Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Jan 21 - March 28, 1994
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions

Data source

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

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
Feb 24, 1987
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
Housing:
collective housing up to a maximum of 5 animals
per cage (Makrolon@ type III)
llumination:
artificial lighting (120 lux) from 7.00 a.m. -7.00 p.m
Temperature:
22 +/- 3°C
Relative humidity:
30-70 %
Measurement:
twice dail

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
A single oral administration of the test article was performed by gavage using a stomach tube. The test article was administered as a 2 % (group I) or a 5 % (group II) dilution in aqua ad iniectabilia in a volume of 10 ml/kg.
Doses:
500 and 200 mg/kg bw
Preliminary range finding tests with doses of 2000, 1000, 500 and 200 mg/kg body weight were conducted using two female rats per dose.
No. of animals per sex per dose:
200 mg//kg bw: 5 males, 5 females
500 mg/kg bw: 5 males, 5 females
Control animals:
no
Details on study design:
Clinical observations:
In each animal a number of clinical-toxicological signs were evaluated according to a modified Irwin-Screening procedure (Screening Methods in Pharmacology, R. A. Turner, 1965, p. 26). Any change from the normal condition was noted (increase or decrease) and the degree of severity of any clinical symptoms was assessed. The animals were examined at the fonowing post-treatment intervals: 10 min, 1 h, 2 h, 6 h, 24 h, and thereafter once daily up to day 14.
Body weights:
The body weights of an animals were recorded immediately before treatment (day 0) and surviving animals were reweighed on days 7 and 14 p.a. (termination).
Necropsy
Animals found dead were immediately necropsied. The surviving animals were sacrificed by CO2 asphyxiation after 14 days and gross pathological examinations were subsequently performed.
LD50 values were calculated by linear interpolation.


Results and discussion

Effect levelsopen allclose all
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
ca. 275 mg/kg bw
Based on:
test mat.
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
ca. 250 mg/kg bw
Based on:
test mat.
Mortality:
at 200 mg/kg bw: 2 of 5 males, 2 of 5 females (after 14 days)
at 500 mg/kg bw: 5 of 5 males, 4 of 5 females (after 14 days)
Clinical signs:
Severe dose-dependent clinical signs were observed mainly 1 and 2 h p.a. The most frequent findings were reduced activity, abnormal gait, abdominal, lateral or squatting position, abnormal body posture, decreased body tone, decreased ear, plantary and corneal reflex, cyanosis of the skin (at 500 mglkg), piloerection and decreased respiratory rate.
Body weight:
Weight gains were normal in the surviving animals.
Gross pathology:
Gross pathological examinations on animals found dead and at 14 days p. a. (terminal necropsy) revealed no test article-related findings.
The liquid filling of the gastro-intestinal tract found in animals which died within a short time after the administration was most probably caused by the administered test substance preparation. Other macroscopic changes observed were attributable to the sacrificing procedure or to minor variations which can occur spontaneously in rats of this strain and age.

Applicant's summary and conclusion

Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
Under the conditions of the present study, after single oral application of the test item to rats the follwing LD50 values were determined:LD50 (rat, male): ca. 250 mg/ kg bw
LD50 (rat, female): ca. 275 mg/ kg bw
LD50 (rat, male): ca. 250 mg/kg bw