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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
other: publication
Adequacy of study:
disregarded due to major methodological deficiencies
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: secondary literature; no details

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Unnamed
Year:
1991
Reference Type:
publication
Title:
Unnamed
Year:
1991
Report Date:
1991

Materials and methods

Principles of method if other than guideline:
no data
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
stock solution of the substance containing 0.01% butylated hydroxytoluene

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals and environmental conditions:
no data

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
oral intubation
Duration of treatment / exposure:
13 weeks
Frequency of treatment:
5 days/week
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 50, 100, 200, 400, 800 mg/kg/day
Basis:
no data
No. of animals per sex per dose:
10 male and 10 female rats per dose
Control animals:
other: yes; 0 mg/kg/day of test substance
Details on study design:
Range finder study was conducted before:
- duration: 14 days
- doses: 0, 300, 600, 1250, 2500, 5000 mg/kg/day
- 5 males and 5 females per dose

Examinations

Observations and examinations performed and frequency:
no data
Sacrifice and pathology:
no data
Other examinations:
no data
Statistics:
no data

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
mortality: observed in the 14 day range finder (all animals killed at doses of 1250, 2500 and 5000 mg/kg/day; not described for main study; clinical signs: central nervous system depression, tremors and gastrointestinal distress in the range finder study
Mortality:
mortality observed, treatment-related
Description (incidence):
mortality: observed in the 14 day range finder (all animals killed at doses of 1250, 2500 and 5000 mg/kg/day; not described for main study; clinical signs: central nervous system depression, tremors and gastrointestinal distress in the range finder study
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
body weight gain depression in main study
Gross pathological findings:
not specified
Description (incidence and severity):
in range finder study no compound related gross changes were observed
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
hyaline droplet degeneration of kidney proximal convoluted tubules in males inmain study; in range finder study no compound related histologic changes were observed
Details on results:
body weight reduction : male: doses 400 and 800 mg/kg; female dose 800 mg/kg
histopathology: males dose related hyaline droplets in renal tubules; females: no compound related changes

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion