Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From January 28, 2009 to October 5, 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report date:
2009

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: JMAFF No 12 Nosan No 8147
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
[(3S,4R,4aR,6S,6aS,12R,12aS,12bS)-3-(cyclopropanecarbonyloxy)-6,12-dihydroxy-4,6a,12btrimethyl-11-oxo-9-(pyridin-3-yl)-1,2,3,4,4a,5,6,6a,12a,12b-decahydro-11H,12Hbenzo[f]pyrano[4,3-b]chromen-4-yl]methylcyclopropanecarboxylate
Cas Number:
915972-17-7
Molecular formula:
C33H39NO9
IUPAC Name:
[(3S,4R,4aR,6S,6aS,12R,12aS,12bS)-3-(cyclopropanecarbonyloxy)-6,12-dihydroxy-4,6a,12btrimethyl-11-oxo-9-(pyridin-3-yl)-1,2,3,4,4a,5,6,6a,12a,12b-decahydro-11H,12Hbenzo[f]pyrano[4,3-b]chromen-4-yl]methylcyclopropanecarboxylate
Test material form:
solid
Details on test material:
- Analytical purity: >94 %
Specific details on test material used for the study:
Lot number: 080722
Expiry: 29 July 2010

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Fuji production facility (Shizuoka, Japan)
- Females nulliparous and non-pregnant: Yes
- Age at study initiation: 8 weeks at dosing
- Weight at study initiation: 130 – 170 g
- Fasting period before study: 8 weeks at dosing
- Housing: Housed in groups of up to four rats in metal cages with wire mesh floors
- Diet: A certified pellet diet MF (Lot. No. 081015, Oriental Yeast Co., Ltd., Tokyo, Japan), ad libitum
- Water: Local tap water, ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 2°C
- Humidity: 50 ± 20%
- Air changes (per hr): 10 times or more
- Photoperiod: 12 hours of artificial light (07.00 – 19.00 GMT) in each 24-hour period

IN-LIFE DATES: From 10 Feb 2009 to 13 Mar 2009

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
methylcellulose
Remarks:
administered in water with 0.5 w/v % methylcellulose solution
Details on oral exposure:
VEHICLE
- Concentration in vehicle: Administered in water with 0.5 w/v % methylcellulose solution
- Lot/batch no.: 080722
- Purity: 95.74%

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

DOSAGE PREPARATION
The test substance formulations were prepared on the day of dosing. The appropriate dose volume of the test substance was administered to each rat by stomach tube.
Doses:
300 mg/kg bw
2000 mg/kg bw
No. of animals per sex per dose:
2 x 3 (two dose groups per dose) females only
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed post dosing at 30 minutes, 3 and 6 hours, and then once daily thereafter until termination. Body weights were taken on days 7 and 14.
- Necropsy of survivors performed: Yes
- Other examinations performed: Macroscopic examination
Statistics:
Not applicable

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred after administration of 300 or 2000 mg/kg bw.
Clinical signs:
None
Body weight:
All animals were considered to have achieved satisfactory bodyweight gains throughout the study.
Gross pathology:
Macroscopic examination of the main organs of the animals revealed no apparent abnormalities.
Other findings:
None

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met