4,4'-methylenebis(2,6-xylidine)

Partition coefficient

Link to relevant study record(s)

Reference

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Study period:

19 February 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

The study was conducted according to an internationally recognised method, and under GLP. No deviation was reported. The test substance is adequately characterised. Therefore full validation applies.

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2004

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Commission Regulation (EU) 2016/266 of adopted 7 December 2015 amending Regu-lation EC No. 440/2008, Method A.24 “Partition Coefficient (N-OCTANOL/WATER), HIGH PERFORMANCELIQUID CHROMATOGRAPHY (HPLC) METHOD

Version / remarks:

2015/2016

Deviations:

no

Principles of method if other than guideline:

not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

GLP compliance programme (inspected on 13 and 14 October 2014 / signed on 08 April 2015)

Type of method:

HPLC method

Partition coefficient type:

octanol-water

Analytical method:

high-performance liquid chromatography

Key result

Type:

log Pow

Partition coefficient:

2.6

Temp.:

25 °C

pH:

7

Findings and Results

Details on the determination of dead time and calibration data of the reference items is included in the experimental report.

Correlation Results

Dead time is 1.394 ± 0.001 minutes, with RSD (relative standard deviation) 0.037%.

 

The RSD of the retention times of the reference items lay all below 0.04 %.

 

Equation of the regression:

log k = 0.3538 * log P_OW– 0.7867
with a coefficient of determination r²= 0.9424

The retention times of the test item are presented in the folowing table:

Table 4.7/1.- Retention Times (RT) Test Item

Measurement	RT
	min.
Measurement 1	3.302
Measurement 2	3.302
Measurement 3	3.300
Mean	3.301
Standard deviation	0.001

 

Calculated Values

The calculated values are presented in the following table:

Table 4.7/2.-Capacity Factor, log Capacity Factor, log P_OWTest Item

Measurement	k	log k	log POW
Measurement 1	1.3678	0.1360	2.608
Measurement 2	1.3678	0.1360	2.608
Measurement 3	1.3668	0.1357	2.607
Mean			2.608
Relative Standard deviation			0.000

 

 

log P_OWwas calculated from the capacity factor as follows:

 

log P_OW= (log k + 0.7867) / 0.3538

Result

Using the correlation log k / log P_OW, the log P_OWof the test item was calculated as 2.608 ± 0.000 (mean ± standard deviation).

Validity

The validity criteria and results are presented in the following table:

Table 4.7/3.- Validity Criteria and Results

Peak	Parameter	Criterion	Found	Assessment
1	Range (Max – Min. log POW)	< 0.1	0.001	valid
	Value within Range of Reference Items	0.30 - 3.60	2.608	valid

Discussion

During calibration a good correlation log k/log P_OWwas found. The coefficient of determination r²was calculated to be 0.9424. This value was considered as sufficiently high to use the calibration function for the determination of the log P_OWof the test item.

Using the correlation log k / log P_OW, the log P_OWof test item was calculated as 2.608 ± 0.000 (mean ± standard deviation)

Therefore, the log P_OWof the test item is stated as 2.6 (mean) at a temperature of 25 ± 0.5 °C and a pH value of 7.

No observations were made which might cause doubts concerning the validity of the study outcome.

Conclusions:

The log POW of the test item was calculated as 2.608.

Executive summary:

The partition coeffitient of the test item was measured under GLP according to the OECD 117/EUA24 guideline, HPLC method. Seven reference items with different retention times and thiourea for the determination of the dead time were used to produce a calibration curve, since retention time on hydrophobic columns and P_OWare correlated. The reference items were chosen based on the results of the pre-test.

One vial was filled with the reference item mix and one vial with the test item solution. The vials were analysed using the HPLC with the program described below. First one injection from the solvent blank methanol/phosphate buffer pH 7 75/25 (v/v) was made. Then three injections were measured from the reference item mix, three injections from the test item and again three injections from the reference item mix.

For each reference item, the capacity factor k was calculated from the retention time of thiourea and the retention time of the respective reference item.

A calibration function (log k versus log P_OW, linear fit) was determined using the literature values for P_OWof the reference items and the retention times in the six determinations.

 

The chromatogram of the test item gave one peak. With the calibration function log k versus log P_OW, the corresponding log P_OWof the peak was calculated with:
2.608 ± 0.000 (mean ± standard deviation).

 

Therefore, the log P_OWof the test itemis stated as2.6 (mean) at a temperature of 25 ± 0.5 °C and a pH value of 7.

Description of key information

The log P_OWof the test item is stated as 2.6 (mean) at a temperature of 25 ± 0.5 °C and a pH value of 7.

Key value for chemical safety assessment

Log Kow (Log Pow):

2.6

at the temperature of:

25 °C

Additional information

A fully reliable experimental study, conducted according to a recognized OECD/EC method and under GLP, is available. Therefore, it is considered as a key study, and the result is retained as key data.