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EC number: - | CAS number: -
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Description of key information
oral: A study examined whether the bioavailability of the read-across substance calcium carbonate could be improved by reducing the particle size. Because nanoscale supplements are novel formulas in health foods, the acute toxicity, sub-chronic toxicity (see separate IUCLID entry) and bioavailability (see separate IUCLID entry) needs to be determined in both sexes of mice in advance.
Standard acute toxicological evaluations of the ICR mice were performed in the initial assessment of the effects of nanoscale calcium carbonate internalisation. Micro calcium carbonate and nano calcium carbonate were administered in a single dose by gavage using a gastric intubation tube. The animals were then observed for a period of 7 days. No mortality or unusual behaviour were observed in an acute oral toxicity study. The NOAEL for both micro calcium carbonate and nano calcium carbonate were reported to be 1.3 g/kg bw, wich was the highest dose tested.
dermal: The acute dermal median lethal dose (LD50) of the read-acorss substance uncoated nano calcium carbonate in the Wistar strain rat was found to be greater than 2000 mg/kg bodyweight.
Key value for chemical safety assessment
Acute toxicity: via oral route
Link to relevant study records
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 19 November 2007 to 11 December 2007
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Test type:
- fixed dose procedure
- Limit test:
- yes
- Specific details on test material used for the study:
- Bulk calcium carbonate
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, Kent, UK
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: 205-237 g
- Fasting period before study: overnight prior to dosing
- Housing: suspended polypropylene cages furnished with soft woodflakes and fitted with stainless steel lids.
- Diet: ad libitum (except overnight prior to dosing and 3-4 hours after dosing)
- Water: ad libitum
- Acclimation period: at least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25 °C
- Humidity (%): 30 to 70%
- Air changes (per hr): At least 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours of continuous artificial light in each 24 hour period. - Route of administration:
- oral: gavage
- Vehicle:
- arachis oil
- Details on oral exposure:
- VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg - Doses:
- 2000 mg/kg
- No. of animals per sex per dose:
- 5
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: general observations - at 0.5, 1, 2 and 4 hours after dosing then again at least once daily for 14 days; bodyweights were recorded on days 0, 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs. - Statistics:
- No data
- Preliminary study:
- The female test animal did not die during the study following a single oral dose of 2000 mg/kg bw. There were no clinical signs during the preliminary study.
- Key result
- Sex:
- female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Sex:
- female
- Dose descriptor:
- LD0
- Effect level:
- > 2 000 mg/kg bw
- Mortality:
- No mortalities occurred.
- Clinical signs:
- other: No clinical signs of systemic toxicity were observed.
- Gross pathology:
- No adverse effects were observed.
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The acute oral median lethal dose (LD50) of the test material in the female Sprague-Dawley rat was estimated to be > 2000 mg/kg bw
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- The study examined whether the bioavailability of calcium carbonate and calcium citrate could be improved by reducing the particle size. Because nanoscale supplements are novel formulas in health foods, the acute toxicity, sub-chronic toxicity (see separate IUCLID entry) and bioavailability (see separate IUCLID entry) needs to be determined in both sexes of mice in advance.
Standard acute toxicological evaluations of the ICR mice were performed in the initial assessment of the effects of nanoscale calcium carbonate internalisation. Micro calcium carbonate and nano calcium carbonate were administered in a single dose by gavage using a gastric intubation tube. The animals were then observed for a period of 7 days. - GLP compliance:
- no
- Specific details on test material used for the study:
- Uncoated nano calcium carbonate
- Species:
- mouse
- Strain:
- ICR
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: National Taiwan University Hospital, Taipei, Taiwan
- Age at study initiation: 8-10 weeks
- Fasting period before study: Animals were fasted overnight
- Diet: Pelleted mouse feed available ad libitum
- Water: Reverse osmosis water available ad libitum
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-25 °C
- Humidity (%): 30-70%
- Photoperiod (hrs dark / hrs light): 12 h/12 h day/night cycle
Sham surgery (n = 6, SHAM) or bilateral ovariectomy (n = 30, OVX) was performed from a dorsal approach at 6 to 8 week old mice. Surgical removal of the ovaries is a well-represented approach to mimic the postmenopausal condition in mice. In the sham operation, ovaries were exteriorised and then replaced. - Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on oral exposure:
- The test materials were administered in a single dose by gavage using a gastric intubation tube.
