4-[4-[4-[(3R, 5R)[5-(2,4-difluorophenyl) tetrahydro-5-(1H-1,2,4-triazol-1-yl-methyl)-furan-3-yl]methyloxy]phenyl]-1-piperazinyl]phenyl-2-[(1S,2S)(1-ethyl-2-phenylmethoxypropyl)]-2,4-dihydro-3Htriazol-3-one

Biodegradation in water: screening tests

Administrative data

Endpoint:

biodegradation in water: ready biodegradability

Type of information:

experimental study

Adequacy of study:

key study

Study period:

18 January 2012 to 16 February 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: This study has been performed according to OECD and/or EC guidelines and according to GLP principles.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 301 B (Ready Biodegradability: CO2 Evolution Test)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method C.4-C (Determination of the "Ready" Biodegradability - Carbon Dioxide Evolution Test)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

ISO DIS 9439 (Ultimate Aerobic Biodegradability - Method by Analysis of Released Carbon Dioxide)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

1-[(2S,3S)-2-(benzyloxy)pentan-3-yl]-4-{4-[4-(4-{[(3R,5R)-5-(2,4-difluorophenyl)-5-[(1H-1,2,4-triazol-1-yl)methyl]oxolan-3-yl]methoxy}phenyl)piperazin-1-yl]phenyl}-4,5-dihydro-1H-1,2,4-triazol-5-one

EC Number:

938-153-9

Molecular formula:

C44H48O4N8F2

IUPAC Name:

1-[(2S,3S)-2-(benzyloxy)pentan-3-yl]-4-{4-[4-(4-{[(3R,5R)-5-(2,4-difluorophenyl)-5-[(1H-1,2,4-triazol-1-yl)methyl]oxolan-3-yl]methoxy}phenyl)piperazin-1-yl]phenyl}-4,5-dihydro-1H-1,2,4-triazol-5-one

Details on test material:

- Identification: Paz-E
- Molecular formula: C44H48O4N8F2
- Molecular weight: 790.9
- Description: White powder

- Test substance storage: At room temperature protected from light in desiccator
- Stability under storage conditions: Stable
- Expiry date: 25 November 2012 (allocated by NOTOX, 1 year after receipt of the test substance)

- Hygroscopic: Yes, in desiccator
- Volatile: No
- Test substance handling: Use amber-coloured glassware or wrap container in tin-foil.
- Stability in water: Unknown
- Solubility in water: <10 mg/mL

Study design

Oxygen conditions:

aerobic

Inoculum or test system:

activated sludge, domestic, non-adapted

Details on inoculum:

Source: The source of test organisms was activated sludge freshly obtained from a municipal sewage treatment plant: 'Waterschap Aa en Maas', 's-Hertogenbosch, The Netherlands, receiving predominantly domestic sewage.

Treatment: The freshly obtained sludge was kept under continuous aeration until further treatment. The concentration of suspended solids was 4.7 g/l in the concentrated sludge (information obtained from the municipal sewage treatment plant). Before use, the sludge was allowed to settle (58 minutes) and the supernatant liquid was used as inoculum at the amount of 10 ml/l of mineral medium.

Duration of test (contact time):

28 d

Initial test substance concentration

Initial test substance concentration 1

Initial conc.:

18 mg/L

Based on:

test mat.

Initial test substance concentration 2

Initial conc.:

12 mg/L

Based on:

other: Total Organic Carbon (TOC)

Parameter followed for biodegradation estimation

Parameter followed for biodegradation estimation:

CO2 evolution

Reference substance

Reference substance:

acetic acid, sodium salt

Results and discussion

% Degradation

% Degradation 1

Parameter:

% degradation (CO2 evolution)

Value:

25

Sampling time:

29 d

Remarks on result:

other: HCl added on the 28th day (last CO2-measurement on the 29th day)

% Degradation 2

Parameter:

% degradation (CO2 evolution)

Value:

10

Sampling time:

29 d

Remarks on result:

other: HCl added on the 28th day (last CO2-measurement on the 29th day)

Details on results:

The relative biodegradation values calculated from the measurements performed during the test period revealed 25 and 10% biodegradation of Paz-E, for the duplicate bottles tested. Thus, the criterion for ready biodegradability (at least 60% biodegradation within a 10-day window) was not met.

In the toxicity control more than 25% biodegradation occurred within 14 days (34%, based on ThCO2). Therefore, the test substance was assumed not to inhibit microbial activity.

BOD5 / COD results

Results with reference substance:

The positive control substance was biodegraded by at least 60% (75%) within 14 days.

Applicant's summary and conclusion

Validity criteria fulfilled:

yes

Interpretation of results:

other: not readily biodegradable (25-10%)

Conclusions:

PAZ-E was not readily biodegradable under the conditions of the modified Sturm test presently performed.