2-methylpentyl 2-hydroxybenzoate

Partition coefficient

Link to relevant study record(s)

Reference

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Study period:

28-05-2020 to 25-06-2020

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

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

Reason / purpose for cross-reference:

other:

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Remarks:

An in-situ generated methanol transesterification product : methyl salicylate (CAS 119-36-8): log Pow = 2.55, Sangster (1994) generated from test item reaction with the mobile phase, was disregarded as not relevant to the substance.

Qualifier:

according to guideline

Guideline:

EU Method A.8 (Partition Coefficient)

Deviations:

no

Remarks:

An in-situ generated methanol transesterification product : methyl salicylate (CAS 119-36-8): log Pow = 2.55, Sangster (1994) generated from test item reaction with the mobile phase, was disregarded as not relevant to the substance.

Qualifier:

according to guideline

Guideline:

EPA OPPTS 830.7570 (Partition Coefficient, n-octanol / H2O, Estimation by Liquid Chromatography)

Deviations:

no

Remarks:

An in-situ generated methanol transesterification product : methyl salicylate (CAS 119-36-8): log Pow = 2.55, Sangster (1994) generated from test item reaction with the mobile phase, was disregarded as not relevant to the substance.

GLP compliance:

yes

Type of method:

HPLC method

Partition coefficient type:

octanol-water

Analytical method:

high-performance liquid chromatography

Key result

Type:

log Pow

Partition coefficient:

5.6

Temp.:

35 °C

pH:

7

Remarks on result:

other: two peaks: log Pow: 2.7 (minor) and 5.6 (major ; 99.6% area) ; minor test item - peak 1 discounted the conclusions of the study. In-situ generated methanol transesterification product : methyl salicylate (CAS 119-36-8): log Pow = 2.55, Sangster (1994)

Key result

Type:

log Pow

Partition coefficient:

5.5

Temp.:

35 °C

pH:

9

Remarks on result:

other: two peaks: log Pow: 2.6 (minor) and 5.5 (major ; 98.1% area) ; minor test item - peak 1 discounted the conclusions of the study. In-situ generated methanol transesterification product : methyl salicylate (CAS 119-36-8): log Pow = 2.55, Sangster (1994)

Preliminary assessment [Calculation Method]

Pow Calculation: the Pow of the test item was calculated to be ca. 1.5 x10^4 (log Pow 4.2) using the Rekker calculation method.

pKa Values : No pKa values for basic groups in the molecular structure of the test item in the logarithm range of 1 - 14 were calculated. The pKa values in the logarithm range of 1 - 14 for acidic groups in the molecular structure of the test item were calculated using the Perrin calculation method. The results indicated :

Acidic : Phenolic : pKa 8.9

Basic : None.

Within an available parallel study (ref: Anon., 2020) the measured pKa of the test item was determined to be 9.8. Based on Henderson-Hasselbalch equation it was considered there will be ca. 15% of the ionized test item at pH 9. Consequentially, it was decided that determination of the partition coefficient (Pow) will be performed at pH 7 and pH 9.

 

HPLC method : buffered pH 7

The results of the HPLC method are given in the Table 2. The calibration curve of the log k’ of the reference substances as function of log Pow had a regression line represented by the equation: log k’ = 0.333 x log Pow – 0.881 (r = 0.997, n = 12).

Table 2. Pow of the substance at pH 7

Substance	Retention time (min)			log Pow	Pow #1	Peak area (%)
	tr,1	tr,2	mean
Formamide (t0)	0.629	0,628	0.629
Benzylalcohol	0.801	0.802	0.802	1.1
Nitrobenzene	0.975	0.977	0.976	1.9
1,4-Dichlorobenzene	1.946	1.951	1.949	3.4
Dibenzyl	4.181	4.201	4.191	4.8
Triphenylamine	7.513	7.546	7.530	5.7
4,4’-DDT	10.903	10.957	10.930	6.5
Test item – peak 1	1.258	1.264	1.261	2.7	4.5x10^2	0.37
Test item – peak 2	6.562	6.582	6.572	5.6	3.7x10^5	99.6

#1 : Log Pow is calculated by interpolation of the calibration curve.

 

HPLC method : buffered pH 9

The results of the HPLC method are given in the Table 3. The calibration curve of the log k’ of the reference substances as function of log Pow had a regression line represented by the equation: log k’ = 0.324 x log Pow – 1.012 (r = 0.994, n = 12).

