6-amino-2-(2,4-dimethylphenyl)-1H-benz[de]isoquinoline-1,3(2H)-dione

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 November 2016 to 15 January 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Reason / purpose for cross-reference:

reference to same study

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:

EU Method A.8 (Partition Coefficient - HPLC Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

1996

Deviations:

no

GLP compliance:

yes

Type of method:

HPLC method

Partition coefficient type:

octanol-water

Specific details on test material used for the study:

- Purity/composition correction factor: Yes, correction factor is 1.031 according to active ingredient

Analytical method:

high-performance liquid chromatography

Key result

Type:

log Pow

Partition coefficient:

0.2

Temp.:

35 °C

pH:

7

Remarks on result:

other: test material peak 1 (13 area %)

Key result

Type:

log Pow

Partition coefficient:

2.3

Temp.:

35 °C

pH:

7

Remarks on result:

other: test material peak 2 (85 area %)

Key result

Type:

log Pow

Partition coefficient:

2.6

Temp.:

35 °C

pH:

7

Remarks on result:

other: test material peak 3 (2.6 area %)

Details on results:

In the chromatogram of the test solution, one major peak and two small test material peaks were observed.
The equation of the regression line was: log k’ = 0.351 x log Pow - 0.828 (r = 0.996, n = 12).

Table 1: Pow of the test material

Substance	tr,1 [min]	tr,2 [min]	mean tr (n=2)	log Pow	Pow	Area %
Formamide (t0)	0.771	0.766	0.769
2-Butanone	0.921	0.905		0.3
Nitrobenzene	1.243	1.236		1.9
Toluene	2.002	1.991		2.7
1,4-Dichlorobenzene	2.593	2.582		3.4
Biphenyl	3.507	3.495		4.0
1,2,4-Trichlorobenzene	4.041	4.028		4.2
Test material - peak 1	0.907	0.898	0.903	0.2*	0.16	13
Test material - peak 2	1.486	1.474	1.480	2.3	180	85
Test material - peak 3	2.486	2.467	2.477	3.4	2200	2.6

*Estimated value, calculated by extrapolation of the calibration curve

Conclusions:

The log Pow values of test material peaks 1, 2 and 3 were 0.2, 2.3 and 3.4, respectively.

Executive summary:

The partition coefficient was determined in accordance with the standardised guidelines OECD 117, EU Method A.8 and US EPA OPPTS 830.7570 under GLP conditions.

The calculation method was used for a preliminary estimation of the Pow of the test material and was calculated to be 4.0 x 10^2 (log Pow 2.6). Therefore it was decided to perform the HPLC method for an accurate determination of the Pow. The determination of the Pow of the test material should be performed in its non-ionised form; therefore, the pKa values of the test material were calculated. Based on the calculations, it was decided to perform the HPLC method at neutral pH.

Solutions of reference substances and the test material were analysed. The capacity factor (k') of each compound was calculated from its retention time. The log k’ values of the reference substances were plotted against the known log Pow values. A linear regression program was used to calculate the calibration curve. Linear regression analysis was performed using the least squares method. The coefficient of correlation (r) was calculated. The log Pow value for the test material was calculated by substituting its mean log k’ in the calibration curve. The value of log Pow obtained from duplicate measurements was within ± 0.1 log units.

In the chromatogram of the test solution, one major peak and two small test material peaks were observed.

The log Pow values of test material peaks 1, 2 and 3 were 0.2, 2.3 and 3.4, respectively. The area % of each peak was 13, 86 and 2.6 for peaks 1, 2 and 3, respectively.

Description of key information

The log Pow values of test material peaks 1, 2 and 3 were 0.2, 2.3 and 3.4, respectively.

Key value for chemical safety assessment

Log Kow (Log Pow):

2.3

at the temperature of:

35 °C

Additional information

The partition coefficient was determined in accordance with the standardised guidelines OECD 117, EU Method A.8 and US EPA OPPTS 830.7570 under GLP conditions. The study was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997).

The calculation method was used for a preliminary estimation of the Pow of the test material and was calculated to be 4.0 x 10^2 (log Pow 2.6). Therefore it was decided to perform the HPLC method for an accurate determination of the Pow. The determination of the Pow of the test material should be performed in its non-ionised form; therefore, the pKa values of the test material were calculated. Based on the calculations, it was decided to perform the HPLC method at neutral pH.

Solutions of reference substances and the test material were analysed. The capacity factor (k') of each compound was calculated from its retention time. The log k’ values of the reference substances were plotted against the known log Pow values. A linear regression program was used to calculate the calibration curve. Linear regression analysis was performed using the least squares method. The coefficient of correlation (r) was calculated. The log Pow value for the test material was calculated by substituting its mean log k’ in the calibration curve. The value of log Pow obtained from duplicate measurements was within ± 0.1 log units.

In the chromatogram of the test solution, one major peak and two small test material peaks were observed.

The log Pow values of test material peaks 1, 2 and 3 were 0.2, 2.3 and 3.4, respectively. The area % of each peak was 13, 86 and 2.6 for peaks 1, 2 and 3, respectively.