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Physical & Chemical properties

Endpoint summary

Administrative data

Description of key information

Additional information

The technical material as manufactured is a liquid with ca. 20% w/w active matter and ca. 80% w/w water. A water-free form of the technical material (dry technical material) is not manufactured or sold for commercial purposes.

There is a requirement for the vast majority of physicochemical studies to be carried out with purified test material. To fulfil this requirement the aqueous technical material was freeze dried in order to produce a small quantity of water-free active substance (dry test material) with a minimum active ingredient content of 99% w/w.

Water-free active substance was used in the following physicochemical studies:

Melting point.

Boiling point.

Relative Density.

Vapour pressure.

Appearance.

IR & NMR spectra.

Solubility in organic solvents.

Flammability

Auto-flammability

Technical material as manufactured (20% a.i.) was used in the following studies:

Surface tension

 

DOPA-Glycinate (anhydrous active substance) is reported to be a white to light yellow sticky, agglomerated solid at 20°C and 1013 hPa.

 

The melting point of DOPA-Glycinate (anhydrous active substance, 99% a.i.) was investigated in a study conducted according to OECD Guideline 102 (Melting point / Melting Range; 1995) and EU Method A.1 (92/69/EEC), using Differential scanning calorimetry. No melting or freezing point could be determined, the substance is considered as amorphous solid (solidified melt) which liquefied under decomposition at 140–145°C.

The boiling point of DOPA-Glycinate (anhydrous active substance, 99% a.i.) was investigated in a study conducted according to OECD Guideline 103 (Boiling point/boiling range; 1995) and EU Method A.2 (92/69/EEC) using differential scanning calorimetry . No boiling point could be determined at atmospheric pressure, since the test item decomposed first (approx. at 145°C).

The density of DOPA-Glycinate (anhydrous active substance, 99% a.i.) was investigated in a study conducted according to OECD Guideline 109 (Density of Liquids and Solids; 1995) and EU Method A.3 (92/69/EEC). The density was determined to be 1.03 g/cm³ (23°C).

According to REACH regulation, Annex VII, 7.14, column 2, a study on particle size distribution (granulometry) is not required, as the substance is only manufactured and marketed as aqueous solution.

The vapour pressure of DOPA-Glycinate (anhydrous active substance, 99% a.i.) was investigated in a study conducted according to OECD Guideline 104 (1995) and EU method A.4 (92/69/EEC) (Effusion method). The vapour pressure was determined to be 1.9E-4 Pa at 20°C.

The experimental determination of the log Pow and the log Dow are not experimentally feasible because DOPA-Glycinate is a mixture and a surfactant.

Log Pow values for the 20 “major components” range from 0.33 to 6.71. The weighted log Pow value = 3.82 (EpiSuite-KOWWIN). Log Pow values for the 24 chemical species making up the active substance ranged from 2.83 – 5.73 (QSAR Calculation using Marvin Sketch – ChemAxon, 2012).

However, the Log Pow QSAR calculations do not take into account that the 24 chemical species are ionisable species at environmental pH. Log Pow QSAR calculations are only appropriate for neutral molecules.

Log Dow is a more applicable endpoint for risk assessment. Log Dow is pH dependent and is applicable to protonated and unprotonated species.

The log Dow ranges for the 24 chemical species are provided below:

pH 5: log Dow = -4.53 to 2.11

pH 7: log Dow = -2.37 to 2.33

pH 9: log Dow = -3.12 to 3.92

DOPA-Glycinate (20% a.i.), constituting an aqueous solution of the pure active substance, was freeze-dried and the mass of the residue determined gravimetrically. The water solubility was determined to be > 20.83% (w/w), corresponding to > 208 g/L.

The pH dependence of the water solubility was checked by adjusting three solutions of test substance to pH 4.0, 7.0 and 9.0. At pH 4 and 7 the solution appeared clear. At pH 9 the solution appeared viscous and foamy and appeared clear after several hours. It was concluded that the solubility of test substance was not pH dependent over the range tested. DOPA-Glycinate (20% a.i.) remained a clear solution regardless of the pH range tested.

Although the available study was not conducted according to guideline EEC A.6, it is nevertheless established without reasonable doubt that the substance is soluble in water at concentrations of at least 200 g/L. Determination of a more accurate figure would be entirely immaterial for the risk assessment. Thus, the conduct of a water-solubility study following EEC A.6 would not provide a relevant contribution to the existing knowledge and is therefore considered to be scientifically unjustified.

The surface tension of DOPA-Glycinate (20% a.i.) was determined according to OECD guideline 115 (1995) and EU method A.5 (1992) using the ring method. The surface tension of 0.2008 g a.i./L DOPA-Glycinate was 27.2 mN/m at 20°C; it is considered to be a surface-active material.

According to REACH Regulation (Annex XI, 1.), a test for determination of the flash point is scientifically not necessary, because the flash point refers to liquids (Guidance in information requirement and chemical safety assessment, chapter R.7b). The test item is a solid at ambient temperature. Therefore determination of the flash point is not required.

