Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
23 April 2013 - 8 May 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Test method according to OECD 423. GLP study.

Data source

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

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): CNSL
- Physical state: Dark Brown Liquid
- Analytical purity: ca 100 %
- Lot/batch No.: 001
- Expiration date of the lot/batch: 01 December 2014
- Storage condition of test material: Controlled Room Temperature (15-25oC)

Test animals

Species:
rat
Strain:
other: CRL:(WI)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, D-97633 Sulzfeld
- Age at study initiation: 8 weeks old
- Weight at study initiation: 196–209 g
- Fasting period before study: Yes, the night before administration.
- Housing: 3 animals/cage. Type II polypropylene/polycarbonate cage with lignoce bedding
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.5 – 23.3 °C
- Humidity (%): 34 – 68 %
- Air changes (per hr): 15 – 20 air exchanges/hour
- Photoperiod (hrs dark / hrs light): 12 hours light / 12 hours dark

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg bw
- Lot/batch no. (if required): BCBH5068V

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg bw (10 mL/kg bw)

DOSAGE PREPARATION (if unusual): The test item was freshly formulated at a concentration of 200 mg/mL in the vehicle. The formulation container was stirred continuously up to finishing the treatment.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: In the lack of any preliminary toxicological information, 2000 mg/kg bw was selected to be the starting dose.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
6 animals, 3 animals/group
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: See below.
- Necropsy of survivors performed: yes
- Examinations performed:
Clinical signs: 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter. Observations: skin, fur, eyes, mucous membranes, respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
Body weight: Recorded on the day before treatment (Day -1), on the day of the treatment (Day 0) and weekly thereafter.
Necropsy: External appearance, the cranial, thoracic and the abdominal cavities were opened and the organs and the tissues were observed. Macroscopic abnormalities were recorded.
Statistics:
The method used was not intended to allow the calculation of a precise LD50 value.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortalities were observed.
Clinical signs:
The test substance did not cause any clinical signs during the 14 days observation period.
Body weight:
Body weight gains during the study showed no indication of a test item-related effect.
Gross pathology:
No macroscopic observations were seen in animals terminated on Day 14.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral LD50 value of the test item was found to be above 2000 mg/kg bw in female CRL:(WI) rats.
Executive summary:

The single-dose oral toxicity of the substance was performed according to the acute toxic class method OECD 423 in CRL: (WI) rats. Initially, three females were treated at a dose level of 2000 mg/kg bw. As no mortality was observed, a confirmatory group was treated at the same dose level. No mortality was observed in the confirmatory group, therefore no further testing was required. Clinical observations were performed at 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter. Body weight was measured on Days -1, 0 and 7 and before necropsy. All animals were subjected to a necropsy and a macroscopic examination. No test item related effects were observed during the study performance. The acute oral LD50 value was found to be above 2000 mg/kg bw.