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Diss Factsheets
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EC number: 267-956-0 | CAS number: 67953-76-8
- 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
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Additional toxicological data
Administrative data
- Endpoint:
- additional toxicological information
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- No data
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- test procedure in accordance with national standard methods with acceptable restrictions
Data source
Reference
- Reference Type:
- publication
- Title:
- Relationship between bone mineralization, Ca absorption and plasma Ca in phosphonate treated rats
- Author:
- Treschel, U, Schenk, R, Bonjour, J-P, Russell, RGG and Fleisch, H
- Year:
- 1 977
- Bibliographic source:
- Am J Physiol, 232, E298 - 303
Materials and methods
- Type of study / information:
- Effects on bone.
Test guideline
- Qualifier:
- no guideline followed
- GLP compliance:
- no
- Remarks:
- pre-GLP
Test material
- Reference substance name:
- Sodium Salts of (1-Hydroxyethylidene)bisphosphonic acid (2-3 Na:1)
- EC Number:
- 701-238-4
- Molecular formula:
- HEDP-2Na C2H6Na2O7P2 HEDP-3Na C2H5Na3O7P2
- IUPAC Name:
- Sodium Salts of (1-Hydroxyethylidene)bisphosphonic acid (2-3 Na:1)
Constituent 1
Results and discussion
Any other information on results incl. tables
Neutralised HEDP (equivalent to 10 mg HEDP/kg bw) resulted in a significant (P<0.001) 3-fold increase in the width of the epiphyseal plate and inhibited mineralization of osteoid and cartilage (n = 38 animals).
Uptake of 45Ca from ligated intestine was inhibited 40% by neutralised HEDP (P<0.001; n = 37 animals).
Plasma calcium was increased 6% (P<0.001) after two subcutaneous injections of 10 mg-equivalent HEDP/kg bw/day, increased 26% (P<0.001) 1-hour after a third injection and increased 5% (P<0.001) 24-hour after a seventh injection (n = 34 - 39 animals). Plasma phosphate was decreased only 24 hours after the seventh injection (9% reduction; P<0.01; n = 34 - 37 animals). Epiphyseal plate width (P<0.001) and plasma calcium (P<0.001) were significantly increased, and intestinal calcium absorption decreased (P<0.001) in rats given 5 mg or 10 mg equivalent HEDP/kg/d (NOAEL = 2.5 mg/kg bw/day) (n = 12 rats/treatment).
Applicant's summary and conclusion
- Conclusions:
- In a well conducted study investigating the effects of HEDP-xNa on bone (reliability score 2), not conducted according to any OECD Test Guideline and pre-GLP study, male and female Wistar rats were given subcutaneous injections of 2.5, 5 or 10 mg/kg bw/day neutralised HEDP on seven consecutive days. Control animals were given an equal volume of saline alone. Blood was collected from the tails on Day 3 (one hour after injection) and Day 8 (24 hours after the final injection) to determine calcium levels. Following seven days of treatment, rats were anaesthetised following overnight fasting, and calcium absorption from the duodenum was estimated. Three frontal sections of the upper part of one tibia were prepared and the width of the epiphyseal plate measured (in triplicate). At a dose of 10 mg/kg bw/day, there was a significant (p<0.001) 3-fold increase in the width of the epiphyseal plate and inhibited mineralisation of osteoid and cartilage. Uptake from ligated intestine was inhibited 40% by neutralised HEDP (p<0.001). Plasma calcium increased by 6% (p<0.001) after 10 mg/kg bw/day, increased 26% (p<0.001) one hour after the third injection, and increased 5% (p<0.001) 24 hours after the seventh injection. Epiphyseal plate width (p<0.001) and plasma calcium (p<0.001) were significantly increased, and intestinal calcium absorption decreased (p<0.001) in rats given 5 and 10 mg/kg bw/day.
Therefore, decreased skeletal mineralisation was associated with decreased intestinal calcium uptake, hypercalcemia and increased epiphyseal plate width. A concluded NOAEL was determined to 2.5 mg/kg bw/day. The authors speculated that impaired intestinal calcium uptake is a secondary homeostatic response to the effect of neutralised HEDP on bone mineralisation.
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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