Registration Dossier

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:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method

Test material

Reference
Name:
Unnamed
Type:
Constituent
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 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:
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 showed hypoactivity at 3 hours after dosing and tremor at 3 and 4 hours after dosing, this and on other animal showed hypoactivity, lateral position and bradypnea on the day following administration.
Body weight:
Supressed bodyweight gain was noted on the day follwoing administration, however, favourable increased gain was seen 3 days after administration or later.

In experiment 3, decreased bodyweight was noted on the day following administration in the dead animals. Supressed bodyweight gain noted the day follwoing administration in the surviving animal, however, favourable increased gain was seen on day 3 after administration.
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.