Phenol, 4-methyl-, reaction products with dicyclopentadiene and isobutylene

Partition coefficient

Link to relevant study record(s)

Reference

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Study period:

10 June 2013 - 19 July 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The study has been performed according to OECD and/or EC guidelines, and according to GLP principles. This study was conducted in response to ECHA Communication Number: CCH-D-0000002986-60-01/D Concerning Notification of a Draft Decision on a Compliance Check under Regulation (EC) No 1907/2006.

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

see below under "principles of method if other than guidelines

Principles of method if other than guideline:

List of deviations
List of protocol deviations
Validation of an analytical method for water samples:
During validation, the mean accuracy at 0.1μg/l and 0.25 μg/l was 53% and 73% respectively. The coefficient of variation was ≤ 20% at both concentration levels. Though the criterion that mean accuracy should be in the range 70-110% was not met at 0.1 μg/l, the method was accepted for analysis in the target concentration range of 0.1 and 0.25 μg/l. During performance of the slow-stirring test, accuracy samples were analysed on each day of analysis. Mean accuracy at 0.1 μg/l was then between 83 and 97% and at 0.25 μg/l between 88 and 102%. This confirmed that the analytical method is suitable for the analysis of the test substance in water in the concentration range
0.1 - 0.25 μg/l. The study integrity was not adversely affected by the deviation.

List of standard operating procedures deviations
There were no deviations from standard operating procedures (SOPs).

GLP compliance:

yes

Type of method:

other: slow stirring.

Partition coefficient type:

octanol-water

Analytical method:

other: LCMSMS with electrospray ionization

Type:

log Pow

Partition coefficient:

7.93

Temp.:

25 °C

Remarks on result:

other: Neutral pH

Details on results:

QSAR calculation of pKa and log Pow
Calculation of the pKa
Using the Perrin calculation method, a pKa between 11.6 and 12.6 was calculated for the phenol groups in the n=1, n=2 and n=3 structure of the test substance. These groups are acidic groups which are in their non-ionised form at neutral pH. The test substance structures do not contain basic groups.

Calculation of the Pow
Using the Rekker calculation method, a log Pow of 11.92, 17.67 and 23.42 was calculated for the n=1, n=2 and n=3 structure of the test substance respectively.

Main study – slow-stirring method
The results of the slow-stirring method are given in Table 8, calculations of the mean and sigma log Pow in Table 9 and the regression of the log Pow against time per sampling point of vessel 1, 2 and 3 are presented in Figure 7, Figure 8 and Figure 9 respectively. Concentrations reported in this chapter are of the test substance based on the response for the n=1 structure.

Equilibrium was achieved when six or seven time points interspersed by a minimum period of five hours yielded a slope that was not significantly different from zero at a p-level of 0.05. The first sample was excluded from the calculations. Appendix 1 presents the calculations and regression of the
1-octanol/water concentration ratio against time over time per sampling point.

The analysed concentration of the stock solution was 9.77 g/l. The recoveries were determined according to this value based on the analysed concentration in 1-octanol assuming the concentration in water as negligible.

A small response at the retention time of the test substance in water was detected in the chromatogram of the blank accuracy sample. The contribution of the response to the LOQ level 2 µg/l was 22%. Since this value was < 30%, the specificity requirements were met and the analytical method was found to be specific for the test substance.

Conclusion
The slow-stirring method was applied for the determination of the partition coefficient (Pow) of
Lowinox® CPL. Based on the response for the n=1 structure of the test substance, the Pow value at neutral pH and 25°C, was determined to be 8.51 x 107. It corresponds with a log Pow value of 7.93.

