6-Heptenoic acid, 7-[4-(4-fluorophenyl)-6-(1-methylethyl)-2-[methyl(methylsulfonyl)amino]-5-pyrimidinyl]-3,5-dihydroxy-, methyl ester, (3R,5S,6E)-

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2010

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

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

Test material information

Constituent 1

Reference substance name:

Methyl(3R,5S,6E)-7-{4-(4-fluorophenyl)-6-(1-methylethyl)-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl}-3,5-dihydroxyhept-6-enoate

Cas Number:

147118-40-9

Molecular formula:

C23H30FN3O6S

IUPAC Name:

Methyl(3R,5S,6E)-7-{4-(4-fluorophenyl)-6-(1-methylethyl)-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl}-3,5-dihydroxyhept-6-enoate

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS- Source: TOXI-COOP ZRT.- Age at study initiation: 10-11 weeks old- Weight at study initiation: 219 - 243 g- Fasting period before study: 24 hours- Housing: 3 animals/cage/Type II polypropylene/polycarbonate cage/laboratory bedding- Diet (e.g. ad libitum): ad libitum (exept after test item administration for 3 hours)- Water (e.g. ad libitum): tap water ad libitum- Acclimation period: 21-29 daysENVIRONMENTAL CONDITIONS- Temperature (°C): 22 +/-3 ºC- Humidity (%): 30-70 % (relative)- Air changes (per hr): 8-12 air changes/ hour by central air condition system.- Photoperiod (hrs dark / hrs light): Artficial light, from 6.a.m. to 6 p.m.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 1 % aquesous MC (methylcellulose)

Details on oral exposure:

VEHICLE- Concentration in vehicle: - Amount of vehicle (if gavage): MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg bw

Doses:

300 mg/kg bw and 2000 mg/kg bw stepwise procedure

No. of animals per sex per dose:

3 female/dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days - Frequency of observations and weighing: observation: 30 minutes, 1 h, 2 h, 3h, 4 h after the treatment, and thereafter once a day. weighing: before treatment (0 day), on the 7th day, on the 15th day with a precision of 1 g.- Necropsy of survivors performed: yes/no yes (macroscopic)

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

1st step: 2000 mg/kd bw no mortality in 5 days in 3 female rats2nd step: 2000 mg/kg bw dlayed deaths in the 4th, 6th, 8th days in 3 female rats3rd step 300 mg/kg bw no mortality4th step 300 mg/kg bw no mortality

Clinical signs:

other: In 1st stepCNS and emotion symptoms (decreased activity and closed eyes), decreased righting reflex, decreased ear and plantary reflex, decreased muscular tension (body-, grip- and limb tone) and disturbances of the autonomic functions (piloerection, cyan

Gross pathology:

Six animals were sacrified unscheduled and six animals were sacrified scheduled during the study. All organs of both died and the survivor animals proved to be free of treatment related gross pathological changes.

Applicant's summary and conclusion

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test item is ranked into classed of GHS described in the OECD Guideline No.: 423 as GHS acute toxicity cathegory 4.