Teflubenzuron

Hydrolysis

Description of key information

The hydrolsis DT50 of teflubenzuron is 8.7 days at a temperature of 25 °C and a pH of 9. The hydrolysis DT50 of teflubenzuron at pH 9 was calculated to be 24.6 days at 12 °C.

Key value for chemical safety assessment

Half-life for hydrolysis:

8.7 d

at the temperature of:

25 °C

Additional information

One valid study on the hydrolysis of teflufbenzuron is available and described as key study.

 

Huntingdon Research Centre (1987a): The Hydrolysis of ¹⁴C-CME 134. DocID according to Draft Assessment Report prepared in compliance with Regulation (EC) No 1107/2009: TZ-322-001; crossreference to Draft Assessment Report according to Regulation (EC) No 1107/2009: 2.9.1/01.

 

The hydrolytic stability of 14C-CMB 134, teflubenzuron, has been investigated following incubation in buffered solutions at pH 5, pH 7 and at pH 9. Solutions at an initial concentration of 40 µg/L were incubated in the absence of light at 25°C.

The recoveries of radioactivity in each buffer solution were measured at zero-time and after 7, 21 and 30 days incubation. In addition, samples incubated at pH 9 were analysed after 1, 3 and 14 days of incubation. These results showed that means of 101% (pH 5), 103% (pH 7) and 97% (pH 9) of applied radioactivity were recovered. Radioactivity in the pH 5 or pH 7 incubates required addition of acetone to obtain these recoveries and enable representative samples to be prepared for analysis. Prior to addition of acetone, 48% (pH 5) or 65% (pH 7) of applied radioactivity was found in the solutions after 30 days of incubation.

The hydrolytic stability of ¹⁴C-CME 134 in the buffer solutions was examined by high performance liquid chromatography using reverse phase conditions with gradient elution and methanol/water eluants. No hydrolysis for ¹⁴C-aniline-CME 134 was observed at pH 5. After 30 days of incubation at pH 7, 96% of applied radioactivity was associated with the parent compound. At pH 9 ¹⁴C-CME 134, radiolabelled in the aniline or benzoyl ring, was extensively hydrolysed so that after 30 days 16% of the applied radioactivity was associated with CME 134. A half-life of 8.7 days was re-calculated by the RMS for hydrolysis of CME 134 at pH 9.

3,5-dichloro-2,4-difluorophenylurea and 2,6-difluorobenzoic acid were indicated as major breakdown products at pH 9, accounting for 61% and 62% of the sample radioactivity respectively after 30 days incubation. About 12% of the radioactivity chromatographed with 3,5-dichloro-2,4-difluoroanillne and with 2,6-difluorobenzamide after incubation at pH 9 for 30 days after which time a minor breakdown product (up to 8% of applied radioactivity) was shown to chromatograph with N-(2,4-difluoro-3,5-dichlorobenzene)-5-fluoro-[3H]-dihydroquinazoline-2,4-dione.

 

A second study on hydrolysis was performed with the major degradation product 3,5-dichloro-2,4-difluoro-phenylurea.

 

This study is summarized in the following for sake of completeness but has however not been documented in a separate IUCLID Endpoint Study Record.

 

Batelle (2003a): (3,5-dichloro-2,4-difluoro-phenyl)urea (CL902374) – Hydrolysis. DocID according to Draft Assessment Report prepared in compliance with Regulation (EC) No 1107/2009: 2003/1009579; crossreference to Draft Assessment Report according to Regulation (EC) No 1107/2009: 7.2.1/01.

 

The hydrolysis of 3,5-dichloro-2,4-difluoro[¹⁴C]phenylurea (CL 902374), a metabolite of teflubenzuron, was investigated in sterilized buffered aqueous solutions at pH values of 4, 7 and 9 at 50 ^°C according to OECD Test Guideline 111.

The radiopurity of 3,5-dichloro-2,4-difluoro[U-¹⁴C]phenylurea was determined at the beginning of the study via HPLC with radio flow detection. The solubility in aqueous solutions of pH 4, 7 and 9 of 3,5-dichloro-2,4-difluoro[U-¹⁴C]phenylurea was determined prior to the pre-test. The preliminary test was carried out at concentrations equivalent to half of the water solubility.

