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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
17 september 2009 to 08 October 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted to OECD guideline and in compliance with GLP

Data source

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

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

Test material

Constituent 1
Chemical structure
Reference substance name:
(1R,2S,10R,11S)-tetracyclo[9.2.1.0²,¹⁰.0³,⁸]tetradeca-3(8),4,6,12-tetraene
EC Number:
700-736-9
Cas Number:
2149571-40-2
Molecular formula:
C14H14
IUPAC Name:
(1R,2S,10R,11S)-tetracyclo[9.2.1.0²,¹⁰.0³,⁸]tetradeca-3(8),4,6,12-tetraene
Details on test material:
- Name of test material (as cited in study report): MTF

- Substance type: Organic
- Physical state: colourless liquid
- Analytical purity: 98.6%

- Lot/batch No.: 20080625005
- Expiration date of the lot/batch: 22 June 2014
- Storage condition of test material: refrigerated
- Other:

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Japan
- Age at study initiation: 9 weeks
- Weight at study initiation: 194 to 227 g
- Fasting period before study: 16 to 17 hours
- Housing: individual
- Diet (e.g. ad libitum): ad libitum from 4 hours afer dosing
- Water (e.g. ad libitum): adlibitum from 4 hours after dosing
- Acclimation period: >6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24 deg C
- Humidity (%): 55%
- Air changes (per hr): 10-20 changes per hour
- Photoperiod (hrs dark / hrs light):12 hrs dark/12 hrs light

IN-LIFE DATES: From: 17 September 2009 To: 15 October 2009

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 30 mg/ml
- Amount of vehicle (if gavage): 10 ml/kg bodyweight
- Justification for choice of vehicle:
- Lot/batch no. (if required): V8A6289
- Purity:

MAXIMUM DOSE VOLUME APPLIED: 10ml/kg bodyweight

DOSAGE PREPARATION (if unusual):

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: guideline
Doses:
Experiments 1 and 2: 300 mg/kg
Esperiment 3: 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
- Frequency of observations and weighing:
Clinical Obs: pre-dose, 0.5, 1, 2, 3 and 4 hrs on day of dosing, daily from Days 2 to 15.
Body weight measurements: before administration and 1, 3, 7 and 14 days after administration.
Pathology of organs and tisues on Day 15
- Necropsy of survivors performed: yes

Results and discussion

Preliminary study:
Experiments 1 and 2 (300 mg/kg bodyweight): mucous stool observed in 1 and 2 animals in experiments 1 and 2 respectively at 1 or 4 hours after dosing. Soiled periproctal regoin in 2 animals in Experiments 1 at 2 hrs after dosing or on day following administration. The findings disappeared by 2 days after administration.

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
1 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: LD50 Cut-off value based on 0/6 deaths seen at 300 mg/kg and 2/3 deaths at 2000 mg/kg.
Mortality:
Two animals died in experiment 3 (2000 mg/kg bodyweight)
Clinical signs:
other: Experiments 1 and 2: Mucous stool observed in 1 and 2 animals in experimetns 1 and 2 respectively, at 1 or 4 hours after dosing. soiled periproctal region in 2 animals in experiment 1 at 2 hours after dosing. Experiment 3: For the dead animals, one sh
Gross pathology:
No abnormalities observed at necropsy in any experiment including dead animals.

Applicant's summary and conclusion

Conclusions:
The LD50 cut off value of MTF was estimated to be 1000 mg/kg under the conditions of this study since death occurred in 2 animals at 2000 mg/kg.