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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:
29-Oct-1996 to 19-Nov-1996
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study (OECD test guideline 401)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996
Report Date:
1996

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Analytical purity: 99.35-99.45 %
- Description: off white solid
- Storage condition of test material: In the original container at room temperature away from direct sunlight

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: BRL Ltd, Wölferstrasse 4, 4414 Füllinsdorf, Switzerland
- Age at study initiation: 8 weeks old (males), 10 weeks old (females)
- Weight at study initiation: 192.9-212.3 g (males), 179.2-188.0 g (females)
- Fasting period before study: overnight fasting prior to the single test item application
- Housing: groups of 5 rats/sex in Makrolon type-4 cages
- Diet: pelleted standard rat maintenance diet (Kliba 343, Kliba Mühlen AG, 4303 Kaiseraugst, Switzerland), ad libitum (with exception of an overnight fasting period prior to dosing; food was provided again 3 hours after dosing)
- Water: tap water, ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Humidity: 40-70 %
- Air changes: 10-15 changes/hour
- Photoperiod: 12 hours dark / 12 hours light

IN-LIFE DATES: 29-Oct-1996 to 19-Nov-1996

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: bidistilled water with a drop of Tween 80
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle: 10 mL/kg bw
- Justification for choice of vehicle: standard vehicle for studies of this type

DOSAGE PREPARATION:
The test article was placed into a glass beaker on a tared Mettler PM 460 balance and the vehicle (bi-distilled water with a drop of TWEEN 80) was added. A weight by volume dilution was prepared using a glass rod and a magnetic stirrer as homogenizers. Homogeneity of the test article in the vehicle was maintained during treatment using the same magnetic stirrer (Janke & Kunkel, 0-79219 Staufen). The preparation was made shortly before dosing.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: four times during day 1 and once daily thereafter
- Frequency of weighing: on days 1 (prior to administration), 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
Statistics:
The LOGIT-model could not be used as no deaths occurred.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred during the study.
Clinical signs:
No clinical signs of toxicity were observed during the study period.
Body weight:
The body weight was within the range of physiological variability known for rats 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 mean lethal dose of the test item after single oral administration to rats of both sexes, observed over a period of 14 days was found to be greater than 2000 mg/kg.
Executive summary:

In a GLP-compliant acute oral toxicity study according to OECD guideline 401, a group of five male and five female HanIbm:WIST (SPF) rats was treated with test material at 2000 mg/kg by oral gavage. The test article was suspended in vehicle (bi-distilled water and a drop of TWEEN 80) at a concentration of 0.2 g/ml and administered at a volume of 10 ml/kg. Four times during day 1 and once daily during days 2-15 the animals were examined for clinical signs. Mortality/viability were recorded together with clinical signs at the same time intervals. Body weights were recorded on day 1 before administration and on days 8 and 15. All animals were necropsied and examined macroscopically. No deaths occurred during the study. No clinical signs of toxicity were observed during the observation period. The body weight of the animals was within the range of physiological variability known for rats of this strain and age. No macroscopic findings were observed at necropsy. In conclusion, the mean lethal dose (LD50) of the test item after single oral administration to rats of both sexes, observed over a period of 14 days, was found to exceed 2000 mg/kg.