Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Acute oral toxicity of Calcium tartrate

Acute oral toxicity of Calcium tartate was evaluated following a single oral administration in rats according to OECD(No. 423, 17th December 2001) and Commission 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 macroscopicpost-mortemexamination. 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.

Macroscopicpost-mortemexamination 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.

Acute dermal toxicity of Calcium tartrate

Tartaric acid and its salts does not have significant acute toxicity.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
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
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
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.
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.
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.
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.
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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Justification for type of information:
Important considerations for the read-across were:
- calcium tartrate (the target chemical) has similar physico-chemical properties as the others members of the Category "Tartaric acids and its salts" (the source chemicals); these properties include molecular weight; logKow and solubility
- there are structural similarities between all the chemicals of the Category
- overall, it is considered that the systemic acute toxicity of tartaric acid is similar to that ones of its salts (i.e. monosodium, monopotassium, sodium potassium, sodium, potassium and calcium tartrate) and, therefore, the assessment of these endpoints may be jointly performed using all available data for these substances.
Remarks on result:
other: Tartaric acid and its salts are deemed to be not acutely toxic.

A complete database is available for the acute toxicity by subcutaneous route. Although it does not contain data obtained by means of tests in accordance with standard testing guidelines, it is constituted by many data which are consistent about the absence of significant acute toxicity. Therefore, further investigation by dermal route are deemed to be not needed.

The acute toxicity of tartaric acid and its salts was investigated by means of several tests principally performed by means of subcutaneous and intravenous administration. Almost all data support the absence of significant acute toxicity for both exposure routes. Moreover, acute oral toxicity data on Calcium tartrate not show acute toxicity.

Overall, it is considered that the systemic acute toxicity of tartaric acid is similar to that ones of its salts (i.e. monosodium, monopotassium, sodium potassium, sodium, potassium and calcium tartrate) and, therefore, the assessment of the acute toxicity endpoints may be jointly performed using all available data for these substances. Therefore, tartaric acid and its salts are deemed to be not acutely toxic.

With regard to the specific target organ toxicity, adverse effects on kidney (i.e. nephritis) were reported in some tests. However, these effects were only observed at very high dose levels close to the lethal dose (> 2000 mg/kg bw).

Interpretation of results:
GHS criteria not met
Conclusions:
Tartaric acid and its salts (e.g. Calcium tartrate) are deemed to be not acutely toxic by dermal route.

According to Regulation (EC) n. 1272/2008, the studies results indicate that the substances should not be classified for acute dermal toxicity because the data currently available are judged as "conclusive but not sufficient for classification".
Executive summary:

The assessment of the acute dermal toxicity of Calcium tartrate was performed by means a read across based on grouping of substances (category approach). The name Category used is "Tartaric acid and its salts".

Tartaric acid and its salts (e.g. Calcium tartrate) are deemed to be not acutely toxic by dermal route. According to Regulation (EC) n. 1272/2008, the studies results indicate that the substances should not be classified for acute dermal toxicity because the data currently available are judged as "conclusive but not sufficient for classification".

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
A complete database is available for the acute toxicity by subcutaneous route. Although it does not contain data obtained by means of tests in accordance with standard testing guidelines, it is constituted by many data which are consistent about the absence of significant acute toxicity. Therefore, further investigation by dermal route are deemed to be not needed.

Additional information

A complete database is available for the acute toxicity by subcutaneous route. Although it does not contain data obtained by means of tests in accordance with standard testing guidelines, it is constituted by many data which are consistent about the absence of significant acute toxicity. Therefore, further investigation by dermal route are deemed to be not needed.

It is considered that the systemic acute toxicity of tartaric acid is similar to that ones of its salts (i.e. monosodium, monopotassium, sodium potassium, sodium, potassium and calcium tartrate) and, therefore, the assessment of these endpoints may be jointly performed using all available data for these substances. Therefore, tartaric acid and its salts are deemed to be not acutely toxic.

With regard to the specific target organ toxicity, adverse effects on kidney (i.e. nephritis) were reported in some tests. However, these effects were only observed at very high dose levels close to the lethal dose (> 2000 mg/kg bw).

Several data are available about the acute toxicity by subcutaneous route. Overall, the assessment of the acute oral toxicity of tartaric acid and its salts are based on the weight of evidence of the available data.

Justification for classification or non-classification

According to Regulation (EC) n. 1272/2008, the study results indicate that the substances should not be classified for acute oral toxicity because data are judged as "conclusive but not sufficient for classification".

According to Regulation (EC) n. 1272/2008, the substances should not be classified for acute inhalation toxicity because of data lacking.

According to Regulation (EC) n. 1272/2008, the study results indicate that the substances should not be classified for acute dermal toxicity because the data currently available are judged as "conclusive but not sufficient for classification".

According to Directive 67/548/EEC and to Regulation (EC) n. 1272/2008, study results indicate that the substances should not be classified for specific target organ toxicity - single exposure because data are judged as "inconclusive".

Categories Display