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Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
3 (not reliable)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1984
Report date:
1984

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The test substance was administered by gavage to six male rats. Rats were dosed at 300 mg/kg/day for 10 days (weekends excluded) over a 2-week period. Six rats were simultaneously dosed with corn oil as a control. All rats were weighed and observed daily during the dosing period. After the tenth dose, three control and three test rats were sacrificed. The remaining rats in each group were weighed and observed through a 14-day recovery period and then sacrificed. All sacrificed rats were examined grossly and selected tissues evaluated histologically.
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Purity: approximately 95%

Test animals

Species:
rat
Strain:
other: Crl:CD
Sex:
male

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
2-weeks
Frequency of treatment:
Daily for 10 days (weekends excluded) over a 2-week period
Doses / concentrations
Remarks:
Doses / Concentrations:
Males: 300 mg/kg
Basis:
actual ingested
No. of animals per sex per dose:
Control and the test group consisted of 6 male rats each. Three control and three test rats were used in a 14-day recovery group.
Control animals:
yes, concurrent vehicle

Results and discussion

Effect levels

Dose descriptor:
conc. level:
Effect level:
300 mg/kg bw/day (actual dose received)
Sex:
male
Basis for effect level:
other: clinical signs (stained and wet perineal area, red oral and nasal discharges, alopecia, aggressive behavior, and limpness); decreased body weight; increased liver/body weight and testes/body weight ratios; histopathology (liver and urinary bladder).

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

CLINICAL SIGNS AND MORTALITY

All rats survived. Clinical signs observed in test rats during the dosing period included stained and wet perineal area, red oral and nasal discharges, alopecia, aggressive behavior, and limpness. Alopecia was observed during recovery.

BODY WEIGHT AND WEIGHT GAIN

Body weights of test rats were significantly lower than those of control rats from Test Day 2 though Test Day 12. Slight to moderate weight loss was observed in test rats during the dosing period. Slight weight loss was observed during recovery.

ORGAN WEIGHTS Following 10 doses, test rats had significantly increased liver/body weight and testis/body weight ratios over control rats. Fourteen days following dosing, there were no significant differences between test rats and controls.

HISTOPATHOLOGY: NON-NEOPLASTIC

Histologically, compound-related changes were found in the liver and urinary bladder. The change in the liver was a lipid-like cytoplasmic vacuolation in hepatocytes at zero days recovery. The change in the bladder was a moderate diffuse hyperplasia of the urothelium at zero days recovery, with a partial recovery after 14 days.

Applicant's summary and conclusion

Conclusions:
All rats survived. Clinical signs and weight loss were observed during the dosing period. Histologic examination revealed compound related effects in the liver and urinary bladder. There was complete recovery in the liver and partial recovery in the urinary bladder in rats given a 14-day recovery period. Increased liver/body weight and testes/body weight ratios were observed in test rats sacrificed after the 10th dose. Fourteen days after dosing, there were no significant differences between test rats and controls.
Executive summary:
The test substance was administered by gavage to six male rats. Rats were dosed at 300 mg/kg/day for 10 days (weekends excluded) over a 2-week period. Six rats were simultaneously dosed with corn oil as a control. All rats were weighed and observed daily during the dosing period. After the tenth dose, three control and three test rats were sacrificed. The remaining rats in each group were weighed and observed through a 14-day recovery period and then sacrificed. All sacrificed rats were examined grossly and selected tissues evaluated histologically. All rats survived. Clinical signs observed in test rats during the dosing period included stained and wet perineal area, red oral and nasal discharges, alopecia, aggressive behavior, and limpness. Alopecia was observed during recovery. Body weights of test rats were significantly lower than those of control rats from Test Day 2 though Test Day 12. Slight to moderate weight loss was observed in test rats during the dosing period. Slight weight loss was observed during recovery. Following 10 doses, test rats had significantly increased liver/body weight and testis/body weight ratios over control rats. Fourteen days following dosing, there were no significant differences between test rats and controls. Gross pathologic examination revealed no compound-related effects. Histologic examination revealed compound-related effects in the liver and urinary bladder. There was complete recovery in the liver and partial recovery in the urinary bladder in rats given a 14-day recovery period.