1H-Imidazole-5-carboxylic acid, 4-(1-hydroxy-1-methylethyl)-2-propyl-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

Study period:

January 14 to January 28, 1992

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Meets generally accepted scientific standards, well documented and acceptable for assessment

Data source

Reference

Reference Type:

review article or handbook

Title:

Unnamed

Year:

1992

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

No guideline available

GLP compliance:

yes

Test type:

other: Not available

Test material

Test material information

Constituent 1

Reference substance name:

144689-63-4

Cas Number:

144689-63-4

IUPAC Name:

144689-63-4

Constituent 2

Reference substance name:

Olmesartan Medoxomil

IUPAC Name:

Olmesartan Medoxomil

Details on test material:

- Name of test material: Olmesartan Medoxomil

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age: 7 week-old
- Weight: males (116-129 g); females (98-107 g)
- Animals were fasted for 24h and fed soon after the test substance administration.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

0.5 %

Doses:

500, 1000 and 2000 mg/kg

No. of animals per sex per dose:

three groups of 5 males and 5 females which received 500, 1000 and 2000 mg/kg

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: at 1, 10 and 30 minutes, at 1, 3 and 5h after administration on the first day and more than once a day for 14 days thereafter. Body weights were measured before administration and on days 3, 7, 10 and 14 after administration.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No treatment-related effects.

Clinical signs:

other: No treatment-related effects.

Gross pathology:

No gross abnormalities

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LD50 value for rats of either sex is greater than 2000 mg/kg. Knowing that Olmesartan Medoxomil is rapidly and completely bioactivated by ester hydrolysis to Olmesartan during absorption from the gastrointestinal tract (see the attachement enzymatic-hydrolysis of Olmesartan medoxomil), the actual acute LD50 of Olmesartan acid is most likely above 2000 mg/kg b.w., the limit for classification.