Registration Dossier

Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2005

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity in Rodents)
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female

Administration / exposure

Duration of treatment / exposure:
30 day
Frequency of treatment:
daily
Doses / concentrationsopen allclose all
Dose / conc.:
50 mg/kg bw/day (nominal)
Dose / conc.:
200 mg/kg bw/day (nominal)
Dose / conc.:
500 mg/kg bw/day (actual dose received)
Dose / conc.:
800 mg/kg bw/day (nominal)
No. of animals per sex per dose:
30 male, 30 female

Examinations

Observations and examinations performed and frequency:
Clinical signs were observed daily, body weight and food consumption were measured weekly and at the completion of treatment period blood samples were taken for haematological and clinical chemistry examinations. At the end of the study, animals were necropsied and major organs were weighed and tissues examined microscopically.

Results and discussion

Results of examinations

Clinical signs:
not specified
Description (incidence and severity):
All animals treated with 800 mg/kg/day exhibited signs including ataxia, clonic convulsions and respiratory paralysis about 20 minutes after dosing. All animals in this dose group died during the first week of treatment, deaths occurring within 1-3 hours of dosing. In the 500 mg/kg/day dose group, ataxia and tonic-clonic convulsions were also observed and some animals died near the end of the study, though the report does not state the number of deaths. Animals treated at 200 mg/kg/day showed signs of restlessness such as irritability and an increase of spontaneous locomotor activity, while animals of the 50 mg/kg/day dose group did not exhibit any abnormal clinical signs.

Effect levels

Dose descriptor:
NOEL
Effect level:
200 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Remarks on result:
not measured/tested

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion