Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
12 june - 27 July 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study (OECD).

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report Date:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
17 December, 2001
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
30 May, 2008
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Version / remarks:
December 2002
Qualifier:
according to
Guideline:
other: Japan MAFF Testing Guideline of 12 Nousan No. 8147
GLP compliance:
yes (incl. certificate)
Remarks:
Bioassay, Labor fuer biologische Analytik GmbH, Heidelberg, Germany
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid - liquid: suspension
Details on test material:
- Name of test material (as cited in study report): L4-Ligand
- Physical state: white solid
- Analytical purity: 97.0g/100g ± 0.3g/100g
- Lot/batch No.: 0005473663
- Expiration date of the lot/batch: 01 February, 2013
- Storage condition of test material: room temperature, under N2, protected against humidity

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Sulzfeld, Germany
- Age at study initiation: approximately 10 weeks
- Weight at study initiation: mean (administration 1) 186.3g ± 4.04g, mean (adminsitration 2) 181.0g ± 3.61g
- Fasting period before study: 16 hours
- Housing: single housing in Makrolon Type III cages
- Diet: VRF1 (P); SDS Special Diets Services, Altrip, Germany
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 3°C
- 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
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 0.4g/mL
- Amount of vehicle: 5 mL/kg bw

MAXIMUM DOSE VOLUME APPLIED: approximately 1 mL

DOSAGE PREPARATION: stirring with a homogenizer and a magnetic stirrer to ensure homogeneity

CLASS METHOD
- Rationale for the selection of the starting dose: by request of the sponsor
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3 (sequential testing of 2 groups)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations for clinical signs are done several time on the day of application and daily thereafter on workdays, individual body weights were determined before administration and on day 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
Calculations were performed using Microsoft Excel 2003 and checked with a calculator.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no mortalities were observed
Mortality:
No mortality occured in both test groups.
Clinical signs:
No clinical signs were observed for both test groups.
Body weight:
The mean body weight of both test groups was within the normal range during the whole study.
Gross pathology:
There were no macroscopic pathological findings at the end of the observation period.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
DSD: not classified
CLP: not classified