4H-Pyrazino[2,1-a]isoquinolin-4-one, 2-acetyl-1,2,3,6,7,11b-hexahydro-

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2004-10-13 to 2005-03-21

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method C.7 (Degradation: Abiotic Degradation: Hydrolysis as a Function of pH)

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Deviations:

no

GLP compliance:

yes

Radiolabelling:

no

Analytical monitoring:

yes

Buffers:

- pH: 4, 7 and 9

Composition of buffer:

-pH 4: 21.01 g citric acid monohydrate were dissolved in 200 mL sodium hydroxide solution (c = 1 mol/L). This solution was filled up to a volume of 1000 mL with distilled water. 44 mL of hydrochloric acid (c = 1 mol/L) were added to 560 mL of this solution and filled up to a volume of 1000 mL with distilled water. The pH value was adjusted to pH 4 for each hydrolysis temperature.

-pH 7: 13.61 g potassium dihydrogen phosphate were dissolved in 1000 mL distilled water. 30 mL of sodium hydroxide solution (c = 1 mol/L) were added to 500 mL of this solution and filled up to a volume of 1000 mL with distilled water. The pH value was adjusted to pH 7 for each hydrolysis temperature.

-pH 9: 7.46 g potassium chloride and 6.18 g boric acid were dissolved in 1000 mL distilled water. 21 mL of sodium hydroxide solution (c = 1 mol/L) were added to 500 mL of this solution and filled up to a volume of 1000 mL with distilled water. The pH value was adjusted to pH 9 for each hydrolysis temperature.

Positive controls:

no

Negative controls:

no

Transformation products:

not measured

% Recovery:

> 90

pH:

4

Temp.:

50 °C

Duration:

5 d

% Recovery:

> 90

pH:

7

Temp.:

50 °C

Duration:

5 d

Key result

pH:

4

Temp.:

25 °C

DT50:

> 1 yr

Key result

pH:

7

Temp.:

25 °C

DT50:

> 1 yr

Results with reference substance:

not applicable

At pH 4 and pH 7 less than 10 % of the reaction is observed after 5 days at 50 DC (t 14 > 1 year). Thus the test substance may be considered hydrolytically stable and according to the guidelines no additional testing is required.

At pH 9 experiments were done at 50 DC, 65 °C and 75 DC. A calculation respectively extrapolation was not possible. At 50 °C an equilibrium was observed at approximately 20 % degradation. A 50 % degradation was not reached. A graphically calculation was not possible.

For the experiments at 65 °C and 75 °C no linear relationship between -log (ct/c0) and t could be observed. The calculation of t1/2was done graphically.

Table 1 Results of the hydrolysis pre-test

pH	Duration	c0 in mg/L	ct in mg/L	Ct/C0	Decomposition in %
4	2.4 h	502.4	496.2	0.9877	1.2
	2.4 h	697.6	652.3	0.9351	6.5
	5d	502.4	493.2	0.9817	1.8
	5d	697.6	655.5	0.9397	6.0
7	2.4 h	619.6	608.9	0.9823	1.7
	2.4 h	651.2	647.9	0.9950	0.5
	5d	619.6	615.6	0.9936	0.6
	5d	651.2	647.4	0.9942	0.6
9	2.4 h	648.0	629.7	0.9717	2.8
	2.4 h	380.0	362.2	0.9531	4.7
	5d	648.0	555.6	0.8575	14.3
	5d	380.0	316.9	0.8333	16.6

Validity criteria fulfilled:

yes

Conclusions:

The test substance may be considered as hydrolytically stable.

Executive summary:

Abiotic degradation of the test item was assessed by means of hydrolysis monitoring as a function of pH in accordance with OECD TG 111. The concentration of the test item in buffered solutions at pH 4, 7 and 9 was analytically monitored over 5 days in a pre-test at 50 °C. At pH 4 and pH 7 less than 10 % of the reaction is observed after 5 days at 50 DC (t 14 > 1 year). Thus the test substance may be considered hydrolytically stable and according to the guidelines no additional testing is required. At pH 9 experiments were done at 50 DC, 65 °C and 75 DC. A calculation respectively extrapolation was not possible. At 50 °C an equilibrium was observed at approximately 20 % degradation. A 50 % degradation was not reached. A graphically calculation was not possible. For the experiments at 65 °C and 75 °C no linear relationship between -log (ct/c0) and t could be observed. The calculation of t1/2 was done graphically. As a result the test item may be considered hydrolytically stable.

Description of key information

The test item is hydrolytically stable according to results of an OECD TG 111 compliant study (reference 5.1.2-1).

Additional information

Abiotic degradation of the test item was assessed by means of hydrolysis monitoring as a function of pH in accordance with OECD TG 111. The concentration of the test item in buffered solutions at pH 4, 7 and 9 was analytically monitored over 5 days in a pre-test at 50 °C. At pH 4 and pH 7 less than 10 % of the reaction is observed after 5 days at 50 DC (t 14 > 1 year). Thus the test substance may be considered hydrolytically stable and according to the guidelines no additional testing is required. At pH 9 experiments were done at 50 DC, 65 °C and 75 DC. A calculation respectively extrapolation was not possible. At 50 °C an equilibrium was observed at approximately 20 % degradation. A 50 % degradation was not reached. A graphically calculation was not possible. For the experiments at 65 °C and 75 °C no linear relationship between -log (ct/c0) and t could be observed. The calculation of t1/2 was done graphically. As a result the test item may be considered hydrolytically stable.