Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
03-Jun-2010 to 24-Jun-2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: 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.
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report date:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
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:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Charcoal, coconut shell
EC Number:
271-974-4
EC Name:
Charcoal, coconut shell
Cas Number:
68647-86-9
Molecular formula:
C
IUPAC Name:
Charcoal, coconut shell
Details on test material:
- Name of test material (as cited in study report): Coconut Shell Charcoal
Description: Dark grey flat particles
CAS Number: 68647-86-9
Batch Number: TEJAFF 13/DEC 2009
Purity: Not specified
Expiry Date: 31-Dec-2020
Storage Conditions: At room temperature (range of 20 ± 5 °C), light protected.

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories B.V., Kreuzelweg 53, 5961 NM Horst / The Netherlands

Age (when treated): 10 weeks

Body Weight Range (when treated): 181.4 g – 197.5 g

- Fasting period before study: Overnight fasting 18 to 19 hours before treatment and for approximately three hours after dosing.

- Housing: The animals were housed in In groups of three in Makrolon type-4 cages with wire mesh tops and standard softwood bedding (‘Lignocel’ J. Rettenmaier&Söhne GmbH&CoKG, 73494 Rosenberg / Germany, imported by Provimi Kliba AG, 4303 Kaiseraugst / Switzerland)

- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, batch no. 83/09 (Provimi Kliba AG, 4303 Kaiseraugst / Switzerland) ad libitum (except for the overnight fasting period prior to intubation and approximately 3 hours post dose).. The diet was routinely analysed and were considered not to contain any contaminants that would reasonably be expected to affect the purpose or integrity of the study.

- Water (e.g. ad libitum): Free access to water. Community tap water from Füllinsdorf ad libitum. The water was routinely analysed and were considered not to contain any contaminants that would reasonably be expected to affect the purpose or integrity of the study.

- Acclimation period: Five to 7 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C

- Humidity (%): Set to achieve limits of 30 to 70%.

- Air changes (per hr): Air-conditioned with 10-15 air changes per hour

- Photoperiod (hrs dark / hrs light): Light controlled by a time switch to give twelve hours continuous light and twelve hours darkness.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Details on oral exposure:
VEHICLE
- Concentration in vehicle: The substance was present at levels of 200 mg/ml in the vehicle.

- Amount of vehicle: Test material was made into a suspension with the vehicle at a dose level of 2000 mg/kg.

- Justification for choice of vehicle: Arachis oil BP was used because the test material did not dissolve in distilled water.

- Lot/batch no. : S60502-099

- Supplier: Sigma-Aldrich Chemie GmbH, 89555 Steinheim / Germany


MAXIMUM DOSE VOLUME APPLIED:
10 ml/kg

The dose formulations were prepared shortly before each dosing occasion using a magnetic stirrer, a spatula and an Ultra-Turrax as homogenizers.
The test item was first ground with a mortar and a pestle and weighed into a tared glass beaker on a suitable precision balance and the vehicle added (weight:volume).

Dosing was performed sequentially.

The volume administered to each animal was calculated according to the fasted bodyweight at the time of dosing. Treatment of animals was sequential. Sufficient time was allowed between each group and each dose level to confirm the survival of the previously dosed animals.
Doses:
2000 mg/kg
No. of animals per sex per dose:
6 females
Control animals:
no
Details on study design:
- Duration of observation period following administration:
The animals were observed for deaths or overt signs of toxicity 1/2, 1, 2, and 5 hours after dosing and subsequently once daily for up to fourteen days.

- Frequency of observations and weighing:
Individual bodyweights were recorded prior to dosing and seven and fourteen days after treatment or at death.

- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs, body weight, necropsy.
Statistics:
None recorded.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No deaths occurred during the study.
Clinical signs:
All animals excreted feces stained in black one day after the administration (test day 2). No other clinical signs were observed during the course of the study.
Body weight:
One animal showed a slight loss of body weight (-1.7%) from test day 8 to day 15. Otherwise, the body weight of the animals was within the range commonly recorded for this strain and age.
Gross pathology:
No macroscopic findings were recorded at necropsy.
Other findings:
not applicable

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
he median lethal dose of Coconut Shell Charcoal after single oral administration to female rats, observed over a period of 14 days, is:

LD50 (female rat): greater than 2000 mg/kg body weight

Based upon the referred classification criteria (Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008), Coconut Shell Charcoal is not classified with respect to acute oral toxicity in the rat.
Executive summary:

Two groups, each consisting of three female RccHan:WIST (SPF) rats, were treated with Coconut Shell Charcoal by single oral gavage administration at a dosage of 2000 mg/kg body weight. The test item was formulated in PEG 300 at a concentration of 0.2 g/mL and administered at a dosing volume of 10 mL/kg.

 

The animals were examined daily during the acclimatization period and mortality, viability and clinical signs were recorded. All animals were examined for clinical signs before treatment, within the first 30 minutes and approximately 1, 2, 3 and 5 hours after treatment on day 1 and once daily during test days 2-15. Mortality/viability was recorded before treatment, within the first 30 minutes and approximately 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2-15. Body weights were recorded on day 1 (prior to administration) and on days 8 and 15.All animals were necropsied and examined macroscopically.

 

No intercurrent deaths occurred during the course of the study.

 

All animals excreted feces stained in black one day after the administration (test day 2). No other clinical signs were observed during the course of the study.

 

One animal showed a slight loss of body weight (-1.7%) from test day 8 to day 15. Otherwise,the body weight of the animals was within the range commonly recorded for this strain and age.

 

No macroscopic findings were recorded at necropsy.