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Toxicological information

Repeated dose toxicity: other routes

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Administrative data

Endpoint:
short-term repeated dose toxicity: other route
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1978

Materials and methods

Principles of method if other than guideline:
Study well documented, meets generally accepted scientific principles, acceptable for assessment
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
monkey
Strain:
other: Rhesus
Sex:
male/female
Details on test animals and environmental conditions:
3 groups of 2 male and 2 female

Administration / exposure

Route of administration:
intravenous
Vehicle:
ethanol
Details on exposure:
0.6 - 1.2 mg/ kg/ day
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
Low dose: 14 days. High dose: 7 days.
Frequency of treatment:
daily
Doses / concentrations
Remarks:
Doses / Concentrations:
Low dose: 0.6 mg/kg/bw/day for 7 days, then 1.2mg/kg/bw/day for 7 days. High dose: 6.0mg/kg/bw/day for 7 days.
No. of animals per sex per dose:
2
Control animals:
yes
Details on study design:
Post-exposure period: 28 days

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
In the high dose group, three out of four animals died.
Mortality:
mortality observed, treatment-related
Description (incidence):
In the high dose group, three out of four animals died.
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Symptoms in high dose animals included reduced  body weight
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Description (incidence and severity):
Symptoms in high dose animals included reduced food intake
Food efficiency:
effects observed, treatment-related
Description (incidence and severity):
Symptoms in high dose animals included
Clinical biochemistry findings:
effects observed, treatment-related
Description (incidence and severity):
In the high dose group included lowered brain cholesterinase and increased serum urea, serum bilrubin and glycosuria. No clinico-chemical findings were observed in the low dose group.
Gross pathological findings:
effects observed, treatment-related
Description (incidence and severity):
In the high dose group, pathological findings included degeneration of the peripheral neuraxons and muscle fibre
Histopathological findings: non-neoplastic:
no effects observed
Description (incidence and severity):
For the low dose group
Histopathological findings: neoplastic:
no effects observed
Description (incidence and severity):
For the low dose group

Effect levels

Dose descriptor:
NOAEL
Effect level:
0.6 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

In low dose animals no abnormal symptoms were detected.   
Symptoms in high dose animals included gastro-intestinal disturbances, pathological reflexes, muscle tremor, and 
reduced food intake and body weight.

Applicant's summary and conclusion