Cyclopropanecarboxylic acid, [(3S,4R,4aR,6S,6aS,12R,12aS,12bS)-3-[(cyclopropylcarbonyl)oxy]-1,3,4,4a,5,6,6a,12,12a,12b-decahydro-6,12-dihydroxy-4,6a,12b-trimethyl-11-oxo-9-(3-pyridinyl)-2H,11H-naphtho[2,1-b]pyrano[3,4-e]pyran-4-yl]methyl ester

Acute Toxicity: oral

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 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:

other: JMAFF No 12 Nosan No 8147

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

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

EC Number:

815-966-6

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: 96.1 %
- Appearance: Solid yellowish
- Batch: COD-001545

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:

other: None

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