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Administrative data

acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline-Study. Non-GLP but very well documented.

Data source

Reference Type:
study report

Materials and methods

Test guideline
according to guideline
EU Method B.1 (Acute Toxicity (Oral))
GLP compliance:
Test type:
acute toxic class method
Limit test:

Test material

Constituent 1
Chemical structure
Reference substance name:
5-amino-3-(morpholin-4-yl)-1,2,3-oxadiazolidin-3-ium chloride
EC Number:
Cas Number:
Molecular formula:
C6 H11 N4 O2 . Cl
5-amino-3-(morpholin-4-yl)-1,2,3-oxadiazolidin-3-ium chloride
Test material form:
solid: particulate/powder
migrated information: powder

Test animals

other: Wistar, Crl:(WI)BR
Details on test animals or test system and environmental conditions:
- Source: Charles River Wiga GmbH, Germany
- Age at study initiation: 50-57 d
- Weight at study initiation:
Male Limittest: 295 +/- 8 g
Male LD50-Test: 303 +/- 11 g
Female Limittest: 214 +/- 8 g
Female LD50-Test: 218 +/- 9 g
- Fasting period before study:
- Housing: Semi barrier husbandry, Makrolon cage type 3, single animal husbandry
- Diet (e.g. ad libitum): Altromin 1326, ad libitum
- Water (e.g. ad libitum): Tab water, ad libitum
- Acclimation period: 5 d

- Temperature (°C): 21-25°C, climate automatic
- Humidity (%): 30-70 %
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12:12 h, Light phase from 6:30-18:30 MEZ

Administration / exposure

Route of administration:
oral: gavage
Details on oral exposure:
Aqua dest.
- Concentration in vehicle: 5, 7.5, 10 and 20 %
- Amount of vehicle (if gavage): 1 ml/kg BW
500 mg/kg BW
750 mg/kg BW
1000 mg/kg BW
2000 mg/kg BW
No. of animals per sex per dose:
5 male + 5 female
Control animals:
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:

Mortality: at application day continuously, then once a day in the morning
clinical signs: at application day continuously, then once a day in the morning
body weight: at 1st, 7th and 14th day. Biometric analysis of body mass development by t-test according to Welch

- Necropsy of survivors performed: yes. Section and macroscopic examination of the animals that died during the study, and the animals that were killed at the end of the follow-up period with an overdose of chloroform.

- Other examinations performed: clinical signs, body weight, pathology

Results and discussion

Effect levelsopen allclose all
Dose descriptor:
Effect level:
>= 504 - <= 956 mg/kg bw
Based on:
test mat.
Dose descriptor:
Effect level:
>= 690 - <= 852 mg/kg bw
Based on:
test mat.
The animals died dose-dependent between one hour and four days after administration of the test substance, with most deaths occurring in the first 6 hours.
The calculation of LD 50 by probit analysis showed that for males a value of 694.9 mg / kg bw (lower limit of 504.5 mg / kg, upper limit of 955.2 mg / kg. Regression coefficient 5.6401). For the females the value was 766.6 mg / kg bw (lower limit of 690.1 mg / kg, upper limit of 851.6 mg / kg. Regression coefficient 26.5735)
Clinical signs:
other: The control animals, which were treated with distilled water, showed a good general condition and normal behavior throughout the test course. The clinical symptoms were substantially similar in type and severity in all dose groups. Immediately on the a
Gross pathology:
The necropsy of the animals, which were killed at the end of the test, did not show any pathological abnormalities, neither in the controll groups nor in the dose groups.
The deceased during the study animals the dose groups 500 to 1000 mg / kg showed blood filling in the liver, a brightening of the spleen, petechial hemorrhages in the lungs and a watery-frothy stomach contents. In animals of the group 2000 mg / kg, no pathological changes were observed.

Any other information on results incl. tables

In a first test linsidomine was administered at a dose of 2000 mg / kg orally to male and female rats. In this case, all the animals came within hours ad exitum, so that for the following experiment, the dosage regimen 500, 700 and 1000 mg / kg was chosen. The LD50 values are in the same range for both sexes: Male 695 and female 767 mg/kg bw.

The immediate appearance of clinical symptoms after application indicates a rapid absorption of the test substance from the gastrointestinal tract. Nature and course of poisoning show a central effect of the test substance. The gross pathological findings in liver and spleen correspond to a circulatory insufficiency due to shock states with congestion of the liver and blood distribution in the spleen. The petechial hemorrhages in the lungs underline the circulatory collapse, which eventually led to the death of the animals.

The foamy-aqueous gastric contents is explained by the refusal of solid feed intake, the administered test substance and the intake of drinking water. The bleeding in the stomach glandular region in the female animal of the group 1000 mg / kg represent a single finding. Due to the peracute course of the poisoning in the highest dose group(2000 mg / kg) no gross pathological changes were determined.

The increased body weight gain in the animals of groups 500 and 750 mg / kg compared to the control animals can be seen as a relaxation effect, especially in the second post observation week.

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category IV
Migrated information Criteria used for interpretation of results: EU
According to Annex I of EU 1272/2008 must be classified as acute toxic cat. 4.