5-fluoro-2-methoxypyrimidin-4(3H)-one

Adsorption / desorption

Link to relevant study record(s)

Reference

Endpoint:

adsorption / desorption: screening

Type of information:

experimental study

Adequacy of study:

other information

Study period:

12 December 2005 to 20 December 2005

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 121 (Estimation of the Adsorption Coefficient (Koc) on Soil and on Sewage Sludge using High Performance Liquid Chromatography (HPLC))

Version / remarks:

2001

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method C.19 (Estimation of the Adsorption Coefficient (KOC) on Soil and Sewage Sludge Using High Performance Liquid Chromatography (HPLC))

Version / remarks:

2001

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of method:

HPLC estimation method

Media:

soil

Radiolabelling:

no

Test temperature:

23.5 to 24.5 °C

Details on study design: HPLC method:

The adsorption coefficient was estimated to be 1 using PCKOC Program (vl.66). In addition, the pKa of the test material were estimated to be -0.01 (H2L+ /HL) and 6.59 (HL/L-) using Pallas-Compon Drug (v 3.1.1.2) program.

HPLC was performed on an analytical column packed with a cyanopropyl solid phase containing lipophilic and polar moieties. As the test material is ionisable, two tests were performed with the following mobile phase:
- Test 1: methanol/buffer (50/50 v/v) at pH 4.0 (non-ionised form)
-Test 2: methanol/buffer (55/45 v/v) at pH 10.5 (ionised form)

EQUIPMENT
Chromatographic conditions: HPLC/UV
- Pump: SERIES 1100 (Agilent Technologies)
- Flow rate: 1 mL/min
- Column: Hypersil CN (AIT), particle size= 3 μm, length= 150 mm, inner diameter = 4.6 mm
- Temperature: 23.5 to 24.5 °C
- Oven: Sup RS Stabitherm
- Detector: SERIES 1100 (Agilent Technologies)
- Wavelength: 210 nm
- Injector: SERIES 1100 (Agilent Technologies)
- Injected volume: 10 μL
- Data acquisition software: Multichrom 2 (Fisons Instruments)
- Analysis time: 1.5 min (for test 2) and 2.2 min (for test 1)

MOBILE PHASES
- For test 1: methanol 50 % and buffer 50 % (buffer: potassium dihydrogenosulfate (13.6 g) was transferred into a 1000-mL volumetric flask and made up to volume with water). The mobile phase was adjusted at pH= 4.0 with phosphoric acid.
- For test 2: methanol 55 % and buffer 45 % (buffer: ammonium acetate (0. 778 g) was transferred into a 1000-mL volumetric flask and made up to volume with water). The mobile phase was adjusted at pH = 10.5 with ammonia solution.

DETERMINATION OF DEAD TIME
- Method: Injection of a solution of formamide was performed in duplicate (1150 ng)

REFERENCE SUBSTANCES
- Identity: Acetanilide, methylbenzoate, naphthalene, 1,2,3-trichlorobenzene, phenanthrene and DDT

DETERMINATION OF RETENTION TIMES
- Quantity of test substance introduced in the column: 99.2 ng
- Quantity of reference substances: Acetanilide 49.5 ng, methylbenzoate 49.0 ng, naphthalene 6.68 ng, 1,2,3-trichlorobenzene 33.0 ng, phenanthrene 18.0 ng and DDT 210 ng.
- Intervals of calibration: Test and reference materials were dissolved in methanol and the mobile phase. Then the reference materials were injected as a mixed standard to determine their retention times. Calibration injections were carried out before and after injections of the test material to confirm retention times and column performance. All injections were carried out on the same day.

REPETITIONS
- Number of determinations: The test material was injected in duplicate and its retention time was determined.

EVALUATION
- Calculation of capacity factors k': The capacity factor k' was calculated from the dead time t0 and retention times according to the equation:
k' = (tr-t0)/ t0
t0: HPLC dead time (min)
tr: HPLC retention time of test and reference materials (min)
- Determination of the log Koc value: The log k' data of the reference materials were then plotted against their log Koc values from batch equilibrium. Using this plot, the Koc values determined for the reference materials were within ± 0.5 log units of the values determined by the batch equilibrium method in the OECD guideline and the log k' value of the test material was then used to determine its log Koc value. The values of the Koc taken from the duplicate analyses were within the range of 0.25 log units.

Key result

Sample No.:

#1

Type:

Koc

Value:

0.098

pH:

4

Temp.:

23.5 °C

Matrix:

Soil (HPLC)

Key result

Sample No.:

#1

Type:

log Koc

Value:

-1.02

pH:

4

Temp.:

23.5 °C

Matrix:

Soil (HPLC)

Details on results (HPLC method):

TEST 1 (pH = 4.0)
Retention data and estimated log Koc values for reference and test materials are presented in Table 1.
As the retention time of the test material was lower than the retention time of acetanilide, an extrapolation was performed to estimate the adsorption coefficient
TEST 2 (pH = 10.5)
Retention data and estimated log Koc values for reference and test materials are presented in Table 2.
As the retention time of test material was lower than the retention time of formamide (dead volume) with a negative value of k', the test was considered not to be applicable. The estimation of the adsorption coefficient (Koc) was not performed.

