Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
March 6 to April 3, 2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study was conducted in 2006 according to OECD Method # 423 and in accordance with GLP. The study material is well characterized.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2006
Report Date:
2006

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
Commission Directive 96/54/EC, B1 tris
Deviations:
no
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:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
white powder; stored at room temperature in the dark

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
With exception of an overnight fast before dosing and 3-4 hours after dosing, free access to mains drinking water and food was allowed. The temperature and relative humidity were set to achieve limits of 19 to 25 C and 30 to 70% respectively. The rate of air exchange was at least 15 changes per hour and the lighting was controlled by a time switch to give 12 hours continuous light and 12 hours of darkness.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
Using all available information on the toxicity of the test material, 300 mg/kg was chosen as the starting dose.
dose level: 2000 mg/kg
concentration: 100 mg/ml
dose volume 10 ml/g
3 females per dose, followed by a group of 3 males per dose
Doses:
Female: 300 mg/kg and 2000 mg/kg bw
No. of animals per sex per dose:
Female: 300 mg/kg bw; number of animals: 3 female
additionally 3 females at 2000 mg/kg and 3 at 300 mg/kg dosed sequentially
Control animals:
no
Details on study design:
All animals were dosed once only by gavage, using a metal cannula attached to a graduated syringe. The volume administered was calculated according to the fasted bodyweight at the time of dosing. Treatment of animals was sequential. Sufficient time was allowed between each group to confirm the survival of the previously dosed animals. The animals were observed for deaths or overt signs of toxicity 1/2, 1, 2 and 4 hours after the final dose and subsequently once daily for fourteen days. At the end of the observation period the animals were killed using ascending concentrations of carbon dioxide. All animals were subjected to gross pathological observations. This consisted of external examination and opening of the abdominal and thoracic cavities for examination of major organs. The appearances of any macroscopic abnormalities were recorded. No tissues were retained.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
300 - 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Female: 2000 mg/kg bw; Number of animals: 3; Number of deaths: 1 found dead, 1 killed in extremis 1 day after dosing
Female: 300 mg/kg bw; Number of animals: 6; Number of deaths: 0
Clinical signs:
Signs of toxicity related to dose levels:
there was no sign of toxicity for animals dosed at 300 mg/kg.

At 2000 mg/kg, hunched posture, lethargy, piloerection,ataxia, decreased respiration rate, laboured respiration, ptosis, pallor of the extremeties, emaciation, red/brown staining around the eyes and tiptoe gait. 1 animal was normal 6 days after dosing.


All animals showed expected gains in bodyweight over the
study period.
Body weight:
All animals showed expected gains in bodyweight over the study period.
Gross pathology:
Effects on organs:
No abnormalities were noted of the animals killed at the end of the study. For the animal that died or was killed in extremis the following was noted haemorrhagic lungs, dark or patchy pallor of the liver, dark kidneys, pale gastric mucosa and pale non-glandular region of the stomach at necropsy.

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral median lethal dose (LD50) of the test material in the Sprague-Dawley CD strain rat was between 300 and 2000 mg/kg bodyweight.