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

Long-term toxicity to aquatic invertebrates

Link to relevant study record(s)

Reference

Endpoint:

long-term toxicity to aquatic invertebrates

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Apr - Sep 2006

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 211 (Daphnia magna Reproduction Test)

GLP compliance:

yes

Analytical monitoring:

yes

Details on sampling:

First test
Sampling: Frequency
At the beginning (fresh) and at the end (spent) of three Intervals of 48 hours (nominal days o and 2, 7 and 9, 12 and 14) and one interval of 72 hours (nominal days 2 and 5). The 'spent' solutions were pooled before sampling.
2 ml from the approximate centre of the tost vessel.
Second test
Sampling: Frequency
At the beginning (fresh) and at the end (spent) of four intervals of 48 hours (nominal days O and 2, 7 and 9, 12 and 14, 19 and 21) and one interval of 72 hours
(nominal days 2 and 5). The 'spent' solutions were pooled before sampling.
2 ml from the approximate centre of the test vessel.

Vehicle:

yes

Remarks:

M7, as prescribed by Dr: Elendt-Schneider (Elendt, .B.·P ., 1990: Selenium deficiency in Crustacea. An ultrastructural approach to antennal damage in Daphnia magna Straus. Protoplasma 154, 25-33)

Details on test solutions:

The standard test procedures required generation of test solutions, which should contain completely dissolved test substance concentrations or stable and homogeneous mixtures or dispersions. The testing of concentrations that disturb the test system should be prevented (e.g. precipitate or a film of the test substance on the water surface).
The batch of VAA489 VAL tested was a white powder with a purity of 99 % and completely soluble at the concentrations tested. Preparation started by adding weighed amounts of test substance to the test medium in 2-litre measuring flasks followed by treatment with ultra-sonic waves for 10 to 20 minutes. Then the flasks were filled until the mark and treated with ultrasonic waves for another 10 to 20 minutes, until all test substance had completely dissolved.
Test solutions prepared at 10 mg/I were used to prepare lower concentrations by subsequent dilution. All final test solutions were clear and colourless.

Test concenll'ations
First test
VAA4S9VAL 10 mg/I
Control Test medium without test substance or other additives (0 mg/I).
Second test
VM4B9VAL 1.0, 1.8, 3.2 and 5.6 mg/I
Controls Test medium without test substance or other additives (0 mg/I).

Test organisms (species):

Daphnia magna

Details on test organisms:

Daphnia magna (Crustacea, Cladocera) (Straus, 1820), at least third generation, obtained by acyclical parthenogenesis under specified breeding conditions
Daphnids originated from a healthy stock. 2nd to 5th brood, showing no signs of stress such as mortality >20%, presence of males, ephippia or discoloured
animals and there was no delay In the production of the first brood.
For the test seiection of young daphnia with an age of < 24 hours, from parental daphnids of more than two weeks old.

Test type:

semi-static

Water media type:

freshwater

Limit test:

no

Total exposure duration:

21 d

Remarks on exposure duration:

Flrst test: 19d Second test: 21 d

Hardness:

between 13 and 16 DH

Test temperature:

19.6 and 20.9°C In the first test and between
19.6 and 20.3°C in the second test

pH:

Flrst test: 7.7 to 8.1
Second test: 7.6 and 8.6

Dissolved oxygen:

> 7 mg/I

Nominal and measured concentrations:

The concentrations of VAA489 VAL measured in the freshly prepared solutions were in agreement with nominal and thus confirmed the repeatability of the preparation of the test concentrations. Measured concentrations remained stable during all renewal periods, both 48 and 72-hour. The concentrations measured in samples taken from 10 mg/I ranged from 94 to 104 % of nominal. The concentraiions measured in the samples taken during the second test ranged betwee 86 and 116 % of nominal. Therefore all results could be based on nominal concentrations.

Reference substance (positive control):

no

Key result

Duration:

21 d

Dose descriptor:

NOEC

Effect conc.:

5.6 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality

Key result

Duration:

21 d

Dose descriptor:

NOEC

Effect conc.:

5.6 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

reproduction

Key result

Duration:

21 d

Dose descriptor:

LOEC

Effect conc.:

10 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality

Key result

Duration:

21 d

Dose descriptor:

LOEC

Effect conc.:

10 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

reproduction

Validity criteria fulfilled:

yes

Conclusions:

Under the condilions of the present study V M489 VAL did not affect survival, reproduction or growth of Daphnia magna sfgnificantly at concantrations up to and including 5.6 mg/I after 21days of exposure (NOEC). The LOEC of VAA489 VAL for survival and reproduction of Daphnia magna was 10 mg/I, the regulatory limit concentration.

Description of key information

Under the condilions of the present study V M489 VAL did not affect survival, reproduction or growth of Daphnia magna sfgnificantly at concantrations up to and including 5.6 mg/I after 21days of exposure (NOEC). The LOEC of VAA489 VAL for survival and reproduction of Daphnia magna was 10 mg/I, the regulatory limit concentration.

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Effect concentration:

5.6 mg/L