Table 3. Pow of the substance at pH 9

Substance	Retention time (min)			log Pow	Pow #1	Peak area (%)
	tr,1	tr,2	mean
Formamide (t0)	0.615	0.613	0.614
Benzylalcohol	0.733	0.728	0.731	1.1
Nitrobenzene	0.857	0.851	0.854	1.9
1,4-Dichlorobenzene	1.596	1.592	1.594	3.4
Dibenzyl	2.973	2.970	2.972	4.8
Triphenylamine	4.859	4.859	4.859	5.7
4,4’-DDT	7.037	7.045	7.041	6.5
Test item – peak 1	1.037	1.037	1.037	2.6	4.2´10^2	1.9
Test item – peak 2	4.278	4.281	4.280	5.5	3.3´10^5	98.1

#1 : Log Pow is calculated by interpolation of the calibration curve.

 

Table 4. Summary of test item data:

	pH 7			pH 9
	Pow	log Pow	Peak area (%)	Pow	log Pow	Peak area (%)
Test item – peak 1	4.5x10^2	2.7	0.37	4.2x10^2	2.6	1.9
Test item – peak 2	3.7x10^5	5.6	99.6	3.3x10^5	5.5	98.1

#1 : Log Pow is calculated by interpolation of the respective pH, calibration curves.

 

During (preliminary chromatograph) test injection of the test item at pH 7, a single peak eluting at 7.1 min was observed. Based on this information reference standards were chosen with the earliest reference item eluting at 2.6 minutes. However, during the main study an additional peak eluted at 1.3 minutes. Therefore a new calibration and Pow estimation at pH 7 was conducted with reference substances such that the earliest reference item eluted at 0.98 minutes (see table 2). Within the study and/or based on expert judgement and referenced information, it is considered that the minor chromatographic peak belongs to an in-situ generated transesterification product. This in-situ product is formed by the reaction of the test item major constituent, with the methanol present within the mobile phase. This minor chromatographic peak has log Pow consistent with measured literature values of the transesterification product. Whilst not characterised within the study, the peak was inferred to be : methyl salicylate (CAS 119-36-8): log Pow = 2.55, Sangster (1994) referenced within US EPA KOWWIN v1.68 model program. Consequently, this minor test item - peak 1 should be discounted the conclusions of the study on the test item itself.

Conclusions:

The partition coefficient of the test item was determined to be as follows:
(i) at 35 °C pH 7 : log Pow range = ≥ 2.7 to ≤ 5.6 ; with two peaks ; log Pow: 2.7 (minor) and 5.6 (major ; 99.6% area)
minor test item - peak 1 discounted from the conclusions of the study as In-situ generated methanol transesterification product : methyl salicylate (CAS 119-36-8): log Pow = 2.55, Sangster (1994)
(ii) at 35 °C buffered pH 7: ≥ 2.6 to ≤ 5.5 ; with two peaks ; log Pow: 2.6 (minor) and 5.5 (major ; 98.1% area)
minor test item - peak 1 discounted from the conclusions of the study as In-situ generated methanol transesterification product : methyl salicylate (CAS 119-36-8): log Pow = 2.55, Sangster (1994)
Conclusion: the test item has a log Pow 5.6 at pH 7 and/or log Pow 5.5 at pH 9.

Executive summary:

The n-octanol/water partition coefficient was determined using the HPLC method within OECD TG 117, EU Method A.8 and US EPA OPPTS 830.7570 in accordance with GLP. The test item was tested at multiple pH. Within the partition coefficient determination: based on preliminary assessment of the test item it was decided to perform the HPLC method test, at pH 7 and pH 9. Calibrations for each pH were completed individually. A 1000 mg/L stock solution of the test item was prepared in methanol. The stock solution was 100-fold diluted to obtain an end solution the same as respective the mobile phases of 75/25 (v/v) methanol / aqueous 0.01 M phosphate buffer pH 7 or 75/25 (v/v) methanol / aqueous 0.01 M boric acid/KCl : 1N NaOH buffer pH 9, as applicable. The final concentration of the test substance solution was 10.0 mg/L injected at 5 µL into the respective mobile phases. Samples of the test item were analysed via HPLC on a C18 column with TUV UV/visible wavelength detector at 210 nm. Calibration was performed using six reference items with known log POW values (given by the guidelines). Calibrations for each pH were completed individually. The dead time (t0) of the HPLC system was determined with Formamide for each pH individually. The dead time and the reference items were measured in duplicate. The test item was injected and measured in duplicate. The partition coefficient of the test item was determined to be as follows: (i) at 35 °C pH 7 : log Pow range = ≥ 2.7 to ≤ 5.6 ; with two peaks ; log Pow: 2.7 (minor) and 5.6 (major ; 99.6% area) ; minor test item - peak 1 discounted from the conclusions of the study as an in-situ generated methanol transesterification product : methyl salicylate (CAS 119-36-8): log Pow = 2.55, Sangster (1994) generated from reaction with the mobile phase ; (ii) at 35 °C buffered pH 7: ≥ 2.6 to ≤ 5.5 ; with two peaks ; log Pow: 2.6 (minor) and 5.5 (major ; 98.1% area). Again the minor test item - peak 1 was discounted from the conclusions of the study as an in-situ generated methanol transesterification product. Under the conditions of this study, the test item has a log Pow 5.6 at pH 7 and/or log Pow 5.5 at pH 9.

