[1,1'-Biphenyl]-2-carboxylic acid, 4'-[(1,4'-dimethyl-2'-propyl[2,6'-bi-1H-benzimidazol]-1'-yl)methyl]-, hydrochloride (1:1)

Toxicity to aquatic algae and cyanobacteria

Administrative data

Endpoint:

toxicity to aquatic algae and cyanobacteria

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

15- 18 December 2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted in GLP compliance and in accordance with an internationally established guideline (OECD, see below). BIBR 277 CL is the hydrochloride of BIBR 277 SE (Telmisartan, free acid).

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 201 (Alga, Growth Inhibition Test)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method C.3 (Algal Inhibition test)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

144701-48-4

Cas Number:

144701-48-4

IUPAC Name:

144701-48-4

Test material form:

solid: crystalline

Details on test material:

- Name of test material (as cited in study report): Telmisartan (4'-[(1,4'-dimethyl-2'-propyl[2,6'-bi-1H-benzimidazol]-1'-yl)methyl]- [1,1'-biphenyl]-2-carboxylic acid;
- Molecular weight (if other than submission substance): 541.63 g/mol
- Substance type: white to yellowish crystalline powder
- Physical state: solid
- Analytical purity: 99.9 %
- Purity test date: 14 May, 2003
- Lot/batch No.:1007523
- Expiration date of the lot/batch: September 2005
- Stability under test conditions:
- Storage condition of test material: room temperature, dark and dry
- Other:
test item is not well soluble in test water

Sampling and analysis

Analytical monitoring:

yes

Details on sampling:

HPLC-UV measurements were carried out at the start and the end of the test.
Determined measured concentrations were 83% - 111% of the nominal test concentration.

Test solutions

Vehicle:

yes

Details on test solutions:

PREPARATION AND APPLICATION OF TEST SOLUTION (especially for difficult test substances)
A supersaturated stock suspension of nominal 100 mg/test item/L was prepared by suspending 50.2 mg test item in to 500 mL test water and stired for 24 hours. The undissolved test tiem was separated by filtration (cellulose nitrate filter , pore size 0.45 µm). the filtrate was used as stock solution

Test organisms

Test organisms (species):

Desmodesmus subspicatus (previous name: Scenedesmus subspicatus)

Details on test organisms:

TEST ORGANISM
- Common name: Desmodesmusw subspicatus CHODAT
- Strain: No. 86.81 SAG
- Source (laboratory, culture collection): Pflanzenphysiologisches Institut der Unversität Göttingen, Germany
- Age of inoculum (at test initiation): 3 days
- Method of cultivation: cultivated under standardized conditions according to test guidelines ; inoculation of a biomass of 10000 algal cells per mL test medium, taken from a exponentially growing pre-culture, which was set up threee days before test start

ACCLIMATION
- Acclimation period:
- Culturing media and conditions (same as test or not):
- Any deformed or abnormal cells observed:

Study design

Test type:

static

Water media type:

saltwater

Limit test:

yes

Total exposure duration:

96 h

Post exposure observation period:

none

Test conditions

Hardness:

0.24 mmol/L (024 mg/L) as CaCO3

Test temperature:

23 °C

pH:

8.0 - 10.3

Details on test conditions:

TEST SYSTEM
- Test vessel: 50mL Erlenmeyer flasks containing 50mL test solution
- Type : closed with glass dishes
- No. of vessels per concentration (replicates): 3
- No. of vessels per control (replicates): 6
- Initial cells density: 1 * 10 exp.5 algal cells per mL test medium
- Control end cells density: 189.7 * 10exp.4 cells /mL after 72 hrs

GROWTH MEDIUM
- Standard medium used: yes

OTHER TEST CONDITIONS
- Photoperiod: continuous illumination
- Light intensity and quality: 8600 -8740 lux


EFFECT PARAMETERS MEASURED (with observation intervals if applicable) :
- Determination of cell concentrations: spectrophotometer, determined at 24, 48, 72 and 96 hrs.

TEST CONCENTRATIONS
- Range finding study: was performed
- Test concentrations: 9.18; 4.71, 2.70, 1.03, 0.49, 0.25 and 0.12 mg test item/L.

Reference substance (positive control):

yes

Remarks:

potassium dichromate (historic control)

Results and discussion

Effect concentrations

Effect concentrations 1

Duration:

96 h

Dose descriptor:

LOEC

Effect conc.:

0.492 mg/L

Nominal / measured:

meas. (initial)

Conc. based on:

test mat.

Basis for effect:

biomass

Effect concentrations 2

Duration:

96 h

Dose descriptor:

NOEC

Effect conc.:

0.249 mg/L

Nominal / measured:

meas. (initial)

Conc. based on:

test mat.

Basis for effect:

biomass

Effect concentrations 3

Duration:

96 h

Dose descriptor:

EC10

Effect conc.:

0.463 mg/L

Nominal / measured:

meas. (initial)

Conc. based on:

test mat.

Basis for effect:

biomass

Effect concentrations 4

Duration:

96 h

Dose descriptor:

EC50

Effect conc.:

1.426 mg/L

Nominal / measured:

meas. (initial)

Conc. based on:

test mat.

Basis for effect:

biomass

Effect concentrations 5

Duration:

72 h

Dose descriptor:

LOEC

Effect conc.:

0.492 mg/L

Nominal / measured:

meas. (initial)

Conc. based on:

test mat.

Basis for effect:

biomass

Effect concentrations 6

Duration:

72 h

Dose descriptor:

NOEC

Effect conc.:

0.249 mg/L

Nominal / measured:

meas. (initial)

Conc. based on:

test mat.

Basis for effect:

biomass

Effect concentrations 7

Duration:

72 h

Dose descriptor:

EC10

Effect conc.:

0.409 mg/L

Nominal / measured:

meas. (initial)

Conc. based on:

test mat.

Basis for effect:

biomass

Effect concentrations 8

Duration:

72 h

Dose descriptor:

EC50

Effect conc.:

1.754 mg/L

Nominal / measured:

meas. (initial)

Conc. based on:

test mat.

Basis for effect:

biomass

Details on results:

- Exponential growth in the control (for algal test): yes/no
- Observation of abnormalities (for algal test): none

Results with reference substance (positive control):

no EC50 data given in study report.

Applicant's summary and conclusion

Validity criteria fulfilled:

yes

Conclusions:

The test item had a statistically significant inhibitory effect on the growth of Desmodesmus subspicatus (reduction of biomass) adter the exposure period of 96h, first at the concentration of .049 mg/L. Thus, the test concentration was determined as the 96h- LOEC.
The 96h NOEC was determined at the concentration of 0.25 mg/L, since up to and including this test concentration, the mean biomass of the algae was statistically not significantly lower than in the control. The 72h LOEC and NOEC were also calculated.