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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
10 March 2010 - 01 June 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Compliant to GLP and testing guideline (observed deviations did not impact the reliability of the study); adequate coherence between data, comments and conclusions

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:
yes
Remarks:
the temperature and relative humidity recorded in the animal room was sometimes outside of the target ranges
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
yes
Remarks:
as cited above
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Reaction mass of barium chromate, copper dichromium tetraoxide and copper oxide
EC Number:
701-287-1
Molecular formula:
CuO, CuCr2O4, BaCrO4
IUPAC Name:
Reaction mass of barium chromate, copper dichromium tetraoxide and copper oxide
Details on test material:
- Name of test material (as cited in study report): Chromite de cuivre
- Substance type: multiconstituents
- Physical state: black powder
- Composition of test material, percentage of components: 34% of copper, 8.5% of baryum, 31% of chrome
- Purity test date: 11 January 2010
- Lot/batch No.: 09/0177
- Expiration date of the lot/batch: 17 August 2014
- Storage condition of test material: in darkness at room temperature

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: breeder Janvier, Le Genest-Saint-Isle, France
- Age at study initiation: 8 weeks old
- Weight at study initiation: mean body weight ± standard deviation of 210 ± 13 g
- Fasting period before study: approximately 18 hours before dosing
- Housing: polycarbonate cages with stainless steel lid
- Diet (e.g. ad libitum): free access to SSNIFF R/M-H pelleted maintenance diet
- Water (e.g. ad libitum): drinking water filtered by a FG Millipore membrane (0.22 micron), provided ad libitum
- Acclimation period: at least 5 days

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

IN-LIFE DATES: From 17 March 2010 to 13 April 2010

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: purified water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 30 mg/mL and 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg
- Purity: purified water prepared by reverse osmosis

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

CLASS METHOD (if applicable)
- 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-level of 300 mg/kg was chosen.
Doses:
300 and 2000 mg/kg
No. of animals per sex per dose:
3 animals/sex/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed frequently during the hours following administration of the test item and then at least once a day, for detection of possible treatment-related clinical signs. Animals were weighed individually just before administration of the test item on day 1 and then on days 8 and 15.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No death occured at 300 and 2000 mg/kg.
Clinical signs:
At 2000 mg/kg, hypoactivity and piloerection were observed in 4/6 animals within 4 hours of treatment. No clinical signs were observed thereafter.
Body weight:
When compared to CIT historical control data, a lower body weight gain was noted between day 8 and day 15 in 1/3 animals given 300 mg/kg (6 g vs. 15 ± 8 g in control data base) and between day 1 and day 8 in 2/6 animals given 2000 mg/kg (26 and 31 g vs. 41 ± 9 g in control data base),
returning to normal thereafter.
No body weight gain was noted between day 8 and day 15 in another female given 2000 mg/kg.
Gross pathology:
Macroscopic examination of the main organs of the animals revealed no apparent abnormalities.

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the experimental conditions of this study, the oral LD50 of the test item Chromite de cuivre was higher than 2000 mg/kg in rats.
Executive summary:

Methods:

The test item was prepared in purified water and was administered by oral route (gavage), under a volume of 10 mL/kg, to groups of three fasted female Sprague-Dawley rats. As no information on the toxic potential of the test item was available, for animal welfare reasons, the starting dose-level of 300 mg/kg was chosen. After the first assay, as no deaths occurred, another assay was carried out on three animals at the next higher dose-level of 2000 mg/kg. As no deaths occurred, the results were confirmed in three other females at the dose-level of 2000 mg/kg.

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.

The interpretation of results was based on the classification critera laid down in Council Directive 67/548/EEC (and subsequent adaptations).

Results:

Dose-level of 300 mg/kg (three females):

Neither mortality nor clinical signs were noted at this dose-level. When compared to CIT historical control data, a lower body weight gain (6 g vs. 15 ± 8 g in control data base) was noted in 1/3 animals between day 8 and day 15.

Dose-level of 2000 mg/kg (three females then confirmation on three other females):

No death occurred. Hypoactivity and piloerection were observed in 4/6 animals within 4 hours of treatment. When compared to CIT historical control data, a lower body weight gain was noted in 2/6 animals between day 1 and day 8 (26 and 31 g vs. 41 ± 9 g in control data base), returning to normal thereafter, and no body weight gain was noted in another female between day 8 and day 15. At necropsy, no apparent abnormalities were observed in any animal treated at 300 or 2000 mg/kg.

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