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Environmental fate & pathways

Hydrolysis

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Endpoint:
hydrolysis
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
Please refer to the analogue approach justification provided in IUCLID section 13.
Reason / purpose:
read-across source
Related information:
Composition 1
Test material information:
Composition 1
Transformation products:
yes
Remarks:
Thiamine and free phosphoric acid (H3PO4).
No.:
#1
Reference substance:
Composition 1
No.:
#2
Reference substance:
Composition 1
% Recovery:
16
pH:
9
Temp.:
50 °C
Duration:
70 h
Remarks on result:
other: 2.9 d
Remarks:
2nd order kinetics, R² = 0.993 / Source: CAS 10023-48-0, Marx, 2017
% Recovery:
50
pH:
9
Temp.:
25 °C
Duration:
ca. 30 d
Remarks on result:
other:
Remarks:
order of kinetics ambiguous / Source: CAS 10023-48-0, Marx, 2017
% Recovery:
100
pH:
9
Temp.:
9 °C
Duration:
ca. 40 d
Remarks on result:
other:
Remarks:
no significant hydrolysis, order of kinetics ambiguous / Source: CAS 10023-48-0, Marx, 2017
% Recovery:
11
pH:
6.9
Temp.:
50 °C
Duration:
150 h
Remarks on result:
other: 6.25 d
Remarks:
first order kinetics, R² = 0.991 / Source: CAS 10023-48-0, Marx, 2017
% Recovery:
ca. 50
pH:
6.9
Temp.:
25 °C
Duration:
ca. 40 d
Remarks on result:
other:
Remarks:
order of kinetics ambiguous / Source: CAS 10023-48-0, Marx, 2017
% Recovery:
100
pH:
6.9
Temp.:
9 °C
Duration:
40 d
Remarks on result:
other:
Remarks:
no significant hydrolysis, order of kinetics ambiguous / Source: CAS 10023-48-0, Marx, 2017
% Recovery:
ca. 60
pH:
4.6
Temp.:
50 °C
Duration:
ca. 40 d
Remarks on result:
other:
Remarks:
order of kinetics ambiguous / Source: CAS 10023-48-0, Marx, 2017
% Recovery:
ca. 50
pH:
4.6
Temp.:
25 °C
Duration:
ca. 40 d
Remarks on result:
other:
Remarks:
order of kinetics ambiguous / Source: CAS 10023-48-0, Marx, 2017
% Recovery:
100
pH:
4.6
Temp.:
9 °C
Duration:
40 d
Remarks on result:
other:
Remarks:
no significant hydrolysis, order of kinetics ambiguous / Source: CAS 10023-48-0, Marx, 2017
pH:
9
Temp.:
25 °C
Half-life:
30 d
Type:
other: order of kinetics ambiguous
Remarks on result:
other:
Remarks:
Source: CAS 10023-48-0, Marx, 2017
pH:
6.9
Temp.:
25 °C
Half-life:
40 d
Type:
other: order of kinetics ambiguous
Remarks on result:
other:
Remarks:
Source: CAS 10023-48-0, Marx, 2017
pH:
4.6
Temp.:
25 °C
Half-life:
40 d
Type:
other: order of kinetics ambiguous
Remarks on result:
other:
Remarks:
Source: CAS 10023-48-0, Marx, 2017
Conclusions:
The dissipation half-life of the target substance at 25 °C is 30 d at pH 9 and 40 d at pH 4.6 and 6.9, based on experimental findings from a structurally closely related source substance (OECD 111, CAS 10023-48-0); read-across
Endpoint:
hydrolysis
Type of information:
experimental study
Adequacy of study:
key study
Study period:
27 Jun - 16 Oct 2017
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
non-GLP
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 111 (Hydrolysis as a Function of pH)
Version / remarks:
2004
Qualifier:
according to
Guideline:
EU Method C.7 (Degradation: Abiotic Degradation: Hydrolysis as a Function of pH)
GLP compliance:
no
Remarks:
In-house study by sponsor with GLP-like documentation.
Test material information:
Composition 1
Analytical monitoring:
yes
Remarks:
31P-NMR
Buffers:
- pH and composition: 4.6 (acetic acid/sodium acetate), 6.9 (Trizma hydrochloride), and 9.0 (boric acid/potassium chloride/sodium)
- Type and final molarity of buffer: 10 mM
Details on test conditions:
TEST SYSTEM
- Measures taken to avoid photolytic effects: Light was excluded by storing the test solution under aluminium foil.
- Other: Stable temperature control outside the spectrometer was achieved by either using a heating block (Ditabis MHR 11 at 25 and 50 °C) or a refrigerator (Liebherr 7081, at 9 °C).
Duration:
68 h
pH:
9
Temp.:
50 °C
Remarks:
2.8 d
Duration:
792 h
pH:
9
Temp.:
25 °C
Remarks:
33 d
Duration:
955 h
pH:
9
Temp.:
9 °C
Remarks:
39.8 d
Duration:
149 h
pH:
6.9
Temp.:
50 °C
Remarks:
6.2 d
Duration:
934 h
pH:
6.9
Temp.:
25 °C
Remarks:
38.9 d
Duration:
936 h
pH:
6.9
Temp.:
9 °C
Remarks:
39 d
Duration:
768 h
pH:
4.6
Temp.:
50 °C
Remarks:
32 d
Duration:
934 h
pH:
4.6
Temp.:
25 °C
Remarks:
38.9 d
Duration:
935 h
pH:
4.6
Temp.:
9 °C
Remarks:
38.9 d
Transformation products:
yes
Remarks:
Thiamine and free phosphoric acid (H3PO4).
No.:
#1
Reference substance:
Composition 1
No.:
#2
Reference substance:
Composition 1
% Recovery:
16
pH:
9
Temp.:
50 °C
Duration:
70 h
Remarks on result:
other: 2.9 d
Remarks:
2nd order kinetics, R² = 0.993
% Recovery:
50
pH:
9
Temp.:
25 °C
Duration:
ca. 30 d
Remarks on result:
other:
Remarks:
order of kinetics ambiguous
% Recovery:
100
pH:
9
Temp.:
9 °C
Duration:
ca. 40 d
Remarks on result:
other:
Remarks:
no significant hydrolysis, order of kinetics ambiguous
% Recovery:
11
pH:
6.9
Temp.:
50 °C
Duration:
150 h
Remarks on result:
other: 6.25 d
Remarks:
first order kinetics, R² = 0.991
% Recovery:
ca. 50
pH:
6.9
Temp.:
25 °C
Duration:
ca. 40 d
Remarks on result:
other:
Remarks:
order of kinetics ambiguous
% Recovery:
100
pH:
6.9
Temp.:
9 °C
Duration:
40 d
Remarks on result:
other:
Remarks:
no significant hydrolysis, order of kinetics ambiguous
% Recovery:
ca. 60
pH:
4.6
Temp.:
50 °C
Duration:
ca. 40 d
Remarks on result:
other:
Remarks:
order of kinetics ambiguous
% Recovery:
ca. 50
pH:
4.6
Temp.:
25 °C
Duration:
ca. 40 d
Remarks on result:
other:
Remarks:
order of kinetics ambiguous
% Recovery:
100
pH:
4.6
Temp.:
9 °C
Duration:
40 d
Remarks on result:
other:
Remarks:
no significant hydrolysis, order of kinetics ambiguous
pH:
9
Temp.:
25 °C
Half-life:
30 d
Type:
other: order of kinetics ambiguous
pH:
6.9
Temp.:
25 °C
Half-life:
40 d
Type:
other: order of kinetics ambiguous
pH:
4.6
Temp.:
25 °C
Half-life:
40 d
Type:
other: order of kinetics ambiguous
Details on results:
PATHWAYS OF HYDROLYSIS
- Description of pathway: Center for hydrolysis identified at oxygen atom (O-18).
- Figures of chemical structures attached: Yes

STABILITY CHECK OF ORGANIC PART OF PARENT COMPOUND

After 30 d the organic back bone of the test item (thiamine) was stable (no hydrolysis).

