Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study run to a method comparable with current guidelines and to GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1994
Report Date:
1994

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Deviations:
no
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Batch No.: 5ABK-003
- Purity: 96.5%

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 1% w/v aqueous methylcellulose
Doses:
A group of ten fasted rats(five males and five femals) was given a single dose by oral gavage of the test substance, formulated in 1% w/v aqueous methylcellulose and administered at an initial dose level of 500 mg/kg bodyweight. A further group of five males and five females rats was dosed at 50 mg/kg bodyweight to determine the discriminating dosage of the test material.
No. of animals per sex per dose:
Preliminary sighting study: 2 (female)
Main study: 5 (male)
Main study: 5 (female)
Control animals:
no
Details on study design:
A group of ten fasted rats(five males and five femals) was given a single dose by oral gavage of the test substance, formulated in 1% w/v aqueous methylcellulose and administered at an initial dose level of 500 mg/kg bodyweight. This dose level was chosen on the basis of preliminary study results and in compliance with the study guideling. A further group of five males and five females rats was dosed at 50 mg/kg bodyweight to determine the discriminating dosage of the test material.

Results and discussion

Preliminary study:
Species/strain: Rat (Sprague-Dawley)
2000 mg/kg bw: Evident toxicity: Y; Mortality: Y
500 mg/kg bw: Evident toxicity: Y; Mortality: N
Observations:
These results were used to set the starting dose for the main study.
Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
discriminating dose
Effect level:
50 mg/kg bw
Based on:
act. ingr.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 50 - < 500 mg/kg bw
Based on:
act. ingr.
Mortality:
Three males and all females at 500 mg/kg died during the study. All deaths occurred within 4 days of dosing.
Female 500 mg/kg bw (fixed dose further) No. with evident toxicity: 5; No. of deaths: 5; No. of animals used: 5
Male 500 mg/kg bw (fixed dose further) No. with evident toxicity: 5; No. of deaths: 3; No. of animals used: 5
Female 50 mg/kg bw (fixed dose further) No. with evident toxicity: 5; No. of deaths: 0; No. of animals used: 5
Male 50 mg/kg bw (fixed dose further) No. with evident toxicity: 5; No. of deaths: 0; No. of animals used: 5
Clinical signs:
Signs of toxicity:
Clinical signs of reaction to treatment included piloerection and hunched posture, seen in all rats at both dosages. In addition, waddling gait, lethargy, decreased respiration, partially closed eyelids, pallor of the extremities, calonic convulsions, walking on toes, unsteadiness, increased lacrimation, body tremors, cold body surfaces, prostration and lack of faeces were observed among rats dosed at 500 mg/kg. Recovery of surviving rats was complete by Day 9.
A slight bodyweight loss was recorded for all decedents.
Body weight:
A slight bodyweight loss was recorded for all decedents.
All surviving rats achieved satisfactory bodyweight gains throughout the study.
Gross pathology:
Effects on organs:
Macroscopic examination of surviving rats killed on Day 15 revealed no abnormalities.
Other findings:
Three males and all females at 500 mg/kg died during the study. All deaths occurred within four days of dosing.

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
LD50 is between 50 and 500 mg/kg bw/day.