Reaction mass of 2,6-bis(1-phenylethyl)phenol and 2,4,6-tris(1-phenylethyl)phenol

Partition coefficient

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

partition coefficient

Type of information:

other: experimental result obtained on one of the two main constituents of the reaction mass of 2,4,6-tris(1-phenylethyl)phenol and Bis(1-phenylethyl) phenol

Adequacy of study:

key study

Study period:

From 30/03/2007 (study initiation) to 17/08/2007 (date of the test report)

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study compliant with OECD guideline and the GLP.

Qualifier:

according to guideline

Guideline:

OECD Guideline 123 (Partition Coefficient (1-Octanol / Water), Slow-Stirring Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of method:

shake-flask method to: flask method

Partition coefficient type:

octanol-water

Analytical method:

other: LC-MS/MS for the aqueous phase

Type:

log Pow

Partition coefficient:

6.24

Temp.:

25 °C

pH:

6

Details on results:

Calculation of the log Pow:
The weighted mean value of logKow has been calculated.

Temperatures :
The measured temperatures showed that they were maintained constant during the test with a variation of less than 1°C.

pH :
The measured pH showed that it was maintained constant during the test at 6.05.

Validity criteria:
The logarithm of the n-octanol / water concentration ratio plotted versus time of at least 4 sampling times lead to a plateau in the plot. Therefore, the validity criterion was fulfilled.

Measured Concentrations of Distyrylphenol and logPow:

		Measured concentration
No	Test duration (h)	in n-octanol phase (µg/L)	in aqueous phase (µg/L)		logPow
1	337	1.74 x 10E7	9.33		6.27
	355	1.70 x 10E7	6.95		6.39
	362	2.32 x 10E7	8.59		6.43
	380	1.93 x 10E7	11.6		6.22
	386	1.91 x 10E7	13.4		6.16
				Mean	6.29
				SD	0.102
				CV	1.62
2	337	1.71 x 10E7	10.2		6.23
	356	1.76 x 10E7	8.88		6.30
	362	1.76 x 10E7	9.66		6.26
	380	2.03 x 10E7	13.2		6.19
	387	1.53 x 10E7	13		6.07
				Mean	6.21
				SD	0.0787
				CV	1.27
3	337	1.75 x 10E7	12.1		6.16
	356	1.89 x 10E7	8.45		6.35
	362	1.93 x 10E7	7.90		6.39
	380	1.97 x 10E7	11.7		6.23
	387	1.88 x 10E7	14.8		6.10
				Mean	6.25
				SD	0.11
				CV	1.76
LogPow weighted mean  : 6.24		SD : 0.0170	CV : 0.272

Conclusions:

The logPow weighted mean of the Distyrenated phenol was determined to be 6.24 at 25°C and pH6. Based on this logPow value, this substance is considered to have a potential for bioaccumulation.

Executive summary:

The partition coefficient (logPow) of Distyrenated phenol was determined using the slow stirring method according to the OECD TG 123 and the GLP.

The test was conducted with a concentration of 20 g/L in the n-Octanol layer. As aqueous phase a buffer solution of pH 6 was used leading to undissociated form of the test item. Three run have been performed at 25°C and for 387 hours. Five samples which demonstrated equilibrium were analysed via LC-MS/MS in aqueous phase and n-octanol phase using external standards.

The logPow weighted mean was determined to be 6.24.

Reference 2

Endpoint:

partition coefficient

Type of information:

other: experimental result obtained on one of the main constituents

Adequacy of study:

key study

Study period:

11.01.2018

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:

2004

Deviations:

yes

Remarks:

Due to technical reasons standards were injected separately instead of simultaneously. This had no influence on the quality or the scientific integrity of the study.

Qualifier:

according to guideline

Guideline:

other: EU Method A.24 (Partition Coefficient)

Principles of method if other than guideline:

DEVIATION FROM THE GUIDELINE:
due to technical reasons standards were injected separately instead of simultaneously. This had no influence on the quality or the scientific integrity of the study

GLP compliance:

yes (incl. QA statement)

Type of method:

HPLC method

Partition coefficient type:

octanol-water

Specific details on test material used for the study:

The test item is a mixture containing:
30.7% 2-(1-phenylethyl)phenol
67.5% 4-(1-phenylethyl)phenol

Analytical method:

high-performance liquid chromatography

Key result

Type:

log Pow

Partition coefficient:

3.03

Temp.:

23.6 °C

Remarks on result:

other: weighted average mean value

Type:

log Pow

Partition coefficient:

2.99

Temp.:

23.6 °C

Remarks on result:

other: for the first signal (4-phenylethylphenol)

Type:

log Pow

Partition coefficient:

3.13

Temp.:

23.6 °C

Remarks on result:

other: for the second signal (2-phenylethylphenol)

Details on results:

- Temperature: mean temperature during experimental phase was within the range of 20 - 25°C +/- 1°C during the study; min.: 23.4; max. 23.7°C.
- Signal-to-noise ratio: for the void time marker, reference items and test item > 3
- Determination of void time (t0): mean after threefold injection of 10 mg/L NaNO3, t0 = 0.750 (min)

Calculation of the weighted average mean value

	log Pow			Area (%)
	1 st Calibration	2nd Calibration	Mean
Signal 1: 4-(1 -phenylethyl) phenol	3.00 ± 0.05  2.87 to 3.14 (95% CI)	2.98 ± 0.05 2.84 to 3.12 (95% CI)	2.99	73.0
Signal 2: 2-(1 -phenylethyl) phenol	3.14 ± 0.05 3.00 to 3.27 (95% CI)	3.12 ± 0.05 2.98 to 3.26 (95% CI)	3.13	27.0
		Weighted Mean	3.03

Calibration data of the reference items

Reference item	log Pow	1st Calibration			2nd Calibration
		tR1 (min)	k	log k	tR2 (min)	k	log k
Benzonitrile	1.6	1.851	1.470	0.167	1.885	1.510	0.180
Nitrobenzene	1.9	2.682	2.580	0.411	2.735	2.650	0.423
Toluene	2.7	6.042	7.060	0.849	6.199	7.270	0.861
Ethylbenzene	3.2	9.489	11.700	1.070	9.742	12.000	1.080
Thymol^1	3.3	5.971	6.960	0.843	6.106	7.140	0.854
Isopropylbenzene	3.7	14.224	18.000	1.250	14.501	18.300	1.260
Biphenyl	4.0	17.645	22.500	1.350	17.903	22.900	1.360
1,2,4-Trichlorobenzene	4.2	20.333	26.100	1.420	20.496	26.300	1.420

tR1: Retention time 1st injection

tR2: Retention time 2nd injection

k: Capacity factor reference item

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

¹: determined to be an outlier via F-test for both calibrations

Conclusions:

The partition coefficient log Pow of the test item was determined at 23.6°C.
4-Phenylethyl phenol was found to have a log Kow of 2.99.
2-Phenylethyl phenol was found to have a log Kow of 3.13.

Executive summary:

The test was performed to determine the partition coefficient (n-octanol / water) of the test item according to OECD TG 117 and EU Method A.24 and in compliance to GLP.

Thet test item contains 30.7% of 2-phenylethyl phenol and 67.5% of 4-phenylethyl phenol. The test was performed with a concentration of approx. 20 mg/L test item in 65% methanol:35% HPLC water. Samples of the test item were analysed via HPLC on a C18 column with diode array detection.

Calibration was performed using seven reference items with known log Pow values. The referene items were measured twice, once before and once after the measurement of the test item. The void time of the HPLC system was determined with sodium nitrate.

For each of the two test item signals, two individual log Pow values were derived under consideration of the first and second calibration and a mean value was calculated from these individual log Pow values. The mean column temperature was determined to be 23.6°C during the study. The identity of the two test item signals was based on the respective peak area and composition as specified. All validity critera vere fulfilled.

The partition coefficient log Pow of the test item was determined at 23.6°C to be 2.99 for the first signal (4-phenylethylphenol) and 3.13 for the second signal (2-phenylethylphenol). The weighted average mean value is 3.03.

Reference 3

Endpoint:

partition coefficient

Type of information:

other: experimental result obtained on one of the two main constituents of the reaction mass of 2,4,6-tris(1-phenylethyl)phenol and Bis(1-phenylethyl) phenol

Adequacy of study:

key study

Study period:

From 29/11/2007 (study initiation) to 26/02/2008 (date of the test report)

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study compliant with OECD guideline and the GLP.

Qualifier:

according to guideline

Guideline:

OECD Guideline 123 (Partition Coefficient (1-Octanol / Water), Slow-Stirring Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of method:

shake-flask method to: flask method

Partition coefficient type:

octanol-water

Analytical method:

high-performance liquid chromatography

other: LC-MS/MS for the aqueous phase

Type:

log Pow

Partition coefficient:

7.77

Temp.:

25 °C

pH:

6

Details on results:

Calculation of the log Pow:
The weighted mean value of logKow has been calculated.

Temperatures :
The measured temperatures showed that they were maintained constant during the test with a variation of less than 0.5°C.

pH :
The measured pH showed that it was maintained constant during the test with a variation of less than 0.1.

Validity criteria:
The logarithm of the n-octanol / water concentration ratio plotted versus time of at least 4 sampling times lead to a plateau in the plot. Therefore, the validity criterion was fulfilled.

Measured Concentrations of Tristyrylphenol, logPow and Mass Balance:

		Measured concentration				MB
No	Test duration (h)	in n-octanol phase (µg/L)	in aqueous phase (µg/L)	Total Mass (mg)	logPow	RR (%)
1	28	1.16 x 10E7	0.147	580	7.90	101
	45	1.15 x 10E7	0.179	573	7.81	100
	53	1.15 x 10E7	0.233	573	7.69	100
	68	1.15 x 10E7	0.226	569	7.71	100
	76	1.14 x 10E7	0.259	563	7.64	99
	92	1.14 x 10E7	0.248	565	7.66	99.4
				Mean	7.74	100
				SD	0.0914	0.619
				CV	1.18	0.619
2	28	1.15 x 10E7	0.185	573	7.79	100
	45	1.15 x 10E7	0.183	574	7.80	100
	53	1.15 x 10E7	0.192	573	7.78	100
	68	1.15 x 10E7	0.158	573	7.86	101
	76	1.14 x 10E7	0.185	567	7.79	100
	92	1.15 x 10E7	0.218	570	7.72	100
				Mean	7.79	100
				SD	0.0408	0.373
				CV	0.524	0.373
3	28	1.12 x 10E7	0.222	561	7.70	97.7
	45	1.13 x 10E7	0.176	563	7.81	98.3
	53	1.14 x 10E7	0.161	570	7.85	100
	68	1.13 x 10E7	0.213	560	7.73	98.2
	76	1.16 x 10E7	0.230	573	7.70	101
	92	1.15 x 10E7	0.250	569	7.66	100
				Mean	7.74	99.2
				SD	0.0667	1.20
				CV	0.862	1.21
LogPow weighted mean		7.77	SD	0.0108	CV	0.139

Conclusions:

The logPow weighted mean of the tristyrenated phenol was determined to be 7.7 at 25°C and pH6. Based on this logPow value, this substance is considered to have a potential for bioaccumulation.

Executive summary:

The partition coefficient (logPow) of Tristyrenated phenol was determined using the slow stirring method according to the OECD TG 123 and the GLP.

The test was conducted with a concentration of 10 g/L in the n-Octanol layer. As aqueous phase a buffer solution of pH 6 was used leading to undissociated form of the test item. Three run have been performed at 25°C and for 92 hours. Six samples which demonstrated equilibrium were analysed via LC-MS/MS (aqueous phase) and HPLC-DAD (n-octanol phase) using external standards.

The logPow weighted mean was determined to be 7.77.

Description of key information

TSP: Log Kow = 7.77 at 25°C and pH 6 (NOACK, 2008) (OECD TG 123, GLP, slow stirring method, test concentration of 10 g/L in the n-Octanol layer, undissociated form, analysis by LC-MS/MS for aqueous phase and HPLC-DAD for n-octanol phase). 

DSP: Log Kow = 6.24 at 25°C and pH 6 (NOACK 2007) (OECD TG 123, GLP, slow stirring method, test concentration of 20 g/L in the n-Octanol layer, undissociated form, analysis by LC-MS/MS).

MSP: The n-­octanol/water partition coefficient (log Kow) of 4-­monostyryl phenol (4-­MSP) and 2-monostyryl phenol (2-­MSP) was determined by means of the HPLC method in accordance with OECD Guidance 117 and EU method A.24.This method was found appropriate and adequate notwithstanding the fact that 4-­MSP was found to be to a certain extent surface active.

The used test material consisted of a mixture containing 30.7% 2-­MSP and 67.5% 4-­MSP. The HPLC analysis used a C18 column with diode array detection. Under the selected HPLC conditions, the test material provided two non-­overlapping signals, which allowed for the determination of an individual Log Kow value for both isomers.

4 ­MSP was found to have a log Kow of 2.99, and the Log Kow of 2-­MSP was found to be 3.13.

Additional information

TSP/DSP: No study are available on the reaction mass of 2,4,6 -tris(1 -phenylethyl)phenol and Bis(1 -phenylethyl)phenol for this endpoint.

The two reliable studies available for the two main components (i.e. Tristyrenated phenol and Distyrenated phenol) were selected as key studies.

In the first study (NOACK, 2008), three run have been performed at 25°C and for 92 hours. The six samples analysed demonstrated equilibrium.

In the second study (NOACK, 2007), three run have been performed at 25°C and for 387 hours. The five samples analysed demonstrated equilibrium.

MSP: Two mono-­styrenated phenol isomers are present in the registered substance: 2-­monostyryl phenol (2 ­MSP) and 4-­monostyryl phenol (4 ­MSP). For the purpose of the PBT and exposure assessments, it is critical to obtain individual octanol-­water partition coefficients for these isomers. For this purpose, the HPLC method (OECD 117) is the most appropriate choice. The different stereo-­isomers are separated during the chromatography, which will allow for the determination of individual log Kow values for both constituents.

However, according to OECD guideline 117, the HPLC method is not applicable to surface active agents, while the surface tension test performed on 4-­MSP indicated that 4-­MSP has some surface active potential. It has nevertheless to be taken into account that the surface tension value of 4 ­MSP – even though being below the 60 mN/m threshold – still is quite high as compared to that of “true surfactants”. The surface activity of 2-­MSP is expected to be even less. It is therefore deemed unlikely that 4-­MSP and 2-­MSP will behave as true surface active substances.

Hence it is anticipated that the advantage of obtaining individual log Kow values outweighs the risk of technical problems in the HPLC test due to surface activity of the substances. This is further substantiated by the fact that thymol – one of the reference substances used in the HPLC method – has a number of structural characteristics in common with MSP: one hydroxyl group as the only hydrophilic group, and a carbon-­substituted benzene ring as the hydrophobic moiety.

The applicability of the HPLC method for the determination of the log Kow value for 2-MSP and 4 ­MSP is confirmed post factum as the chromatogram of the test item run shows sharp peaks that are adequately separated.