CONCLUSION

The hydrolysis rates increased with temperature and pH. Hence, the fastest hydrolysis occurred at T = 50 °C and pH 9.

The order of kinetics could only be determined at T = 50 °C, pH 6.9 and 9.0. No order of kinetics could be determined at the remaining test conditions because hydrolysis equilibrium had either been attained or hydrolysis rates were significantly low.

A 1H NMR check confirmed the stability of the organic part of the parent compound.

Description of key information

50% recovery after 30 d (pH 9.0) and 40 d (pH 4.6 and 6.9) at 25 °C (OECD 111); read-across

Key value for chemical safety assessment

Half-life for hydrolysis:
40 d
at the temperature of:
25 °C

Additional information

There is no study available, in which the hydrolysis of the target substance 2-[3-[(4-Amino-2-methylpyrimidin-5-yl)methyl]-4-methyl-1,3-thiazoniol-5-yl]ethyl dihydrogen diphosphate (CAS 136-09-4) was tested as a function of pH and temperature. Therefore, a read-across to the structurally related source substance 2-{3-[(4-amino-2-methylpyrimidin-5-yl)methyl]-4-methyl-1,3-thiazol-3-ium-5-yl}ethyl hydrogen phosphate (CAS 10023-48-0) was conducted in accordance with Regulation (EC) No 1907/2006 Annex XI, 1.5. Based on the very high degree of structural and physico-chemical similarity, the source substance is considered a suitable representative for the assessment of hydrolysis of the target substance. A detailed read-across justification is provided in the analogue justification in IUCLID section 13.

The available hydrolysis study with the source substance (CAS 10023-48-0) was performed according to OECD guideline 111. The oxygen atom of the phosphateester bond (O-18) in the parent compound was identified as potential center for hydrolysis, which is expected to yield the reaction products thiamine and free phosphoric acid (H3PO4). Furthermore, it was assumed that the resulting (free) thiamine group of the parent compound remains unchanged. Hence, a kinetic study was performed using31P-NMR, a technique allowing an easy and specific distinction of the spectral signals of the parent compound and the expected hydrolysis product. The test item was dissolved in pH adjusted, standardized buffer solutions at pH 4.6, 6.9 and 9.0 and hydrolysis was tested and monitored at 9, 25 and 50 °C for up to approximately 935 h.

Results showed that hydrolysis rates increase with temperature and pH. The fastest hydrolysis occurred at 50 °C and pH 9 where test item concentrations decreased to 16% within 70 h following second order kinetics (R² = 0.993). At pH 6.9 (and 50 °C) test item concentrations decreased to 11% within 150 h following first order kinetics (R² = 0.991). At 25 °C test item concentrations dropped down to about 50% within ca. 30 d (at pH 9) and 40 d (at pH 4.6 and 6.9) but the order of kinetics was ambiguous. At 9 °C, no hydrolysis occurred in all pH conditions. In general, no noteworthy hydrolysis occurred within approximately 40 d at pH 6.9 and T = 9 or 25 °C and as well as at pH 4.6 and all tested temperatures (T = 9, 25, and 50 °C) and no order of kinetics could be calculated either because hydrolysis equilibria had been attained or because no significant hydrolysis occurred at all.1H NMR confirmed the stability of the organic back bone of the parent compound (thiamine) after 30 d.

Based on the high degree of structural and chemical similarity between the target and source substance, the target substance is expected to exhibit a similar environmental fate as the source substance. Therefore, it can be concluded that the target substance 2-[3-[(4-Amino-2-methylpyrimidin-5-yl)methyl]-4-methyl-1,3-thiazoniol-5-yl]ethyl dihydrogen diphosphate (CAS 136-09-4) is stable at environmentally relevant conditions (T = 25 °C and pH 4.6, 6.9, and 9.0) over time frames relevant for ecotoxicity testing according to OECD guidelines (≥ 30 d).