Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
September 2005 - November 2005
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2006
Report Date:
2006

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
2001
Deviations:
yes
Remarks:
the temperature recorded in the animal room was sometimes outside of the target ranges specified in the Study Plan: minor deviation not considered to have compromised the validity and integrity of the study
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Janvier, le Genest-Saint-Isle, France
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8 week old
- Weight at study initiation: 196 +/- 8 g
- Fasting period before study: yes
- Housing: polycarbonate cages. 3 rats per cage
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-2 °C
- Humidity (%): 30 to 70%
- Air changes (per hr): 12 / hour
- Photoperiod (hrs dark / hrs light): 12h/12h

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
The dosage form preparations were administered to the animals under a volume of 10 mL/kg.
The administration was performed in a single dose by oral route using a metal gavage tube fitted to a 2 mL plastic syringe.
The volume administered to each animal was adjusted according to body weight determined on the day of treatment.
Doses:
As no information on the toxic potential of the test item was available, for animal welfare reasons, the starting dose-level of 300 mg/kg was chosen.
1st dose : 300 mg/kg
2nd dose : 2000 mg/kg
No. of animals per sex per dose:
300 mg/kg : 3
2000 mg/kg : 3 + 3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations : after adminstration and at least once a day after
- Freqency of weighing: aon day 1, day 8 and day 15
- Necropsy of survivors performed: yes

Results and discussion

Preliminary study:
no
Effect levels
Key result
Sex:
female
Dose descriptor:
LD0
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
not determinable due to absence of adverse toxic effects
Mortality:
No mortality observed at 300 or 2000 mg/kg/day.
Clinical signs:
No clinical signs at 300 mg/kg/day.
Hypoactivity and piloerection observed in 3/6 animals treated with 2000 mg/kg/day on day 1 only.
Body weight:
When compared to historical control animals, a slightly reduced body weight gain was seen in 2/3 given 300 mg/kg during the second week of the study.
At the 2000 mg/kg dose-level, a reduced body weight gain was recorded in 1/6 females during the first week of the study and in 2/6 females during the second week of the study.
The overall body weight gain of the other animals was not considered to be affected by treatment with the test item.
Gross pathology:
Macroscopic examination of the main organs of the animals revealed no apparent abnormalities.
Other findings:
no

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the experimental conditions of this study, the oral LD50 of the test item was higher than 2000 mg/kg/day.
Executive summary:

The acute oral toxicity of the test item was evaluated in rats according to the OECD guideline 423 and the GLP principles.

The test item was prepared in corn oil and was administered by oral route (gavage), under a volume of 10 mL/kg to groups of 3 fasted female Sprague-Dawley rats. Clinical signs, mortality and body weight gain were checked for a period of up to 14 days following the single administration of the test item.

As no information on the toxic potential of the test item was available, for animal welfare reasons, the starting dose-level of 300 mg/kg was chosen. No mortality and clinical signs were observed at this dose. So two other groups were treated with 2000 mg/kg/day. No mortality occured but hypoactivity and piloerection were observed in 3/6 animals on day 1 only.

A slighlty reduced body weight gain was seen in 2/3 given 300 mg/kg during the second week of the study. At the 2000 mg/kg dose-level, a reduced body weight gain was recorded in 1/6 females during the first week of the study and in 2/6 females during the second week of the study. The overall body weight gain of the other animals was not considered to be affected by treatment with the test item.

At necropsy, no apparent abnormalities were observed in any animal.

Under the experimental conditions of this study, the oral LD50 of the test item was higher than 2000 mg/kg/day.