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EC number: 200-848-3 | CAS number: 75-20-7
- 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
Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
Data source
Referenceopen allclose all
- Reference Type:
- publication
- Title:
- Foetal development in rats fed AIN-76A diets supplemented with excess calcium
- Author:
- Shackelford ME, Collins TF X, Welsh JJ, Black TN, Ames MJ, Chi RK and O'Donnell M W
- Year:
- 1 993
- Bibliographic source:
- Fd Chem. Toxic. Vol. 31, No. 12, pp. 953-961
- Reference Type:
- publication
- Title:
- Mineral interactions in rats fed AIN-76A diets with excess calcium
- Author:
- Shackelford ME, Collins TF X, Black TN, Ames MJ, Dolan S, Sheikh NS, Chi RK and O'Donnell M W
- Year:
- 1 994
- Bibliographic source:
- Fd Chem. Toxic. Vol. 32, No. 3, pp. 255-263. 1994
Materials and methods
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- The main objective of the study (Shackelford et al., 1993) was to examine potential effects of high dietary calcium in rats on pregnancy and development of the foetus. Female rats were fed a diet containing various levels of calcium, 6 weeks before mating, throughout mating and 20 days during gestation. Non pregnant animals and pregnant animals fed with normal calcium levels were used as controls. On gestation day 20, the animals were killed and caesarian sections were performed. The uterine contents were examined and the foetuses were evaluated for soft tissue and skeletal changes. In a further publication (Shackelford et al., 1994), the effect of high calcium intake on other mineral tissue levels was analyzed. Some data of this publication are also added in this endpoint summary, cause they provide a better insight on the experimental procedures of the study.
- GLP compliance:
- not specified
- Remarks:
- not applicable for publications
- Limit test:
- no
Test material
- Reference substance name:
- Calcium carbonate
- EC Number:
- 207-439-9
- EC Name:
- Calcium carbonate
- Cas Number:
- 471-34-1
- Molecular formula:
- CH2O3.Ca
- IUPAC Name:
- calcium carbonate
- Test material form:
- solid: particulate/powder
- Remarks:
- migrated information: powder
- Details on test material:
- US- Pharmacopeia-grade calcium carbonate (Pfizer)
-Purity: 98.62%
Constituent 1
Test animals
- Species:
- rat
- Strain:
- other: CD/VAF Plus
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Laboratories Inc.
- Age at study initiation: 52 days
- Housing: stainless steel
- Diet: modified AIN-76A
The animals were kept on a 6 day quarantine before the initiation of the study.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-27
- Humidity (%): 25-72
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- oral: feed
- Vehicle:
- unchanged (no vehicle)
- Details on exposure:
- The detailed composition of the diet is provided in Table 1 of the attached document (see below).
- Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- Yes, method of the Association of Official Analytical Chemists.
- Details on mating procedure:
- - Impregnation procedure: cohoused
- M/F ratio per cage: 1/2
- Length of cohabitation: from 4.30 pm till morning
- Further matings after two unsuccessful attempts: no data
- Proof of pregnancy: sperm in vaginal smear referred to as day 0 of pregnancy - Duration of treatment / exposure:
- 6 weeks before mating, throughout mating and 20 days during gestation (only female animals were exposed)
- Frequency of treatment:
- daily
Doses / concentrationsopen allclose all
- Dose / conc.:
- 5 000 mg/kg diet
- Dose / conc.:
- 7 500 mg/kg diet
- Dose / conc.:
- 10 000 mg/kg diet
- Dose / conc.:
- 12 500 mg/kg diet
- No. of animals per sex per dose:
- 291 animals participated in the study in total. 15 rats were selected randomly for evaluation of the tissue mineral status and histopathology (baseline animals).
- Control animals:
- yes
- Details on study design:
- - Dose selection rationale: no data
- Rationale for animal assignment (if not random): random
Examinations
- Maternal examinations:
- CLINICAL OBSERVATIONS: Yes
BODY WEIGHT: Yes
FOOD CONSUMPTION: Yes
- Food consumption for each animal was determined 3 days per week during the 6 wk pre-mating period
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 20
All organs/tissues were examined grossly. Histopathological examination was performed for the heart, liver, kidneys and bones
-Organ weights measured: liver, kidney, heart - Ovaries and uterine content:
- The uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: No data
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes - Fetal examinations:
- Uterine position, sex, weight and length were recorded for each foetus.