- Doses:
- Vitamin D3 (261 U/ kg bw) plus micro calcium carbonate: 1.3 g/kg bw
Vitamin D3 (261 U/ kg bw) plus nano calcium carbonate: 1.3 g/kg bw - No. of animals per sex per dose:
- 8 animals/sex/dose
- Control animals:
- yes
- Details on study design:
- On day seven, all the animals were weighed and any signs of toxicity were noted.
- Sex:
- male/female
- Dose descriptor:
- other: NOAEL
- Effect level:
- 1 300 mg/kg bw
- Mortality:
- No mortality was observed.
- Clinical signs:
- other: Throughout the study, no unusual behaviour or differences between groups were observed (i.e. no laboured breathing, difficulty moving, hunching or unusual interactions with cage mates were observed).
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- No mortality or unusual behaviour were observed during the course of the study. The NOAEL for both micro calcium carbonate and nano calcium carbonate were reported to be 1.3 g/kg bw.
Referenceopen allclose all
Table 1: Body weight and mortality during the 7-day acute toxicity test
Dose |
Sex (n) |
Initial body weight (g) |
Final body weight (g) |
Mortality dead/treated |
Control |
Male (8) Female (8) |
33.2 ± 3.3 32.5 ± 3.7 |
35.3 ± 3.9 34.2 ± 3.8 |
0/8 0/8 |
Micro calcium carbonate (1.3 g/kg bw) |
Male (8) Female (8) |
33.4 ± 3.2 32.7 ± 3.4 |
34.9 ± 3.2 34.3 ± 3.6 |
0/8 0/8 |
Nano calcium carbonate (1.3 g/kg bw) |
Male (8) Female (8) |
32.5 ± 3.6 33.1 ± 2.9 |
33.7 ± 4.1 34.9 ±3.8 |
0/8 0/8 |
Data are mean ± SE values
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
Acute toxicity: via inhalation route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Acute toxicity: via dermal route
Link to relevant study records
- Endpoint:
- acute toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 06 January 2010 - 20 January 2010
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 402 (Acute Dermal Toxicity)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.3 (Acute Toxicity (Dermal))
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Test type:
- standard acute method
- Limit test:
- yes
- Specific details on test material used for the study:
- Uncoated nano calcium carbonate
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Harlan Laboratories UK Limited, Bicester, Oxon, UK
- Age at study initiation: 8-12 weeks
- Weight at study initiation: at least 200 g
- Fasting period before study: No data
- Housing: The animals were housed in suspended solid floor polypropylene cages furnished with woodflakes. The animals were housed individually during the 24-hour exposure period and in groups of five, by sex, for the remainder of the study.
- Diet (e.g. ad libitum): Food (2014 Teklad Global Rodent diet) was available ad libitum.
- Water (e.g. ad libitum): Mains drinking water was available ad libitum.
- Acclimation period: At least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25 °C
- Humidity (%): 30-70%
- Air changes (per hr): at least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): twelve hours continuous light (06:00 to 18:00) and twelve hours darkness - Type of coverage:
- semiocclusive
- Vehicle:
- arachis oil
- Details on dermal exposure:
- TEST SITE
- Area of exposure: back and flanks of each animal
- % coverage: approximately 10% of the total body surface area
- Type of wrap if used: A piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self-adhesive bandage.
REMOVAL OF TEST SUBSTANCE
- Washing (if done): After the 24-hour contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with arachis oil BP to remove any residual test material.
