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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:
2003-09-03 - 2003-11-21
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study (OECD TG 423) performed under GLP

Data source

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

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
adopted on 22nd March 1996
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Test material form:
solid: bulk
Details on test material:
Please refer to "Confidential details on test material".

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Janvier, Le Genest-Saint-Isle, France
- Age at study initiation: approximately 8 weeks old
- Body weight at study initiation: 306 ± 25 g (males), 220 ± 3 g (females)
- Housing: 3 animals/sex/cage in polycarbonate cages with stainless steel lid (48 cm x 27 cm
x 20 cm), each cage contained one to seven animals during the acclimation period
- Diet: A04 C pelleted diet (SAFE, Villemoisson, Epinay-sur-Orge, France), ad libitum, except for an overnight fasting period prior to testing (free access to water)
- Water: Drinking water filtered by a FG Millipore membrane (0.22 micron), ad libitum
- Acclimation period: at least 5 days before the beginning of the study

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 2 °C
- Humidity: 30 - 70%
- Air changes: approximately 12 air changes/hour
- Photoperiod: 12 h / 12 h

IN-LIFE DATES: From: 2003-09-11 To: 2003-10-02

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: methylcellulose
Details on oral exposure:
VEHICLE:
- Concentration in vehicle: 20 or 200 mg/mL, based on dose volume
- Amount of vehicle/dose volume: 10 mL/kg bw
- Justification for choice of vehicle: to make dosing by gavage possible
- Purity: no data

DOSAGE PREPARATION:
- The test item was prepared in a 0.5% suspension of methylcellulose in purified water.

CLASS METHOD:
- Rationale for the selection of the starting dose: As no information on the toxic potential of the test item was available, for animal welfare
reasons, the starting dose of 200 mg/kg bw was chosen.
Doses:
200 and 2000 mg/kg bw (tested concentrations)
No. of animals per sex per dose:
3 males (200 mg/kg)
3 males/ 3 females (2000 mg/kg)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days

- Mortality/Viability and frequency of observations (clinical signs): The animals were observed frequently during the 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.

- Frequency of weighing: The animals were weighed individually just before administration of the test item on day 1 and then on days 8 and 15. The body weight gain of the treated animals was compared to that of CIT control animals with the same initial body weight.

- Necropsy of survivors performed: yes, on day 15, all animals were killed by carbon dioxide asphyxiation and examined macroscopically. All study animals were subjected to a macroscopic examination as soon as possible after death. After opening the thoracic and abdominal cavities, a macroscopic examination of the main organs (digestive tract, heart, kidneys, liver, lungs, pancreas, spleen and any other organs with obvious abnormalities) was performed. No organ samples were taken.
Statistics:
No statistical testing was performed.

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 at any dose level tested.
Clinical signs:
No clinical signs were observed in the animals given 200 mg/kg bw. At the 2000 mg/kg bw dose-level, piloerection and dyspnea, together with hypoactivity in females, were observed in all animals on day 1.
Body weight:
When compared to CIT historical control animals, a slightly reduced body weight gain was recorded in 2/3 males given 200 mg/kg bw during the first or second week of the study. At 2000 mg/kg bw, a reduced body weight gain was noted in 1/3 females during the second week of the study. The overall body weight gain of the other animals was not affected by the treatment with the test item.
Gross pathology:
Macroscopic examination revealed no apparent abnormalities.

Applicant's summary and conclusion