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EC number: 205-181-1 | CAS number: 135-16-0
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Water solubility
Administrative data
Link to relevant study record(s)
- Endpoint:
- water solubility
- Remarks:
- Stability of the substance in aqueous solutions
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Principles of method if other than guideline:
- no guideline followed. Study was performed to determine the stability of the test substance in different aqueous media to clarify the feasibility and design of experimental studies regarding physico-chemical, environmental fate and ecotoxicological properties.
- GLP compliance:
- no
- Type of method:
- other: Half-life of the substance was determined in 0.01 M aqueous calcium chloride solution (OECD TG 106), in buffered aqueous media at pH 4, 7 and 9 (OECD TG 111) and in algae dilution water (OECD TG 201) by LC-MS
- Key result
- Conc. based on:
- test mat.
- Loading of aqueous phase:
- 100 mg/L
- Remarks on result:
- other: Determination of stability in aqueous solutions
- Remarks:
- Water solubility was not determined due to hydrolytical instability
- Conclusions:
- The water solubility of Tetrahydrofolic acid could not be determined due to fast hydrolysis of the substance in aqueous solutions. The half-lifes were determined in 0.01 M CaCl2 solution, in buffer solutions at pH 4, 7 and 9 and in Algae Dilution Medium. T1/2 was 0.4 h in 0.01M CaCl2, and 0.0594 h for pH 4, 0.257 h for pH 7 and 0.712 h for pH 9 with LC-MS. Plots of the stability of Tetrahydrofolic acid in Algae Dilution Medium showed a decline of the parent substances and an increase of two hydrolysis products 2-amino-6-methylpteridin-4(1H)-one and (2S)-2-(4-aminobenzamido)pentanedioic acid.
Reference
The stability of the test item is limited due to hydrolysis in aqueous environment. Decline rates and half-lives were determined in 0.01 M CaCl2 solution and in buffer solutions at pH 4, 7 and 9.
Hydrolysis in 0.01 M CaCl2
Two replicates were measured. The reaction rate constant k was determined to be 5.01E-4 1/s and half-life t1/2 was determined to be 0.4 h.
Hydrolysis in Buffer Solutions at pH 4, 7 and 9
The reaction rate constants k were determined to be 3.24 E-3 1/s for pH 4, 7.49 E-4 1/s for pH 7 and 2.70 E-4 1/s for pH 9. The half-life t1/2 was determined to be 0.0594 h for pH 4, 0.257 h for pH 7 and 0.712 h for pH 9.
Table3: Determination of Hydrolysis in Aqueous Phase –0.01 M CaCl2
Nominal concentration, test item: 10 mg/L
0.01 M CaCl2 |
|||
Time [h] |
Mean c |
ln c |
% |
0.00 |
10.2 |
2.32 |
- |
0.5 |
5.61 |
1.73 |
55 |
1 |
3.10 |
1.13 |
31 |
1.5 |
1.11 |
0.105 |
11 |
2 |
0.251 |
-1.38 |
2 |
Mean c = mean concentration of two test item replicates, internal standard taken into account
% = percent of initial concentration, t0 set to 100%
Table4: Hydrolysis in Aqueous Phase –0.01 M CaCl2
0.01 M CaCl2 |
|
Slope of regression graph |
-1.80 |
Correlation factor [r2] |
0.956 |
Reaction rate constantk[1/s] |
5.01 ∙ 10-4 |
Half-lifeT½[h] |
0.4 |
Table5: Determination of Hydrolysis in Aqueous Phase – pH 4
Nominal concentration, test item: 100 mg/L
pH 4 |
|||
Time [h] |
Peak Area |
ln Peak Area |
% |
0.000 |
33509948 |
17.3 |
- |
0.183 |