- Time after start of exposure: 24 h
TEST MATERIAL
The appropriate amount of test material, moistened with arachis oil BP, was applied as evenly as possible to an area of shorn skin using a graduated syringe. - Duration of exposure:
- 24 h
- Doses:
- 2000 mg/kg
- No. of animals per sex per dose:
- 5 animals/ sex/ dose
- Control animals:
- not specified
- Details on study design:
- The animals were observed for deaths or overt signs of toxicity 0.5, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days.
After removal of the dressings and subsequently once daily for fourteen days, the test sites were examined for evidence of primary irritation and scored according to the scale from Draize (1977).
Individual bodyweights were recorded prior to application of the test material on Day 0 and on Days 7 and 14.
At the end of the study the animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained. - Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Mortality:
- There were no deaths.
- Clinical signs:
- other: There were no signs of systemic toxicity or dermal irritation.
- Gross pathology:
- No abnormalities were noted at necropsy.
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The acute dermal median lethal dose (LD50) of the test material in the Wistar strain rat was found to be greater than 2000 mg/kg bodyweight.
Reference
Table 1: Individual clinical observations and mortality data
Dose level (mg/kg) |
Animal no. & sex |
Effects noted after initiation of exposure (hours) |
Effects noted after initiation of exposure (days) |
||||||||||||||||
0.5 |
1 |
2 |
4 |
1 |
2 |
3 |
4 |
5 |
6 |
7 |
8 |
9 |
10 |
11 |
12 |
13 |
14 |
||
2000 |
Males (1-1, 1-2, 1-3 & 1-4) |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
Females (2-1, 2-2, 2-3 & 2-4) |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 = no signs of systemic toxicity
Table 2: Individual dermal reactions – Males
Dose level (mg/kg) |
Animal no. & sex |
Observation |
Effects noted after initiation of exposure (days) |
|||||||||||||
1 |
2 |
3 |
4 |
5 |
6 |
7 |
8 |
9 |
10 |
11 |
12 |
13 |
14 |
|||
2000 |
Males (1-1, 1-2, 1-3 & 1-4) |
Erythema |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
Oedema |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
||
Other |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 = No reactions
Table 3: Individual dermal reactions – Females
Dose level (mg/kg) |
Animal no. & sex |
Observation |
Effects noted after initiation of exposure (days) |
|||||||||||||
1 |
2 |
3 |
4 |
5 |
6 |
7 |
8 |
9 |
10 |
11 |
12 |
13 |
14 |
|||
2000 |
Females (2-1, 2-2, 2-3 & 2-4) |
Erythema |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
Oedema |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
||
Other |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 = No reactions
Table 4: Individual bodyweights and weekly bodyweight changes
Dose level (mg/kg) |
Animal no. & sex |
Bodyweight (g) at Day |
Bodyweight change (g) during week |
|||
0 |
7 |
14 |
1 |
2 |
||
2000 |
1-0 Male |
232 |
256 |
278 |
24 |
22 |
1-1 Male |
235 |
255 |
270 |
20 |
15 |
|
1-2 Male |
242 |
268 |
288 |
26 |
20 |
|
1-3 Male |
224 |
246 |
270 |
22 |
24 |
|
1-4 Male |
234 |
261 |
279 |
27 |
18 |
|
2-0 Female |
220 |
228 |
239 |
8 |
11 |
|
2-1 Female |
203 |
204 |
216 |
1 |
12 |
|
2-2 Female |
211 |
216 |
218 |
5 |
2 |
|
2-3 Female |
217 |
220 |
230 |
3 |
10 |
|
2-4 Female |
212 |
213 |
220 |
1 |
7 |
Table 5: Individual necropsy findings
Dose level (mg/kg) |
Animal no. & sex |
Macroscopic observations |
2000 |
Males (1-1, 1-2, 1-3 & 1-4) |
No abnormalities detected |
Females (2-1, 2-2, 2-3 & 2-4) |
No abnormalities detected |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
Additional information
Justification for classification or non-classification
Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available data for acute toxicity are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on this data, the substance is not considered to be classified for acute toxicity under Regulation (EC) No 1272/2008, as amended for the eighteenth time in Regulation (EU) 2022/692.
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