Registration Dossier

Toxicological information

Acute Toxicity: oral

Currently viewing:

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:
comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1982
Report Date:
1982

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:
yes

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: animals were purchased from KFM, CH-4414 Fülllinsdorf, Switzerland.
- Age at study initiation: young adult, age not specified.
- Weight at study initiation: ranged between 140 and 180 g.
- Fasting period before study: access of food only was prevented approximately 18 hours prior and 4 hours after the dosing. The water bottles were withdrawn 2 hours prior and 4 hours after dosing.
- Housing: housed individually in Macroron cages.
- Diet: standard laboratory pelleted diet (KLIBA no. 24-343-7 from Klingentatmühle AG, Basle). The batch of diet used for the study was analysed for chernical 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: 50 ± 10 %
- Air changes: approximately 15 changes/hour.
- Photoperiod: the light/dark cycle was 12 hours.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
DMSO
Details on oral exposure:
- Test fomulation: test item was dissolved in DMSO; the test sample was prepared immediately before dosing.
- Dose volume: 15 mI per kg body weight.
Doses:
5350 mg/kg bw, higher dosages were not applicable.
No. of animals per sex per dose:
5 male and 5 female.
Details on study design:
- Duration of observation period following administration: the animals, on both the preliminary and the main studies, were observed for 14 days after dosing.
- 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 were recorded on day 1, 7 and 14.
- Necropsy of survivors performed: 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.

PRELIMINARY TEST
A preliminary study was carried out to establish a dosing regimen, using groups of two males and two females at two dosage, using 10-15 ml/kg body weight.
Statistics:
The acute oral LD50 was determined using the probit method of L.C. Miller and M.L. Tainter (Proc. Soc. exper. Biol. Med. 57 (1944) p. 26) or calculated by computer using the method of D.J. Finney (3rd. ed., 1971). The given doses always referred to the test material.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 350 mg/kg bw
Based on:
test mat.
Remarks on result:
not determinable due to absence of adverse toxic effects
Mortality:
No death occurred during the range-finding experiment.
During the main experiment, one female died 59 hours after dosing.
Clinical signs:
No overt symptoms of poisoning were observed.
Gross pathology:
No special findings could be detected.

Any other information on results incl. tables

Mortality ratio and group mean bodyweight (g) of rats

Sex Dosage Bodyweight (g) at Mortality ratio
Dosing 1 wk 2wks
Male Test item, 5350 mg/kg bw 177 207 246 0/5
Female Test item, 5350 mg/kg bw 166 163 183 1/5

Applicant's summary and conclusion

Interpretation of results:
other: not classified, according to CLP Regulation (EC 1272/2008)
Conclusions:
LD50 > 5350 mg/kg bw (males and females)
Executive summary:

Test item was dissolved in DMSO; the test sample was prepared immediately before dosing. A preliminary study was carried out to establish a dosing regimen, using groups of two males and two females at two dosage, using 10-15 ml/kg body weight. In the main experiment, groups of five male and five female rats were dosed at levels selected using the results of the preliminary study. The animals were dosed by oral gavage by means of a stomach tube and the dosed volume was 15 ml per kg body weight. The animals on both, the preliminary and the main studies were observed for 14 days after dosing.

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.

One female died 59 hours after dosing. No overt symptoms of poisoning were observed. No special findings could be detected.

Conclusion

LD50 > 5350 mg/kg bw (males and females)