Zinc EDDHA

Partition coefficient

Link to relevant study record(s)

Reference

Endpoint:

partition coefficient

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The stability of the EDDHA complexes is pH-dependent. While at low pH values protonation of the EDDHA complexes is decisive for their stability, it is determined by hydrolysis at higher pH values. Protonation of the hydroxyl- and carboxyl-groups binding the metal leads to instability of the complex. The formation of the first protonated species was shown to imply the protonation of the phenolic group in para position (López-Rayo (2012), Yunta (2003a, b)). This results in the opening of the structure. A second protonation occurs in the ortho phenolic group. The formation of the first protonated species which probably implies the protonation of the phenolic group in para position and is the main species below pH 10.22 for o,p-EDDHA/Zn2+. A second protonation constant has also been obtained, occurring in the second ortho phenolic group. However, the close values for the Mn stability constants obtained for o,o-EDDHA and o,p-EDDHA supports the fact that the axial donor groups may be only weakly interacting with the metallic ion, which is also in agreement with existing corresponding data for Zn (López-Rayo 2012).
Iron, on the other hand, was shown to form stable unprotonated complexes with EDDHA and EDDHMA over wide ranges of pH (Ahrland 1990). With increasing pH, manganese and iron are likely to precipitate as a result of hydrolysis. Generally, the stability constants for o,o-EDDHA and o,p-EDDHA complexed with Fe3+, Mn2+ and Zn2+ are in the following order: Fe3+> Zn2+> Mn2+. This is due to the larger electropositive character, the higher oxidation state and the smaller size of Fe3+ with respect to Mn2+and Zn2+, and also because Zn2+is smaller than Mn2+ (López-Rayo 2012).
In conclusion, based on the available data for the structure itself and the structural analogues, the target substance is considered as stable to hydrolysis at environmentally relevant pH values.


Ahrland S, Dahlgren A; Persson I. (1990) Stabilities and hydrolysis of some iron(III) and manganese(III) complexes with chelating ligands. Acta Agric. Scand. 1990, 40, 101.
López-Rayo, S., Correas, C., Lucena, J.J. (2012). "Novel chelating agents as manganese and zinc fertilisers: characterisation, theoretical speciation and stability in solution." Chemical Speciation & Bioavailability 24(3): 147-158.
Yunta F, Garcia-Marco S, Lucena JJ. (2003a) Theoretical speciation of ethylene-N-(o-hydroxyphenylacetic)-N-(p-hydroxyphenylacetic) acid (o,p-EDDHA) in agronomic conditions. J. Agric. Food Chem., 51, 5391-5399
Yunta F, Garcia-Marco S, Lucena JJ, Gomez-Gallego M, Alcazar R, Sierra MA. (2003b) Chelating Agents Related to Ethylenediamine Bis(2-hydroxyphenyl)acetic Acid (EDDHA): Synthesis, Characterization, and Equilibrium Studies of the Free Ligands and Their Mg2+, Ca2+, Cu2+, and Fe3+ Chelates. Inorg. Chem. 2003, 42, 5412-5421


2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Please refer to test material.

3. ANALOGUE APPROACH JUSTIFICATION
As the test substance is considered to be unstable in the sense, that the complex can degrade into the ligand and the free metal the endpoint "partition coefficient" is covered by the degradation products, the ligand and the free metal. As the partition coefficient is waived for inorganic substances due to technical reasons it is fully justified to fulfil the data requirements of Regulation EC No 1907/2006 Annex VII for this endpoint with data on the degradation product o,o-EDDHA.

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: EU Method A.24

Deviations:

no

GLP compliance:

no

Type of method:

HPLC method

Partition coefficient type:

octanol-water

Type:

log Pow

Partition coefficient:

< 0.3

Temp.:

25 °C

pH:

6

Details on results:

Although area is not necessarily correlated to the absolute concentration, if a UV detector is used, it is assumed that the test item consists mainly of two peaks.
The two peaks lie outside the dead time of the method and so not within the range of log Pow’s of the reference items.
Therefore, the log Pow of the test item is stated as < 0.3 (lowest log Pow of a reference item (2-Butanone)) at the temperature of 25.0 ± 0.5°C.

The values for log k and log POW of the reference items are presented in the following table:

Compound	log k	log POW
2 -Butanone	-0.6487	0.3
Benzyl alcohol	-0.4874	1.1
Acetophenone	-0.2809	1.7
Benzene	0.0654	2.1
Toluene	0.2836	2.7
Naphthalene	0.4088	3.6

Dead time is 1.430 ± 0.000 minutes, with RSD (relative standard deviation) 0.0%. The RSD of the retention times of the reference items lay all below 0.1 %.

Equation of the regression: log k = 0.3569 x log P_OW - 0.7939 with a coefficient of determination r² = 0.9461

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

Measurement	RT 1 [min.]	RT 2 [min.]
1	0.950	1.070
2	0.947	1.063
3	0.947	1.063
Mean	0.948	1.066
Standard deviation	0.002	0.004

log P_OW was not able to calculated from the capacity factor because the factor was negative, as the retention time of the test item is below the dead-time.

Conclusions:

The log Pow of the sample is stated as < 0.3 (lowest log Pow of a reference item (2-Butanone)) at the temperature of 25.0 ± 0.5°C.

Executive summary:

The partition coefficient of the test item was determined in a non-GLP study according to OECD Guideline 117 and EU Method A.24.

The study was performed using a HPLC with a C18 column. Six 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.

One vial was filled with the reference item mix and one vial with the test item solution. The vials were analysed using HPLC. First one injection from the solvent blank methanol/water 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_OW of the reference items and the retention times in the six determinations.

The chromatogram of the test item gave two peaks. Although area is not necessarily correlated to the absolute concentration, if a UV detector is used, it is assumed that the test item consists mainly of two peaks.

The two peaks lie outside the dead time of the method and so not within the range of log P_OW’s of the reference items.

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.

Therefore, the log P_OW of the test item is stated as < 0.3 (lowest log P_OW of a reference item (2-Butanone)) at the temperature of 25.0 ± 0.5°C.

Description of key information

As the test substance is considered to be unstable in the sense, that the complex can degrade into the ligand and the free metal the endpoint "partition coefficient" is covered by the degradation products, the ligand and the free metal. As the partition coefficient is waived for inorganic substances due to technical reasons it is fully justified to fulfil the data requirements of Regulation EC No 1907/2006 Annex VII for this endpoint with data on the degradation product o,o-EDDHA:

The partition coefficient of the test item was determined in a non-GLP study according to OECD Guideline 117 and EU Method A.24.

The study was performed using a HPLC with a C18 column. Six 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.

One vial was filled with the reference item mix and one vial with the test item solution. The vials were analysed using HPLC. First one injection from the solvent blank methanol/water 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_OW of the reference items and the retention times in the six determinations.

The chromatogram of the test item gave two peaks. Although area is not necessarily correlated to the absolute concentration, if a UV detector is used, it is assumed that the test item consists mainly of two peaks.

The two peaks lie outside the dead time of the method and so not within the range of log P_OW’s of the reference items.

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.

Therefore, the log P_OW of the test item is stated as < 0.3 (lowest log P_OW of a reference item (2-Butanone)) at the temperature of 25.0 ± 0.5°C.

Key value for chemical safety assessment

Log Kow (Log Pow):

0.3

at the temperature of:

25 °C

Additional information

The key value above is a kind of worst-case value, because an exact value is not determinable. The value is in any case not higher, which means, that the substance is rather soluble in the aqueous phase than in the organic phase.