N-octylpyridin-4-amine

Partition coefficient

Administrative data

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Experimental starting date: 09 April 2018, Experimental completion date: 12 April 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 107 (Partition Coefficient (n-octanol / water), Shake Flask Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of method:

flask method

Partition coefficient type:

octanol-water

Test material

Test material information

Constituent 1

Reference substance name:

N-octylpyridin-4-amine

EC Number:

265-019-0

EC Name:

N-octylpyridin-4-amine

Cas Number:

64690-19-3

Molecular formula:

C13H22N2

IUPAC Name:

N-octylpyridin-4-amine

Study design

Analytical method:

not specified

Results and discussion

Partition coefficient

Partition coefficient 1

Key result

Type:

log Pow

Partition coefficient:

2.28

Temp.:

22.5 °C

pH:

7

Partition coefficient 2

Type:

Pow

Partition coefficient:

191

Temp.:

22.5 °C

pH:

7

Any other information on results incl. tables

Preliminary Estimate

The estimated partition coefficient was222at22.5± 0.5 °C, log P_owof2.35, with a total phase recovery of 105%. The aqueous phase pH was 7.0.

Definitive Test

The mean peak areas obtained for the standard, stock and sample solutions are shown in the following two tables:

Table 3            Organic Phase

Solution	Mean Peak Area
Standard 20.7 mg/L	5.1992 x 10^6
Standard 21.0 mg/L	5.2244 x 10^6
Organic phase matrix blank	none detected
Organic Sample 1	4.9760 x 10^6
Organic Sample 2	5.0873 x 10^6
Organic Sample 3	5.0490 x 10^6
Organic Sample 4	5.1114 x 10^6
Organic Sample 5	5.0339 x 10^6
Organic Sample 6	5.1442 x 10^6
Stock solution A	5.2219 x 10^6
Stock solution B	5.3237 x 10^6

Table 4 – Aqueous Phase

Solution	Mean Peak Area
Standard 20.7 mg/L	5.0771 x 10^6
Standard 21.0 mg/L	5.0841 x 10^6
Aqueous phase matrix blank	none detected
Aqueous Sample 1	6.8811 x 10^5
Aqueous Sample 2	5.6174 x 10^5
Aqueous Sample 3	7.1646 x 10^5
Aqueous Sample 4	5.2840 x 10^5
Aqueous Sample 5	3.2104 x 10^5
Aqueous Sample 6	1.9963 x 10^5

The mean peak areas obtained for the standard, stock and sample solutionsfrom the additional ratioare shown in the following two tables:

Table 5            Organic Phase

Solution	Mean Peak Area
Standard 22.6 mg/L	5.4962 x 10^6
Standard 21.0 mg/L	5.0931 x 10^6
Organic phase matrix blank	1.9321 x 10^5
Organic Sample 7	5.0786 x 10^6
Organic Sample 8	5.0866 x 10^6
Stock solution A	5.1932 x 10^6
Stock solution B	5.1872 x 10^6

Table 6 – Aqueous Phase

Solution	Mean Peak Area
Standard 22.6 mg/L	5.4119 x 10^6
Standard 21.0 mg/L	5.0848 x 10^6
Aqueous phase matrix blank	none detected
Aqueous Sample 7	7.4594 x 10^5
Aqueous Sample 8	7.3609 x 10^5

The analyzed concentration (mg/L) and test item weight (mg) of the respective phases are shown in the following table:

Table 7

Flask	Total Weight (mg)*	Organic Phase		Aqueous Phase			% Recovery
		Analyzed Concentration (mg/L)	Weight (mg)†	Analyzed Concentration (mg/L)	Weight (mg)†	pH
1	14.8	9.97 x 10^2	14.0	5.66	0.317	7.0	96.5
2	1.58	1.02 x 10^3	15.3	4.62	0.277	7.0	98.2
3	10.6	1.01 x 10^3	10.2	5.89	0.471	7.0	100
4	8.45	1.02 x 10^3	8.19	4.34	0.278	7.0	100
5	4.75	1.01 x 10^3	4.54	2.64	0.190	7.0	99.5
6	4.75	1.03 x 10^3	4.64	1.64	0.118	7.0	100
7	25.7	1.05 x 10^3	25.1	6.20	0.298	7.0	99.0
8	27.8	1.05 x 10^3	27.2	6.12	0.318	7.0	99.1

pH of n-octanol saturatedpH 7 buffer:         7.0

The partition coefficient determined for each flask is shown in the following table:

Table 8

Flask	Organic/Aqueous Volume Ratio	Partition Coefficient	Log10Pow	Mean Partition Coefficient
1	1:4	176	2.25	198
2		221	2.34
3	1:8	172	2.23	204
4		236	2.37
5	1:16	382	2.58	505
6		628	2.80
7	1:2	169	2.23	170
8		171	2.23

Overall P_ow:   191
log₁₀P_ow:        2.28
Temperature:  22.5 ± 0.5°C

Validation

The linearity of the detector response with respect to concentrationfor the organic phase analysiswas assessed over the nominal concentration range of 5 to 50 mg/L. The results were satisfactory with a correlation coefficient (r) of 0.998 being obtained.

The linearity of the detector response with respect to concentrationfor the aqueous phase analysiswas assessed over the nominal concentration range of 5 to 50mg/L. The results were satisfactory with a correlation coefficient (r) of 1.000 being obtained.

Discussion

The shake-flask method was chosen over the HPLC method as the test item contained an amine functional group; amines can have secondary interactions which would affect the result generated by the HPLC method.

The test item had an estimated dissociation constant of 8.32. Therefore, to be fully in its non-ionized form the aqueous pH would need to be at least 10.3. As this was considered higher than the environmentally relevant pH range, it was discussed with the Sponsor and agreed to perform the test at a neutral pH which was considered more environmentally relevant. At this pH the test item would mostly be in its ionized form.

With the aqueous phase being required to be pH 7, a pH 7 buffer was mutually saturated withn-octanol prior to testing.

The organic phase matrix blank for the additional ratio analysis had a small peak at the retention time of the test item. It was considered that this was probably contamination and as it didn’t appear in other matrix blanks it was not considered intrinsic to the matrix and was therefore not accounted for in the calculations.

Two additional flasks at a ratio of 1:2 were performed due to the higher and inconsistent results obtained at a ratio of 1:16. It was considered that the small volume of stock solution was not enough during the 5 minutes of shaking to full partition into the aqueous phase.

For additional information and as a comparison with the pH 7 result, another single shake-flask was performed during the preliminary test but with the aqueous phase buffered to pH 9.3. As for pH 7, the buffer was mutually saturated withn-octanol prior to testing. At this pH the test item was mostly in its non-ionized form and close to the environmentally relevant pH range. The result produced was a log P_owof approximately 4.1. 

* From analysis of the stock solution

† From analysis of the respective phase

Applicant's summary and conclusion

Conclusions:

The partition coefficient of the test item at pH 7 has been determined to be 191 at 22.5 ± 0.5 °C, and a log10 Pow of 2.28.