Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Meets the criteria for classification as Reliable without restriction according to Klimisch et al (1997)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Version / remarks:
92/69/EEC
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
other: Rat (Hsd:Sprague-Dawley(CD))
Strain:
Sprague-Dawley
Sex:
male/female

Administration / exposure

Vehicle:
other: 1% aqueous methylcellulose

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
211 mg/kg bw
95% CL:
175 - 253
Remarks on result:
other: Slope of the mortality curve: 11.4
Mortality:
Male: 250 mg/kg bw; Number of animals: 5; Number of deaths: 4
Female: 250 mg/kg bw; Number of animals: 5; Number of deaths: 4
Female: 200 mg/kg bw; Number of animals: 5; Number of deaths: 2
Female: 100 mg/kg bw; Number of animals: 5; Number of deaths: 0
Clinical signs:
Signs of toxicity related to dose levels:
Two females at 200mg/kg and four males and four females at
250 mg/kg died during the study. All deaths occurred within
three days of dosing.

A slight bodyweight loss was recorded for the majority of
decedents.


Piloerection was observed in all rats within six minutes of
dosing. This sign persisted and was accompanied later on Day
1 and / or at later intervals during the study by hunched
posture, unsteady gait, and lethargy in all rats at all
dosages.

Respiratory distress was seen in all females at 200mg/kg and
in two males and two females at 25mg/kg.

Other signs of toxicity included partially closed eyelids,
soft to liquid faeces, increased salivation, cold body
surfaces and brown staining around the nose or mouth in rats
at one or more dose levels.
Gross pathology:
Effects on organs:
Males and Females 250mg/kg


Congestion of the brain, heart, lungs and kidneys,
(characterised by dark appearance/prominent blood vessels
and inflammation), with congestion and atrophy of the
spleen. Congestion, fluid contents and gaseous distention
were noted in the stomach and along the alimentary tract
with fluid contents also observed in the urinary bladder.


Females 200mg/kg


Congestion of the subcutaneous tissue, brain, heart lungs
liver and kidneys were noted. Congestion, fluid contents and
gaseous distension of the stomach and along the alimentary
tract were noted and grey/black fluid contents also observed
in the urinary bladder.


No abnormalities were revealed at the macroscopic
examination of surviving animals on Day 15.

Applicant's summary and conclusion

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