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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
7th April 2011 to 26th April 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: A GLP compliant study performed in line with appropriate guidelines.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011
Report date:
2011

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
fixed dose procedure
Limit test:
yes

Test material

Constituent 1
Details on test material:
- Physical state: off-white solid
- Storage condition of test material: room temperature in the dark

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories Ltd., Oxon., UK
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 170-185 g
- Fasting period before study: overnight
- Housing: groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes
- Diet (e.g. ad libitum): 2014C Teklad Global Rodent diet ad libitum
- Water (e.g. ad libitum): mains water ad libitum
- Acclimation period: at least five days

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

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 bodyweight
- Justification for choice of vehicle: The test material did not dissolve or suspend in distilled water
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
Five
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: morbidity and mortality checks were made twice daily.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical observations were made at ½, 1, 2 and 4 hours after dosing and subsequently one daily for fourteen days. Individual bodyweights were recorded at days 0, 7 and 14.
Statistics:
Evaluation of data included identification of number of animals that died during the study and determination of the nature, severity, onset and duration of toxic effects. Effects in bodyweights and abnormalities at necroscopy were noted. Mortality data was used to determine an acute oral median lethal dose (LD50).

Results and discussion

Preliminary study:
2000 mg/kg bw was chosen as the starting point and given to one animal (dose volume 10 mL/kg bw; concentration 200 mg/mL) as a sighting study. In the absence of toxicity, an additional group of four animals were treated in the same way.
Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
All animals survived until the termination of the study.
Clinical signs:
An isolated and transient incident of red/brown staining around the snout was noted in one animal 30 minutes and one hour after dosing.
Body weight:
All animals showed expected bodyweight gains over the course of the study.
Gross pathology:
No abnormalities were noted at necroscopy.

Any other information on results incl. tables

Table 1: Individual bodyweights and bodyweight gains

 Dose level (mg/kg bw) Animal number Bodyweight (g) at day   Bodyweight gain (g) during week
    0 7 14 1 2
 2000 1-0 175 192 208 17 16
 2000 2-0 185 190 202 5 12
 2000 2-1 185 191 202 6 11
 2000 2-2 170 178 193 8 15
 2000 2-3 173 181 198 8 17

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the study, the acute oral toxicity of the test substance gave an LD50 value of >2000 mg/kg bw.
Executive summary:

In a GLP compliant acute oral toxicity study conducted in line with OECD Guideline 420 and EU Method B.1bis, the acute oral toxicity of the test substance was determined using the fixed-dose method. The LD50 of the substance was determined to be >2000 mg/kg bw.

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