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

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

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:

1990

Report date:

1990

Materials and methods

Principles of method if other than guideline:

Four week old male mice (Crl:CD1[IGR]BR strain) were used in the study. Mice were not fasted before oral administration of the substance. Five mice were used at each dose level. The results of this study are presented below and are based on a 48-hour observation period. Doses: 808, 1050, 1366, 1775, 2308, 3000 mg/kg.

GLP compliance:

not specified

Remarks:

no GLP statement but perfomred in licensed institute

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

losartan potassium

IUPAC Name:

losartan potassium

Constituent 2

Reference substance name:

L-158, 086-005H

IUPAC Name:

L-158, 086-005H

Details on test material:

L-158,086-005H

Test animals

Species:

mouse

Strain:

other: Crl

Sex:

male

Administration / exposure

Route of administration:

oral: unspecified

Vehicle:

water

Doses:

808, 1050, 1366, 1775, 2308, 3000 mg/kg

No. of animals per sex per dose:

5

Control animals:

not specified

Results and discussion

Effect levels

Sex:

male

Dose descriptor:

LD50

Effect level:

2 248 mg/kg bw

Based on:

test mat.

95% CL:

1 977 - 2 557

Applicant's summary and conclusion

Conclusions:

The acute oral 48 hr LD50 is 2248 mg/kg.

Executive summary:

An acute oral toxicity study was conducted in four week old male mice with L-158,086-005H. Five mice were used at each dose level and were observed for a 48 hour observation period.  Signs of toxicity following the oral administration of the test compound were ataxia, decreased activity, bradypnea and ptosis. The signs were seen at the 3000 mg/kg dose level in ~15 minutes and at the 2308 mg/kg dose level within 90 minutes. No signs were seen at lower doses. Deaths occurred in about 3 to 4.5 hours and were preceded by a loss of righting reflex. Surviving mice appeared normal in 3 to 4 hours. On the second day ataxia and bradypnea were seen at the 1775 mg/kg dose only and by the end of the second day all survivors appeared normal.