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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1999
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1999
Report Date:
1999

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Principles of method if other than guideline:
not applicable
GLP compliance:
not specified
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: orange solid
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 188719.4
- Expiration date of the lot/batch: November 2003

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at room temperature (approx. 20 °C) away from direct sunlight.
- Stability under test conditions: Stable under storage conditions
- Solubility and stability of the test substance in the solvent/vehicle: 24 hours at room temperature

Test animals

Species:
rat
Strain:
Wistar
Remarks:
Hanlbm: WIST (SPF)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: RCC Ltd, Biotechnology & Animal Breeding Division, CH-4414 Füllinsdorf / Switzerland
- Age at study initiation: Females: 10 weeks, Males: 8 weeks
- Weight at study initiation: Females: 181.6-186.0 g, Males: 201.0-206.4 g
- Fasting period before study: Approx. 17.5 to 19.5 h
- Housing: Groups of three in Makrolon type-4 cages with standard softwood bedding ("Lignocel", Schill AG, CH-4132 Muttenz)
- Diet: Pelleted standard Kliba 3433, batch no. 28/98, rat maintenance diet (Kliba Mühlen AG, CH-4303 Kaiseraugst) (ad libitum except for the overnight fasting period prior to intubation)
- Water: Tap water (ad libitum)
- Acclimatization: Under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study.
- Identification: By unique cage number and corresponding color-coded spots on the tail.

ENVIRONMENTAL CONDITIONS
- Temperature: 22±3 °C
- Humidity: 40-70 % (values above 70% during cleaning process possible)
- Air changes: 10-15 air changes/h
- Photoperiod: 12 h dark/12 h light cycle

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Details on oral exposure:
Test substance preparation:
The test substance was placed into a glass beaker on a tared Mettler PG 503-S balance and the vehicle (polyethylene glycol) was added. A weight by volume dilution was prepared using a magnetic stirrer as homogenizer. Homogeneity of the test substance in the vehicle was maintained during treatment. The preparation was made shortly before each dosing.

Treatment
The animals received a single dose of the test substance on a mg/kg bw basis by oral (gavage) following fasting for approx. 17.5 to 19.5 h, but with free access to water. Food was provided again approx. 3 h after dosing.
Dose/kg body weight 2000 mg
Application volume / kg body weight: 10 mL
concentration: 0.2 g/mL
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 d
- Other examinations performed: Clinical signs, body weight,organ weights, histopathology, other:
-Mortality / Viability: Four times during test Day 1 and once daily during Days 2-15.
- Body weights: On test Day 1 (pre-administration), 8 and 15.
- Clinical signs: Each animal was examined for changes in appearance and behavior four times during Day 1, and once daily during Days 2-15.
- Necropsy of survivors performed: yes, at the end of the observation period all animals were sacrificed by intraperitoneal injection of NARCOREN at a dose of at least 2 mL/kg bw (equivalent to at least 320 mg sodium pentobarbitone/kg bw). The animals were examined macroscopically and all abnormalities recorded. Thereafter, they were discarded.
Statistics:
No statistical analysis was used as no deaths occurred.

Results and discussion

Preliminary study:
not applicable
Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 1 920 mg/kg bw
Based on:
act. ingr.
Mortality:
No deaths occurred during the study.
Clinical signs:
No clinical signs were observed troughout the study period.
Body weight:
The body weight of the animals was within the range commonly recorded for animals of this strain and age.
Gross pathology:
No macroscopic findings were observed at necropsy.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The oral LD50 of the test substance was found to be >2000 mg/kg bw (i.e. ca. >1920 mg a.i./kg bw) in rats.
Executive summary:

A study was conducted to assess the acute oral toxicity of the test substance in Wistar rats according to OECD Guideline 423 and EU Method B.1. Two groups, each using three female or three male fasted rats, received a single oral (gavage) dose of 2000 mg/kg bw. The test substance was suspended in vehicle (polyethylene glycol) at a concentration of 0.2 g/mL and administered at a volume of 10 mL/kg. The animals were examined for clinical signs four times during test day 1 and once daily during test days 2-15. Mortality/viability were recorded together with clinical signs at the same time intervals. Body weights were recorded on day 1 prior to administration and on days 8 and 15. All animals were necropsied and examined macroscopically after 15 days of observation. No death occurred during the study. No clinical signs were observed during the observation period. The body weight of the animals was within the range commonly recorded for animals of this strain and age. No macroscopic findings were observed at necropsy.

Based on the findings of the study, the oral median lethal dose (LD50) of the test substance was found to be > 2000 mg/kg bw (i.e. ca. 1920 mg a.i./kg bw) in rats.