1H-Imidazole-5-methanol, 2-butyl-4-chloro-1-[[2'-(2H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]-

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Although the study was conducted according to GLP and well documented methods, " Practical guide 10: How to avoid unnecessary testing on animals", Section 3.3.2 states it is important that the reliability indicator (Klimisch score) reflects the assumptions of similarity. Thus, a score of 1 (reliable without restrictions) should normally not be used for results derived from read-across.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1993

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

other: US FDA Guideline 4.01

Principles of method if other than guideline:

Doses (measured): control, 96.4, 143, 245, 381, 659, and 1130 mg/L

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Losartan (MK-0954)

IUPAC Name:

Losartan (MK-0954)

Constituent 2

Reference substance name:

Losartan potassium

IUPAC Name:

Losartan potassium

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Specific details on test material used for the study:

Details on properties of test surrogate or analogue material (migrated information):
- Name of test material (as cited in study report): Losartan (MK-0954)

- Substance type: white powder
- Physical state: solid
- Analytical purity: 99.8%

- Lot/batch No.:L-158086-005H035

- Storage condition of test material: freezer

Test organisms

Test organisms (species):

Raphidocelis subcapitata (previous names: Pseudokirchneriella subcapitata, Selenastrum capricornutum)

Details on test organisms:

TEST ORGANISM
- Common name:green alga
- Strain:Printz (UTEX 1648)
- Source (laboratory, culture collection): University of Texas at Austin
- Age of inoculum (at test initiation):7
- Method of cultivation: freshwaer algal medium (ASTM, 1990) under continuous illumination yielding approximately 50 microEinsteins per square meter per second. Cultures were maintained ta 24 +/-2 deg C.

Study design

Test type:

static

Water media type:

freshwater

Total exposure duration:

10 d

Test conditions

Details on test conditions:

TEST SYSTEM
- Test vessel:250 ml Erlenmeyer flask
- Type (delete if not applicable): capped with gas exchange caps

- Initial cells density: 3000 cells/mL

- No. of vessels per concentration (replicates):4



TEST MEDIUM / WATER PARAMETERS
- Source/preparation of dilution water:deionized water

- Particulate matter: filter sterilized to 0.45 um prior to use.


OTHER TEST CONDITIONS

- Adjustment of pH: yes, to 7.5

EFFECT PARAMETERS MEASURED (with observation intervals if applicable) :
- Determination of cell concentrations: Cell counts using hemacytometer counting chamber with compound microscope every 48 hours


TEST CONCENTRATIONS
- Spacing factor for test concentrations:1.66
- Range finding study: yes.
- Test concentrations: 78, 130, 216, 360, 600, and 1000 mg MK-0954/L
- Results used to determine the conditions for the definitive study:0% inhibition at 100mg/L, 100% inhibition at 1000mg/L

Results and discussion

Effect concentrations

Effect concentrations 1

Duration:

10 d

Dose descriptor:

LOEC

Effect conc.:

245 mg/L

Nominal / measured:

meas. (geom. mean)

Conc. based on:

test mat.

Basis for effect:

other: maximum standing crop

Effect concentrations 2

Duration:

10 d

Dose descriptor:

LOEC

Effect conc.:

381 mg/L

Nominal / measured:

meas. (geom. mean)

Conc. based on:

test mat.

Basis for effect:

growth rate

Effect concentrations 3

Duration:

10 d

Dose descriptor:

NOEC

Effect conc.:

143 mg/L

Nominal / measured:

meas. (geom. mean)

Conc. based on:

test mat.

Basis for effect:

other: maxium standing crop

Effect concentrations 4

Duration:

10 d

Dose descriptor:

NOEC

Effect conc.:

245 mg/L

Nominal / measured:

meas. (geom. mean)

Conc. based on:

test mat.

Basis for effect:

growth rate

Details on results:

The measured test temperature during the 10-day exposure ranged from 22.0 to 24.6 deg C. Initial pH of the test solutions and controls was 7.5 to 7.6. After 10 days, the pH of the controls was 7.7; pH ranged from 7.8 to 8.0 in all Losartan treatments.

Applicant's summary and conclusion

Conclusions:

The 10 day LOEC (biomass) was determined to be 245 mg/L and NOEC (biomass) was determined to be 143 mg/L.

The 10 day LOEC (growth rate) was determined to be 381 mg/L and NOEC (growth rate) was determined to be 245 mg/L.

Executive summary:

Observations of cell morphology detected no changes in losartan exposed cells as compared to cells in controls. After 10 days of exposure, reduction in cell growth ranged from 12 percent at 96.4 to 99 percent at 1130 mg/L. Maximum standing crop occurred by day 8. The NOEC and MIC values based on maximum standing crop were 143 and 245 mg/L. The largest specific growth rate (u-max) occurred between days 0 and 2. The NOEC and MIC values based on u-max were 245 and 381 mg/L.