Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2008-06-10 to 2008-07-17
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report Date:
2008

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Version / remarks:
, adopted 2001-12-17
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Version / remarks:
, 2004
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
signed 2007-10-15
Test type:
fixed dose procedure
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: crystalline
Details on test material:
- Physical state: solid, whitish to white crystals
- Storage condition of test material: room temperature in the dark

Test animals

Species:
rat
Strain:
other: Sprague-Dawley CD
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan UK Limited, Bicester, Oxon, UK
- Age at study initiation: eight to twelve weeks of age
- Weight at study initiation: 151 g - 190 g
- Fasting period before study: overnight fast immediately before dosing and for approximately three to four hours after dosing
- Housing: housed in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes.
- Diet (ad libitum; exception: see "Fasting period before study" above): Certified Rat and Mouse Diet
- Water (ad libitum): mains drinking water
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature : 19 to 25 °C
- Relative humidity: 30 to 70 %
- Air changes: at least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
arachis oil
Remarks:
BP
Details on oral exposure:
VEHICLE
- Justification for choice of vehicle: arachis oil BP was used because the test material did not dissolve/suspend in distilled water.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg; the volume administered to each animal was calculated according the the fasted bodyweight at the time of dosing.


Doses:
300 mg/kg (sighting study)
2000 mg/kg (sighting study / main study)
No. of animals per sex per dose:
300 mg/kg: one female (sighting study)
2000 mg/kg: five females (sighting study/main study)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days

- Frequency of observations and weighing:
clinical observations: 0.5, 1, 2 and 4 hours after dosing and then daily for fourteen days.
morbidity and mortality checks: twice daily
individual bodyweights: Day 0 (the day of dosing) and on Days 7 and 14.

- Necropsy of survivors performed: yes, at the end of the observation period the animals were killed and all animals were subjected to gross necropsy consisting of external examination and opening of the abdominal and thoracic cavities.
Statistics:
Using the mortality data obtained, an estimate of the acute oral median lethal dose (LD50) was made.

Results and discussion

Preliminary study:
First, a single animal was treated with 300 mg/kg. There was no mortality. No signs of systemic toxicity were noted and the animal showed expected gains in body weight during the observation period. No abnormalities were noted at necropsy.
In the absence of toxicity, an additional animal was treated with 2000 mg/kg. In the absence of toxicity, an additional group of four animals was treated with 2000 mg/kg.

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
2000 mg/kg: 100 % survival.
Clinical signs:
2000 mg/kg: no signs of systemic toxicity during observation period.
Body weight:
2000 mg/kg: expected gains in bodyweight in all animals over the observation period.
Gross pathology:
2000 mg/kg: no abnormalities were observed at the necropsy

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
LD50 (female rats) > 2000 mg/kg bw
According to the Regulation (EC) No 1272/2008 and subsequent adaptations, the test item is not acutely toxic via the oral route.
Executive summary:

The acute oral toxicity of the test substance was investigated according to the OECD guideline 420 (2001). Four female Sprague-Dawley CD rats received a single dose of 2000 mg/kg bw in peanut oil by gavage. All animals were subjected to gross necropsy. Mortality, clinical signs or abnormalities at necropsy were not observed during the study. Furthermore, all animals gained the expected weight during the observation period. Thus, the LD50 is estimated with > 2000 mg/kg bw for female rats. According to the Regulation (EC) No 1272/2008 and subsequent adaptations, the test item is not acutely toxic via the oral route.