Registration Dossier

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

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material: Olmesartan Medoxomil

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals 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:
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.