D-Glucose, 5,6-O-(1-methylethylidene)-1-C-(4-methyl-1-piperazinyl)-5-C-[(phenylmethoxy)methyl]-2,3,4-tris-O-(phenylmethyl)-

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 01 to 21 May 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study run to a method comparable with current guidelines and to GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

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

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

(2R,3S,4S)-2,3,4-tris(benzyloxy)-4-[(4R)-4-[(benzyloxy)methyl]-2,2-dimethyl-1,3-dioxolan-4-yl]-1-(4-methylpiperazin-1-yl)butan-1-one

EC Number:

809-911-5

Cas Number:

1431329-07-5

Molecular formula:

C43H52N2O7

IUPAC Name:

(2R,3S,4S)-2,3,4-tris(benzyloxy)-4-[(4R)-4-[(benzyloxy)methyl]-2,2-dimethyl-1,3-dioxolan-4-yl]-1-(4-methylpiperazin-1-yl)butan-1-one

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Analytical purity: 98%
- Lot/batch No.: CPo84700201-022901

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: Approx. 10 or 11 weeks old
- Weight at study initiation: Body weight variation did not exceed +/- 20% of the sex mean
- Fasting period before study: Overnight prior to dosing
- Housing: Labeled Makrolon cages containing sterilized sawdust as bedding material and paper as cage-enrichment
- Diet (e.g. ad libitum): Pelleted rodent diet
- Water (e.g. ad libitum): Tap water
- Acclimation period: At least 5 days before start of treatment under laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 24
- Humidity (%): 40 to 70
- Air changes (per hr): at least 10 air changes/hour
- Photoperiod (hrs dark / hrs light): 12-hour light/12-hour dark cycle

IN-LIFE DATES: From 01 to 21 May 2014

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

propylene glycol

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL
- Justification for choice of vehicle: The vehicle was selected based on trial formulations formed at WIL Research Europe and on test substance data supplied by the sponsor

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg (10 mL/kg) body weight

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The toxicity of the test substance was assessed by stepwise treatment of groups of 3 females.
The first group was treated at a dose level of 2000 mg/kg. The absence or presence of mortality of animals dosed at one step determined the next step, based on the test procedure defined in the guidelines.

Doses:

2000 mg/kg

No. of animals per sex per dose:

3 females at a dose level of 2000 mg/kg

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Viability: Twice daily.
Body weights: Days 1 (pre-administration), 8 and 15.
Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15.
- Necropsy of survivors performed: yes, at the end of observation period, all animals were sacrificed by oxygen/carbon dioxide procedure and subjected to necropsy.
- Other examinations performed: no.

Statistics:

No statistical analysis was performed.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: Hunched posture and pioerection were noted for all animals between Day 1 and 12. Lean appearance was noted for one animal between Days 7 and 9.

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Other findings:

No information provided.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The oral LD50 value of the test substance in Wistar rats was established to exceed 2000 mg/kg bodyweight.