 

The autoflammability of DOPA-Glycinate (99% a.i.) was investigated in a study according to EU method A.16 (1992). The substance is not auto-flammable and showed no exothermal reaction up to the maximum test temperature of 402°C.

 

The flammability of DOPA-Glycinate (99% a.i.) was investigated in a study according to EU method A.10 (1992). The test item melted in the preliminary test. A main test is therefore not required. DOPA-Glycinate is non-flammable.

 

According to REACH Regulation (Annex VII, 7.11, column 2), a study on explosiveness does not need to be conducted as structural aspects and estimated thermodynamic properties indicate that the substance does not have explosive properties.

 

According to REACH Regulation (Annex VII, 7.13, column 2), testing of oxidising properties needs not to be conducted as the test substance does not contain any structural groups known to be correlated with a tendency to react exothermically with combustible material.

 

According to REACH Annex IX, 7.15, column 1, a study on stability in organic solvents is only required if stability of the substance is considered to be critical. Since the final products do not contain organic solvents, data on stability in organic solvents are not considered to be required.

 

It is not technically feasible to experimentally determine the dissociation constants of DOPA-Glycinate (REACH Regulation, Annex XI, 1.) due to the material being a mixture of a number of soluble components. It should also be noted that OECD guideline number 112 only applies to active substances if the water solubility cannot be measured.

The components making up the substance are assumed to be ionised in the environmental pH range (4 – 9) based on the presence of acidic (pKa ~ 4) and basic (pKa ~ 10) functional groups in the respective structures.

This is confirmed bythe provision of pKa values for the indivdual components of DOPA-Glycinate using QSAR (generated by MarvinSketch).The following observations were made regarding the QSAR generated pKa values:

(1) Structure class “1” - R-NH-C3H6-NH2:

These substances represent propylene diamine molecules of varying chain length; they cannot dissociate, instead they are protonated under physiological and environmental conditions due to their high PK value of 10.8.

(2) Structure classes 2-5:

These groups of molecules contain not only amine, but also carboxyl groups. As such, they may contain both protonated (cationic) as well as dissociated (anionic) structures at environmental or physiologically relevant pH.

(3) The „minor constituents“ included in the substance contain either amine or carboxyl groups, or both and therefore may contain both protonated (cationic) as well as dissociated (anionic) structures at environmental or physiologically relevant pH.

 

QSAR-calculated pKa values for the components of DOPA Glycinate (see attached document):

Structure (incl. pKa values)

pKa values

1:R=C16

-NH-: 10.80

-NH2: 8.44

1: R=C14

-NH-: 10.80

-NH2: 8.44

1: R=C12

-NH-: 10.80

-NH2: 8.44

1: R=C10

-NH-: 10.80

-NH2: 8.44

2: R=C16

-NH-: 10.79

-NH2: 8.90

-OH: 2.07

2: R=C14

-NH-: 10.79

-NH2: 8.90

-OH: 2.07

2: R=C12

-NH-: 10.79

-NH2: 8.90

-OH: 2.07

2: R=C10

-NH-: 10.79

-NH2: 8.90

-OH: 2.07

3: R=C16

-NH-: 10.90

-NH-: 8.67

-OH: 2.14

3: R=C14

-NH-: 10.90

-NH-: 8.67

-OH: 2.14

3: R=C12

-NH-: 10.90

-NH-: 8.67

-OH: 2.14

3: R=C10

-NH-: 10.90

-NH-: 8.67

-OH: 2.14

4: R=C16

-NH-: 10.68

-N-: 6.37

-OH: 3.54

-OH: 2.81

4: R=C14

-NH-: 10.68

-N-: 6.37

-OH: 3.54

-OH: 2.81

4: R=C12

-NH-: 10.68

-N-: 6.37

-OH: 3.54

-OH: 2.81

4: R=C10

-NH-: 10.68

-N-: 6.37

-OH: 3.54

-OH: 2.81

5: R=C16

-N-: 10.98

-OH: 1.38

-NH-: 8.67

-OH: 2.13

5: R=C14

-N-: 10.98

-OH: 1.38

-NH-: 8.67

-OH: 2.13

5: R=C12

-N-: 10.98

-OH: 1.38

-NH-: 8.67

-OH: 2.13

5: R=C10

-N-: 10.98

-OH: 1.38

-NH-: 8.67

-OH: 2.13

Dodecylamine

-NH2: 10.21

Tetradecylamine

-NH2: 10.21

Bis-(3-amino-propyl)-dodecyl-amine

-NH2: 9.49

-NH2: 10.89

-N-: 7.05

{3-[(3-Amino-propyl)-dodecyl-amino]-propylamino}-acetic acid

-NH: 29.72

-NH: 10.97

-N-:7.06

-OH:2.07

 

Overall, based on the above mentioned properties, dissociation is not relevant under practical conditions, since at neutral, environmental and physiological pH conditions, >90% of the constituents should be in the ionic form.

According to REACH Annex XI, 1 a study on viscosity is technically not feasible, as the substance is a solid at ambient temperature.