Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
14 March 2001 to 6 April 2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001
Report Date:
2001

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, Kent, UK
- Age at study initiation: approximately 8 weeks
- Weight at study initiation: Males: 225 - 238 g; Females: 201 - 205 g
- Fasting period before study: Overnight fast immediately before dosing
- Housing: solid-floor polypropylene cages furnished with woodflakes
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

The diet, drinking water and bedding were routinely analysed and were considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25 °C
- Humidity (%): 30 - 70 %
- Air changes (per hr): at least 15 per hour
- Photoperiod (hrs dark / hrs light): 12 hours dark, 12 hours light


IN-LIFE DATES: NDA

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/ml
- Amount of vehicle (if gavage): 10 ml/kg
- Justification for choice of vehicle: NDA
- Lot/batch no. (if required): NDA
- Purity: NDA


MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg


DOSAGE PREPARATION (if unusual): The test material was freshly prepared, as required, as a suspension at the appropriate concentration in arachis oil BP.


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: NDA - although it is reasonable to assume the testing laboratory had prior information leading to the selection of the inital dose level of 2000 mg/kg.
Doses:
2000 mg/kg bodyweight
No. of animals per sex per dose:
2000 mg/kg: 3 male, 3 female
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for deaths or overt signs of toxicity 0.5, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days. Individual bodyweights were recorded prior to dosing and seven and fourteen days after treatment.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: NDA
Statistics:
NDA

Results and discussion

Preliminary study:
Not applicable
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 500 mg/kg bw
Mortality:
Male: 2000 mg/kg bw; Number of animals: 3; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 3; Number of deaths: 0
Clinical signs:
Signs of toxicity related to dose levels: there were no signs of systemic toxicity
Body weight:
All animals showed expected gains in bodyweight over the study period.
Gross pathology:
Effects on organs: no abnormalities were noted at necropsy.
Other findings:
- Organ weights: NDA
- Histopathology: NDA
- Potential target organs: NDA
- Other observations: NDA

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral median lethal dose (LD50) of the test material in the Sprague-Dawley CD (Crl: CD® (SD) IGS BR) strain rat was estimated from the attached flow chart (Test Procedure with a Starting Dose of 2000 mg per kg bodyweight.pdf) as being greater than 2500 mg/kg bodyweight.
No mortalities were noted in animals treated with 2000 mg/kg bodyweight.
Executive summary:

In an acute oral toxicity study (656/089), a group of 6 fasted eight week old Sprague Dawley strain rats (three male and three female) were given a single oral dose of Experimental 11214-70 in arachis oil at a dose level of  2000  mg/kg bw and observed for 15 days.

Combined Oral LD50(estimated):>2500 mg/kg bw

No mortality occurred. No signs of systemic toxicity were noted during the study, and no abnormalities were noted at necropsy.