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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:
july 2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study (OECD 423)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report date:
2008

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 (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Tangled Multi-Walled Carbon Nanotubes
EC Number:
701-160-0
Cas Number:
7782-42-5
Molecular formula:
Hollow tubular carbon, 1-dimensional nano structures with hexagonal arrangement of carbon atoms
IUPAC Name:
Tangled Multi-Walled Carbon Nanotubes
Constituent 2
Reference substance name:
GRAPHISTRENGTH C100
IUPAC Name:
GRAPHISTRENGTH C100
Test material form:
solid: nanoform

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
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
- Weight at study initiation: 189 +/- 6g
- Fasting period before study:18 hours before dosing
- Housing: polycarbonate cages with stainless steel lid (48cmx27cmx20cm)
Each cage contained one to seven animals during the acclimatation period and three rats of the same group during the treatment period. Each cage contained autoclaved sawdust; Sawdust is analysed by the supplier for the composition and contaminant levels.
- Diet :SsniffR/M-H pelleted diet, ad libitum
- Water :filtered by a FG Millipore membrane (0.22 micron), ad libitum
- Acclimation period:at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C):22+/-2
- Humidity (%):30 to 70
- Air changes (per hr):approximately 12 cycles/hour of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light):12h/12h

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 0.5% methycellulose
Details on oral exposure:
The administration was performed once (300mg/Kg) or twice (2000mg/Kg) at a 2 hours interval by oral route using a metal gavage fitted to a 2 or 5 mL plastic syringe. The volume administered to each animal was adjusted according to body weight determined on the day of treatment.

VEHICLE
- Concentration in vehicle:0.5% methycellulose
- Amount of vehicle (if gavage):no data
- Justification for choice of vehicle:The test item was not soluble at the concentration of 100mg/mL in purifies water, 0.5% methycellulose and corn oil. At the maximal concentration of 70 mg/mL, a suspension was obtained in purified water or in 0.5% methycellulose. As the suspension was more homogeneous in 0.5% methycellulose, this vehicule was retained.
- Lot/batch no. (if required):no data
- Purity:no data

MAXIMUM DOSE VOLUME APPLIED: 10mL/Kg (for a dose-level of 300mg/Kg)
14.3mL/Kg (for a dose-level of 2000mg/Kg)

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose:yes
The dose-level used as the starting dose-level was selected from one of four fixed levels, 5, 50, 300 or 2000mg/Kg body weight.
As no information on the toxic potential of the test item was available, for animal welfare reasons, the starting dose-level of 300mg/Kg was chosen.
Doses:
starting dose-level = 300mg/Kg
After the first assay, as no deaths occured, another assay was carried out on three animals at 2000mg/Kg.
After the second assay, as no deaths occured,another assay was carried out on three animals at 2000mg/Kg.

No. of animals per sex per dose:
3 females/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations :frequently during the hours following administration.Thereafter at least once a day.
- Frequency of weighing:individually just before administration on day 1, 8 and 15.
- Necropsy of survivors performed: yes
Statistics:
no

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD0
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no mortality
Mortality:
no
Clinical signs:
at 300mg/Kg: no clinical signs
at 2000mg/Kg: hypoactivity, piloerection, dyspnea, we were noted in 3/6 animals on day 1.
Body weight:
The body weight gain of the treated animals was compared to that of CIT control animals with the same initial body weight.
Gross pathology:
Sacrifice on day 15 of all animals by carbon dioxide asphyxiation.
Macroscopic examination as soon as possible after death of the main organs (digestive tract, heart, kidneys, liver, lungs, pancreas, spleen and any organs with ovious abnormalities).

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: other: Regulation n°1272/2008
Conclusions:
The oral LD0 of the test item GRAPHISTRENGTH C100 micronised was equal to or higher than 2000mg/Kg in rats.
Executive summary:

The acute oral toxicity of GRAPHISTENGTH C100 micronised was evaluated in rats according to OECD n°423 and Good Laboratory Pratice Regulations. The test item was prepared in 0.5% methylcellulose and was administrated by oral route (gavage), to groups of three fasted females 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. All animals were subjected to necropsy.

No deaths and no clinical signs were noted at 300mg/Kg. No deaths occured but hypoactivity, piloerection and dyspnea were noted in 3/6 animals on day 1, at 2000mg/Kg. The oral LD0 of GRAPHISTRENGTH C100 micronised was equal to or higher than 2000mg/Kg in rats.