2-{3-[(4-amino-2-methylpyrimidin-5-yl)methyl]-4-methyl-1,3-thiazol-3-ium-5-yl}ethyl hydrogen phosphate

Hydrolysis

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)

Key value for chemical safety assessment

Half-life for hydrolysis:

40 d

at the temperature of:

25 °C

Additional information

There is one study available, in which the hydrolysis of 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) as a function of pH and temperature was tested according to OECD 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 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.

In conclusion, the test item 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).