Description of key information

log Pow = 5.6 at 35 °C and pH 7, and/or 5.5 at 35 °C and pH 9, OECD TG 117 - HPLC Method, 2020

Further information: the pKa values in the logarithm range of 1 - 14 for acidic groups in the molecular structure of the test item were calculated using the Perrin calculation method. The calculation results indicated : Acidic : Phenolic group: pKa 8.9. Within an available study, the measured pKa of the test item was determined to be 9.8. Based on Henderson-Hasselbalch equation it was considered there will be ca. 15% of the ionized test item at pH 9. Consequentially, for the HPLC study it was decided that determination of the partition coefficient (Pow) would be performed at pH 7 and pH 9.

Conclusion: the substance was tested at pH 7 and pH 9, the log Pow observed was found to be insignificantly affected by the effects of ionisation between pH 7 and pH 9 (i.e. ± 0.1 log units). Refer to Section 4.21: Dissociation Constant for further information.

Key value for chemical safety assessment

Log Kow (Log Pow):

5.6

at the temperature of:

35 °C

Additional information

Key study : OECD TG 117, 2020 : The n-octanol/water partition coefficient was determined using the HPLC method within OECD TG 117, EU Method A.8 and US EPA OPPTS 830.7570 in accordance with GLP. The test item was tested at multiple pH. Within the partition coefficient determination: based on preliminary assessment of the test item it was decided to perform the HPLC method test, at pH 7 and pH 9. Calibrations for each pH were completed individually. A 1000 mg/L stock solution of the test item was prepared in methanol. The stock solution was 100-fold diluted to obtain an end solution the same as respective the mobile phases of 75/25 (v/v) methanol / aqueous 0.01 M phosphate buffer pH 7 or 75/25 (v/v) methanol / aqueous 0.01 M boric acid/KCl : 1N NaOH buffer pH 9, as applicable. The final concentration of the test substance solution was 10.0 mg/L injected at 5 µL into the respective mobile phases. Samples of the test item were analysed via HPLC on a C18 column with TUV UV/visible wavelength detector at 210 nm. Calibration was performed using six reference items with known log POW values (given by the guidelines). Calibrations for each pH were completed individually. The dead time (t0) of the HPLC system was determined with Formamide for each pH individually. The dead time and the reference items were measured in duplicate. The test item was injected and measured in duplicate. The partition coefficient of the test item was determined to be as follows: (i) at 35 °C pH 7 : log Pow range = ≥ 2.7 to ≤ 5.6 ; with two peaks ; log Pow: 2.7 (minor) and 5.6 (major ; 99.6% area) ; minor test item - peak 1 discounted from the conclusions of the study as an in-situ generated methanol transesterification product : methyl salicylate (CAS 119-36-8): log Pow = 2.55, Sangster (1994) generated from reaction with the mobile phase ; (ii) at 35 °C buffered pH 7: ≥ 2.6 to ≤ 5.5 ; with two peaks ; log Pow: 2.6 (minor) and 5.5 (major ; 98.1% area). Again the minor test item - peak 1 was discounted from the conclusions of the study as an in-situ generated methanol transesterification product. Under the conditions of this study, the test item has a log Pow 5.6 at pH 7 and/or log Pow 5.5 at pH 9.

Further information: the pKa values in the logarithm range of 1 - 14 for acidic groups in the molecular structure of the test item were calculated using the Perrin calculation method. The calculation results indicated : Acidic : Phenolic group: pKa 8.9. Within an available OECD TG 112 study, the measured pKa of the test item was determined to be 9.8. Based on Henderson-Hasselbalch equation it was considered there will be ca. 15% of the ionized test item at pH 9. Consequentially, for the HPLC study it was decided that determination of the partition coefficient (Pow) would be performed at pH 7 and pH 9.

Conclusion: the substance was tested at pH 7 and pH 9, the log Pow observed was found to be insignificantly affected by the effects of ionisation between pH 7 and pH 9 (i.e. ± 0.1 log units).

Refer to Section 4.21: Dissociation Constant for further information.