Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

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

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
no
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: KFM, CH-4414 Fullinsdorf, Switzerland.
- Age at study initiation: young adult, age not specified.
- Weight at study initiation: ranged between 150 and 200 g.
- Fasting period before study: access of food only was prevented approximately 18 hours prior and four hours aiter the dosing. The water bottles were with-drawn two hours prior and four hours after dosing.
- Housing: rats were housed individually in Macrolon cages.
- Diet: standard laboratory pelleted diet (KLIBA no. 24-343-4 from Klingentalmuhle AG., Basle), ad libitum. The batch of diet used for the study was analysed for chemical and microbiological contaminants.
- Water: ad libitum.
- Acclimation period: animals were acclimatised to the experimental environment for a period of about five days prior to the start of the study.

ENVIRONMENTAL CONDITIONS
- Temperature: 23 ± 2 °C
- Humidity: 30 - 70 %
- Air changes: approximately 15 changes/hour.
- Photoperiod: 12 hrs dark / 12 hrs light.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
DMSO
Details on oral exposure:
Dosed volume: 15 ml per kg body weight.
Doses:
1600, 2500, 3200 and 4000 mg/kg bw
No. of animals per sex per dose:
five male and five female rats
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: animals were observed soon after dosing, then at hourly intervals for the remainder day 1. On the subsequent days the animals were observed once in the morning and once in the late afternoon. Clinical signs were recorded at each observation.
- Frequency of weighing: individual body weights on day 1, 7 and 14.
- Necropsy of survivors performed: yes. Surviving animals were killed after two weeks. All animals which died during the study and those killed after two weeks were subjected to a macroscopic postmortem examination. The macroscopic appearance of the abnormal organs was recorded.

DOSE SELECTION
A preliminary study was carried out to establish a dosing regimen, using groups of two males and two females at three dosages, using 10 - 15 ml/kg body weight.

Results and discussion

Preliminary study:
Mortality: at 1000 mg/kg bw 0 %; at 2400 mg/kg bw 50 %; at 4800 mg/kg bw 100 %
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 730 mg/kg bw
Based on:
test mat.
Mortality:
Mortality: at 1600 mg/kg bw 20 %; at 2500 mg/kg bw 30 %; at 3200 mg/kg bw 60 %; at 4000 mg/kg bw 90 %
Clinical signs:
The animals were weak and dazed and their movement decreased. Labored respiration.
Gross pathology:
No special findings

Any other information on results incl. tables

Cumulative mortality

Dose No males died No females died Mortality %
1600 1 1 20
2500 1 2 30
3200 4 2 60
4000 4 5 90

Sex Dose Mortality ratio Time of death after dosing
Males 1600 1/5 50'
2500 1/5 58'
3200 4/5 55', 3.5h, 4.5h, 4.5h
4000 4/5 36', 45', 4h, 5h
Females 1600 1/5 -
2500 2/5 50', 4.5h
3200 2/5 35', 6h
4000 5/5 30', 53', 91', 5h, 5.5h

Applicant's summary and conclusion

Interpretation of results:
other: not classified, according to the CLP Regulation (EC 1272/2008)
Conclusions:
LD50 (male and female): 2730 mg/kg bw ± 233 mg
Executive summary:

The study was performed to assess the acute oral toxicity of the test material in the Han-Wistar rat. Following a range-finding study, fours groups of ten fasted animals (five males and five females) were given the following oral doses (test item in DMSO): 1600, 2500, 3200 and 4000 mg/kg bw.

The animals were observed for fourteen days after the day of dosing and were then killed for gross pathological examination.

Mortality resulted to be 20 % at 1600 mg/kg bw, 30 % at 2500 mg/kg bw, 60 % at 3200 mg/kg bw and 90 % at 4000 mg/kg bw. The animals were weak and dazed and their movement decreased. Labored respiration. No special findings were recorded from pathology examination.

Conclusion

LD50 (male and female): 2730 mg/kg bw ± 233 mg