Reaction mass of [3R-(3α,3aβ,6α,7β,8aα)]-octahydro-3,6,8,8-tetramethyl-1H-3a,7-methanoazulen-6-ol and [3R-(3α,3aβ,6α,7β,8aα)]-octahydro-3,6,8,8-tetramethyl-1H-3a,7-methanoazulen-5-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:

2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

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 2013; signature: November 2013

Type of method:

HPLC method

Partition coefficient type:

octanol-water

Analytical method:

high-performance liquid chromatography

Type:

log Pow

Partition coefficient:

>= 2.71 - <= 6.86

Temp.:

22.3 °C

pH:

ca. 7

Remarks on result:

other: Two chromatographically resolved peaks corresponding to the above log Pow range of the test item.

HPLC method

The mean void time (t0) was determined to be 0.485 minutes.

The results of the HPLC method 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 = 3.709 × log k’+ 0.0761 (r = 0.9906, n = 20 and r2 = 0.9812).

Calibration 2: log Pow = 3.816 × log k’+ 0.0724 (r = 0.9905, n = 20 and r2 = 0.9811).

 

Table 2. Calibration data

Reference item	log POW	1st Calibration			2nd Calibration
		tR1 [min]	k	log k	tR2 [min]	k	log k
Ethyl benzoate	2.6	2.727	4.62	0.665	2.727	4.62	0.665
Chlorobenzene	2.8	3.304	5.81	0.764	3.308	5.82	0.765
Allyl phenyl ether	2.9	3.182	5.56	0.745	3.187	5.57	0.746
Ethylbenzene	3.2	4.459	8.19	0.913	4.463	8.20	0.914
Phenyl benzoate	3.6	4.056	7.36	0.867	4.059	7.37	0.867
Biphenyl	4.0	5.804	11.0	1.04	5.805	11.0	1.04
n‑Butylbenzene	4.6	9.833	19.3	1.29	9.839	19.3	1.29
Triphenylamine	5.7	16.683	33.4	1.52	16.694	33.4	1.52
DDT	6.5	24.014	48.5	1.69	24.052	48.6	1.69

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)

 

Table 3. Test item determination

First signal (lowest retention time)	tR [min]	k	log k	log POW
				1st Calibration	2nd Calibration
	2.969	5.12	0.709	2.71 ± 0.09 2.48 to 2.93 (95 % CI)	2.70 ± 0.10 2.48 to 2.93 (95 % CI)
	2.970	5.12	0.709
Mean	2.970	5.12	0.709	2.71
Last signal (highest retention time)	tR [min]	k	log k	log POW
				1st Calibration	2nd Calibration
	32.948	66.9	1.83	6.86 ± 0.16 6.48 to 7.25 (95 % CI)	6.86 ± 0.17 6.47 to 7.26 (95 % CI)
	32.902	66.8	1.82
Mean	32.925	66.9	1.83	6.86

tR : Retention time

k : Capacity factor test item

POW : Partition Coefficient (n-octanol / water)

CI : Confidence Interval

 

Additional comments:

For the signal with the lowest retention time, an individual log POW value of 2.71 ± 0.09 (95 % CI 2.48 to 2.93) was obtained with the first and of 2.70 ± 0.10 (95 % CI 2.48 to 2.93) with the second calibration curve. The individual values did not differ more than ± 0.1 log POW units. Based on these data a mean log POW value of 2.71 was derived. For the last signal with the highest retention time, an individual log POW value of 6.86 ± 0.16 (95 % CI 6.48 to 7.25) was obtained with the first and of 6.86 ± 0.17 (95 % CI 6.47 to 7.26) with the second calibration curve. The individual values did not differ more than ± 0.1 log POW units. Based on these data a mean log POW value of 6.86 was derived. These values needed to be extrapolated, as they outranged the calibration range.

Conclusions:

The partition coefficient of the test substance was determined to be in the range log Pow = 2.71 to 6.86 at 22.3 °C and ca. pH 7.0

Executive summary:

The n-octanol-water partition coefficient was determined using the HPLC method of OECD Method 117 and EU Method A.8. The test was performed with a concentration of 100 mg test item/L in 60 % acetonitrile : 40 % HPLC water. Samples of the test item were analysed via HPLC on a C18 column with diode array detection. Calibration was performed using ten 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. Multiple chromatographic signals were observed for the test item. In order to address the log POW range, the signals with the lowest and highest retention times were evaluated. Two individual log POW values for the test item were derived under consideration of the first and second calibration and finally, a mean value was calculated from these individual log POW values for the first and the last chromatographically resolved signal of the test item with the lowest and highest retention time, respectively. Based on these data, the log POW of the test item was determined to be in the range of 2.71 to 6.86 at mean temperature 22.3 °C and approximately neutral pH.

Description of key information

log Pow = range: 2.71 - 6.86 at 22 ± 1 °C, OECD TG 117, 2016

Additional information

The n-octanol-water partition coefficient was determined using the HPLC method of OECD Method 117 and EU Method A.8. The test was performed with a concentration of 100 mg test item/L in 60 % acetonitrile : 40 % HPLC water. Samples of the test item were analysed via HPLC on a C18 column with diode array detection. Calibration was performed using ten 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. Multiple chromatographic signals were observed for the test item. In order to address the log POW range, the signals with the lowest and highest retention times were evaluated. Two individual log POW values for the test item were derived under consideration of the first and second calibration and finally, a mean value was calculated from these individual log POW values for the first and the last chromatographically resolved signal of the test item with the lowest and highest retention time, respectively. Based on these data, the log POW of the test item was determined to be in the range of 2.71 to 6.86 at mean temperature 22.3 °C and approximately neutral pH.