Pyrolytic sugar

Partition coefficient

Administrative data

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Study period:

March 2021

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2021

Report date:

2021

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

April 2004

Deviations:

yes

Remarks:

uncritical deviation: The reference item mix was dissolved in a different solvent than the eluent (metha-nol/water 75/25 % v/v instead of 65/35 % v/v) in the first determination. Deviation had no impact on the retention times.

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: EU method A.24 “Partition Coefficient (N-OCTANOL/WATER), HIGH PERFORMANCE LIQUID CHROMATOGRAPHY (HPLC) METHOD"

Version / remarks:

December 2015

Deviations:

yes

Remarks:

as above

GLP compliance:

yes (incl. QA statement)

Type of method:

HPLC method

Partition coefficient type:

octanol-water

Test material

Test material information

Constituent 1

Reference substance name:

1,6-anhydro-β-D-glucose

EC Number:

207-855-0

EC Name:

1,6-anhydro-β-D-glucose

Cas Number:

498-07-7

Molecular formula:

C6H10O5

IUPAC Name:

(1R,2S,3S,4R,5R)-6,8-dioxabicyclo[3.2.1]octane-2,3,4-triol

Constituent 2

Reference substance name:

Glycollaldehyde

EC Number:

205-484-9

EC Name:

Glycollaldehyde

Cas Number:

141-46-8

Molecular formula:

C2H4O2

IUPAC Name:

2-hydroxyacetaldehyde

Constituent 3

Reference substance name:

Organic acids

IUPAC Name:

Organic acids

Constituent 4

Reference substance name:

Ketones

IUPAC Name:

Ketones

Constituent 5

Reference substance name:

Phenols

IUPAC Name:

Phenols

Constituent 6

Reference substance name:

Water

EC Number:

231-791-2

EC Name:

Water

Cas Number:

7732-18-5

Molecular formula:

H2O

IUPAC Name:

water

Constituent 7

Reference substance name:

Oligomers of sugars and anhydrosugars

IUPAC Name:

Oligomers of sugars and anhydrosugars

Test material form:

liquid: viscous

Study design

Analytical method:

high-performance liquid chromatography

Results and discussion

Partition coefficient

Partition coefficient 1

Type:

log Pow

Partition coefficient:

< 0.3

Remarks on result:

other: Peak 1

Partition coefficient 2

Type:

log Pow

Partition coefficient:

ca. 1.2 - ca. 2.3

Remarks on result:

other: Peak 2

Partition coefficient 3

Type:

log Pow

Partition coefficient:

ca. 2.3 - ca. 2.4

Remarks on result:

other: peak 3

Partition coefficient 4

Type:

log Pow

Partition coefficient:

ca. 2.4 - ca. 3.4

Remarks on result:

other: peak 4

Details on results:

The chromatogram of the test item gave three major and one minor peaks.
Since the peaks are very wide, the log k versus log POW calibration function is used to determine the corresponding log POW values of the start and end of the main peaks and a log POW range for each peak were determined.
As peak 3, show a relative area < 5%, they is considered as minor peak and is not taken into account in the determination of log POW of the test item.
Although area is not necessarily correlated to the absolute concentration, if a UV detector is used, it is assumed that the detected peaks are representative components of the test item.

Discussion
Variations in the retention times of reference items and test item are very small. Therefore a stable configuration of the HPLC-column can be assumed.
A peak in the blank value of methanol/water is a known artifact originating from dissolved air, which has no influence on the retention times of the test item.
The correlation log k/log POW is good: the coefficient of determination r2 was calculated to be 0.9714. This value was considered as sufficiently high to use the calibration function for the determination of the log POW of the test item Pyrolytic Sugar.
Since the peaks are very wide, the log k versus log POW calibration function was used to determine the corresponding log POW values of the start and end of the main peaks for determination of a log POW range for each peak.
No observations were made which might cause doubts concerning the validity of the study outcome.

