		1:2		2:1
2-Trimethylazaniumylethyl phosphate chloride,tetrahydrate concentration in water phase   [g/L]	0.978	0.982	0.774	0.756	1.566	1.540

 

Table 4. Measured pH values of water phase

Vial number	1	2	3	4	5	6
pH before test	5.96	5.96	5.96	5.96	5.96	5.96
pH after test	7.26	7.24	7.21	7.21	7.36	7.37

 

Solubility of the 2 -Trimethylazaniumylethyl phosphate chloride, tetrahydrate in 1 -octanol

Table 5. Results of the preliminary test

0.1g in x ml 1-octanol Result	0.1	0.5	1	2	10	100	> 100
Soluble, [+/-]	-	-	-	-	-	-	+
Approximate solubility, [g/L]	> 1000	1000 to 200	200 to 100	100 to 50	50 to 10	10 to 1	< 1

 

Conclusions:

Estimate from the ratio approximate solubility of the test item in the pure solvents value of logarithm to base 10 of 2 -trimethylazaniumylethyl phosphate chloride, tetrahydrate partition coefficient 1-
octanol/water (log Pow) at 20.0 °C is < -2.3.

Executive summary:

The determination of the partition coefficient 1-octanol/water of 2 -trimethylazaniumylethyl phosphate chloride, tetrahydrate at one pH value was performed according to OECD 107 and EU method A.8 following GLP. Due to the impossibility to find any distinct UV-VIS spectrum in the range of 200-400 nm for the test item, no UV detector for HPLC analysis could be used. The potentiometric titration method was selected for analysis. However, the concentration of the test item couldn't be determined in octanol phase using the potentiometric titration method (approximate solubility of the test item in 1-octanol was determined to be < 1 g/L). Additionally, the log Pow value of the test item seems to be < -2. Consequently, neither the shake flask method nor the high-performance liquid are applicable and an estimated value based on individual n-octanol and water solubilities is provided. Estimate from the ratio approximate solubility of the test item in the pure solvents value of logarithm to base 10 of 2-Trimethylazaniumylethyl phosphate chloride, tetrahydrate partition coefficient 1-octanol/water (log Pow) at 20.0 °C is < -2.3.

Reference 2

Endpoint:

partition coefficient

Data waiving:

study technically not feasible

Justification for data waiving:

other:

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
Study technically not feasible: In accordance with section 2 of REACH Annex XI, testing for a specific endpoint may be omitted, if it is technically not possible to conduct the study as a consequence of the properties of the substance. Please, for more information refer to the experimental study reported.

Reason / purpose for cross-reference:

data waiving: supporting information

Reference 3

Endpoint:

partition coefficient

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 valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification

Justification for type of information:

1. SOFTWARE
EPI-SUITE EPA (USA)

2. MODEL (incl. version number)
KOWWIN v1.68

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
SMILES : OP(O)(=O)OCCN(C)(C)(C)

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
The QMRF is available in "Attached justification".

5. APPLICABILITY DOMAIN
The QPRF is available in “Attached justification”.

6. ADEQUACY OF THE RESULT
The QPRF is available in “Attached justification”.

Guideline:

other: REACH Guidance on QSARs R.6

Principles of method if other than guideline:

Meylan, W.M. and P.H. Howard. 1995. Atom/fragment contribution method for estimating octanol-water partition coefficients. J. Pharm. Sci. 84: 83-92.

GLP compliance:

no

Type of method:

other: estimated by calculation

Partition coefficient type:

octanol-water

Specific details on test material used for the study:

SMILES : OP(O)(=O)OCCN(C)(C)(C)

Key result

Type:

log Pow

Partition coefficient:

-3.99

Remarks on result:

other: Temperature and pH not provided.

Conclusions:

The calculated partition coefficient of calcium phosphorylcholine chloride is -3.99 (EPI-Suite, KOWWIN v1.68 estimate).

Executive summary:

The calculated partition coefficient of calcium phosphorylcholine chloride with EPI-Suite, KOWWIN v1.68 estimate is -3.99.

Description of key information

Data waiving (study technically not feasible): In accordance with section 2 of REACH Annex XI, testing for a specific endpoint may be omitted, if fit is technically not possible to conduct the study as a consequence of the properties of the substance.

Weight of evidence:

Estimation study (solubility ratio): OECD 107 and EU A.8. GLP study. Estimate from the ratio approximate solubility of the test item in the pure solvents value of logarithm to base 10 of 2-Trimethylazaniumylethyl phosphate chloride, tetrahydrate partition coefficient 1-octanol/water (log Pow) at 20.0 °C is < -2.3.

Calculation QSAR: Internationally accepted calculation method, EPI-Suite EPA (USA). The estimated partition coefficient of calcium phosphorylcholine chloride expressed as Log Pow is -3.99 (EPI-Suite, KOWWIN v1.68 estimate).

Based on the available data, and assuming the worst case, it can be concluded that the Log Kow (LogPow) of calcium phosphorylcholine chloride is -2.3.

Key value for chemical safety assessment

Log Kow (Log Pow):

-2.3

at the temperature of:

20 °C

Additional information

Weight of evidence:

- The determination of the partition coefficient 1-octanol/water of 2 -trimethylazaniumylethyl phosphate chloride, tetrahydrate at one pH value was performed according to OECD 107 and EU method A.8 following GLP. Due to the impossibility to find any distinct UV-VIS spectrum in the range of 200-400 nm for the test item, no UV detector for HPLC analysis could be used. The potentiometric titration method was selected for analysis. However, the concentration of the test item couldn't be determined in octanol phase using the potentiometric titration method (approximate solubility of the test item in 1-octanol was determined to be < 1 g/L). Additionally, the log Pow value of the test item seems to be < -2. Consequently, neither the shake flask method nor the high-performance liquid are applicable and an estimated value based on individual n-octanol and water solubilities is provided. Estimate from the ratio approximate solubility of the test item in the pure solvents value of logarithm to base 10 of 2-Trimethylazaniumylethyl phosphate chloride, tetrahydrate partition coefficient 1-octanol/water (log Pow) at 20.0 °C is < -2.3.

- The estimated partition coefficient of calcium phosphorylcholine chloride expressed as Log Pow is -3.99 (EPI-Suite, KOWWIN v1.68 estimate).

Taking into account the worst case, the partition coefficient 1-octanol/water (log Pow) of the test item is considered < -2.3.