Table 8  Main study – P_owof the test substance

Vessel	Sampling point	Date and time of sampling	Analysed concentration				Pow	Log Pow
			1-octanol [g/l]	water [g/l]		Rec^2 [%]		individual	mean
1	1	12-jul-2013 09:45	9.89	2.12 x 10^-7		101	4.66 x 10^7	7.67^1	8.04
	2	12-jul-2013 14:50	10.1	7.53 x 10^-8		103	1.34 x 10^8	8.13
	3	15-jul-2013 08:20	10.1	1.26 x 10^-7		103	7.98 x 10^7	7.90
	4	15-jul-2013 13:45	10.3	8.58 x 10^-8		105	1.20 x 10^8	8.08
	5	16-jul-2013 09:40	10.1	9.14 x 10^-8		103	1.10 x 10^8	8.04
	6	16-jul-2013 15:05	10.2	8.67 x 10^-8		104	1.18 x 10^8	8.07
2	1	12-jul-2013 09:45	9.69	6.72 x 10^-7		99	1.44 x 10^7	7.16^1	7.72
	2	12-jul-2013 14:50	10.2	2.26 x 10^-7		104	4.51 x 10^7	7.65
	3	15-jul-2013 08:20	11.1	2.49 x 10^-7		114	4.48 x 10^7	7.65
	4	15-jul-2013 13:45	11.9	1.94 x 10^-7		122	6.13 x 10^7	7.79
	5	16-jul-2013 09:40	10.1	1.53 x 10^-7		103	6.57 x 10^7	7.82
	6	16-jul-2013 15:05	10.6	1.45 x 10^-7		109	7.30 x 10^7	7.86
	7	19-jul-2013 08:40	9.63	2.63 x 10^-7		99	3.66 x 10^7	7.56
3	1	12-jul-2013 09:45	9.82	1.56 x 10^-7		100	6.31 x 10^7	7.80^1	7.94
	2	12-jul-2013 14:50	10.3	1.35 x 10^-7		105	7.61 x 10^7	7.88
	3	15-jul-2013 08:20	11.2	2.18 x 10^-7		114	5.13 x 10^7	7.71
	4	15-jul-2013 13:45	9.92	8.40 x 10^-8		101	1.18 x 10^8	8.07
	5	16-jul-2013 09:40	10.5	8.51 x 10^-8		108	1.24 x 10^8	8.09
	6	16-jul-2013 15:05	10.2	8.94 x 10^-8		105	1.14 x 10^8	8.06
	7	19-jul-2013 08:40	10.2	1.44 x 10^-7		102	6.89 x 10^7	7.84
		Meanlog Pow ^3			7.93
		Mean Pow ^3			8.51 x 10^7
		Average sigma log Pow ^3			0.1

¹The calculations were performed with exclusion of sample 1, because the equilibrium was not reached yet.

² Recovery (Rec) was calculated from the concentration analysed in the 1-octanol sample. Concentration in the water sample was considered negligible.

³Calculations presented inTable 9.
Table 9  Calculations of mean and sigma P_ow

	Vessel 1^1	Vessel 2^1	Vessel 3^1	Average
P value slope	0.93	0.86	0.57
log Pow, i / av	8.04	7.72	7.92	7.93
Variance	0.00577	0.0114	0.0202
Weigthing factor (wi)	173	88.0	49.5
log Pow* weigthing factor	1394	679	392
log Pow, i - log Pow, av	0.11	-0.21	-0.0118
wi * (log Pow, i - log Pow, av)^2	2.11	3.91	0.00684
wi * (n-1)	347	176	98.9
var log Pow, av				0.0097
sigma log Pow, av				0.098

¹ The calculations were performed with exclusion of sampling point 1 because equilibrium was not reached yet.

 

 

Conclusions:

The slow-stirring method was applied for the determination of the partition coefficient (Pow) of Lowinox® CPL. Based on the response for the n=1 structure of the test substance, the Pow value at neutral pH and 25°C, was determined to be 8.51 x 107. It corresponds with a log Pow value of 7.93.

Executive summary:

This study was conducted in response to ECHA Communication Number: CCH-D-0000002986-60-01/D Concerning Notification of a Draft Decision on a Compliance Check under Regulation (EC) No 1907/2006. The slow-stirring method was applied for the determination of the partition coefficient (Pow) of Lowinox® CPL. Based on the response for the n=1 structure of the test substance, the Pow value at neutral pH and 25°C, was determined to be 8.51 x 107. It corresponds with a log Pow value of 7.93.

Description of key information

The HPLC method was used to determine the log Pow range of the test substance: the major components of the substance have log Pow between 7.17 and 8.17. At the request of ECHA, Communication Number: CCH-D-0000002986-60-01/D Concerning Notification of a Draft Decision on a Compliance Check under Regulation (EC) No 1907/2006, the slow-stirring method was applied for the determination of the partition coefficient (Pow) of Lowinox® CPL. Based on the response for the n=1 structure of the test substance, the Pow value at neutral pH and 25°C, was determined to be 8.51 x 107. It corresponds with a log Pow value of 7.93.

Key value for chemical safety assessment

Log Kow (Log Pow):

7.93

at the temperature of:

25 °C

Additional information

Two GLP studies were originally available to cover this endpoint of which 1 was not useful because the wrong method was chosen (shake-flask method is not applicable for this substance). The result of 1 study was originally considered, i.e. the result of the HPLC method. The HPLC method was used to determine the log Pow range of the test substance: the major components of the substance have log Pow between 7.17 and 8.17. At the request of ECHA, Communication Number: CCH-D-0000002986-60-01/D Concerning Notification of a Draft Decision on a Compliance Check under Regulation (EC) No 1907/2006, the slow-stirring method was applied for the determination of the partition coefficient (Pow) of Lowinox® CPL. Based on the response for the n=1 structure of the test substance, the Pow value at neutral pH and 25°C, was determined to be 8.51 x 107. It corresponds with a log Pow value of 7.93.