diethyl 1-(2,4-dichlorophenyl)-5-methyl-4,5-dihydro-1H-pyrazole-3,5-dicarboxylate

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EPA Guideline Subdivision N 161-1 (Hydrolysis)

GLP compliance:

yes

Radiolabelling:

no

Buffers:

- Composition of buffer: All buffer solutions (0.01, 0.1 and 0.2 mol/L) were prepared by Analytisches Laboratorium, Hoechst AG. Water of highest quality available (bi-distilled water) was used for buffer preparation. Preparation of 0.01 M buffers is explained below (preparation of 0.1 M and 0.2 M buffers proceeded analogeously).

pH 4: 18.75 g sodium citrate monohydrate (0.089 mol) were dissolved in 176 mL aqueous sodium hydroxide (1 mol/L) and filled up to a volume of 500 mL with bi-distilled water. A 280 mL aliquot was taken, diluted with 220 mL aqueous hydrochloric acid (0.1 mol/L) and filled up to a volume of
5000 mL with bi-distilled water

pH 5: 10.5 g sodium citrate monohydrate (0.05 mol) were dissolved in 4800 mL bi-distilled water. This solution was titrated with aqueous sodium hydroxide (1 mol/L) to pH 5 and is finally brought to a volume of 5000 mL with bi-distilled water.

pH 7: 6.8 g potassium dihydrogen phosphate were dissolved in nearly 4800 mL of bidistilled water and titrated with sodium hydroxide solution (1 mol/L) to pH 7 and then filled up with water to a volume of 5 L.

pH 9: 3.7 g potassium chloride and 3.09 g boric acid were dissolved in 4800 mL bi-distilled water, adjusted with sodium hydroxide solution (1 mol/L) to pH 9 and then made up with water to a volume of 5000 mL.

Details on test conditions:

TEST SYSTEM
- Type, material and volume of test flasks, other equipment used: sterilised glassware
- Sterilisation method: at 180°C for two hours
- Lighting: darkness

Duration:

30 d

pH:

4

Temp.:

25 °C

Initial conc. measured:

9 mg/L

Duration:

30 d

pH:

5

Temp.:

25 °C

Initial conc. measured:

9 mg/L

Duration:

30 d

pH:

7

Temp.:

25 °C

Initial conc. measured:

9 mg/L

Duration:

30 d

pH:

9

Temp.:

25 °C

Initial conc. measured:

9 mg/L

Number of replicates:

One replicate for pH 4, three replicates for pH 5, 7 and 9.

Transformation products:

yes

No.:

#1

No.:

#2

No.:

#3

Details on hydrolysis and appearance of transformation product(s):

1-(2,4-dichlorophenyl)-5-methyl-2-pyrazoline-3,5-dicarboxylic acid (Hoe 109453)
1-(2,4-dichlorophenyl)- 5-ethoxycarbonyl- 5-methyl-2-pyrazoline- 3-carboxylic acid (Hoe 113225)
1-(2,4-dichlorophenyl)- 5-ethoxycarbonyl- 5-methyl-3-pyrazoline- 3 carboxylic acid (no Hoe-code available)

pH:

4

Temp.:

25 °C

DT50:

> 365 d

Type:

(pseudo-)first order (= half-life)

pH:

5

Temp.:

25 °C

DT50:

> 365 d

Type:

(pseudo-)first order (= half-life)

pH:

7

Temp.:

25 °C

DT50:

25.8 - 40.9 d

Type:

(pseudo-)first order (= half-life)

pH:

9

Temp.:

25 °C

DT50:

0.31 - 0.35 d

Type:

(pseudo-)first order (= half-life)

Findings:

As a typical ester compound hydrolysis was slow at pH 4 and 5 but increased significantly with increasing pH (pH 7 and 9). At neutral pH, the hydrolysis is accelerated by buffer solutions with higher ionic strength (0.01 M versus 0.2 M). Besides mefenpyr-ethyl AE F113225 (maximum 77% at pH 9) and the dicarboxylic acid AE F109453 (maximum 34% at pH 9), a tautomer component of AE F113225 with report title “Hoe X” (maximum 10% at pH 9) was identified by HPLC/MS as 1-(2,4-dichlorophenyl)-5-ethoxycarbonyl-5-methyl-3-pyrazoline-3-carboxylic acid. The pyrazole carboxylic acid AE F094270 or the monoethyl ester AE F114952 were not observed during the incubation of 30 days. Since the material balance was 95% or better, no further than the reported metabolites are to be expected from hydrolysis. The results were summarized in the table.

 

Table: Half-life times of aqueous hydrolysis of AE F107892 at 25°C

pH	4	5	5	5	7	7	7	9	9	9
Buffer conc. [mole/L]	0.01	0.01	0.1	0.2	0.01	0.1	0.2	0.01	0.1	0.2
DT50[days]	>365	>365	>365	>365	40.9	25.9	25.8	0.35	0.34	0.31

  

Conclusion:

The hydrolytic stability of mefenpyr-diethyl under abiotic conditions is strongly dependant on pH. There is slow to no hydrolysis at a pH of 7 or below. At pH-values of more than 7, hydrolysis increases significantly to form mefenpyr-ethyl AE F113225 and the dicarboxylic acid AE F109453 as the predominant hydrolysis products.

It should be noted that hydrolysis is speeded up significantly under biotic conditions also at pH-values at or below 7 due to exo-enzymes like esterases released by microbia into the environment.

Description of key information

Due to the carboxylic ester groups in the molecule, the substance is in principle susceptible to biotic hydrolysis. In sterile aqueous buffer solution abiotic hydrolysis of the substance is strongly pH-dependent. At 25°C, the substance is stable to hydrolysis at pH4 and 5. The specific half-lives at 25°C are 40.9 days (pH7) and 0.4 days (pH9).

Key value for chemical safety assessment

Half-life for hydrolysis:

40.9 d

at the temperature of:

25 °C

Additional information

The hydrolysis of the substance was investigated in a study following EPA Guideline Subdivision N 161-1 (Hydrolysis). Due to the carboxylic ester groups in the molecule, the substance is in principle susceptible to hydrolysis. The hydrolysis of the substance in sterile aqueous buffer solution is strongly pH-dependent, i.e. fast in alkaline media and slowing down under slightly acidic to neutral conditions of pH. At 25°C, the substance is stable to hydrolysis at pH 4 and 5. The specific half-lives at 25°C are 40.9 days at pH 7 and 0.4 days at pH 9 respectively. At pH-values > 7, hydrolysis increases significantly and mono- and dicarboxylic acids are formed as the main products of hydrolysis.

The rate of aqueous hydrolysis increases significantly at biotic conditions and pH-values ≤ 7 due to exo-enzymes, like esterases, released into the environment by microbia.