Any other information on results incl. tables

 Measurement Data

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

Measurement	Start Peak 1	End * Peak 1	End * Peak 2	End * Peak 3	End * Peak 4
	min.	min.	min.	min.	min.
Measurement 1	0.872	2.460	4.125	4.347	9.009
Measurement 2	0.900	2.457	4.117	4.372	9.322
Measurement 3	0.892	2.442	4.100	4.364	9.060
Mean	0.888	2.453	4.114	4.361	9.130
Standard Deviation	0.014	0.010	0.013	0.013	0.168

* The end time of one peak is identical with the start time of the following peak

 

Peak Areas Test Item

Measurement	Relative Area Peak 1	Relative Area Peak 2	Relative Area Peak 3	Relative Area Peak 4
	%	%	%	%
Measurement 1	69.97	23.86	0.95	5.21
Measurement 2	68.46	24.85	1.04	5.65
Measurement 3	68.03	25.10	1.17	5.70
Mean	68.82	24.60	1.05	5.52
RSD	1.48	2.65	10.20	4.87

Calculated Values

The calculated values are presented in the following table:

Peak	Measurement No.	k	log k	log POW
1 (Start)	1	-0.3914	n.c*	n.c.*
	2	-0.3718	n.c.*	n.c.*
	3	-0.3775	n.c.*	n.c.*
	Mean			n.c.*
	Standard Deviation			n.c.*
1 (End) = 2 (Start)	1	0.7172	-0.1443	1.227
	2	0.7148	-0.1458	1.223
	3	0.7044	-0.1522	1.208
	Mean			1.219
	Standard Deviation			0.010
2 (End) = 3 (Start)	1	1.8794	0.2740	2.266
	2	1.8735	0.2727	2.263
	3	1.8620	0.2700	2.256
	Mean			2.262
	Standard Deviation			0.005
3 (End) = 4 (Start)	1	2.0341	0.3084	2.352
	2	2.0515	0.3121	2.361
	3	2.0458	0.3109	2.358
	Mean			2.357
	Standard Deviation			0.005
4 (End)	1	5.2880	0.7233	3.382
	2	5.5066	0.7409	3.426
	3	5.3241	0.7262	3.389
	Mean			3.399
	Standard Deviation			0.023

*n.c. = not calculable, log P_OWwas not able to be calculated from the capacity factor because the factor was negative.

log P_OW was calculated from the capacity factor as follows:

 

log P_OW = (log k + 0.6383) / 0.4026

 

Validity

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

Peak	Parameter	Criterion	Found	Assessment
1 (start)	Range (Max – Min. log POW)	< 0.1	n.c*	not valid
	Retention time within Range of Reference Items	1.883 - 15.779	0.888	not within range
1 (end) =2 (Start)	Range (Max – Min. log POW)	< 0.1	0.019	valid
	Retention time within Range of Reference Items	1.883 - 15.779	2.453	within range
2 (end) =3 (Start)	Range (Max – Min. log POW)	< 0.1	0.010	valid
	Retention time within Range of Reference Items	1.883 - 15.779	4.114	within range
3 (end) =4 (Start)	Range (Max – Min. log POW)	< 0.1	0.009	valid
	Retention time within Range of Reference Items	1.883 – 15.779	4.361	within range
4 (end)	Range (Max – Min. log POW)	< 0.1	0.044	valid
	Retention time within Range of Reference Items	1.883 - 15.779	9.130	within range

* n.c. not calculable

Applicant's summary and conclusion

Conclusions:

the log POW range of the test item components is < 0.3 – 3.4

Executive summary:

The study was performed using a HPLC with a C18 column according to OECD guideline 117.

Eight 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_OW are correlated. The reference items were chosen based on the results of the pre-test.

The chromatogram of the test item gave three major and one minor peaks. Since the peaks are very wide, the log k versus logP_OW calibration function is used to determine the corresponding logP_OW values of the start and end of the main peaks and a logP_OW range for each peak were determined:

 

Peak	Relative Area	Retention Time start	Retention Time end	Log POW ± Standard Deviation
	[%]	[min]	[min]
1	68.82	0.888	2.453	< 0.3* – 1.2±0.01
2	24.60	2.453	4.114	1.2±0.01 – 2.3±0.01
3	1.05	4.119	4.361	2.3±0.01 – 2.4±0.01
4	5.52	4.361	9.130	2.4±0.01 – 3.4±0.02

*Peak start lay within the dead time of the method and not within the range of log P_OW values of the reference items. Therefore, the corresponding log P_OWvalue should be stated as < 0.3

These values are the means ± standard deviations of three independent determinations.

Although area is not necessarily correlated to the absolute concentration, if a UV detector is used, it is assumed that the detected peaks are representative components of the test item, indicating that the log P_OW range of the test item components is < 0.3 – 3.4.