675904 |
13.4 |
2 |
0.364 |
179466 |
12.1 |
0.5 |
0.547 |
43528 |
10.7 |
0.1 |
% = percent of initial concentration, t0set to 100%
Table6: Hydrolysis in Aqueous Phase – pH 4
pH 4 |
|
Slope of regression graph |
-0.117 |
Correlation factor [r2] |
0.923 |
Reaction rate constantk[1/s] |
3.24 ∙ 10-3 |
Half-lifeT½[h] |
0.0594 |
Half-lifeT½[min] |
3.56 |
Table7: Determination of Hydrolysis in Aqueous Phase – pH 7
Nominal concentration, test item: 100 mg/L
pH 7 |
|||
Time [h] |
Peak Area |
ln Peak Area |
% |
0.000 |
56905440 |
17.9 |
- |
0.183 |
29781291 |
17.2 |
52 |
0.3651) |
52813611) |
15.51) |
91) |
0.736 |
7279096 |
15.8 |
13 |
0.919 |
4985612 |
15.4 |
9 |
1.10 |
3174099 |
15.0 |
6 |
1.28 |
1808882 |
14.4 |
3 |
1.47 |
1143522 |
14.0 |
2 |
1.65 |
600828 |
13.3 |
1 |
1.83 |
357862 |
12.8 |
1 |
% = percent of initial concentration, t0set to 100%
1)= outlier, not taken into account
Table8: Hydrolysis in Aqueous Phase – pH 7
pH 7 |
|
Slope of regression graph |
-2.70 |
Correlation factor [r2] |
0.997 |
Reaction rate constantk[1/s] |
7.49 ∙ 10-4 |
Half-lifeT½[h] |
0.257 |
Half-lifeT½[min] |
15.4 |
Table9: Determination of Hydrolysis in Aqueous Phase – pH 9
Nominal concentration, test item: 100 mg/L
pH 9 |
|||
Time [h] |
Peak Area |
ln Peak Area |
% |
0.000 |
128982791 |
18.7 |
- |
0.183 |
86149063 |
18.3 |
67 |
0.365 |
64018083 |
18.0 |
50 |
0.547 |
50905504 |
17.8 |
39 |
0.730 |
43442552 |
17.6 |
34 |
0.913 |
35485067 |
17.4 |
28 |
1.10 |
30533632 |
17.2 |
24 |
1.28 |
26036767 |
17.1 |
20 |
1.46 |
22208419 |
16.9 |
17 |
1.64 |
19819906 |
16.8 |
15 |
2.01 |
15356634 |
16.6 |
12 |
2.19 |
12085931 |
16.3 |
9 |
2.38 |
10140678 |
16.1 |
8 |
% = percent of initial concentration, t0set to 100%
Table10: Hydrolysis in Aqueous Phase – pH 9
pH 9 |
|
Slope of regression graph |
-0.974 |
Correlation factor [r2] |
0.977 |
Reaction rate constantk[1/s] |
2.70 ∙ 10-4 |
Half-lifeT½[h] |
0.712 |
Half-lifeT½[min] |
42.7 |
Description of key information
- non-GLP study, determination of stability of Tetrahydrofolic acid in aqueous solutions, half-lifes were determined in 0.01 M CaCl2 solution, in buffer solutions at pH 4, 7 and 9 and in Algae Dilution Medium, T1/2 was 0.4 h in 0.01M CaCl2, and 0.0594 h for pH 4, 0.257 h for pH 7 and 0.712 h for pH 9 with LC-MS, breakdown products: 2-amino-6-methylpteridin-4(1H)-one and (2S)-2-(4-aminobenzamido)pentanedioic acid
Key value for chemical safety assessment
Additional information
The water solubility of Tetrahydrofolic acid could not be determined due to fast hydrolysis of the substance in aqueous solutions. The half-lifes were determined in 0.01 M CaCl2 solution, in buffer solutions at pH 4, 7 and 9 and in Algae Dilution Medium. T1/2 was 0.4 h in 0.01M CaCl2, and 0.0594 h for pH 4, 0.257 h for pH 7 and 0.712 h for pH 9 with LC-MS. Plots of the stability of Tetrahydrofolic acid in Algae Dilution Medium showed a decline of the parent substances and an increase of two hydrolysis products 2-amino-6-methylpteridin-4(1H)-one and (2S)-2-(4-aminobenzamido)pentanedioic acid. Based on these results Tetrahydrofolic acid is considered to be not stable in aqueous solutions and testing of water solubility is scientifically not justified.
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