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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:
23 May 2007 to 20 June 2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to valid guidelines and the study was conducted under GLP conditions.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report Date:
2007

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): Cellcore MX
- Physical state: solid
- Appearance: black powder
- Storage condition of test material: room temperature in the dark

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Strain: CD (Crl:CD (SD) IGS BR)
- Age at study initiation: 8 - 12 weeks old
- Weight at study initiation: 199 - 232 g (the body weight variation did not exceed ± 20 % of the initial mean body weight of any previously dosed animals)
- Fasting period before study: yes (overnight, before dosing and for approximately 3 - 4 hours after dosing)
- Housing: in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes
- Diet: ad libitum Certified Rat and Mouse Diet
- Water: ad libitum access to mains drinking water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 – 25 °C
- Humidity (%): 30 – 70 % (relative)
- Air changes (per hr): at least 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours light (06:00 to 18.00)

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: arachis oil BP
Details on oral exposure:
PREPARATION OF DOSING FORMULATION
The test material was freshly prepared, as required, as a suspension in the vehicle.

VEHICLE
- Concentration in vehicle: 30 mg/mL and 200 mg/mL
- Justification for choice of vehicle: Arachis oil BP was selected as vehicle as 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 to the fasted body weight at the time of dosing.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: using available information on the toxicity of the test material, 300 mg/kg was chosen as the starting dose.
Doses:
300 and 2000 mg/kg
No. of animals per sex per dose:
A single animal was treated at 300 mg/kg.
In the absence of toxicity at 300 mg/kg, an additional animal was dosed at 2000 mg/kg.
In the absence of toxicity at 2000 mg/kg, an additional group of 4 animals was dosed at 2000 mg/kg.

Treatment of animals was sequential. Sufficient time was allowed between each dose level to confirm the survival of the previously dosed animal(s).
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: clinical observations were made at ½, 1, 2 and 4 hours after dosing and then daily thereafter
- Frequency of weighing: individual body weights were recorded on days 0, 7 and 14
- Necropsy of survivors performed: yes
- Sacrifice: animals were killed by cervical dislocation.
- Examinations performed at necropsy: all animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Results and discussion

Preliminary study:
The single animal dosed at 300 mg/kg survived until the end of the observation period, no signs of systemic toxicity were noted. The animal showed the expected gain in body weight. No abnormalities were detected at necropsy.
The initial animal dosed at 2000 mg/kg survived until the end of the observation period, no signs of systemic toxicity were noted. The animal showed the expected gain in body weight. No abnormalities were detected at necropsy.
Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
None of the animals died during the study.
Clinical signs:
No signs of systemic toxicity were noted during the study.
Body weight:
All animals showed expected gains in body weight over the observation period.
Gross pathology:
No abnormalities were detected at gross necropsy.

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 LD50 of the test material was determined to be in excess of 2000 mg/kg bw.
Executive summary:

The acute oral toxicity of the test material was investigated in the Sprague-Dawley CD strain rat in a study which was conducted under GLP conditions and in accordance with the standardised guidelines OECD 420 and EU Method B.1 bis, using the fixed dose method.

Following a sighting test in which there was no mortality in a single animal dosed at 300 mg/kg and no mortality in a single initial animal dosed at 2000 mg/kg, a further group of four fasted females was given a single oral dose of test material, as a suspension in arachis oil BP, at a dose level of 2000 mg/kg bw. Clinical signs and body weight were monitored during the 14 day observation period following dose administration. At the end of the observation period all animals were subjected to gross necropsy.

None of the animals died during the study and no clinical signs were noted during the observation period. All of the animals gained weight during the study and no abnormalities were noted at gross necropsy.

Therefore, under the conditions of the study, the LD50 of the test material was determined to be in excess of 2000 mg/kg bw and as such the test material requires no classification in accordance with EU criteria.