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EC number: 215-137-3 | CAS number: 1305-62-0
- 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
![](https://echa.europa.eu./o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Direct observations: clinical cases, poisoning incidents and other
Administrative data
- Endpoint:
- direct observations: clinical cases, poisoning incidents and other
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- supporting study
- Reliability:
- other: high
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- Well documented, peer-reviewed publication following basic scientific principles. Under physiological conditions, the hydroxyl-ions released from lime following oral adminstration have been neutralised in the GI tract and are therefore not relevant for consideration of toxicokinetics. Therefore for assessment of the metabolic fate of the systemically relevant species of lime following administration via the oral route, the calcium ion Ca2+ is the chemical species of interest. In the current study, calcium was administered in the form of calcium carbonate. The carbonate ion is released as CO2 following reaction with gastric juice and is therefore toxicologically not relevant. The objective of the study was the evaluation intestinal absorption of calcium from various sources. In view of the the limited relevance of the anionic counter-ions discussed here, calcium released both from calcium hydroxide and calcium carbonate can be considered as structurally equivalent, and the results of the study can be used by read-across.
Cross-reference
- Reason / purpose for cross-reference:
- reference to same study
Data source
Reference
- Reference Type:
- publication
- Title:
- An evaluation of the importance of gastric acid secretion in the absorption of dietary calcium
- Author:
- Bo-Linn, G.W.; Davis, G.R.; Buddrus, D.J.; Morawski, S.G.; Santa Ana, C.; Fordtran, J.S.
- Bibliographic source:
- J Clin Invest 73(3): 640–647
Materials and methods
- Study type:
- study with volunteers
- Endpoint addressed:
- basic toxicokinetics
Test guideline
- Qualifier:
- no guideline available
- Principles of method if other than guideline:
- Absorption measured in human subjects.
Following GI tract lavage, calcium was administered by either a low calcium meal, a low calcium meal supplemented with CaCO3 or calcium citrate, or a high calcium meal. Rectal effluent collected, Ca measured by AAS, and net absorption calculated as Ca ingested minus Ca in effluent. For assessment of the significance of gastric pH on absorption, a large dose of cimetidine was administered, reducing gastric acid secretion. - GLP compliance:
- no
Test material
- Reference substance name:
- Various calcium sources, either dieatary or in the form of carbonate or citrate
- IUPAC Name:
- Various calcium sources, either dieatary or in the form of carbonate or citrate
- Details on test material:
- 1)
- Name of test material (as cited in study report): Calcium citrate
- Molecular formula (if other than submission substance): C12H10Ca3O14
- Molecular weight (if other than submission substance): 498.44 g/mol
- Physical state: Solid
- Analytical purity: No data
- Impurities (identity and concentrations): No data
- Purity test date: No data
- Lot/batch No.: No data
- Expiration date of the lot/batch: No data
- Stability under test conditions: No data
- Storage condition of test material: No data
- Other: Supplier: Miles Laboratories, Inc., Elkhart, IN, USA; effervescent tablets, containing calcium carbonate and citric acid; when added to water, they effervesce, thus liberating calcium citrate.
2)
- Name of test material (as cited in study report): Calcium carbonate
- Molecular formula (if other than submission substance): CaCO3
- Molecular weight (if other than submission substance): 100.09 g/mol
- Physical state: Solid
- Analytical purity: No data
- Impurities (identity and concentrations): No data
- Purity test date: No data
- Lot/batch No.: No data
- Expiration date of the lot/batch: No data
- Stability under test conditions: No data
- Storage condition of test material: No data
- Other: Supplier: Marion Laboratories, Kansas City, MO, USA; Os-Cal tablets; calcium carbonate is contained as crushed oyster shell.
Constituent 1
Method
- Type of population:
- general
- Subjects:
- - Number of subjects exposed: 16
- Sex: Male and female (12/4)
- Age: 21-36 (mean: 28) years
- Race: No data
- Demographic information: No data
- Known diseases: The above subjects were reported to be healthy. In addition, one female subject (aged 57 years) was included who had pernicious anaemia and, following s.c. injection of 6 µg/kg bw pentagastrin, gastric achlorhydria (lowest gastric pH = 7.4); four additional subjects with chronic renal disease on haemodialysis took part in the validation studies, but not in experiments on the effects of gastric acid on absorption .
- Other: No data - Ethical approval:
- confirmed and informed consent free of coercion received
- Remarks:
- Project approved by the Institutional Review Board for Human Protection at Baylor University Medical Center
- Route of exposure:
- oral
- Reason of exposure:
- intentional
- Exposure assessment:
- measured
- Details on exposure:
- Low calcium meal:
170 g sirloin steak, seasoned with salt and pepper, 25 g white bread with 5 g margarine, 40 g lettuce with 30 g French salad dressing, 250 mL tea with 5 g sugar, and 10 g of PEG. Ca content: 71 ± 1 mg (verified by AAS).
High calcium meal:
Ditto, except that 250 mL skim milk was substituted for the tea and 57 g Swiss cheese was melted on the steak. Ca content: 852 ± 1 mg (verified by AAS).
Meal for validation studies only:
57 g sirloin steak, 25 g white bread, 40 g lettuce with 30 g French salad dressing, 30 g Swiss cheese, 250 ml tea with 5 g sugar, and 10 g PEG. Ca content: 290 ± 3 mg (verified by AAS).
