(2S)-3-Methyl-2-[N-({2'-(1H-1,2,3,4-tetrazol-5-yl)-[1,1-biphenyl]-4-yl}methyl)pentanamido]alkanoic acid

Sediment toxicity

Link to relevant study record(s)

Reference

Endpoint:

sediment toxicity: long-term

Type of information:

experimental study

Adequacy of study:

key study

Study period:

May - Oct 2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 218 (Sediment-Water Chironomid Toxicity Test Using Spiked Sediment)

GLP compliance:

yes

Analytical monitoring:

yes

Details on sampling:

During the test singular samples for analysis were taken according to the schedule below. The method of analysis is described in the appended Analytical Reports
Samples - Stock solution
- Overlying water, pore water and sediment.
Frequency Day of sampling Samples
-2 Stock solution
0, 7,28 Overlying water, pore water and sediment from the nominal
concentration of 1000 mg/kg d.w.
Number of samples Singular samples.


Volume Overlying water, pore water 1.0 ml.
Sediment: complete sediment.

Separation procedure The water layer was separated from the test vessels
by decantation. The pore water was separated from
the sediment by centrifugation (30 minutes, 10.000 g).

Additionally, remaining pore and overlying water taken from 1000 mg/kg d.w. were stored for possible analysis. If not already used, these samples were stored in a freezer for a maximum of three months after delivery of the draft report, pending on the decision of the sponsor for additional analysis.

Details on sediment and application:

The batch of VALSART AN/DS 21 tested was a white powder which was treated as 100% pure. The range finding test was performed with unlabelled VALSARTAN/DS 21. The final test was performed with a mixture of 14C-labelled and unlabelled VALSARTAN/DS 21.The ratio of 14C-labelled and unlabelled test substance was chosen in a way that the amount of radioactivity in the samples is sufficient to allow adequate quantification of the radioactivity.
Since the test substance was not sufficiently soluble in Milli-RO water, ethanol (Merck,Darmstadt, Germany) was used as a solvent. Preparation of the test concentration started with a stock solution of 60 mg/ml ethanol. The obtained solution was clear and colourless. If applicable (in the range finding test), lower stocks were prepared by subsequent dilutions of the highest stock in ethanol. For each vessel the stock solution was mixed with sand in a proportion:
1 ml/ 10 g sand/ test vessel. Solvent control vessels were prepared comparably.
In the final test the total amount of wet sediment was on average 83 g per test vessel, consisting of 10 g treated sand and 73 g OECD medium. This corresponds with approximately 60 g dry sediment per vessel.

Test organisms (species):

Chironomus riparius

Details on test organisms:

The entire life cycle lasts approximately 4 weeks at a temperature of ca. 20°C. The fertilized egg masses hatch 2 to 3 days after having been laid in water.
Thereafter the larvae undergo four stages. After the fourth stage, the larvae change into pupae.
Immediately after the pupa moves to the surface of the water the midge emerges from the pupal skin. The emergence of male midges starts earlier than that of
the females. Females are a little larger and darker than males.
Males have plumose antennae. Mating occurs in swarming. After 1-2 days the female midge lays an egg mass, 2 to 3 days later a second,
but smaller, egg mass can be produced. Midges have a life span of four to eight days.

Study type:

laboratory study

Test type:

static

Water media type:

freshwater

Type of sediment:

natural sediment

Limit test:

yes

Duration:

28 d

Exposure phase:

larvae from first generation (P)

Hardness:

196 and 232 mg

Test temperature:

18.9-19.8

pH:

8.0-8.6

Dissolved oxygen:

5.4-9.4

Details on test conditions:

Water hardness was between 196 and 232 mg CaC03/I throughout the test and the ammonium
concentration varied from O at the beginning to 10 mg/I at the end of the test in the controls and
the test concentration. The corresponding free ammonia concentrations (4% at pH 8) are
acceptable for Chironomus riparius.
All measured parameters were within the ranges specified in the protocol.

Reference substance (positive control):

no

Key result

Duration:

28 d

Dose descriptor:

EC50

Effect conc.:

> 400 mg/kg sediment dw

Nominal / measured:

meas. (initial)

Conc. based on:

test mat.

Basis for effect:

emergence rate

Key result

Duration:

28 d

Dose descriptor:

EC50

Effect conc.:

> 400 mg/kg sediment dw

Nominal / measured:

meas. (initial)

Conc. based on:

test mat.

Basis for effect:

development rate

Key result

Duration:

28 d

Dose descriptor:

NOEC

Effect conc.:

400 mg/kg sediment dw

Nominal / measured:

meas. (initial)

Conc. based on:

test mat.

Basis for effect:

emergence rate

Key result

Duration:

28 d

Dose descriptor:

NOEC

Effect conc.:

400 mg/kg sediment dw

Nominal / measured:

meas. (initial)

Conc. based on:

test mat.

Basis for effect:

development rate

Validity criteria fulfilled:

yes

Conclusions:

Under the conditions of the present study with Chironomus riparius, no reduction of emergence or development rate was observed at the concentration of 400 mg/kg d.w. (NOEC).
The LOEC and the 28-day EC50 for emergence and development rate were higher than 400 mg/kg d.w.

Description of key information

Under the conditions of the present study with Chironomus riparius, no reduction of emergence or development rate was observed at the concentration of 400 mg/kg d.w. (NOEC).

The LOEC and the 28-day EC50 for emergence and development rate were higher than 400 mg/kg d.w.

Key value for chemical safety assessment

EC50 or LC50 for freshwater sediment:

400 mg/kg sediment dw

EC10, LC10 or NOEC for freshwater sediment:

400 mg/kg sediment dw