Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1983
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1983
Report Date:
1983

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
1981
Qualifier:
according to
Guideline:
other: "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics", by the Staff of the Division of Pharmacology, FDA
Version / remarks:
1959
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Winkelmann, Paderborn
- Age at study initiation: not specified
- Weight at study initiation: 190-200 g
- Fasting period before study: 16 h
- Housing: single cages
- Diet: laboratory standarddiet (Altromin, Lage)
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24 °C
- Humidity (%): 45 - 55 %
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): 12 h /12 h

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: unchanged and Tylose (2 lower concentrations)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 10 and 20 %
- Justification for choice of vehicle: not specified

MAXIMUM DOSE VOLUME APPLIED: 4 mL/kg bw
Doses:
1, 2, 3 and 4 mL/kg bw, equal to 1087, 2174, 3261 and 4348 mg/kg bw
No. of animals per sex per dose:
4348 mg/kg: 2 male, 2 female
other doses: 3 male, 3 female
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 24 h, 7 and 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, macroscopy

Results and discussion

Effect levelsopen allclose all
Key result
Sex:
male/female
Dose descriptor:
LD50
Remarks:
after 24 h
Effect level:
3 098 mg/kg bw
Based on:
test mat.
95% CL:
> 2 761 - < 3 467
Key result
Sex:
male/female
Dose descriptor:
LD50
Remarks:
after 14 days
Effect level:
2 717 mg/kg bw
Based on:
test mat.
95% CL:
> 2 402 - < 3 076
Mortality:
1087 mg/kg bw: no mortality
2174 mg/kg bw: 1 dead animal after 7 days
3261 mg/kg bw: 3 dead animals after 24h, 1 dead animal after 7 days
4348 mg/kg bw: 4 dead animals after 24 h (100%)
Clinical signs:
In all dosage groups animals seemed paralysed with fear and compound caused abdominal ache syndrome, pinched eyes, ataxia, disturbances of coordination and decreased readiness for reflection. These symptoms changed into sedation and coma. Furthermore, two late mortalities did occur within 72 hours.
Body weight:
The survival animals did not show test specific changes or dose-related weight gains. Clear decreased weight gains compared to the normal body-weights occurred.
Gross pathology:
At autopsy of acute mortalities and final autopsy no treatment-related anatomical-pathological findings were made macroscopically in the thorax and cranium cavity. Alone the belly cavity appeared with hyperemiae in the gastro-intestinal tract of acute mortalities. Final autopsy of surviving animals did not show any other alterations.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Based on the results of the acute oral toxicity study in rats, the LD50 value was determined to be 3098 mg/kg bw after 24 h and 2717 mg/kg bw after 14 days.
Executive summary:

The acute oral toxicity of the test substance was examined in a GLP-compliant study according to OECD 401. Four concentrations of the test substance were administered orally to male and female Wistar rats. All animals were monitored for clinical signs and body weight changes during a 14-day observation period after administration. They were subjected to a necropsy at the end of the observation period. Effects of the application:

1087 mg/kg bw: no mortality

2174 mg/kg bw: 1 dead animal after 7 days

3261 mg/kg bw: 3 dead animals after 24h, 1 dead animal after 7 days

4348 mg/kg bw: 4 dead animals after 24 h (100%)

In all dosage groups animals seemed paralysed with fear and compound caused abdominal ache syndrome, pinched eyes, ataxia, disturbances of coordination and decreased readiness for reflection. These symptoms changed into sedation and coma. Furthermore, two late mortalities did occur within 72 hours. The surviving animals did not show test specific changes or dose-related weight gains. Clear decreased weight gains compared to the normal body-weights occurred. At autopsy of acute mortalities and final autopsy no treatment-related anatomical-pathological findings were made macroscopically in the thorax and cranium cavity. Alone the belly cavity appeared with hyperemiae in the gastro-intestinal tract of acute mortalities. Final autopsy of surviving animals did not show any other alterations. Based on these results, the LD50 value was determined to be 3098 mg/kg bw after 24 h and 2717 mg/kg bw after 14 days.