Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
18 September 2009 to 29 October 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
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
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report):

- Physical state: clear colorless liquid (non-GLP)
- Analytical purity: 99.5% (non-GLP)

- Lot/batch No.: 20080625003
- Expiration date of the lot/batch: 22 June 2009
-
- Storage condition of test material: refrigerator in the cold
- Other:

Test animals

Species:
rat
Strain:
other: Crl:CD(SD)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories Japan Inc.
- Age at study initiation: 9 weeks
- Weight at study initiation: Experiment 1 = 195-205g; Experiment 2 = 185-189g
- Fasting period before study: 16-17 hours
- Housing:
- Diet (e.g. ad libitum):
- Water (e.g. ad libitum):
- Acclimation period:

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

IN-LIFE DATES: From: To: 18 September to 02 October 2009

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 30 mg/L and 200 mg/L
- Amount of vehicle (if gavage): 10 mL/kg bodyweight

- Lot/batch no. (if required): V8A6289


MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg bodyweight

DOSAGE PREPARATION (if unusual):

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: guideline recommendations
Doses:
300 mg/kg bodyweight in Experiments 1 and 2; 2000 mg/kg in Experiment 3
No. of animals per sex per dose:
3 per sex
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days (or other)
- Frequency of observations and weighing: observations before dosing, at 30 minutes and 1, 2, 3 and 4 hours on day of administration and daily from days 2 to 15. Bodyeight determinaiton on day of dosing and on days 1, 3, 7 and 14 days thereafter
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: all organs and tissues examined macroscopically
Statistics:
Mean and standard deviations of bodyweights calculated; no conducted statistical analysis

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
500 mg/kg bw
Based on:
test mat.
Mortality:
Experiment 1: 1/3 animals died on day 3
Experiment 2: 1/3 animals died on day 2
Experiment 3: 3/3 animals died between 1 to 4 hours after dosing
Clinical signs:
Mucous stools in 2/3 and 3/3 animals in experiments 1 and 2 respectively at 1 to 3 hours after dosing or on the following day of administration.
Mucous stools 2/3 animals in experiment 3 at 1 and 2 hours after dosing.

Soiled periproctal region in 1/3 and 2/3 animals in experiments 1 and 2 respectively at 1 to 3 hours after dosing or on the following day of administration.
Soiled periproctal region in1/3 animals in experiment 3, at 2 hours after dosing,

Salivation and clonic convulsion in 2 animals in experiment 3 at 2 or 4 hours after dosing.
Body weight:
Decreased bodyweight or supressed bodyweight gain was noted on the day following administration, favourable increased gain was observed 3 days after administration (Day 4) or later.
Gross pathology:
No abnormalities observed at necropsy including the dead animals.
Other findings:
Death was considered to be caused by actions on the central nerve system or emaciation due to deterioration of general conditions.

Any other information on results incl. tables

In surviving animals in experiments 1 and 2, mucous stool or soiled periproctal region all disappeared by 2 days after administration. Although the decreased body weight or suppressed body weight gain was noted on the following day of administration, favorable increased gain was observed on 3 days after administration or later in experiments 1 and 2.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The LD50 cut off value of TCD was estimated to be 500 mg/kg under the conditions of this study.