Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2002-02-13 until 2002-04-02
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: OECD test under GLP
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002
Report Date:
2002

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: 96/54/EG, B.1tris (Akute-toxische-Klassen-Methode); OECD 423
Deviations:
no
Principles of method if other than guideline:
not applicable
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Winkelmann GmbH, D-33178 Borchen
- Weight at study initiation: male: step 1: 135 - 155 g, female: step 2: 143 - 148 g, male: step 3: 159 - 168 g
- Fasting period before study: yes
- Housing: semi barrier in an air-conditioned room
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: adequate


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3 °C
- Humidity (%): 55 +/- 10 % rel. humidity
- Air changes (per hr): 10/h
- Photoperiod (hrs dark / hrs light): 12 h dark, 12 h light

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
cotton seed oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: In the first and second step 200 mg of the test item were solved in cottonseed oil ad 10 ml; In the third step 2000 mg of the test item were solved in cottonseed oil ad 10 ml.
- Justification for choice of vehicle: non-toxic characteristics

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg bw

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: not stated in the report
Doses:
200 mg/kg bw (step 1 and 2), 2000 mg/kg bw (step 3)
No. of animals per sex per dose:
3 (step 1), 3 (step 2), 3 (step 3)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: three times in first four hours postdose. Animals were observed once a day thereafter. Weighting on days 0, 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
not applicable

Results and discussion

Preliminary study:
not applicable
Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
> 200 mg/kg bw
Remarks on result:
other: step 1
Sex:
female
Dose descriptor:
LD50
Effect level:
> 200 mg/kg bw
Remarks on result:
other: step 2
Sex:
male
Dose descriptor:
LD50
Effect level:
< 2 000 mg/kg bw
Remarks on result:
other: step 3
Mortality:
No mortality has been observed in step 1 and 2.
The dosage of 2000 mg/kg bw caused compound-related mortality in animal No. 1 within 5 hours and in animals No. 2 and 3 within 3 hours p. appl. in step 3.
Clinical signs:
No clinical signs have been observed in step 1 and 2.
Any of the animals of step 3 showed reduced spontaneous activity, prone position, apathy and respiratory distress.
Body weight:
Throughout the 14-days observation period no weight loss was recorded in the animals of step 1 and 2.
Gross pathology:
No gross pathological changes were found in all animals of step 1 and step 2.
In step 3 animal No. 1 showed no gross pathological changes. In animal No. 2 as well as animal No. 3 stomach partly was reddened and the third section of small intestine was red/bloody.
Other findings:
- Other observations: none

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Considering the reported data of this toxicity test it can be stated that the test item has acute toxic characteristics.
According to the results obtained the LD50 was determined to be between 300 and 500 mg/kg bw.
Executive summary:

An acute toxicity test according the acute toxic class method (OECD 423) was performed. In the first step the test item was given at a dose of 200 mg/kg bw to a group of 3 male rats (HsdBrlHan:WIST) in a single exposure via oral gavage. In the second step the test item was given at the same dose to a group of 3 female rats (HsdBrlHan:WIST) in a single exposure via oral gavage. The dosage of 200 mg/kg bw caused no compound-related mortality neither in the three male nor in the three female animals within 14 days p. appl.. According to the acute toxic class method regime, in a third step the test item was given to a further group of three male animals in a dose of 2000 mg/kg bw. Any of the animals of step 3 showed reduced spontaneous activity, prone

position, apathy and respiratory distress. The dosage of 2000 mg/kg bw caused compound-related mortality in animal

No. 1 within 5 hours and in animals No. 2 and 3 within 3 hours p. appl.. According to the acute toxic class method regime, no further testing was required. According to the results obtained the LD50 was determined to be between 300 and 500 mg/kg bw.