Registration Dossier

Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
no data
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Test compliant with GLP and Guideline OECD 408

Data source

Reference
Reference Type:
other: Body responsible for the test
Title:
Unnamed
Year:
1988

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity in Rodents)
Deviations:
not specified
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
other: Tif: RAIf (SPF)
Sex:
male/female

Administration / exposure

Route of administration:
oral: unspecified
Vehicle:
other: 0.5% carboxymethylcellulose 0.1% Tween 80 in distilled water
Details on oral exposure:
Method of administration:gavage
Duration of treatment / exposure:
Test duration: 90 days
Frequency of treatment:
Dosing regime: 5 days/week
No. of animals per sex per dose:
Male: 10 animals at 10 mg/kg bw/day
Male: 10 animals at 25 mg/kg bw/day
Male: 10 animals at 75 mg/kg bw/day
Male: 10 animals at 220 mg/kg bw/day
Female: 10 animals at 10 mg/kg bw/day
Female: 10 animals at 25 mg/kg bw/day
Female: 10 animals at 75 mg/kg bw/day
Female: 10 animals at 220 mg/kg bw/day

Results and discussion

Results of examinations

Details on results:
Clinical observations:
Mortality:
No treatment related mortality occurred.
Signs of systemic toxicity:
In animals treated with 220 mg/kg bw paresis of the hind limbs and loss of hair was observed. The effects on locomotor activity became less at the end of the study.
Starting the second week of treatment dim and opaque eyes at the highest dose level were noted.
Laboratory findings:
Hematology and blood chemistry:
The number of segmented neutrophiles and plateles were increased in females at 75 mg/kg bw and 220 mg/kg bw. Small effects on liver-derived enzymes were observed in the highes dose group.
Effects in organs:
Eye cataract formation and segmental demyelination of peripheral nerve fibres was noted. In some animals spleen hemosiderosis was observed.

Effect levels

open allclose all
Dose descriptor:
NOAEL
Effect level:
75 mg/kg bw/day (nominal)
Basis for effect level:
other: original NCD unit is mg/kg/day
Dose descriptor:
NOEL
Effect level:
10 mg/kg bw/day (nominal)
Basis for effect level:
other: original NCD unit is mg/kg/day

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion