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Environmental fate & pathways

Hydrolysis

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Endpoint:
hydrolysis
Type of information:
experimental study
Adequacy of study:
disregarded due to major methodological deficiencies
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Non-guideline and very old study.
Qualifier:
no guideline followed
GLP compliance:
no
Radiolabelling:
no
Analytical monitoring:
yes
Duration:
300 min
Temp.:
100 °C
Hydrolysis rate constant:
0.002
DT50:
ca. 290 min
Type:
(pseudo-)first order (= half-life)
Remarks on result:
other: DT50 derived from graphical results by the Registrant, rate constant from data in Series V.
Validity criteria fulfilled:
no
Endpoint:
hydrolysis
Type of information:
experimental study
Adequacy of study:
disregarded due to major methodological deficiencies
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Non-guideline study.
Qualifier:
no guideline followed
GLP compliance:
no
Radiolabelling:
no
Analytical monitoring:
yes
pH:
7.1
Temp.:
100 °C
Hydrolysis rate constant:
0.013 min-1
DT50:
54 min
Type:
(pseudo-)first order (= half-life)
Remarks on result:
other: Rate constant and half life calculated from graphical results by the Registrant.
Temp.:
100 °C
Hydrolysis rate constant:
ca. 0.022 min-1
DT50:
ca. 32 min
Remarks on result:
other: pH=8-10.6; Rate constant and half life calculated from graphical results by the Registrant.
pH:
11.6
Temp.:
100 °C
Hydrolysis rate constant:
0.053 min-1
DT50:
13 min
Type:
(pseudo-)first order (= half-life)
Remarks on result:
other: Rate constant and half life calculated from graphical results by the Registrant.

Rate constants extrapolated to zero buffer concentration. pKa = 7.54, measured at 100°C, ionic strength 1M.

Validity criteria fulfilled:
no
Endpoint:
hydrolysis
Type of information:
experimental study
Adequacy of study:
disregarded due to major methodological deficiencies
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Non-guideline study.
Qualifier:
no guideline followed
GLP compliance:
no
Radiolabelling:
no
Analytical monitoring:
yes
pH:
2
Temp.:
90 °C
Hydrolysis rate constant:
0.002 min-1
DT50:
370 min
Type:
(pseudo-)first order (= half-life)
pH:
8
Temp.:
90 °C
Hydrolysis rate constant:
0.001 min-1
DT50:
750 min
Type:
(pseudo-)first order (= half-life)
Validity criteria fulfilled:
no
Endpoint:
hydrolysis
Type of information:
experimental study
Adequacy of study:
disregarded due to major methodological deficiencies
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Non-guideline study.
Reason / purpose:
reference to same study
Qualifier:
no guideline followed
GLP compliance:
no
Radiolabelling:
no
Analytical monitoring:
yes
Duration:
4 h
pH:
1.1
Temp.:
37.5
Duration:
4 h
pH:
8.2
Temp.:
37.5
Duration:
8 h
pH:
8.2
Temp.:
37.5
Number of replicates:
3 replicates in the 4h trials, 2 replicates in the 8h trial
Transformation products:
not measured
% Recovery:
96.6
St. dev.:
1.7
pH:
1.1
Temp.:
37.5 °C
Duration:
4 h
% Recovery:
94.3
St. dev.:
0.7
pH:
8.2
Temp.:
37.5 °C
Duration:
4 h
% Recovery:
93.3
St. dev.:
1.8
pH:
8.2
Temp.:
37.5 °C
Duration:
8 h
Details on results:
Control for salicylamide extraction: 94.7%
Validity criteria fulfilled:
no

Description of key information

Hydrolysis occurs under aqueous acid and alkaline conditions at ca. 100°C.

Key value for chemical safety assessment

Additional information

Experimental work has demonstrated hydrolysis under both alkaline and acid conditions, but only at elevated temperatures (ca. 100°C). Reid (Reid, E.E., Am. Chem. J., 1899, 21(4), 281-348) carried out a series of experiments on aromatic amides and demonstrated that ortho-substituted species were significantly stabilised towards hydrolysis. Koshy (Koshy, K.T., J. Pharm. Sci., 1959, 58(5), 560-563) calculated first-order rate constants under acid (1M HClO4, 1.88x10-3min-1) and alkaline (1M NaOH, 0.93x10-3min-1) conditions at 90°C. Bruice et al (Bruice, T.C., et al, J. Org. Chem., 1965, 30(5), 1668-1669) carried out pH dependent hydrolysis studies of several aromatic amides to identify the reaction mechanism, again at elevated temperatures (100°C). The rate constants for salicylamide were determined in the range pH=7.1 - 11.6 and showed an unusual S-shaped curve, which had previously been demonstrated in a similar compound, with similar reaction mechanism (Bender, M.L., et al, J.Am.Chem.Soc., 1963, 85(19), 3017-3024). Both compounds had a constant reaction-rate plateau above the pKa, before increasing under significantly alkaline conditions. The lowest reaction rates were under acid conditions, below the pKa. For the test substance the reaction rates were determined: pH=7.1, 0.013min-1; pH ca. 8-10.6, 0.022min-1; pH=11.6, 0.053min-1. It was mentioned that borate and phosphate buffers were unsuitable due to complexing with o-hydroxyamides. Brodie (Brodie, D.C., et al, J. Am. Pharm. Assoc., 1951, 40(8), 414-415) investigated hydrolysis under physiological conditions in vitro, at room temperature. No hydrolysis was observed in a 4h or 8h period, within experimental error.

The experimental work demonstrated hydrolysis under both alkaline and acid conditions, but only at elevated temperatures (ca. 100 °C). No experimental data under environmentally relevant conditions are available.