A preliminary test was performed at three pH values: 4, 7 and 9. A series of quartz cuvettes containing duplicate sterile buffered solutions (3 mL) dosed with 3,5-dichloro-2,4-difluoro[U-¹⁴C]phenylurea were immersed into a water bath at a constant temperature of 50 ± 0.5°C for five days. Potential hydrolytic degradation products formed in aqueous solution were profiled by high performance liquid chromatography (HPLC) with radioflow detection. A radioactive mass balance of > 90% of applied dose was established by analysis via Liquid Scintillation Counting (LSC) for day 0 and day 5 samples.

After 5 days, one degradation product was present at levels of applied dose of 8.91% at pH 4, 9.09% at pH 7 and 8.61% at pH 9. It co-chromatographed with 3,5-dichloro-2,4-difluoroaniline, a known metabolite of teflubenzuron. 3,5-dichloro-2,4-difluoro[14C]phenylurea was hydrolysed to 3,5-dichloro-2,4-difluoroaniline.The results of the preliminary test demonstrated that 3,5-dichloro-2,4-difluoro[U-¹⁴C]phenylurea was hydrolysed less than 10% after five days at any of the three pH values (4, 7 and 9). Therefore, no further testing was necessary and the test substance 3,5-dichloro-2,4-difluoro[14C]phenylurea can be considered stable to hydrolysis.

 

 

Conclusion

In the hydrolysis study with the teflubenzuron two major breakdown products, 3,5-dichloro-2,4-difluorophenylurea (from the aniline ring labelled CME 134) and 2,6-difluorobenzoic acid (from the benzoyl ring labelled CME 134) were detected at pH 9, accounting for 61% and 62% of the sample radioactivity respectively after 30 days incubation. About 12% of the radioactivity chromatographed with 3,5-dichloro-2,4-difluoroaniline (from the aniline ring labelled CME 134) and also 12% with 2,6-difluorobenzamide (from the benzoyl ring labelled CME 134) after incubation at pH 9 for 30 days, after which time a minor breakdown product (up to 8% of applied radioactivity) was shown to chromatograph with N-(2,4-difluoro-3,5-dichlorobenzene)-5-fluoro-[3H]-dihydroquinazoline-2,4-dione. The RMS re-calculated a hydrolysis DT₅₀ value for teflubenzuron of 8.7 days at pH 9, using non-linear regression first order kinetics.

 

The hydrolysis DT50 of teflubenzuron at pH 9 was calculated to be 24.6 days at 12 °C (Chapter R.7b, p.222: Endpoint specific guidance Version 4.0 – June 2017):

 

DT50hydr_{water_temp env} = DT50hydr_{water_temp test *} e ^{(0.08*(TEMPtest-TEMPenv))}

 

Input
DT50hydrwater_temp test	half-life for hydrolyses in water at a temperature of the data set	[d]
TEMPtest	temperature of the measured data in simulation test	[K]
TEMP	environmental temperature	[K]
Output
DT50hydrwater_temp env	half-life for hydrolyses in water at the environmental temp.	[d]

 

In a second study the hydrolysis of 3,5-dichloro-2,4-difluoro[¹⁴C]phenylurea a metabolite of teflubenzuron in sterilized buffered aqueous solutions was investigated at pH values of 4, 7 and 9 at 50 ^°C according to OECD Test Guideline 111. After 5 days, one degradation product was present at levels of applied dose of 8.91% at pH 4, 9.09% at pH 7 and 8.61% at pH 9. It co-chromatographed with 3,5-dichloro-2,4-difluoroaniline, a known metabolite of teflubenzuron. 3,5-dichloro-2,4-difluoro[¹⁴C]phenylurea was hydrolysed to 3,5-dichloro-2,4-difluoroaniline. As after 5 days, less than 10% of the test compound was degraded at all 3 pH values, no further testing was necessary. Therefore the test substance 3,5-dichloro-2,4-difluoro[¹⁴C]phenylurea can be considered stable to hydrolysis.