Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
July 9, 1990 - August 12, 1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Conducted equivalent to OECD 401 and GLP principles.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report Date:
1991

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
other: Japanese Guideline for Toxicity Study of Drugs (1989)
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): NBDI
- Physical state: liquid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Japan
- Age at study initiation: 5 weeks
- Weight at study initiation: 120-130 g for males and 95-110 g for females
- Housing: polycarbonate cage with hard wood chip bedding
- Acclimation period: 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 25 C
- Humidity (%): 40 to 70%
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
olive oil
Details on oral exposure:
VEHICLE: Olive oil
MAXIMUM DOSE VOLUME APPLIED: 1 mL/100 g bw
Doses:
700 mg/kg
1000 mg/kg
1400 mg/kg
2000 mg/kg
(both sexes)
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical signs of all rats were inspected and recorded 0.5, 1, 3 and 6 hours after administration and at least once a day thereafter for 14 days.
The bodyweight of all rats was measured shortly before administration and on the 3rd, 7th and 14th day after administration (defining the day of administration as the 0th day)
- Necropsy of survivors performed: yes (and the dead animals were autopsied at discovery)
- Other examinations performed: no

Results and discussion

Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LD50
Effect level:
1 201 mg/kg bw
95% CL:
826 - 1 744
Sex:
male
Dose descriptor:
LD50
Effect level:
1 842 mg/kg bw
95% CL:
1 387 - 2 446
Mortality:
Male: 700 mg/kg bw; Number of animals: 5; Number of deaths: 0
Male: 1000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Male: 1400 mg/kg bw; Number of animals: 5; Number of deaths: 1
Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 3
Female: 700 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 1000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 1400 mg/kg bw; Number of animals: 5; Number of deaths: 3
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 4
Clinical signs:
Rats of both sexes at all dose levels had soiled hair around the anus, soft feces and diarrhea between 30 minutes and the second day after administration. One male rat of the 1400 mg/kg dose group had reduced spontaneous movement on the next day after administration and died on the second day. All female rats had the same symptom 3 hours or more after administration. Of them, 3 rats with severe symptoms had crouching or irregular respiration and then died by the second day after administration. All male rats of the 2000 mg/kg dose group had reduced spontaneous movement 3 hours or more after administration, and crouching only at 6 hours. Of them, 3 rats with severe symptoms died on the next day after administration. Furthermore, some male rats had irregular respiration and cyanosis up to the second day after administration. All female rats of the 2000 mg/kg dose group had reduced spontaneous movement 3 hours or more after administration and crouching at 6 hours or more. Of them, 3 rats with severe symptoms died on the next day after administration and another on the second day.
Body weight:
Surviving rats of both sexes had normal weight gains.
Gross pathology:
-Autopsy at the end of the observation period revealed thickening of the stomach internal wall in all rats
-Greyish changes at the stomach wall and yellow contents in the small intestines (females: 1400 and 2000 mg/kg; males: 2000 mg/kg bw only)
-Testes atrophy at the highest dose in males

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The LD50 oral was 1842 mg/kg for male rats (95% confidence limits: 1387 to 2446 mg/kg) and 1201 mg/kg for female rats (95% confidence limits: 826 to 1744 mg/kg).
Executive summary:

The substance was administered orally to SD strain rats (SPF) of both sexes and its acute toxicity was determined. The dosage levels were 700, 1000, 1400 and 2000 mg/kg for rats of both sexes. Each dose group consisted of 5 rats.

The LD50 oral was 1842 mg/kg for male rats (95% confidence limits: 1387 to 2446 mg/kg) and 1201 mg/kg for female rats (95% confidence limits: 826 to 1744 mg/kg).