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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
December 2002 - January 2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted in compliance with agreed protocols, with no deviations from standard test guidelines and no methodological deficiences, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2003

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Description: colorless liquid
Assay: 99.32%w
Water: 60 mg/kg
Container: glass flask
Storage conditions: at room temperature and protected from light

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
On the day of treatment, the animals were approximately 6 weeks old and had a body weight ± standard deviation of 184±5 g for the males and 166±5 g for the females.
Females were nulliparous and non pregnant.
Acclimatation: at least 5 days before the beginning of the study.
Identification: individually by earnotches.

The conditions in animal room were set as follows:
- temperature: 22±2°C
- relative humidity: 30 to 70%
- light/dark cycle: 12h/12h
- ventilation: approximately 12 cycles/hour of filtered, non-recycled air.

All the animals had free access to A04C pelleted diet.
Each batch of food is analysed by the supplier for composition and contaminant levels.

Drinking water filtered by a FG Millipore membrane (0.22 µm) was provided ad libitum.
Bacteriological and chemical analyses of water are performed regularly by external laboratories. These analyses include the detection of possible contaminants (pesticides, heavy metals and nitroamines).
No contaminants were known to have been present in the diet, drinking water or bedding material at levels which may be expected to have interfered with or prejudiced the outcome of the study.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
The animals were fasted for an overnight period approximately 18 hours before dosing, but had free access to water. Food was given back approximately 4 hours after administration of the test item.

The dossage form preparations were administred 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 à 5 ml glass syringue (0.05 ml graduations).
The volume administred to each animal was adjusted according to body weight determined on the day of treatment.
Doses:
200 mg/kg and 2000 mg/kg
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
Three animals of one sex were used for each step. Males were used in the initial step.
The dose-level used as the starting dose was selected from one of three fixed levels, 25, 200 or 2000 mg/kg body weight.
As no information on the toxic potential of the test item was available, for animal welfare reasons, the starting dose of 200 mg/kg was chosen.
After the first assay, as 0/3 animals died, another assay was carried out on three males at the next higher dose-level (2000 mg/kg).
After the second assay, as 0/3 animals died, the results were confirmed in three females at 2000 mg/kg.

The single administration was performed in the morning of day 1 ; it was followed by a 14-day observation period.

The animals were observed frequently during hours following administration of the test item, for detection of possible treatment-related clinical signs. Thereafter, observation of the animals was made at least once a day.
Type, time of onset and duration of clinical signs were recorded for each animal individually.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed
Clinical signs:
At the 2000 mg/kg dose-level, hypoactivity was noted in all males within the 30 minutes following the treatment. Then, dyspnea and/or piloerection were recorded up to day 3.
In females, except for piloerection noted one hour after the treatment, no clinical signs were recorded.

No clinical signs and no mortality were observed in the animals given 200 mg/kg.
Body weight:
The body weight gain of the treated animals was similar to that of CIT historical control animals.
Gross pathology:
Macroscopic examination of the main organs of the animals revealed no apparent abnormalities.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test material does not require classification according to Regulation 1272/2008
Executive summary:

In a GLP-compliant acute toxicity study conducted in accordance with standardised guideline OECD 423, the LD50 of the test material was calculated by exposing 5 males and 5 females Sprague Dowley rats to a dose of 2000 mg/kg of body weight by oral gavage. Under the conditions of the test no systemic signs of toxicity were reported over a period of 14 days and the LD50 was determined to be > 2000 mg/kg.