Ethanone, 1-(4-methoxyphenyl)-2-[(3-methoxyphenyl)thio]-

Hydrolysis

Administrative data

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

June 2006 to Feb 2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Principles of method if other than guideline:

The following deviations from protocol occurred during the study:Hydrolysis as a Function of pHThe protocol stated that the preliminary test would meet the guideline requirements for Test 1 (at least four determinations in the range 20 to 70% hydrolysis). Due to the rate of hydrolysis, only two determinations met this requirement (24 hours and 48 hours). The objective of Test 1, as described in the test guideline, is to show that hydrolysis is pseudo-first order. This was achieved in the prelimi nary test conducted with a good linear fit over 10 determinations, consequently the deviation is not considered to be significant. In addition, the linearity of the Arrhenius plot suggests that the data are sufficient. This is not considered to have affected the outcome of the study.

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

469-300-0

EC Name:

-

Cas Number:

63675-73-0

Molecular formula:

Hill Empirical Formula: C16H16O3S CAS Empirical Formula: C16H16O3S

IUPAC Name:

1-(4-methoxyphenyl)-2-[(3-methoxyphenyl)sulfanyl]ethan-1-one

Test material form:

solid: particulate/powder

Details on test material:

Sponsor batch no: 151105Purity: 99.9%

Radiolabelling:

no

Study design

Analytical monitoring:

yes

Details on sampling:

Stock buffer solutions were made up at pH 4, 7 and 9, using ConvoL buffer concentrates (Merck) diluted with sterile water, and degassed with nitrogen. Solutions of test substance were prepared in the above buffers at a nominal concentration of 0.75 µg/mL. Aliquots of these solutions were dispensed into colour-coded, septum-sealed vials, and were incubated under light-free conditions at appropriate temperatures that were maintained by a temperature-controlled bath. A preliminary test was performed at pH 4, pH 7 and pH 9 at nominally 50°C.Following evaluation of the results from the preliminary test, further tests were performed at pH 9 at nominal temperatures of 20°C and 35 °C. At each temperature, five vials containing nominally 100 mL of test solution were prepared for incubation. Samples were withdrawn at intervals and the pH of each sample recorded. Up until Day 19 in dividual vials were removed for analysis. After Day 24 sampling, the vial was returned to the water bath and incubation continued. At further intervals, samples were withdrawn from the same vial. This became necessary as results from Day 19 showed that Jong term storage of samples gave rise to unreliable results.

Buffers:

Buffer pH 4 BDH, Convol; concentrated buffer solution, pH 4 (VWR, UK), Composed of Citric acid, sodium hydroxide and hydrochloric acid.Buffer pH7 BDH, Convol; concentrated buffer solution, pH 7 (VWR, UK), Composed of Potassium dihydrogen orthophosphate and disodium hydrogen orthophosphateBuffer pH 9 BDH, Convol; concentrated buffer solution, pH 9 (VWR, UK), Composed of Boric acid, potassium chloride and sodium hydroxide .

Number of replicates:

2 replicates for each test

Results and discussion

Preliminary study:

The rate of hydrolysis of Beta Ketosulfide was evaluated at pH4, 7 and 9 in preliminary studies. No hydrolysis was observed at pH4. No significant hydrolysis was observed at pH7. At pH 9, significant hydrolysis was observed in the preliminary test and further testing was triggered

Test performance:

At pH4, the % lost after 5 days was calculated to be zero. At pH 7 the percentage lost after 5 days was calculated to be zero. At pH 7 the percentage lost after 5 days was calculated to be 2.45%. Co nsequently, further evaluation at these pH values was not required, because there was less than 10% hydrolysis over a period of five days. In accordance with the test guideline, on the basis of these results, the equivalent half lives at pH4 and pH7 at 25C are considered to be greater than one year.At pH 9, the percentage lost after 5 days was calculated to be 95.22% corresponding to a half-life of 27.3 hours (l.14 days). The rate constant was 2.53 x 10·2 /hr. This triggered further testing at two additional temperatures.The protocol stated that the preliminary test would meet the guideline requirements of Test 1 (at least four determinations in the range 20 to 70% hydrolysis). Due to the rate of hydrolysis, only two determinations met this requirement (24 hours and 48 hours). The purpose of Test 1 is to show that hydrolysis is pseudo-first order. This was achieved with a good linear fit over 10 determinations, consequently the deviation is not considered to be significant.

Transformation products:

no

Total recovery of test substance (in %)

Total recovery of test substance (in %) 1

% Recovery:

0

pH:

4

Duration:

5 d

Total recovery of test substance (in %) 2

% Recovery:

95.22

pH:

9

Duration:

5 d

Dissipation DT50 of parent compound

Dissipation DT50 of parent compound 1

pH:

9

Temp.:

50 °C

Hydrolysis rate constant:

0.025 h-1

DT50:

27.3 h

Dissipation DT50 of parent compound 2

pH:

9

Temp.:

20 °C

Hydrolysis rate constant:

0.001 h-1

DT50:

965 h

Dissipation DT50 of parent compound 3

pH:

9

Temp.:

35 °C

Hydrolysis rate constant:

0.003 h-1

DT50:

239 h

Dissipation DT50 of parent compound 4

pH:

4

Temp.:

25 °C

DT50:

> 1 yr

Dissipation DT50 of parent compound 5

pH:

7

Temp.:

25 °C

DT50:

> 1 yr

Details on results:

See above under test performance.

Applicant's summary and conclusion

Validity criteria fulfilled:

yes

Conclusions:

Significant hydrolysis was observed at pH9 which triggered further testing. The Arrhenius plot generated from the results of testing at temperatures of 20C, 35C and 50C was linear and prediction fo the half-life at 20C compared favourably with the experimental value. The rate constant was evaluated as 0.01481 / hour, an dthe predicted half-life at 20C was 46.81 days.

Executive summary:

Testing was carried out in accordance with EC Directive 92/69/EEC Method C7. The rate of hydrolysis of Beta Ketosulfide was evaluated at pH 4, 7 and 9. No hydrolysis was observed at pH 4. No significant (i.e. less than 10% in 5 days at 50^oC) hydrolysis was observed at pH 7.

At pH 9 significant hydrolysis was observed in the preliminary test and further testing triggered. The Arrhenius plot generated from the results of testing at temperatures of 20^oC, 35^oC and 50^oC was linear and prediction of the half-life at 20oC compared favourably with the experimental value.