4,5-bis(hydroxymethyl)-2-phenyl-1H-imidazole

Partition coefficient

Link to relevant study record(s)

Reference

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 15 September 2021 to 04 November 2021

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 117 (Partition Coefficient (n-octanol / water), HPLC Method)

Version / remarks:

2004

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: EU Method A.24: "Partition coefficient (n-octanol/water), High Performance Liquid Chromatography (HPLC) method"

Version / remarks:

2016

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Date of inspection: 18-20 August 2020, Date on certificate: 04 March 2021

Type of method:

HPLC method

Partition coefficient type:

octanol-water

Analytical method:

high-performance liquid chromatography

Key result

Type:

log Pow

Partition coefficient:

1.45

Temp.:

30 °C

pH:

5

Details on results:

See Any other information on results incl. tables below.

Reference Items

Retention times and capacity factors

The retention times of the reference items are presented in the table below

Compound	tR 1 (min)	tR 2 (min)	ΔtR (min)	tR mean (min)	Δ tR / tR mean	Equilibrium? (<2%)
aniline	5.66	5.68	0.02	5.67	0.35%	YES
benzonitrile	8.37	8.34	0.03	8.36	0.36%	YES
nitrobenzene	11.89	11.84	0.05	11.87	0.42%	YES
anisole	15.2	15.15	0.05	15.18	0.33%	YES
methylbenzoate	16.12	16.03	0.09	16.08	0.56%	YES
toluene	28.27	28.14	0.13	28.21	0.46%	YES

with:

t_R = retention time

Δt_R = absolute value of the retention times difference

The retention times observed for the peak of formamide, used for the determination of the dead time, was 2.96 in the first injection of the mix and 2.95 in the second injection.

log k over log P_OW

The following table presents, for each reference item, their log P_OW, the calculated retention factor for the two injections (k₁ and k₂), the mean of k₁ and k₂ (k mean), and log (k mean):

Compound	log Pow	k1	k2	k mean	log (k mean)
aniline	0.9	0.91	0.93	0.92	-0.04
benzonitrile	1.6	1.83	1.83	1.83	0.26
nitrobenzene	1.9	3.02	3.01	3.02	0.48
anisole	2.1	4.14	4.14	4.14	0.62
methylbenzoate	2.1	4.45	4.43	4.44	0.65
toluene	2.7	8.55	8.54	8.55	0.93

The logarithms of the mean capacity factors, log k, are plotted as a function of the logarithms of the partition coefficient, log P_OW.

The determination coefficient R² observed is 0.9869 and the correlation coefficient R is 0.9934. The equation of the line issued from this linear regression will be used for the test item log POW calculation

 

Test Item

Retention times and capacity factors

A typical chromatogram of the test item is constituted of one peak. The retention times obtained are presented in the table below:

	Injection 1 tR (min)	Injection 2 tR (min)	Injection 3 tR (min)	Mean (min)	Relative standard deviation
Dead time t0	2.96	2.96	2.96	2.96	0.0%
Test item	8.06	8.14	8.15	8.12	0.6%

 

Calculation of k, log k and log P_OW

The calculated values for the test item peak are presented in the following table. log P_OW is calculated using the regression equation obtained from the reference items:

log P_OW = (log k + 0.5668) / 0.5576

Measurement No.	k	log k	log Pow
#1	1.72	0.24	1.45
#2	1.75	0.24	1.45
#3	1.75	0.24	1.45
log POW mean			1.45
Standard Deviation			0.00

The pH value measured in the ultrapure water used for the mobile phase was 5.

The temperature of the oven containing the HPLC column varied between 29.9 °C and 30.1 °C during the test.

 

Validity criteria of the study

The study was considered as valid since:

• the system was in an equilibrium state: the difference of the reference items retention times did not exceed 2 % (calculated as the retention times difference divided by the mean);


• the correlation coefficient R of the calibration function was superior to 0.95;


• repeatability of individual log P_OW determinations did not differ by more than ± 0.1 unit.

Conclusions:

Using the HPLC method, the following partition coefficient was determined for the test item: log Pow = 1.45
This value is the mean of three independent measurements.

Executive summary:

A study was performed to assess the partition coefficient of the test item by the HPLC method in accordance with GLP. The method followed was designed to be compliant with the OECD Guideline for Testing of Chemicals No. 117, “Partition Coefficient (n-octanol/water): HPLC Method” (13 April 2004).

 

Six reference items with different retention times were used to produce the calibration curve. They were chosen in relation with the expected retention time of the test item. For each reference item, two determinations were performed. The capacity factor k was calculated from the retention time of formamide (dead time) and the retention time of the respective reference item. A calibration function (log k versus log P_OW, linear fit) was determined based on literature values of log P_OW for the reference items (0.9 to 2.7).

The following partition coefficient was determined for the test item:

log P_OW = 1.45.
This value is the mean of three independent measurements.

Description of key information

log P_OW = 1.45; OECD 117; Mata, L. (2021)

Key value for chemical safety assessment

Log Kow (Log Pow):

1.45

at the temperature of:

30 °C