2-ethylhexanoic acid, manganese salt

Dissociation constant

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

dissociation constant

Remarks:

dissociation of salts into individual ions

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Qualifier:

no guideline followed

Principles of method if other than guideline:

zero-sink test that measures the dissociation of the metal carboxylate substance in two contrasting test media (low and neutral pH) based on the free metal ion concentration in the presence of a selective adsorbent that acts as a zero-sink for the metal cation

GLP compliance:

no

Dissociating properties:

yes

No.:

#2

Temp.:

20 °C

Remarks on result:

other: 101±<1% dissociation after 1h in simulated gastric fluid (pH 1.5)

No.:

#3

Temp.:

20 °C

Remarks on result:

other: 93±1% dissociation after 1h in simulated interstitial fluid (pH 7.4)

Simulated gastric fluid 

Solution composition

The measured metal concentration of the reference compound MnCl₂.4H₂O and metal carboxylate 2-ethylhexanoic acid, manganese salt in the gastric medium is given in Table 5. 2-ethylhexanoic acid, manganese salt is almost completely dissolved in the gastric fluid after 12h, the percentage dissolved material at 1 g/L is 86 ± < 1%. The reference compound is completely dissolved (> 100%) in the gastric fluid. 

Table 5 Measured total metal concentration (CM) dissolved during 12h in the simulated gastric fluid and percent solubility (fsol) ± standard deviation. For the metal carboxylate (MC), the nominal concentration is the expected metal concentration in solution based on the exact dilution prepared from the initial stock solution. 

Free metal ion concentration measurement 

For the reference salts (MnCl₂.4H₂O) the Mn concentration in solution decreased to < 2% of the initial concentration after 1h due to sorption of the metal on the resin (Table 6). The measured Mn concentration in all diluted test solutions is still above the quantification limit (LOQ) of the ICP-MS analysis. The concentration in solution is the free metal in equilibrium with the resin. Binding of Mn to the resin is instantaneous since no differences are observed between measurements at 1h, 6h and 24h. The strong binding of the metal to the resin at the composition and pH of the gastric medium is in agreement with speciation calculations using Visual Minteq. The model predicts an equilibrium Mn concentration in solution that corresponds well with the measured concentration (Table 6, reference salts). 

The initial Mn concentration of 2-ethylhexanoic acid, manganese salt after 12h dissolution in gastric medium, but before addition of the zero sink resin is within the concentration range of the reference samples. The Mn concentration in solution of the substance also decreased to < 2% of the initial concentration after 1h due to sorption of the metal on the resin. The metal carboxylate salt undergoes a dissociation reaction and exists in equilibrium with its dissociation products. The dissociated metal reacts with the resin. The metal concentration in solution of the metal carboxylate salt is thus, in theory, the free metal in equilibrium with the zero-sink and undissociated metal carboxylate. The free metal concentration is calculated from the reference compounds and is after 1h equal to 37.1 ± 0.2 μM Mn. This approximates the total measured metal concentration in solution of 19.5 ± 0.4 μM Mn. After 1h, the calculated dissociated fraction of metal carboxylate is 101 ± <1%. Therefore, this test indicates that 2-ethylhexanoic acid, manganese salt dissociates fully in the test media representing gastric fluid. The metal concentration in solution for the reference salt and MC remained constant in time after 1h. This indicates that 2-ethylhexanoic acid, manganese salt dissociates instantaneously (< 1h) in the test media relevant for gastric fluid. 

Table 6 Measured metal concentration in solution at the start (CM,i) and after equilibration (CM,e) and concentration sorbed on the zero sink (CM,s) ± standard deviation at different time points for the reference salts and 2-ethylhexanoic acid, manganese salt dissolved in the gastric medium. For the metal carboxylate salt, the equilibrium free metal concentration CM2+ is calculated from the reference compounds and used to calculate the dissociated fraction (fdiss). The CM2+ values of the reference compounds are also calculated with ion exchange principles using Visual Minteq. 

Simulated interstitial fluid 

Solution composition 

The measured metal concentration of the reference compound MnCl₂.4H₂O and metal carboxylate 2-ethylhexanoic acid, manganese salt in the interstitial fluid is given in Table 7. 2-ethylhexanoic acid, manganese salt has low solubility in the interstitial fluid, after 12h the percentage dissolved material of this substance at 1 g compound/L is only 13 ± <1%. The reference compound MnCl₂.4H₂O at a concentration of 30 μM Mn is completely dissolved (> 100%) in the interstitial fluid. At a higher concentration of 3000 μM Mn the reference salt precipitated in the interstitial fluid, and is therefore not included in the analysis. 

Table 7 Measured total metal concentration (CM) dissolved during 12h in the simulated interstitial fluid and percent solubility (fsol) ± standard deviation. For the metal carboxylate (MC), the nominal concentration is the expected metal concentration in solution based on the exact dilution prepared from the initial stock solution. 

Free metal ion concentration measurement 

For the reference salt (MnCl₂.4H₂O) the Mn concentration in solution decreased to about 20% of the initial concentration after 1h due to sorption of the metal on the resin (Table 8). The measured Mn concentration in all diluted test solutions is above the quantification limit (LOQ) of the ICP-MS analysis. The concentration in solution is the free metal in equilibrium with the resin. Binding of Mn to the resin is instantaneous since no differences are observed between measurements at 1h, 6h and 24h. The binding of the metal to the resin in the interstitial fluid is less strong than in the acid gastric medium due to competition between protons and metal cations to bind to the resin, that binding is also well predicted with speciation calculations using Visual Minteq (Table 8). The model predicts an equilibrium Mn concentration in solution that corresponds well with the measured concentration. 

