[1R-(1α,2β,5α)]-2-isopropyl-5-methylcyclohexyl 5-oxo-L-prolinate

Partition coefficient

Link to relevant study record(s)

Reference

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Study period:

12-13 April 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

The study was conducted according to an internationally recognised method, and under GLP. The substance is considered to be adequately characterised. Therefore full validation applies.

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

1995

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method A.8 (Partition Coefficient - HPLC Method)

Version / remarks:

2008

Deviations:

no

Principles of method if other than guideline:

not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

GLP certificate (inspected on 15 to 16 November 2017 / signed on 15 May 2018)

Type of method:

flask method

Partition coefficient type:

octanol-water

Analytical method:

gas chromatography

Type:

log Pow

Partition coefficient:

3.13

Temp.:

22 °C

pH:

ca. 6.3

The pH values which were measured in the aqueous phases were presented in the report. They are between 6.03 and 6.53.

Table 4.7/1: Analytical determinations in n-octanol:

Step	Area Test Item [pA*s]	Area ISTD [pA*s]	Conc.	Volume	Amount test item
#			[mg/L]	Octanol [mL]	in Octanol [mg]
1a	772.00	2120.91	2525.90	10	25.259
	801.70	2212.10
1b	813.26	2204.10	2516.09	10	25.161
	809.45	2284.52
2a	805.29	2205.91	2562.97	5	12.815
	915.04	2451.90
2b	796.49	2246.12	2454.05	5	12.270
	822.62	2357.67
3a	798.81	2256.21	2470.58	20	49.412
	817.49	2304.57
3b	843.76	2361.41	2523.58	20	50.472
	920.93	2500.03

Table 4.7/2: Analytical determinations in water:

Step	Area Test Item [pA*s]	Area ISTD [pA*s]	Conc.	Volume Water [mL]	Amount test item
#			[mg/L]		in Water [mg]
1a	122.19	2593.94	1.86	20	0.037
	134.43	2724.94
1b	121.99	2630.10	1.85	20	0.037
	131.91	2659.74
2a	119.72	2422.17	1.88	20	0.038
	122.22	2520.34
2b	123.22	2743.39	1.80	20	0.036
	128.76	2703.96
3a	131.23	2536.26	1.93	20	0.039
	125.61	2520.55
3b	123.66	2693.76	1.77	20	0.035
	106.61	2382.93

The log Pow for each determination, the mean, standard deviation and relative standard deviation of the six determinations are presented in the following table.

Table 4.7/3: log Pow:

Step	log POW	Mean log POW	Range log POW	Standard	Relative Standard Deviation
			(Difference)	Deviation
1a	3.134	3.133	3.107 – 3.154 (0.048)	0.014	0.5 %
1b	3.134
2a	3.135
2b	3.135
3a	3.107
3b	3.154

The log Pow of the test item was calculated as (log Pow ± stand. dev.): 3.133 ± 0.014.

The six log POWs should lie in the range of ± 0.3 units. The difference between the values was 0.048, corresponding to the range of ± 0.024. Therefore, the validity was given.

Table 4.7/4 : Mass balance:

Step	Amount in n-Octanol [mg]	Amount in H2O [mg]	Total Amount [mg]	Nominal Amount [mg]	Difference [mg]	Recovery [%]
1a	25.259	0.037	25.296	25.0	0.296	101.2
1b	25.161	0.037	25.198	25.0	0.198	100.8
2a	12.815	0.038	12.852	12.5	0.352	102.8
2b	12.270	0.036	12.306	12.5	-0,194	98.4
3a	49.412	0.039	49.450	50.0	-0,55	98.9
3b	50.472	0.035	50.507	50.0	0.507	101.0

The mass balances of the individual determinations showed 98.4 - 102.8 % recovery from nominal amount with the mean value of 100.5 %.

Executive summary:

The partition coefficient of the test substance was measured, under GLP, according to the OECD 107 / EU method A8 guidelines using the flask method.

Three volume ratios of n-octanol : water (0.5 : 1; 0.25 : 1; 1 : 1) were tested in duplicate. Samples were collected from n-octanol and water phases and analysed using a fully validated GC-FID method to determine the concentration of test item in each phase. Then the logPow was calculated.

The difference between the six log Pow values was 0.048, corresponding to the range of ± 0.024 < 0.3 units . Therefore, the validity was given. The mass balances of the individual determinations showed 98.4 - 102.8 % recovery from

nominal amount with the mean value of 100.5 %.

The partition coefficient (log Kow) of the test substance has been determined to be 3.13 (at 22°C, and pH ca 6.3).

Description of key information

log Kow (exp) = 3.13 at 22°C (logKow < 4)

Key value for chemical safety assessment

Log Kow (Log Pow):

3.13

at the temperature of:

22 °C

Additional information

A fully reliable experimental study, conducted in accordance with conditions recommended in OECD/EU method (flask method) and under GLP, is available. It is considered as a key study. The result is retained as key data.