3-ethyl 5-methyl 4-(2-chlorophenyl)-1,4-dihydro-2-[2-(1,3-dihydro-1,3-dioxo-(2H)isoindol-2-yl)-ethoxymethyl]-6-methyl-3,5-pyridinedicarboxylate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Reference

Name:

Unnamed

Type:

Constituent

Details on test material:

- Name of test material (as cited in study report): Phthaloyl Amlodipine
- Physical state: pale yellow crystalline powder
- Lot/batch No.: 130306
- Expiration date of the lot/batch: May 2007
- Purity test date: 09 05 2006
- Storage condition of test material: in brown powder-flask, at ambient temperature, dry

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: CHARLES RIVER (EUROPE) LABORATORIES INC.
TOXICOOP LTD.
- Age at study initiation: 8-9 weeks old, healthy adult
- Weight at study initiation: 177 - 213 g
- Fasting period before study: overnight
- Housing: 3 animas/cage type II polypropylene/polycarbonate; laboratory bedding
- Diet (e.g. ad libitum): ad libitum ssniff SM R/M-Z+H
- Water (e.g. ad libitum): tap water from municipal supply from 500ml-bottle ad libitum
- Acclimation period: 6 days (at least)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 ºC
- Humidity (%): 30-70 %
- Air changes (per hr): 8-12
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30 mg/l and 200 mg/l
- Amount of vehicle (if gavage): 10 ml/kg bw)

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg bw

Doses:

300 mg/kg bw and 2000 mg/kg bw

No. of animals per sex per dose:

4 groups of female rats, 3 rats/group , 2 dose / group

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observation: 30 min., 1, 2, 3, 4, 6 hours after the treatment, and thereafter once a day
weighing: shortly after treatment, on the 7th day, on the 14th day (accuracy to the next 1 g)
- Necropsy of survivors performed: yes/no yes

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

approximate LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

no mortality

Clinical signs:

no signs

Body weight:

in the normal range

Gross pathology:

group 1: (300 mg/kg bw): 1 case of hydrometra
2: (300 mg/kg bw): 1 case of hydrometra
3: (2000 mg/kg bw): 1 case of pinprick-sized haemorrhages and 1 case of hydrometra
4: (2000 mg/kg bw): macroscopic alteration could not be found

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU