Willow, Salix alba, ext.

Partition coefficient

Link to relevant study record(s)

Reference

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2019-01-16 to 2019-02-05

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:

adopted April 2004

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: EU Method A.24. PARTITION COEFFICIENT (N-OCTANOL/WATER), HIGH PERFORMANCELIQUID CHROMATOGRAPHY (HPLC) METHOD

Version / remarks:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of method:

HPLC method

Partition coefficient type:

octanol-water

Analytical method:

high-performance liquid chromatography

Key result

Type:

log Pow

Partition coefficient:

< 0.3

Temp.:

25 °C

pH:

7

Remarks on result:

other: below the lowest log Pow value of calibration substances (2-Butanone)

Type:

log Pow

Partition coefficient:

-2.2

Temp.:

25 °C

pH:

7

Remarks on result:

other: via extrapolation

Details on results:

Please see IUCLID section "Any other information on results incl. tables" below.

Preliminary visual estimation of the n-octanol solubility

A defined amount of the test item was stirred with increasing volumes of n-octanol at room temperature and visually checked for any undissolved particles.

Results of the 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
27.6	2	2	1.25	not dissolved (precipitate)
	3	5	1.5	not dissolved (cloudy)
	10	15	2	not dissolved (cloudy)
	85	100	16	not dissolved (cloudy)

According to this preliminary test the solubility of the test item in n-octanol was below 276 mg/L.

HPLC-Method - Results

The dead time t_0 was determined using formamide and two sparate HPLC runs - results:

t_0 (1) = 1.21 min;

t_0 (2) = 1.21 min;

t_0 (mean) = 1.21 min

Calibration data of the fist and second injection:

		1^strun	1^strun	1^strun	2^ndrun	2^ndrun	2^ndrun
Calibration substance	log POW [1]	tR / min	k	log k	tR / min	k	log k
2-Butanone	0.3	1.39	0.15	-0.82	1.40	0.15	-0.82
Acetanilide	1.0	1.47	0.21	-0.68	1.47	0.21	-0.68
Cinnamyl alcohol	1.9	1.73	0.42	-0.37	1.72	0.42	-0.38
2,6-Dichlorobenzonitrile	2.6	2.14	0.77	-0.11	2.14	0.77	-0.12
Allyl phenyl ether	2.9	2.99	1.47	0.17	2.98	1.46	0.16
Benzophenone	3.2	2.73	1.25	0.10	2.72	1.24	0.09
Cumene	3.7	5.38	3.44	0.54	5.36	3.42	0.53
Diphenyl ether	4.2	4.97	3.10	0.49	4.95	3.09	0.49
Fluoranthene	5.1	9.95	7.21	0.86	9.93	7.19	0.86
4,4’-DDT	6.5	25.59	20.11	1.30	25.54	20.07	1.30

[1] OECD guideline 117, adopted 2004

Regression first run:   log Pow = a + b*log(k)    

Parameters:       a = 2.740

                         b = 2.737

                         r²= 0.9824

log P_OW of the test item – 1^st injection:

Test item	tR/ min	k	log k	log POW
White Willow Bark Extract	1.23	0.02	-1.78	< 0.3[1] (-2.1)[2]

[1] below the lowest log P_OW value of calibration substances (2-Butanone)

[2] via extrapolation

Regression second run:  log Pow = a + b*log(k)   

Parameters:        a = 2.743

                          b = 2.739

                          r²= 0.9824

log P_OW of the test item – 2^nd injection:

Test item	tR/ min	k	log k	log POW
White Willow Bark Extract	1.23	0.02	-1.80	< 0.3[1] (-2.2)[2]

^[1]below the lowest log P_OWvalue of calibration substances (2-Butanone)

^[2]via extrapolation

Final results (mean values from first and second determination):

log Pow < 0.3 (below the lowest log Pow value of calibration substances (2-Butanone))

(log Pow - 2.2 (via extrapolation)

Conclusions:

Partition coefficient n-octanol / water (OECD 117) determined at pH 7 / 25 °C:
log Pow < 0.3 (below the lowest log Pow value of calibration substances (2-Butanone))
log Pow -2.2 (via extrapolation)

Executive summary:

In a reliable and valid study performed compliant with GLP the partition coefficient n-octanol / water (Pow) was determined for the submission substance according to OECD 117 (HPLC method). This method was found to be most applicable due to the UVCB character of the substance as well as the anticipated low Pow value as judged from solubility in n-octanol (<276 mg/L as determined from preliminary experiments within this study) and solubility in water (Siemens, 2019 - study number PS20180395-4).

From the study on water solubility (Siemens study number PS20180395-4 - see IUCLID section 4.8) it was known that the test item induces alkaline pH upon dissolution and is of higher solubility at alkaline pH compared to neutral pH. Consequently, partition coefficient n-octanol-water could be dependent on pH as well. To account for this, HPLC was performed with mixtures of methanol / potassium dihydrogen phosphate buffer adjusted to pH 7.

Two replicate HPLC runs were performed, resulting in extrapolated values differing no more than 0.1 log units (log Pow -2.1 and -2.2). As such, the study fulfilled the validity criterion of OECD 117.

Final results:

Partition coefficient n-octanol / water (OECD 117) determined at pH 7 / 25 °C:

log Pow < 0.3 (below the lowest log Pow value of calibration substances (2-Butanone))

log Pow -2.2 (via extrapolation)

Description of key information

Partition coefficient n-octanol / water (OECD 117) determined at pH 7 / 25 °C:

log Pow < 0.3 (below the lowest log Pow value of calibration substances (2-Butanone))

log Pow -2.2 (via extrapolation)

Key value for chemical safety assessment

Log Kow (Log Pow):

0.3

at the temperature of:

25 °C

Additional information

In a reliable and valid study performed compliant with GLP the partition coefficient n-octanol / water (Pow) was determined for the submission substance according to OECD 117 (HPLC method). This method was found to be most applicable due to the UVCB character of the substance as well as the anticipated low Pow value as judged from solubility in n-octanol (<276 mg/L as determined from preliminary experiments within this study) and solubility in water (Siemens, 2019 - study number PS20180395-4).

From the study on water solubility (Siemens study number PS20180395-4 - see IUCLID section 4.8) it was known that the test item induces alkaline pH upon dissolution and is of higher solubility at alkaline pH compared to neutral pH. Consequently, partition coefficient n-octanol-water could be dependent on pH as well. To account for this, HPLC was performed with mixtures of methanol / potassium dihydrogen phosphate buffer adjusted to pH 7.

Two replicate HPLC runs were performed, resulting in extrapolated values differing no more than 0.1 log units (log Pow -2.1 and -2.2). As such, the study fulfilled the validity criterion of OECD 117.

Final results:

Partition coefficient n-octanol / water (OECD 117) determined at pH 7 / 25 °C:

log Pow < 0.3 (below the lowest log Pow value of calibration substances (2-Butanone))

log Pow -2.2 (via extrapolation)

Because extrapolation over such a wide range is associated with considerable uncertainty and no relational operator ("<") can be specified for the key value field, log Kow of 0.3 is given as the key value for chemical safety assessment.