Calcium supplements:
Calcium carbonate tablets were swallowed with 200 mL water.
Calcium citrate was taken by effervescing tablets in 200 mL water after cessation of effervescence.
Supplements were taken 1 h after start of the meal (unless otherwise stated).
Procedure:
After an overnight fast, subjects underwent gastric lavage using Golytely (Braintree Scientific, Inc., Braintree, MA, USA), received either orally as 300 mL portions every 10 min, or by intragastric infusion (30 mL/min). After 4 h lavage, the rectal effluent was totally clear and contained no unabsorbed dietary nutrients (previous studies from this laboratory). The rectal effluent from the first washout was discarded.
The test meal was taken 4 h after completion of this first lavage. 12 h after the meal, without further ingestion of food or drink, the subjects underwent a second (final) lavage, lasting 3 h. The rectal effluent from this final lavage was combined with any stool (usually none) that had been passed since the meal was eaten. - Examinations:
- The rectal effluent was collected and homogenised in Waring commercial blender. 10 mL 2-octonol were added as a foam suppressant. 20 mL homogenate were transferred to acid-washed glass flasks and digested with 20 ml of 16 N nitric acid to dissolve any insoluble calcium. The homogenate was then brought to 100 ml volume with deionised water in an acid-washed volumetric flask. Duplicate aliquots were analysed for calcium by atomic
spectroscopy (model 2380, Perkin-Elmer Corp., Norwalk, CT).
Homogenised but undigested samples were analysed for PEG by the method of Hyden (1955). - Medical treatment:
- Not applicable
Results and discussion
- Clinical signs:
- Not applicable.
- Results of examinations:
- Sensitivity study:
Average net calcium absorption (n=9) in relation to Ca intake was found to be as follows (mean ± SE):
Intake 321 mg: 90 ± 27 mg (28.0 %)
Intake 571 mg: 198 ± 30 mg (34.7 %)
Intake 1071 mg: 318 ± 50 mg (29.7 %)
Main absorption study:
Net calcium absorption (n=6) in relation to Ca intake is presented in detail in Table 1 ("any other information on results incl. tables") below. Thus, when calcium was supplemented, net absorption was 23.6-29.7 %, whereas dietary calcium was absorbed by 15.5 %.
Gastric acid suppressed by cimetidine:
See the attached figure; precise values are never reported in the publication nor are these extractable from the figure. However, the graphical presentation demonstrates that calcium is absorbed at a similar rate from both carbonate and citrate, irrespective of gastric acid being suppressed or not.
Studies in a patient with gastric achlorhydria:
In the achlorhydric patient, net calcium absorption was higher than in normal patients, irrespective of being treated with cimetidine or not - see attached figure for details.
Studies with gastric pH maintained at 3.0 and 7.4:
Absorption was similar on test days with gastric pH maintained at 3.0 and 7.4, achieving approximately 41-43 % (see Table 2 below). - Effectivity of medical treatment:
- Not applicable.
- Outcome of incidence:
- Not applicable.
Any other information on results incl. tables
Table 1: Net calcium absorption results from the main absorption study (n=6)
Calcium intake [mg] | Ca in effluent [mg] | Net absorption [mg] | Net absorption [%] | |
Fast | 0 | 42 ± 5 | - | - |
Low Ca meal | 71 | 110 ± 23 | 3 ± 22 | n.a. |
Low Ca meal + CaCO3 tablets | 1071 | 860 ± 61 | 255 ± 58 | 23.8 |
Low Ca meal + Ca citrate | 1071 | 802 ± 48 | 310 ± 52 | 29.0 |
High Ca meal | 852 | 760 ± 49 | 132 ± 50 | 15.5 |
Table 2: Net calcium absorption when gastric pH is maintained at 7.4 or 3.0 by in vivo intragastric titration
|
Calcium intake [mg] |
Calcium in effluent [mg] |
Net calcium absorption [mg] |
Net calcium absorption [%] |
Fast |
0 |
41.4 ± 4 |
– |
– |
Gastric pH 7.4 |
1063 |
645 ± 87 |
458 ± 87 |
43.1 |
Gastric pH 3.0 |
1063 |
662 ± 63 |
441 ± 63 |
41.5 |
Results are given as mean ± SE. Calcium intake was 1063 mg, mainly in the form of calcium carbonate (n = 8) (low calcium meal [minus lettuce and salad dressing] supplemented with 1000 mg calcium as CaCO3). |
Applicant's summary and conclusion
- Conclusions:
- This study demonstrates that, contrary to intuitive expectation, gastric pH is not negatively correlated with intestinal calcium absorption. Calcium from supplement of low (CaCO3) and high (Ca-citrate) water solubility are equally well absorbed. Therefore, physiological factors in the intestine instead of solubility of a specific salt or gastric pH are likely to determine bioavailability. An intestinal absorption rate of approximately 30 % can be derived for supplementary calcium.
Since lime will be exposed to the same pH regimes if ingested, also lime can be expected to be subjected to equivalent physiological processes. An absorption rate of approximately 30 % can therefore be assumed for lime by read-across from calcium carbonate.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
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