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
Study period:
1992-02-05 to 1992-02-19
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report Date:
1992

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
adopted February 24, 1987.
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Version / remarks:
September 1984
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
Ceramide III
Specific details on test material used for the study:
The formulations were prepared immediately prior to dosing. The test substance was weighed into a glass flask on an analytical balance and the vehicle (w/w) was added. Adjustment was made for specific gravity of vehicle. Homogeneity of the test substance in vehicle was obtained using a homogeniser and a spatula.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: BRL Ltd., Basel, Switzerland
- Age at study initiation: approx. 8 weeks
- Weight at study initiation: Male= 198 to 209 g, female= 150 to 164 g
- Fasting period before study: yes, feed was withheld overnight prior to dosing until approximately 3-4 hours after administration of the test substance.
- Housing: Collection caging in polycarbonate cages / max. 5 rats
- Diet (e.g. ad libitum): laboratory animal diet (KLIB 343 from Klingentalmühle AG, Kaiseraugst, Switzerland)
- Water (e.g. ad libitum): ad libitum, tap water
- Acclimation period: 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 °C
- Humidity (%): 55 %
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 hours daily

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
propylene glycol
Details on oral exposure:
Dose volume: 10 mL/kg bw
DOSAGE PREPARATION: 5000 mg/kg bw were achieved by administration of two times 2500 mg/kg bw
Doses:
5000 mg/kg bw, given as 2 dosages of 2500 mg/kg bw within 24 hours. Multiple dosages given within 24 hours are regarded as a single dose.
No. of animals per sex per dose:
5 males, 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations:
mortality: twice daily
clinical signs: 0, 2, 4 h, daily thereafter
- Frequency of weighing: Days 1 (pre-administration), 8 and 15
- Necropsy of survivors performed: yes

Results and discussion

Preliminary study:
-Pilot study with three groups, each comprising of 1 male and 1 female rat
-orally dosed with test material in propylene glycol at 5000 (2x2500 within 24 hours), 2000 or 1000 mg/kg body weight
- no animal died.
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
act. ingr.
Mortality:
No mortality occurred.
Clinical signs:
Signs of ill health or behavioural changes included ataxia only observed in all animals approximately 2 hours after each dosing.
Body weight:
The body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain.
Gross pathology:
Macroscopic post mortem examination of the surviving animals at termination did not reveal any abnormalities that were not commonly noted among rats of this age and strain or that were considered toxicologically significant. Pelvic dilation (left and right kidney) in a single female rat was considered not to be related to the treatment.
Other findings:
None reported.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
In this acute oral toxicity study, the oral LD50 value of the test item in rats of either sex was exceeding 5000 mg/kg bodyweight.
Executive summary:

In an acute oral toxicity study according to OECD guideline 401 (adopted February 24, 1987) and EU Method B.1 (September 1984), 5 male and 5 female, fasted, 8-9 weeks old Wistar strain rats were given a single oral dose of Ceramide III in propylene glycol by gavage at a dose of 5000 mg/kg bw and daily observed for 14 days. Body weight was determined at day 1 (pre-administration), 8 and 15.

Ceramide III was administered as 2 dosages of 2500 mg/kg bw within 24 hours. Multiple dosages given within 24 hours are regarded as a single dose.

No animal died. Apart from ataxia noted after each dosing, no other signs of ill health or behavioural changes were observed during the study period and no macroscopic toxicologically significant abnormalities were noted at necropsy at the end of the experimental period.

Oral LD50 (rat) > 5000 mg/kg bodyweight