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Description of key information

The test substance was stable in pH 4 and pH 7 sterile buffer for at least 5 days at 50°C in the dark. In pH 9 buffer the DT50 values were 1261 days at 10ºC, 133 days at 25ºC and 9.84 days at 50ºC. In pH 9 buffer at 10 and 25°C, no degradation products were observed that exceeded 10% of the total applied radioactivity (TAR). However, at 50°C in pH 9 buffer, M440I001, M440I002, and nicotinic acid exceeded 10% TAR. The product M440I003 was also identified, but at levels <10% TAR. Hydrolysis is unlikely to be an important degradation process at most environmentally relevant pH and temperature levels.

Key value for chemical safety assessment

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

Additional information

The purpose of a study (Huntington Life Sciences, JHW0005, 2014) according to EPA OPPTS 835.2120 (Hydrolysis of Parent and Degradates as a Function of pH at 25°C, 1998) was to provide information on the hydrolytic degradation of the test substance when introduced into sterile aqueous solutions buffered at a pH of 4, 7 and 9. Buffer solutions were treated with radiolabelled test substance at a nominal initial concentration of 2.0 mg/L. Preliminary experiments at 50°C in the dark indicated that the test substance was hydrolytically stable at pH 4 and pH 7, with half‑lives estimated to be greater than one year at 25 °C. Thus, it was not necessary to conduct further testing at these pH values. A more extensive test was conducted at pH 9 which examined the effect of temperature. Buffer solutions (pH 9) were incubated at 10°C, 25°C and 50 °C for periods of up to 30 days in the absence of light and oxygen. Samples were analyzed for total radioactivity using LSC and for the distribution of radioactive products by direct injection using HPLC with radiochemical detection. Hydrolysis product identities were confirmed using co-chromatography with authentic reference standards in two chromatographic systems (reversed phase TLC and normal phase TLC).

The calculated half‑lives were 1261 days at 10 °C, 133 days at 25°C and 9.84 days at 50°C. The rate constants from the kinetic data was used to generate an Arrhenius plot for the estimation of other DT50 values. Estimated DT50 values at pH 9 for 20°C and 25°C were 294 days and 157 days, respectively, when calculated by the Arrhenius equation.


Following incubation at 10°C and 25°C there were no degradation products greater than 8.7% AR (applied radioactivity). After incubation at 50°C, three degradation products reached levels of more than 10% AR and they were identified by chromatography using authentic material as reference standards as nicotinic acid, M440I001, and M440I002. Ten other minor components were detected, and they accounted for a maximum of 4.0% AR, one of which was identified as M440I003.

Based on the various pH buffers examined, it can be concluded that hydrolysis would be a possible degradation route in the aquatic environment only under basic conditions.