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EC number: 231-826-1 | CAS number: 7757-93-9
- 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
Specific investigations: other studies
Administrative data
- Endpoint:
- specific investigations: other studies
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Follows basic scientific and laboratory principles, article has been peer-reviewed.
Data source
Reference
- Reference Type:
- publication
- Title:
- Dietary phosphate modulates Atherogenesis and Insulin Resistance in Apolipoprotein E Knockout mice.
- Author:
- Ellam T, Wilkie M, Chamerlain J, Crossman D, Eastell R, Francis S and Chico JA
- Year:
- 2 011
- Bibliographic source:
- Arteriosclerosis, Thrombosis and Vascular Biology. 31:00-00
- Report date:
- 2011
Materials and methods
Test guideline
- Qualifier:
- no guideline available
- Principles of method if other than guideline:
- Apolipoprotein E knockout mice were fed an atherogenic diet with low (0.2%), standard (0.6%), or high (1.6%) phosphate content.
- GLP compliance:
- not specified
- Type of method:
- in vivo
- Endpoint addressed:
- repeated dose toxicity: oral
Test material
- Reference substance name:
- Calcium bis(dihydrogenorthophosphate)
- EC Number:
- 231-837-1
- EC Name:
- Calcium bis(dihydrogenorthophosphate)
- Cas Number:
- 7758-23-8
- Molecular formula:
- CaH4O8P2
- IUPAC Name:
- calcium dihydrogen phosphate
- Reference substance name:
- Calcium hydrogenorthophosphate
- EC Number:
- 231-826-1
- EC Name:
- Calcium hydrogenorthophosphate
- Cas Number:
- 7757-93-9
- Molecular formula:
- CaHPO4
- IUPAC Name:
- calcium hydrogen phosphate
- Details on test material:
- - Name of test material (as cited in study report): study states that calcium monophosphate and calcium diphosphate were used in the study (assumed to be calcium bis(dihydrogenorthophosphate) and calcium hydrogenorthophosphate).
Constituent 1
Constituent 2
Test animals
- Species:
- mouse
- Strain:
- other: Apolipoprotein E knockout mice
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: JAX LABS (JAX 2052) - breeding colony maintained in the laboratory.
- Age at study initiation: 8 weeks
- Weight at study initiation: no data
- Fasting period before study: no data
- Housing: no data
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 8 weeks
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 6 light/6 dark
Administration / exposure
- Route of administration:
- oral: feed
- Vehicle:
- not specified
- Details on exposure:
- DIET: atherogenic diets (21% fat, 0.2% cholesterol, 0.03% cholate)
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Phosphate content of test diets was confirmed by independent laboratory assessment (N.P, Analytical Laboratories, USA). Data not presented in article.
- Duration of treatment / exposure:
- 12 and 20 weeks
- Frequency of treatment:
- Daily
- Post exposure period:
- No post-exposure period
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0.2, 0.6 and 1.6% phosphate
Basis:
nominal in diet
- No. of animals per sex per dose:
- 5 to 8 per group
Examinations
- Examinations:
- Blood Pressure Measurement
Systolic and diastolic blood pressure measurements were performed twice weekly on 4 animals per dietary group (total N=12) using tail cuff measurements (Visitech 2000, Visitech Systems, NJ, USA). Mean arterial pressure was calculated from each pair of systolic/diastolic measurements.
Biochemical Analyses
Fasting glucose was measured on whole blood (Medisense, Optium Xceed). Commercial sandwich ELISA assays were used to quantify plasma insulin (Crystalchem, USA), adiponectin (R&D systems, UK), parathyroid hormone (Immutopics, USA) and FGF23 (KAINOS laboratories, Japan), according to the manufacturers’ instructions. All other plasma biochemistry measurements were performed by autoanalyzer (Beckman Coulter DxC). LDL cholesterol was calculated from other lipid fractions according to the Friedewald formula1. Insulin resistance was measured by standard homeostatic model assessment2 (HOMA-IR) = fasting glucose (mmol/l) × fasting insulin (mU/l)/22.5.
Tissue collection
Mice were sacrificed by intraperitoneal injection of an overdose of pentobarbitone (4mg) and blood aspirated by cardiac puncture. The vasculature was then flushed with phosphate-buffered saline and perfusion-fixed by ventricular injection of 10% formalin. Thoracic aortae were dissected free of connecting tissue from the heart to the level of the diaphragm and fixed in 4% paraformaldehyde. Following fixation in 10% formalin, hearts and livers were dehydrated and embedded in paraffin wax. Epididymal fat pads, kidneys, lungs, livers and spleens were dissected free of connective tissue before weighing.
Results and discussion
- Details on results:
- Effects of Dietary Phosphate Group on Urea, Weight and Blood Pressure
Dietary phosphate intake had no significant effect on urea (7.3±0.5mmol/L, 8.0±0.5mmol/L and 7.0±0.5mmol/L for low, standard and high dietary phosphate groups respectively). Lower dietary phosphate intake was associated with a trend towards greater chow consumption and BMI, with a
significantly greater final weight and body length. With the exception of liver and epididymal fat pads, other organ weights (heart, lung, kidneys, and spleen) did not differ between groups. Blood pressure also did not differ between groups.
Increased dietary phosphate intake had no effect on aortic sinus atheroma at 12 weeks but was associated with significantly more atheroma at 20 weeks.
Calcification was absent by von Kossa staining, and lesions did not differ in vascular smooth muscle cell or macrophage content.
Epididymal fat pad mass was significantly greater in the low versus high dietary phosphate. Insulin resistance measured by homeostatic model assessment was increased 4-fold on a low-phosphate diet in comparison with other dietary groups.This was not accounted for by adiponectin, which did not differ between low and standard dietary phosphate groups. Hepatic steatosis was induced in the low-phosphate group and was accompanied by greater liver weight and alanine transaminase.
Applicant's summary and conclusion
- Conclusions:
- The authors conclude that a high-phosphate diet accelerates atherogenesis in apolipoprotein E K/O mice, whereas low phosphate intake induces insulin resistance. These data indicate that controlling dietary phosphate intake may influence development of both atherosclerosis and the metabolic syndrome.
It is worth noting that the dose levels used in the study are not representative of a typical human diet; the standard P diet used contained 2X the amount of phosphate found in a typical human diet and no effects were noted at this dose level. Further investigation of the conclusions drawn from this investigation will be required to prove beyond doubt the link between phosphorus and heart disease.
It is therefore concluded that although these finding may be of use to the medical community they are not relevant for assessment of calcium phosphates under REACH. As with all essential elements it is likely that an increase or a decrease in phosphate levels may have a detrimental effect on the health of the individual. However the normal levels of intake for inorganic phosphates fall well within the safe range identified in this study and the maximum tolerable daily intake of 70 mg/kg bw of P/day, from all sources, is not considered to induce any of the effects noted in the study. The levels of occupational exposure to inorganic phosphates will not significantly contribute to the overall daily intake of phosphrous and it is therefore not considered appropriate to investigate this further for the purpose of REACH registration.
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