Table 1: Test 1 Retention times and measured log Koc values for test and reference materials

Material		Mean							Log Koc expected		Bias
		Retention time	k’		Log k’		Log Koc measured
Formamide		2.06	-		-		-		-		-
Acetanilide		2.48	0.202		-0.696		0.872		1.25		-0.378
Methylbenzoate		2.94	0.425		-0.371		1.97		1.80		0.165
Naphthalene		3.89	0.885		-0.0531		3.04		2.75		0.289
1,2,3-Trichlorobenzene		4.29	1.08		0.0319		3.33		3.16		0.166
Phenanthrene		6.27	2.04		0.309		4.26		4.09		0.171
DDT		10.1	3.92		0.593		5.22		5.63		-0.413
Linear least squares regression: a =3.37, b = 3.22, r2=0.962
	Replicate			Retention time		k’		Log k’		Log Koc measured
Test material	1			2.18		0.06		-1.254		-1.01
	2			2.18		0.05		-1.262		-1.04
	Mean			2.18		0.06		-1.258		-1.02

Table 2: Test 2 Retention times and measured log Koc values for test and reference materials

Material		Mean							Log Koc expected		Bias
		Retention time	k’		Log k’		Log Koc measured
Formamide		2.07	-		-		-		-		-
Acetanilide		2.30	0.114		-0.944		0.847		1.25		-0.403
Methylbenzoate		2.51	0.216		-0.666		1.95		1.80		0.151
Naphthalene		2.92	0.413		-0.384		3.07		2.75		0.324
1,2,3-Trichlorobenzene		3.10	0.499		-0.302		3.40		3.16		0.242
Phenanthrene		3.82	0.849		-0.0710		4.32		4.09		0.229
DDT		4.80	1.32		0.122		5.09		5.63		-0.544
Linear least squares regression: a =3.98, b = 4.60, r2=0.945
	Replicate			Retention time		k’		Log k’		Log Koc measured
Test material	1			1.45		-0.30		NC		NC
	2			1.46		-0.29		NC		NC
	Mean			1.46		-0.30		NC		NC

NC = Not calculated

Validity criteria fulfilled:

yes

Conclusions:

Under the condition of this study, the estimated adsorption coefficient of the test material on soil was Koc 0.0977 and Log Koc -1.02 at pH 4.

Executive summary:

The adsorption coefficient of the test material was estimated in accordance with the standardised guidelines OECD 121 and EU Method C.19 under GLP conditions using the HLPC method.

The adsorption coefficient of the test material was estimated to be 1 using PCKOC Program (v1.66). In addition, the pKa of the test material were estimated to be -0.01 (H2L+ /HL) and 6.59 (HL/L-) using Pallas-Compon Drug (v 3.1.1.2) program.

HPLC was performed on an analytical column packed with a cyanopropyl solid phase containing lipophilic and polar moieties. As the test material is ionisable, two tests were performed with the following mobile phases: in test 1 methanol/buffer (50/50 v/v) at pH 4.0 (non-ionized form) and in test 2 methanol/buffer (55/45 v/v) at pH 10.5 (ionised form). The adsorption coefficient was deduced from the capacity factor (k') using a calibration plot of log k' versus log Koc of selected reference materials.

For pH 4.0, the retention time of test material was lower than the retention time of acetanilide (the reference material with the shortest retention time), therefore an extrapolation was performed to estimate the adsorption coefficient (Koc) of the test material.

For pH 10.5, the retention time of test material was close to the retention time of formamide (dead volume) with a negative value of k', therefore the test was not considered to be applicable. No estimation of the adsorption coefficient (Koc) was performed.

Under the condition of this study, the estimated adsorption coefficient of the test material on soil was Koc 0.0977 and Log Koc -1.02 at pH 4.

Description of key information

Under the condition of this study, the estimated adsorption coefficient of the test material on soil was Koc 0.0977 and Log Koc -1.02 at pH 4.

Key value for chemical safety assessment

Koc at 20 °C:

0.098

Additional information

The adsorption coefficient of the test material was estimated in accordance with the standardised guidelines OECD 121 and EU Method C.19 under GLP conditions using the HLPC method. The study was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997).

The adsorption coefficient of the test material was estimated to be 1 using PCKOC Program (v1.66). In addition, the pKa of the test material were estimated to be -0.01 (H2L+ /HL) and 6.59 (HL/L-) using Pallas-Compon Drug (v 3.1.1.2) program.

HPLC was performed on an analytical column packed with a cyanopropyl solid phase containing lipophilic and polar moieties. As the test material is ionisable, two tests were performed with the following mobile phases: in test 1 methanol/buffer (50/50 v/v) at pH 4.0 (non-ionized form) and in test 2 methanol/buffer (55/45 v/v) at pH 10.5 (ionised form). The adsorption coefficient was deduced from the capacity factor (k') using a calibration plot of log k' versus log Koc of selected reference materials.

For pH 4.0, the retention time of test material was lower than the retention time of acetanilide (the reference material with the shortest retention time), therefore an extrapolation was performed to estimate the adsorption coefficient (Koc) of the test material.

For pH 10.5, the retention time of test material was close to the retention time of formamide (dead volume) with a negative value of k', therefore the test was not considered to be applicable. No estimation of the adsorption coefficient (Koc) was performed.

Under the condition of this study, the estimated adsorption coefficient of the test material on soil was Koc 0.0977 and Log Koc -1.02 at pH 4.

[LogKoc: -1.02]