Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Between 14, July 1993 and 18, October 1993
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
GLP-Guideline study [the Good Laboratory Practice (GLP) standard (the Ministry of Health and Welfare of Japan, Yakuhatsu No. 313 enforced on March 31, 1982); the Guidelines for Toxicity Studies of Drugs (the Ministry of Health and Welfare of Japan, Yakuhin 1 No. 24 enforced on September 11, 1989)].

Data source

Reference
Reference Type:
other company data
Title:
Unnamed
Year:
2008
Report Date:
2008

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: the Guidelines for Toxicity Studies of Drugs (Japan)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Physical state: White crystal powder
Analytical purity: 99.9%
Impurities (identity and concentrations): No data
Composition of test material, percentage of components: No data
Isomers composition: No data
Manufacture, supplier, source of supply : Yuki Gosei Kogyo Co., Ltd.
Lot/batch No.: 404676

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
-Age at study initiation: at 7 weeks of age
- Weight at study initiation: male: 212-224 g, female: 153-168 g

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-24 °C
- Humidity (%): 53-66 %
- Air changes (per hr): ventilated (all fresh air system) 10 times more per hour
- Photoperiod (hrs dark / hrs light): a 12-hour light-dark cycle (light on 7:00-19:00)

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
-Manufacture, supplier, source of supply : Yuki Gosei Kogyo Co., Ltd.
- Lot/batch No.: 404676
Doses:
0, 5000 mg/kg
No. of animals per sex per dose:
6 animals/sex/dose
Control animals:
yes
Details on study design:
Duration of observation period following administration: 14 days

Frequency of observations and weighing:
Clinical observation : 0 to 30 minutes, 1, 3 and 6 hours after dosing. On day 2, all rats were observed twice daily. During Day 3 to Day 15, all rats were observed once daily.
Morbidity and mortality : 0, 30 minutes, 1, 3, 6 hours after dosing. During the Day 2 to Day 15, the mortality was observed twice daily.
Bodyweight : Day 1 (before dosing), Day 8 and Day 15.

Necropsy of survivors performed: yes

Other examinations performed: no

Statistics:
Body weigth : Scheffe's multiple comparison procedure, Clinical sign : Fischer's exact test

Results and discussion

Preliminary study:
In the preliminary test, no mortality was occurred at 5000 mg/kg, which was the maximum dose level could be administered. Therefore, 5000 mg/kg was determined as the dosage level.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No male or female rats in any groups died throughout the observation period.
Clinical signs:
No male or female rats with abnormal findings were observed in the control group throughout the observation period.
In the 5000 mg/kg group, decrease in voluntary movement was observed in 4 male and 6 female rats for the first 0 to 30 minutes after dosing, and the incidences of the finding in male and female rats of the 5000 mg/kg group were significantly higher than those in the control group. In the 5000 mg/kg group, diarrhea was observed in male rat for the first 0 to 30 minutes after dosing, 2 male rats at 3 hours and 3 male and 3 female rats at 6 hours after dosing.
Body weight:
The body weights in male and female rats of the 5000 mg/kg group were not siginificantly different from those in the control group throughout the observation period.
Gross pathology:
No abnormal gross findings were observed in any male or female rats of the control and 5000 mg/kg group.
Other findings:
Organ weights: No data
Histopathology: No data
Potential target organs: No data
Other observations: No data

Any other information on results incl. tables

Table 1. Clinical signs (5,000 mg/kg group)

0 to 30 min 3 hr 6 hr
male decrease in voluntary movement  4/6 0 0
diarrhea 1/6 2/6 3/6
female decrease in voluntary movement  6/6 0 0
diarrhea 0 0 3/6

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information