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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:
November 05, 2012 - December 13, 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report Date:
2013

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Qualifier:
according to
Guideline:
other: Japan MAFF 8147
Qualifier:
according to
Guideline:
other: Commission Regulation (EC) No 440/2008
GLP compliance:
yes (incl. certificate)
Remarks:
Bioassay, Labor für biologische Analytik GmbH, INF 515, 69120 Heidelberg
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Physical state: solid/white
- Analytical purity: 99.0 g/100 g determined by 1H-MR spectroscopy
- Expiration date of the lot/batch: July 15, 2015
- Storage condition of test material: Room temperature; avoid temperatures > 35°C

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at study initiation: approx. 10 - 11 weeks
- Weight at study initiation: 174 - 207 g
- Fasting period before study: Feed was withdrawn from the animals at least 16 hours before administration, but water was available ad libitum
- Housing: Single housing in Makrolon cages, type III
- Diet: VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany)
- Water: Tap water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C +/- 3
- Humidity (%): 30 - 70
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
olive oil
Remarks:
Ph.Eur
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 20 g/ml
- Amount of vehicle (if gavage): 10 ml/kg
Doses:
2000 mg/kg
No. of animals per sex per dose:
2 groups of 3 female animals
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual body weights shortly before administration (day 0), weekly thereafter and on the last day of observation. Recording of clinical signs several times on the day of administration, and at least once daily thereafter each workday for the individual animals. A check for any dead or moribund animals was made at least once each workday.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
In two out of three animals of the first test group impaired general state, dyspnoea and piloerection were observed at hour 0 and 1 after administration. On study day 2 and 3 all animals showed impaired general state and piloerection. In all animals of this test group reduced feces was noted from study day 1 until study day 3 after administration.
In the second 2000 mg/kg bw dose group all three animals showed impaired general state and piloerection from study day 1 until study day 3. In two of these animals these findings were observed until study day 9. In all animals reduced feces were observed on study day 2 only. Additionally light brown discolored feces were noted in two animals on study day 2 and 3 after administration.
Body weight:
The mean body weight of the test groups increased throughout the study period within the normal range.
Gross pathology:
There were no macroscopic pathological findings in the animals sacrificed at the end of the observation period.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this study the median lethal dose of the test article after oral administration was found to be greater than 2000 mg/kg bw in rats.
Executive summary:

In a GLP-compliant acute oral toxicity study performed according to the Acute Toxic Class method (OECD 423), 2000 mg/kg bw of the test item (preparation in olive oil Ph.Eur.) were administered to two test groups of three fasted Wistar rats by gavage. The following test substance-related clinical observations were recorded:

2000 mg/kg (first test group):

- No mortality occurred

- Impaired general state in all animals

- Dyspnoea in two out of three animals

- Piloerection in all animals

- Reduced feces in all animals  

2000 mg/kg (second test group):

- No mortality occurred

- Impaired general state in all animals

- Piloerection in all animals

- Reduced feces in all animals

- Light brown discoloration of feces in two out of three animals

The mean body weight increased within the normal range throughout the study period. There were no macroscopic pathological findings in the animals sacrificed at the end of the observation period. The acute oral LD50 in rats was calculated to be > 2000 mg/kg bw.