Reaction mass of (1RS)-1-[(1RS)-3,3-dimethylcyclohexyl]ethyl [(2RS,3RS)-3-ethyloxiran-2-yl]acetate and (1RS)-1-[(1RS)-3,3-dimethylcyclohexyl]ethyl [(2SR,3SR)-3-ethyloxiran-2-yl]acetate and (1RS)-1-[(1SR)-3,3-dimethylcyclohexyl]ethyl [(2RS,3RS)-3-ethyloxiran-2-yl]acetate and (1RS)-1-[(1SR)-3,3-dimethylcyclohexyl]ethyl [(2SR,3SR)-3-ethyloxiran-2-yl]acetate

Partition coefficient

Link to relevant study record(s)

Reference

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Study period:

11-11-2015 to 18-12-2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study performed under GLP. All relevant validity criteria were met.

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method A.8 (Partition Coefficient)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

inspected: June 2016 ; signature: January 2017

Type of method:

HPLC method

Partition coefficient type:

octanol-water

Analytical method:

high-performance liquid chromatography

photometric method

Type:

log Pow

Partition coefficient:

ca. 4.56

Temp.:

23.3 °C

pH:

7

Remarks on result:

other: 12 peaks in total were considered for data evaluation. Peak 8 was considered to be the test item, the major constituent, based on a combination of the DAD and MS/MS-detection.

HPLC method

The mean void time (t0) was determined to be 0.489 minutes.

The results of the HPLC method (LC-MS/MS detection) are given in the Table 3. The calibration curves of the log k’ of the reference substances as function of log Pow had an regression line represented by the equations:

Calibration 1: log Pow = 4.042 × log k' - 0.2573 (r = 0.9884, n = 6 and r2 = 0.9942).

Calibration 2: log Pow = 4.079 × log k' - 0.2982 (r = 0.9858, n = 6 and r2 = 0.9929).

 

Table 2. Calibration data (LC-MS/MS detection method)

Reference Item	Log P	1^stCalibration			2^ndCalibration
		tr1 /min	k	Log K	tr2 / min	k	Log k
Isopropylbenzene	3.7	4.895	9.24	0.966	4.898	9.25	0.966
Biphenyl	4.0	5.736	11.0	1.04	5.735	11.0	1.04
n-Butylbenzene	4.6	8.414	16.6	1.22	8.423	16.6	1.22
2,6 -Diphenylpyridine	4.9	9.785	19.5	1.29	9.785	19.5	1.29
Triphenylamine	5.7	16.038	32.6	1.51	16.019	32.5	1.51
DDT	6.5	20.632	42.2	1.63	20.611	42.1	1.62

tR1 Retention time 1. Injection

tR2 Retention time 2. Injection

k Capacity factor reference item

log Pow Decadic logarithm of the Partition Coefficient (n-octanol / water)

* Fluoranthene ; not included - outlier (F-Test)

 

Table 3. Test item determination – peak 8 (main constituent identified by LC-MS/MS)

	tr / min	k	Log k	Log P
Peak 8				1^stCalibration	2^ndCalibratrion
	7.942	15.6	1.19
	7.947	15.6	1.19	4.55 ± 0.06 4.40 to 4.71 (95% CI)	4.56 ± 0.06 4.39 to 4.73 (95% CI)
Mean	7.945	15.6	1.19	4.56

tR : Retention time

k : Capacity factor test item

Pow : Partition Coefficient (n-octanol / water)

CI : Confidence Interval

Twelve peaks in total were considered for data evaluation. Peak 8 was considered to be the test item, the major constituent, based on LC-MS/MS-detection.