The initial Mn concentration of 2-ethylhexanoic acid, manganese salt after 12h dissolution in simulated interstitial fluid, but before addition of the zero sink resin is a factor 10 higher than the concentration of the reference sample, but Visual Minteq still predicts linear sorption of Mn to the resin at the higher concentration. The Mn concentration in solution of 2-ethylhexanoic acid, manganese salt decreased to about 25% of the initial concentration after 1h due to sorption of the metal on the resin. The metal carboxylate salt undergoes a dissociation reaction and exists in equilibrium with its dissociation products. The dissociated metal reacts with the resin. The metal concentration in solution of the metal carboxylate salt is thus, in theory, the free metal in equilibrium with the zero-sink and undissociated metal carboxylate. The predicted free metal concentration after 1h is 54.4 ± 0.2 μM Mn, this is slightly lower than the measured Mn concentration of 74.3 ± 2.1 μM Mn, the difference being attributed to undissociated metal carboxylate. The undissociated fraction is low (< 10%). After 1h, the calculated dissociated fraction of metal carboxylate is 93 ± < 1%.Therefore, this test indicates that 2-ethylhexanoic acid, manganese salt almost completely (> 90%) in the test media representing interstitial fluid. The metal concentration in solution for the reference salt and 2-ethylhexanoic acid, manganese salt remained constant in time after 1h which means that the dissociation is instantaneously (< 1h) in the test media relevant for interstitial fluid. 

Table 8 Measured metal concentration in solution at the start (CM,i) and after equilibration (CM,e) and concentration sorbed on the zero sink (CM,s) ± standard deviation at different time points for the reference salts and 2-ethylhexanoic acid, manganese salt dissolved in the interstitial medium. For the metal carboxylate salt, the equilibrium free metal concentration CM2+ is calculated from the reference compounds and used to calculate the dissociated fraction (fdiss). The CM2+ values of the reference compounds are also calculated with ion exchange principles using Visual Minteq. 

Conclusions:

2-ethylhexanoic acid, manganese salt almost completely (> 90%) in the test media representing gastric fluid and interstitial fluid. The manganese concentration in solution for the reference salt MnCl2.2H2O and for 2-ethylhexanoic acid, manganese salt remained constant in time after 1h which means that the dissociation is instantaneously (< 1h) in both test media. 

Reference 2

Endpoint:

dissociation constant

Remarks:

dissociation of salts into individual ions

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Qualifier:

according to guideline

Guideline:

OECD Guideline 112 (Dissociation Constants in Water)

GLP compliance:

no

Dissociating properties:

yes

No.:

#1

Temp.:

25 °C

Remarks on result:

other: 125±1% dissociation after 1h in water

Solution composition 

The measured concentration of metal and organic carbon in solution of the reference compounds and metal carboxylate is given in Table 2. The metal carboxylate slowly dissolved, the percentage dissolved material of the substance prepared at 1 g/L was 16 ± 7% after 1h and increased to 59 ± 19% after 24h. After 24h the measured Mn concentration in solution (1.68 ± 0.46 mM Mn) is still lower than the expected concentration prepared at 1g/L compound (2.85 mM Mn or 0.157 g Mn/L) given the high theoretical solubility of the compound (11.2 ± 1.2 g MC/L or 1.70 g Mn/L). The molar metal/organic carbon ratio in solution ranged 0.056-0.064 throughout the experiment. The compound is pure, multi-element analysis with ICP-MS did not show important concentration of other elements in solution, which could interfere with the electrical conductivity measurements. Both reference compounds are completely dissolved (> 100%) after 1h. 

Electrical conductivity measurements 

The measured electrical conductivity and concentration of metal and ligand for the metal carboxylate and reference compounds in function of time is given in Table 3. The dissociated fraction is calculated from the measured electrical conductivity. The dissociated fraction of reference compounds is expected to approach 100%, the deviation for both reference compounds (<100% for MnCl2.4H2O and >100% for NaC8H16O2) might be related to inaccuracies of the model, i.e. the theoretical λ0 values. The electrical conductivity of the metal carboxylate increased about a factor 3 with time, this is due to the increasing dissolution of the compound in time (the metal concentration in solution also increased about a factor 3), not to slow dissociation kinetics because the dissociated fraction is constant, similarly as the reference compounds (Table 3). The dissociated fraction of the metal carboxylate is > 90% throughout the test, which indicates that 2-ethylhexanoic acid, manganese salt dissociates completely and is relatively constant in time after 1h, which means that the dissociation is instantaneously. 

Conclusions:

The dissociated fraction of 2-ethylhexanoic acid, manganese salt in water is > 90% throughout the test, which indicates that it dissociates completely and is relatively constant in time after 1h, which means that the dissociation is instantaneously. 

Description of key information

The electrical conductivity test in pure water and the zero-sink test in simulated gastric medium (pH 1.5) and simulated interstitial medium (pH 7.4) all conclude that the dissociation of 2-ethylhexanoic acid, manganese salt into manganese and 2-ethylhexanoate ions is complete (≥ 93%) and instantaneous (within 1h).