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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
16 November 2010 - 10 January 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011

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:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Calcium tartrate
EC Number:
221-621-5
EC Name:
Calcium tartrate
Cas Number:
3164-34-9
Molecular formula:
C4H6O6.Ca
IUPAC Name:
Calcium carbonate
Test material form:
solid: particulate/powder
Specific details on test material used for the study:
- Name of test material (as cited in study report): TARTRATE DE CALCIUM
- Physical state: amber powder
- Analytical purity: 93.44%
- Lot/batch No.: CAMP 09-10
- Expiration date of the lot/batch: December 2011
- Storage conditions of test material: at room temperature, protected from light and humidity.

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: on the day of treatment, the animals were approximately 8 weeks old
- Weight at study initiation: a mean body weight ± standard deviation of 209 g ± 5 g
- Fasting period before study: the animals were fasted during the night before treatment
- Housing: polycarbonate cages with stainless steel lid (43 cm x 22 cm x 20 cm)
- Diet (e.g. ad libitum): SSNIFF R/M-H pelleted diet
- Water (e.g. ad libitum): access to bottles containing tap water (filtered with a 0.22 m filter)
- Acclimation period: at least 5 days before the beginning of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2°C
- Humidity (%): 50 ± 20%
- Air changes (per hr): approximately 12 cycles/hour of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12 h/12 h (7:00 - 19:00)

IN-LIFE DATES: From: 26 November 2010 To: 30 December 2010.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
purified
Details on oral exposure:
VEHICLE

- Concentration in vehicle: a homogeneous suspension was obtained with the test item at the concentration of 200 mg/mL in purified water. Purified water was therefore used as vehicle in this study.
The test item was administered as a suspension in the vehicle.
The test item was prepared under magnetic agitation at the chosen concentrations in the vehicle.
Fresh dosage form preparations were made extemporaneously of the day of each administration and the dosage form preparations were stored at
room temperature prior to use and delivered to the study room in brown flasks.

- Amount of vehicle (if gavage): 10 mL/kg

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. After the first assay, as no deaths occurred, another assay was carried out on three animals at the next higher dose-level (2000 mg/kg). After the second assay, as no animals died, the results were confirmed in three other females at 2000 mg/kg.
Doses:
300 and 2000 mg/kg.
No. of animals per sex per dose:
3 females per treatment step (300, 2000 and 2000 mg/kg).
Control animals:
no
Details on study design:
- Duration of observation period following administration: a period of up to 14 days
- Frequency of observations and weighing: each animal was observed after dosing at least once during the first 30 minutes, periodically during the
first 24 hours for detection of possible treatment-related clinical signs and then at least once a day for 14 days.
Type, time of onset and duration of clinical signs were recorded for each animal individually.
- Necropsy of survivors performed: yes.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality were observed in the animals during the study.
Clinical signs:
No clinical signs were observed in the animals during the study.
Body weight:
When compared to CIT historical control data, no body weight gain was noted between day 8 and day 15 in 1/6 females given 2000 mg/kg.
The body weight gain of the other animals given 300 or 2000 mg/kg was not affected by treatment with the test item.
Gross pathology:
Macroscopic post-mortem examination of the main organs of the animals revealed no apparent abnormalities.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The oral LD50 of the test item, TARTRATE DE CALCIUM, was higher than 2000 mg/kg in rats.
Executive summary:

The objective of this study was to evaluate the toxicity of the test item, TARTRATE DE CALCIUM, following a single oral administration in rats according to OECD(No. 423, 17th December 2001) andCommission Regulation (EC) (No. 440/2008, B.1tris, 30 May 2008) guidelines.

The study was conducted in compliance with the principles of Good Laboratory Practice.

 

Methods

The test item, TARTRATE DE CALCIUM, was administered once by oral route (gavage) to three groups of three fasted female Sprague-Dawley rats under a dosage-volume of 10 mL/kg. The test item was prepared in purified water.

As no information on the potential test item toxicity was available, the starting dose-level of 300 mg/kg was chosen. After the first assay, the next higher dose-level of 2000 mg/kg was tested. Then, as no toxicity was observed at this higher dose-level, the results were confirmed in other females.

Each animal was observed at least once a day for mortality and clinical signs for a period of up to 14 days following the single administration. Body weight was recorded on day 1 and then on days 8 and 15.

On completion of the observation period, the animals were sacrificed and then submitted for a macroscopic post-mortem examination. No organ samples were taken.

The interpretation of results was based on the classification criteria laid down in Regulation (EC) No. 1272/2008/CE.

 

Results

No mortality and no clinical signs were observed in the animals during the study.

When compared to CIT historical control data, no body weight gain was noted between day 8 and day 15 in 1/6 females given 2000 mg/kg. The body weight gain of the other animals given 300 or 2000 mg/kg was not affected by treatment with the test item.

Macroscopic post-mortem examination of the main organs of the animals revealed no apparent abnormalities.

 

Conclusion

Under the experimental conditions of this study, the oral LD50of the test item, TARTRATE DE CALCIUM, was higher than 2000 mg/kg in rats.

According to the classification criteria laid down in Regulation (EC) No. 1272/2008 of the European parliament and of the council of 16 December 2008 on classification, labeling and packaging of substances and mixtures,concerning the potential toxicity by oral route, the test item should not be classified.

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