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EC number: 248-660-0 | CAS number: 27794-93-0
- 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
Endpoint summary
Administrative data
Link to relevant study record(s)
Description of key information
Key value for chemical safety assessment
Additional information
Introduction
Based on the available data, no major differences appear to exist between animals and humans with regard to the absorption, distribution and elimination of phosphonic acid compoundsin vivo. Unless otherwise stated the following information comes from the SIDS Initial Assessment Report for SIAM 18. Category: Phosphonic Acid Compounds Group 1. Annex VI.
Absorption
Oral
The physicochemical properties of phosphonic acid compounds, notably their high polarity, charge and complexing power, suggests that they will not be readily absorbed from the gastrointestinal tract. This is supported by experimental data which confirm that absorption after oral exposure is low, averaging 2-7% in animals (2.2 % in Hotz et al., 1995) and 2-10% in humans. Gastrointestinal pH is a major determinant influencing uptake, and is relatively acidic in the stomach (range: pH 1 - 4) and slightly more alkaline in the intestine (pH 4 - 7). The number of ionisations of the phosphonic acid moiety increases with increasing pH, rising from 1 - 2 at low pH (i.e. stomach) to 4 - 6 at more neutral pH (reflective of conditions in the intestine). The negative charge on each molecule also increases with each ionisation, further reducing the already low potential for uptake. Stability constants for the interaction of phosphonic acids with divalent metal ions are high, and indicate strong binding, especially at lower pHs. Complexation of a metal with a phosphonic acid would produce an ion pair of charge close to neutral which might favour absorption; however, the overall polarity of the complex would remain high thereby counteracting this potential. Overall, these considerations indicate that ingested phosphonic acid compounds will be retained within the gut lumen.
Dermal
ATMP is too hydrophilic to be absorbed through the skin.
Inhalation
The vapour pressure of ATMP is extremely low (<10E-08 Pa). Consequently, inhalation of ATMP vapour is not possible. It is possible that a dust (from solid) or aerosol (from aqueous solution) of ATMP could be inhaled. The potential particle size distributions that workers and consumers could be exposed to for these forms of ATMP are not currently known.. However, the very high water solubility of this substance suggests that absorption will be low.
Distribution
Blood / tissue ratios demonstrate that ATMP has a strong affinity for bone, with a 158-fold increase of14C present in femur (relative to that in blood) following gavage administration of 150 mg/kg bw, and a 1211-fold increase after intravenous (i.v.) treatment with 15 mg/kg bw. Bone specificity of the substance is further supported in a study by Bartnik & Zimmerman (1983) following oral administration. Levels were also increased in tibia (191-fold) and sternum (76-fold) after oral (gavage) treatment (not determined following injection). In contrast, amounts present in soft tissue (e.g. liver, kidney, spleen) and carcass were largely unaltered after gavage exposure (increase 8-fold or less) while i.v. injection was associated with greater increases (soft tissues elevated 3 to 30 fold; carcass 50 fold) (Hotz et al., 1995).
Whole body autoradiography studies confirm the above tissue distribution findings, with pronounced deposition of14C-ATMP (150 mg/kg bw, by gavage) in the epiphyseal plate of the long bones and also the nasal turbinates, with additional radioactivity present in gut contents and bone marrow. By 10 d post-treatment, intense localisation of label was still apparent in the epiphyseal plate of the long bones, with some material present also in stomach lining and kidneys (Holtz et al., 1995).
Metabolism
Unchanged ATMP accounts for 25% of material recovered from rat urine 0-24 hr after oral administration (150 mg/kg bw, by gavage), with 46% present as an N-methyl derivative and 29% as an unknown metabolite. In contrast, the parent substance predominated (64% of total) in urine after i.v. dosing (15 mg/kg bw), with approximately equivalent amounts of the N-methyl derivative (21%) and the unknown metabolite (14%) also present (Hotz et al., 1995).
Excretion
Faecal elimination of unabsorbed material predominates after ingestion (up to 90% of dose). Renal clearance of any material absorbed from the gut is rapid, with urinary half-lives of 5 hr and 70 hr reported. This second phase of excretion may represent mobilisation of material initially sequestered by bone, since deposition studies have shown preferential accumulation of these substances in the epiphyseal plate and other regions of the long bonesin vivo.
In a well designed and reported study, Hotz et al. (1995) demonstrated that faecal excretion was the principal route of elimination following gavage administration of14C-ATMP to male rats (150 mg/kg bw; 28.76 μCi/kg bw); 74% of the dose eliminated in 24 hr, 83% at 48 hr, up to a maximum 84% at 10 d. Trace amounts of radioactivity were present in urine (approx. 1% of dose) and blood, tissues and carcass (total approx. 0.3%) but not in exhaled air. Overall mean recovery from all sources was 85.9%. In contrast, renal clearance predominated after i.v. injection (15 mg/kg bw; 1.93 μCi/kg bw), with 46% of the dose recovered in urine 6 hr post-dosing, rising to 50% after 24 hr (maximum 53% accounted for over 10 d). Overall mean recovery was 88.9%. Approx. 4 to 5% of the dose was eliminated via faeces, while blood, tissues and carcass contained a total of 23% of the dose. Based upon relative urinary excretion after gavage and i.v. administration, gastrointestinal uptake was calculated as 2.15%. Kinetic analyses indicate that ATMP is excreted in a biexponential manner by the rat, with urinary half-lives of 5 hr or 70 hr after oral exposure, and 2 hr or 127 hr after i.v. treatment (Hotz et al., 1995).
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