Conclusions:

The partition coefficient of the test item was determined to be log Pow = 4.56 at 23.3°C and ca. pH 7.0

Executive summary:

The n-octanol/water partition coefficient was determined using the HPLC method within OECD TG 117 and EU Method A.8. The test was performed with a concentration of 7500 mg/L (DAD) or 5 mg test item/L (LC-MS/MS) in 75% methanol : 25% HPLC water. Samples of the test item were analysed via HPLC on a C18 column with diode array detection and/or LC-MS/MS with additional analyte identification by LC-MS/MS detection method. Calibration was performed using six or more reference items with known log POW values (given by the guidelines). The reference items were measured twice, once before and once after the measurement of the test item, for which one replicate was double injected. The void time of the HPLC system was determined with sodium nitrate. Two individual log POW values for each of the chromatographic resolved test item signals which were analytically identified by LC-MS/MS to be the test item were derived under consideration of the first and second calibration and resolved chromatographic peaks. Finally, a mean value was calculated from these individual log Pow values. The log Pow was 4.56 (peak 8) in duplicate. The partition coefficient of the test substance was determined to be log Pow = 4.56 at mean temperature 23.3°C and approximately neutral pH.

Description of key information

log Pow = 4.56 ± 0.06 at 23.3 °C and ca. pH 7.0, OECD TG 117, 2017

Supporting information:

biodegradants partition coefficients: log Pow = > 2.1 and < 3.3 at 25°C and ca. pH 7.0, OECD TG 117, 2016

Key value for chemical safety assessment

Log Kow (Log Pow):

4.56

at the temperature of:

23.3 °C

Additional information

Key study : OECD TG 117, 2017 : The n-octanol/water partition coefficient was determined using the HPLC method within OECD TG 117 and EU Method A.8. The test was performed with a concentration of 7500 mg/L (DAD) or 5 mg test item/L (LC-MS/MS) in 75% methanol : 25% HPLC water. Samples of the test item were analysed via HPLC on a C18 column with diode array detection and/or LC-MS/MS with additional analyte identification by LC-MS/MS detection method. Calibration was performed using six or more reference items with known log POW values (given by the guidelines). The reference items were measured twice, once before and once after the measurement of the test item, for which one replicate was double injected. The void time of the HPLC system was determined with sodium nitrate. Two individual log POW values for each of the chromatographic resolved test item signals which were analytically identified by LC-MS/MS to be the test item were derived under consideration of the first and second calibration and resolved chromatographic peaks. Finally, a mean value was calculated from these individual log Pow values. The log Pow was 4.56 (peak 8) in duplicate. The partition coefficient of the test substance was determined to be log Pow = 4.56 at mean temperature 23.3°C and approximately neutral pH.

Key study : Metabolites data : OECD TG 117, 2016 : The n-octanol/water partition coefficient was determined using the HPLC method within OECD TG 117. The test item was first subjected to 28d biodegradation: prior to testing in the current study of the (bio)degradants observed. The sample for LC-MS analysis of the test solution (sludge+ test item) (Vessel- 3) prepared in the cross-referenced biodegradation study (study no. cited in the full study report) was diluted to twice with the eluent (methanol/water 70:30) in order to prepare the test item solution. The sample for LC-MS analysis of the test solution (control blank) (Vessel-5) was diluted by the same way in order to use for the confirmation whether blank peaks were detected around the peak positions of the test item on the LC-MS chromatogram. The samples for LC-MS analysis, which were prepared in the biodegradation study and stored in a freezer for about six months, were (re-)analysed by the same GC methods as the biodegradation study in the current study. As a result, retention times of the detected peaks in this analysis were same as those of the converted products A-E in the biodegradation study. It was confirmed that the test items were stable under the described storage conditions (freezing). A calibration was performed in duplicate using six reference items.  The void time was determined with thiourea. The test item solution was injected and analysed by LC-MS. The individual partition coefficients were: A: 2.1, B: 2.4, C and D: 3.0 and 3.1 (unresolved) and E: 3.3. The partition coefficient of the test item biodegradants was determined to be log Pow = > 2.1 and < 3.3 at 25°C and ca. pH 7.0