Registration Dossier

Administrative data

acute toxicity: oral
Adequacy of study:
other information

Data source

Reference Type:
other: Body responsible for the test

Materials and methods

Test guideline
according to
other: Annex V (Acute toxic class)
GLP compliance:
Test type:
standard acute method
Limit test:

Test animals

other: Rat (CD)

Administration / exposure

other: 1% w/v aqueous methylcellulose

Results and discussion

Effect levels
Dose descriptor:
Effect level:
> 300 mg/kg bw
Female: 300 mg/kg bw; Number of animals: 3; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 3; Number of deaths: 3
Clinical signs:
Signs of toxicity related to dose levels:
All females dosed at 2000 mg/kg were found dead on Day 2.
Clinical signs prior to death comprised partially closed
eyelids (both) and flat posture seen in all animals. In
addition, piloerection, hunched posture, underactivity,
reduced body temperature, post dose salivation, abnormal
gait (uncoordination), tremors, convulsions and irregular
respiration were seen in two females. Abnormal gait
(unsteady), dark extremities, lacrimation and salivation
were seen in one female. These signs were first observed
from approximately seventeen minutes after dosing. A loss in
bodyweight was recorded for two decedents.

Clinical signs of reaction to treatment in animals which
were dosed at 300 mg/kg comprised hunched posture,
piloerection, abnormal gait (unsteady), seen in all six
females. In addition, underactivity, poor righting reflex,
fast respiration and reduced body temperature, were seen in

four females. FasciculationÆs were seen in three females,
lacrimation, tremors (tremors only during handling) and
partially closed eyelids (both) were seen in two animals,
dark extremities and salivation were seen in one female.
These signs were first observed approximately 30 minutes
after dosing and recovery, as judged by external appearance
and behaviour, by Day 2.

All surviving animals were considered to have achieved
satisfactory bodyweight gains throughout the study.
Gross pathology:
Effects on organs:
Macroscopic examination of the decedents treated at 2000
mg/kg revealed congestion (characterised by darkened
tissues/organs or blood vessels injected) of the brain,
liver, stomach, duodenum, caecum, small and large intestines
in all animals, subcutaneous tissue, heart, lungs and
spleen was seen in two animals. In addition, small (atrophy)
heart in one animal, pallor of the kidneys in two animals
and white/yellow contents of the stomach, duodenum, caecum,
small and large intestines seen in two/three animals.

No abnormalities were seen in the surviving animals at the
macroscopic examination at study termination on Day 15.

Applicant's summary and conclusion

Interpretation of results:
Migrated information Criteria used for interpretation of results: EU