4-[4-[4-[(3R, 5R)[5-(2,4-difluorophenyl) tetrahydro-5-(1H-1,2,4-triazol-1-yl-methyl)-furan-3-yl]methyloxy]phenyl]-1-piperazinyl]phenyl-2-[(1S,2S)(1-ethyl-2-phenylmethoxypropyl)]-2,4-dihydro-3Htriazol-3-one

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

November 23rd 1998 - December 9th 1998.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: They follow OECD methods and were conducted in accordance with GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

1999

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

1-[(2S,3S)-2-(benzyloxy)pentan-3-yl]-4-{4-[4-(4-{[(3R,5R)-5-(2,4-difluorophenyl)-5-[(1H-1,2,4-triazol-1-yl)methyl]oxolan-3-yl]methoxy}phenyl)piperazin-1-yl]phenyl}-4,5-dihydro-1H-1,2,4-triazol-5-one

EC Number:

938-153-9

Molecular formula:

C44H48O4N8F2

IUPAC Name:

1-[(2S,3S)-2-(benzyloxy)pentan-3-yl]-4-{4-[4-(4-{[(3R,5R)-5-(2,4-difluorophenyl)-5-[(1H-1,2,4-triazol-1-yl)methyl]oxolan-3-yl]methoxy}phenyl)piperazin-1-yl]phenyl}-4,5-dihydro-1H-1,2,4-triazol-5-one

Details on test material:

White powder

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River UK
- Age at study initiation: 8-12 weeks
- Weight at study initiation:male: 220-225 grams; females 204-213 g
- Fasting period before study: yes
- Housing: solid floor polypropylene cages with woodflakes
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C):19-21 C
- Humidity (%): 44-66%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: November 23, 1998 To:December 9, 1998

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

2000 mg/kg

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days (or other?): observed for dealth or overt signs of toxicity at 1/2 ,1 ,2 and 4 hours after dosing and then once a day for 14 days
- Frequency of observations and weighing: individual bodyweights were recorded prioir to dosing and then at day 7 and day 14 after treatment
- Necropsy of survivors performed: yes- gross pahtological changes - macroscopic observation, no tissues were retained.
- Number of animals dying were recorded

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 500 mg/kg bw

Based on:

test mat.

Mortality:

None noted

Clinical signs:

other: none noted

Gross pathology:

NOne noted

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral median lethal dose (LD50) of the test material, Sch.56592-U, in the Sprague-Dawley CD strain rat was estimated to be greater than 2500 mg/kg bodyweight.

Executive summary:

The acute oral median lethal dose (LD50) of the test material, Sch.56592-U, in the Sprague-Dawley CD strain rat was estimated to be greater than 2500 mg/kg bodyweight.