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

Toxicity to soil microorganisms

Administrative data

Endpoint:

toxicity to soil microorganisms

Type of information:

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

Adequacy of study:

supporting 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:

1993

Report date:

1993

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: FDA Guideline 4.02

Principles of method if other than guideline:

The organims were grown on the appropriate medias. The test inoculum was preapred by harvesting five isolaed colonies of each organism and inoculating into Mueller Hinton Broth. The cultures were allowed to incubate overnight at the appropriate temperatures. The overnight broth culture was then diluted to ~10^6 organisms/mL using a barium sulfate standard. This was the test suspension to be inoculated on the chemical-agar mix plate.

The Losartan-agar plates were made up in advance in order to allow them to solidify and dry. The plates were prepared using Mueller-Hinton agar. The agars were autoclaved in pour tubes and then placed in a waterbath to cool to ~45 degC. Then 2 mL of each concentration of test solution was added to 18 mL agar pour tubes at 45 degC. These tubes were inverted two times to mix the chemical-agar solution, then quickly poured in 100 mm plastic petri dishes. The plates were allowed to dry and then spot inoculated with the microorganism test suspension. The inoculations were made with a loop calibrated to deliver 0.001-0.002mL. Each plate was inoculated at three spots. The plates were allowed to stand for a few minutes and tehn transferred to the appropriate incubators for 24-72 hours. The Losartan-agar plates as well as the control plates were duplicated and a blank control agar plate was placed in each incubator to check the sterility of the medium.

Doses-screening test: 5.0 to 100 mg/L. Second test series: 1000 mg/L

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Losartan

IUPAC Name:

Losartan

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

Losartan (MK-0954)
Lot: L158086-005H035
White powder
Purity 99.8%

Test organisms

Test organisms (inoculum):

other: Mueller Hinton Broth

Study design

Total exposure duration:

72 h

Test conditions

Test temperature:

45 deg C

Details on test conditions:

TEST SYSTEM

- Test container (type, material, size): Agar plate
- Amount of soil:none
- No. of replicates per concentration: 2
- No. of replicates per control:2
- No. of replicates per vehicle control:1


EFFECT PARAMETERS MEASURED (with observation intervals if applicable) : inhibition of growth

VEHICLE CONTROL PERFORMED: yes

RANGE-FINDING STUDY
- Test concentrations:
- Results used to determine the conditions for the definitive study:

Nominal and measured concentrations:

Nominal 5.0, 12.5, 25.0, 50.0, 100 and 1,000 mg/L

Results and discussion

Effect concentrations

Duration:

72 h

Dose descriptor:

NOEC

Effect conc.:

> 1 000 other: mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

other: growth (observed)

Remarks on result:

other: for all tested species, no effect observed

Applicant's summary and conclusion

Validity criteria fulfilled:

yes

Conclusions:

Losartan potassium, and therefore losartan free acid, by read-across, is not toxic to microbial organism species utilised in this test.