4-[4-(4-acryloyloxybutoxycarbonyl)-cyclohexylcarboxy]-benzoic acid 4-[2-[4-[2-[4-[2-[4-[2-[4-[4-[4-(4-acryloyloxybutoxycarbonyl)-cyclohexylcarboxy]-benzoyloxy]-4'-pentyl-[1,1']-bicyclohexyl-4-yl]-ethynyl]-phenyl]-ethynyl]-phenyl]-ethynyl]-phenyl]-ethynyl

Partition coefficient

Link to relevant study record(s)

Reference

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Study period:

July 17, 2018 - August 23, 2018

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)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: A.24. Partition coefficient n-octanol/water

Version / remarks:

European Commission Regulation (EC) No. 440/2008 and No. 2016/266

Deviations:

no

GLP compliance:

no

Type of method:

HPLC method

Partition coefficient type:

octanol-water

Analytical method:

high-performance liquid chromatography

Key result

Type:

log Pow

Partition coefficient:

> 6.5

Temp.:

25 °C

pH:

6

Remarks on result:

other: above the highest log Pow value of calibration substances (4,4'-DDT)

Preliminary test:

Preliminary visual estimation of the n-octanol solubility

 

Amount of test item (mg)	Added volume of n-octanol (mL)	Total volume of n-octanol (mL)	Stirring time (h)	Appearance of mixture
8.2	10	10	~ 1	Not dissolved
8.2	90	100	~ 19	Not dissolved
8.2	100	200	~ 7	Not dissolved

 

According to the preliminary test the solubility of the test item in n-octanol was below 41 mg/L (without correction for the purity).

 

Calculation of the partition coefficient log Pow from the preliminary test

 

Pre-estimation of the partition coefficient of the test item using a calculation method The program KOWWIN (part of EPI Suite) was used for calculating the log Pow of the test item. The calculated value was30.

Therefore, according to the guidelines, the partition coefficient n-octanol/water of the test item at room temperature was determined by the HPLC method.

 

HPLC method

The results from the HPLC method are summarized in Table 1 to Table 5.

 

Table 1: Determination of the dead time t0

Dead time marker	tR/min 1stinjection	tR/min 2ndinjection	tR/min 3rdinjection
Formamide	0.92	0.92	0.92

 

Table 2: Calibration data 1stinjection

Calibration substance	tR/min	k	Log k	Log Pow
2-Butanone	1.09	0.19	-0.72	0.3
Acetanilid	1.00	0.09	-1.05	1.0
Cinnamyl alcohol	1.07	0.16	-0.79	1.9
2,6-Dichlorobenzonitrile	1.18	0.28	-0.55	2.6
Allyl phenyl ether	1.34	0.46	-0.34	2.9
Benzophenone	1.22	0.33	-0.48	3.2
Cumene	1.54	0.68	-0.17	3.7
Diphenyl ether	1.37	0.50	-0.31	4.2
Fluoranthene	1.34	0.45	-0.34	5.1
4,4'-DDT	1.58	0.72	-0.14	6.5

 

Regression: logPow= a+ b · log k

Parameters: a=5.733, b= 5.309, r2=0.6919 (r = 0.8318)

 

Table 3: Log Powof the test item 1stinjection

	tR/min	k	Log k	Log Pow
Test item	5.61	5.11	0.711	>6.5

 

Table 4: Calibration data 2ndinjection

Calibration substance	tR/min	k	Log k	Log Pow
2-Butanone	1.09	0.18	-0.73	0.3
Acetanilid	1.00	0.09	-1.04	1.0
Cinnamyl alcohol	1.07	0.16	-0.79	1.9
2,6-Dichlorobenzonitrile	1.18	0.28	-0.55	2.6
Allyl phenyl ether	1.34	0.46	-0.34	2.9
Benzophenone	1.22	0.33	-0.48	3.2
Cumene	1.55	0.68	-0.17	3.7
Diphenyl ether	1.37	0.49	-0.31	4.2
Fluoranthene	1.33	0.45	-0.35	5.1
4,4'-DDT	1.58	0.72	-0.15	6.5

 

Regression: logPow= a+ b · log k

Parameters: a =5.767, b =5.368, r2=0.6977 (r = 0.8353)

 

Table 5: Log Powof the test item 2ndinjection

	tR/min	k	Log k	Log Pow
Test item	5.60	5.09	0.71	>6.5

 

According to the Guideline the correlation coefficient r for the relationship between log k and log Pow for a set of calibration substances should be around 0.9, corresponding to an octanol/water partition coefficient of log Pow +/- 0.5 log units. The correlation coefficient r in the present study was approx. 0.8. This was caused by the use of the mobile phase THF/demin. water and the resulting short mobile phase methanol/demin. water or acetonitrile/demin. water the test item was not soluble. However, the low correlation coefficient did not influence the quality of the results of this measurement, as the resulting log Pow was very high and was therefore given as to be above the highest low Pow value of the used calibration substances (4,4'-DDT).

Conclusions:

The partition coefficient n-octanol/water of the test item was determined according to the HPLC method.
lt was found to be: log Pow > 6.5.

Executive summary:

A study was conducted in accordance with OECD TG 117 and Regulation (EC) No 440/2008 method A.8 to determine the partition coefficient of the test substance using the HPLCmethod. The n-octanol/water partition coefficient of the test substance was derived from its retention time and the calibration graph. The retention time of the test item was above the retention time of the highest calibration standard (logPow 6.5) and thus out of the calibration range. Therefore, the partition coefficient n-octanol/water of the test substance was determined to be above 6.5

Description of key information

Therefore, the partition coefficient n-octanol/water of the test substance was determined to be above 6.5

Additional information

A study was conducted in accordance with OECD TG 117 and Regulation (EC) No 440/2008 method A.8 to determine the partition coefficient of the test substance using the HPLCmethod. The n-octanol/water partition coefficient of the test substance was derived from its retention time and the calibration graph. The retention time of the test item was above the retention time of the highest calibration standard (logPow 6.5) and thus out of the calibration range. Therefore, the partition coefficient n-octanol/water of the test substance was determined to be above 6.5