- Visceral examinations: Yes: all per litter
- Soft tissue examinations: Yes: half per litter
- Skeletal examinations: Yes: half per litter - Statistics:
- The incidence of clinical observations: Fisher's exact test. Feed consumption: (ANOVA) and protected least-significant difference (LSD) test (two-tailed). Weight gain: (ANOCOVA), after adjusting for the initial body weight, and an LSD test (two-tailed). Trend analysis was done on feed consumption. It was not done on body weight data, because we analysed these data by covariance. No of corpora lutea, average No of implantations, average No of viable foetuses/litter, average No male or female foetuses/ litter : ANOVA and an LSD test (one-tailed). Implantation efficiency, early deaths, late deaths and total resorptions (early and late deaths): Freeman-Tukey arcsine transformation for binomial proportions (Freeman-Tukey, 1950). Transformed data for each litter by ANOVA and an LSD test (one-tailed), comparing the control group with experimental groups. Data on litters runts and resorbed litters comparing control to treated: Fisher's exact test. Foetal body weights and crown-rump lengths: nested ANOVA (Sokal and Rohlf, 1981) & LSD test (one-tailed). Specific litter incidence of sternebral, skeletal andvisceral variations, control with treatment groups: Fisher's exact test. Proportions of litters with foetuses showing external variations: Fisher's exact test. Average No of foetuses with variations/ litter: Freeman-Tukey arcsine transformation, ANOVA and protected LSD test (one-tailed). Litters that had foetuses with one or more sternebral, skeletal and visceral variations were analysed with Fisher's exact test. Trend analysis on the litter data for external variations, using the Cox exact one-tailed test for unadjusted positive trend. A trend is significant if the P value is below 0.05. Trend analysis was not done on data that were analysed by using the Freeman-Tukey arcsine transformation for binomial proportions.
Results and discussion
Results: maternal animals
Maternal developmental toxicity
- Details on maternal toxic effects:
- Maternal toxic effects:no effects
Details on maternal toxic effects:
Clinical: alopecia, exudate around the eyes, exudate around the nose, bent teeth, lesion, lump in the left flank or leg and mammary lump. However, no dose response association. Three females died during the study (non-treatment related). The treatment showed some variations on the food consumption; however, not all differences were statistically significant. No body weight gain effects were detected. Relative organ weights to body weights of the treated groups were not significantly different from the controls. Implantations, resorptions and litter sizes were comparable to controls and did not appear influenced by the high calcium consumption.
Effect levels (maternal animals)
open allclose all
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 227.5 other: mg calcium/day
- Based on:
- act. ingr.
- Basis for effect level:
- other: developmental toxicity
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 288.75 other: mg calcium/day
- Based on:
- act. ingr.
- Basis for effect level:
- other: developmental toxicity
Results (fetuses)
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:no effects
Details on embryotoxic / teratogenic effects:
No adverse effects were detected on the foetuses. Foetal body weights and lengths were within the normal control values. No effect related to the treatment was seen on the number of litters.
Effect levels (fetuses)
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 1.25 other: % in diet
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: no adverse effects observed
Fetal abnormalities
- Abnormalities:
- not specified
Overall developmental toxicity
- Developmental effects observed:
- not specified
Any other information on results incl. tables
More details on the results are presented in the attached pdf document.
Applicant's summary and conclusion
- Conclusions:
- There was no adverse developmental/teratogenic effects related to high dietary calcium intake, i.e. 1.25% of the daily diet, of animals, 6 weeks before mating, throughout mating and 20 days during pregnancy. Additionally, such levels did not affect the reproductive performance parameters examined in this study.
- Executive summary:
In the present study, the potential effects of high dietary calcium on pregnancy and development of the foetus were studied in rats. Female Charles River CD/VAF Plus rats were fed a diet containing various levels of calcium, i.e. 0.5 (control), 0.75, 1.00, or 1.25% as calcium carbonate, 6 weeks before mating, throughout mating and 20 days during gestation. On gestation day 20, the animals were killed and caesarian sections were performed. The uterine contents were examined and the foetuses were evaluated for soft tissue and skeletal changes. The treatment showed some variations on the food consumption of the females. Nonetheless, not all differences were statistically significant, and they could not be attributed to the treatment. No body weight gain effects were detected. Relative organ weights to body weights of the treated groups were not significantly different from the controls. Implantations, resorptions and litter sizes were comparable to controls and did not appear influenced by the high calcium consumption. It can be concluded, that calcium up to 1.25% in the diet, is not foetotoxic or teratogenic.
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