Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 200-909-4 | CAS number: 75-86-5
- 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
Under physiological conditions, 2-hydroxy-2-methylpropionitrile (named ACH in the quoted ECETOC report) decomposes to yield its molar equivalent in hydrogen cyanide and acetone. The intrinsic toxicological properties of 2-hydroxy-2-methylpropionitrile are determined for the most part by the degradation product hydrogen cyanide.
(Following quotation taken with kind permission from ECETOC JACC report no. 53; Cyanides of Hydrogen, Sodium and Potassium, and Acetone Cyanohydrin (CAS No. 74-90-8, 143-33-9, 151-50-8 and 75-86-5):
“Commercial and technical grade ACH are stabilised by the addition of 0.01% sulphuric or phosphoric acid. Stabilised ACH will exert a significant vapour pressure, primarily due to the presence of more volatile HCN, at room temperature. Under physiological conditions, acid-stabilised ACH will be buffered by the intracellular buffering capacity resulting in its rapid and quantitative decomposition to HCN and acetone. Hence, ACH will exhibit the combined characteristics of HCN and acetone (Frank et al, 2002).”
“The predominant speciation of all inorganic cyanide in the body is HCN due to the weak acid dissociation constant (pKa = 9.11). This is also the form in which cyanide is absorbed into the blood after oral, dermal or inhalation exposure. It is rapidly absorbed via all exposure routes. The main route of metabolism is enzymatic (rhodanese) trans-sulphuration into thiocyanate. The liver metabolises nearly all cyanide at subtoxic dose levels via the enzyme rhodanese. So there is a first-pass effect via the oral route. However, the overall maximum detoxification capacity in humans derived from the difference in acute toxicity data at different exposure times is limited to about 0.008 mg CN-/kg bw/min. Detoxification rates for other species ranged between 0.01 and 0.03 mg CN-/kg bw/min and were thus a little higher.
The detoxifying enzyme rhodanese is not only found in the liver but also in muscles and other tissues. Rhodanese in muscles contributes considerably to the detoxification of cyanide in the body to thiocyanate. In the absence of sulphur donating agents in the human body, the maximum detoxification rate was claimed to be as low as 0.9 μg CN-/kgbw/min (Schulz et al, 1982). However, a re-analysis of the data suggests a rate of 3.0 μg CN-/kg bw/min (80 min mean infusion duration), based on the dose rate at which no clinical symptoms occurred.
Inter-individual variation in serum rhodanese activity can vary by a factor of 6 (Nawata et al, 1991) or 3 to 8 (Narendranathan et al, 1989). However, rhodanese is present in all body tissues in considerable excess and not rate-limiting (Himwich and Saunders, 1948; Schulz et al, 1982), unlike thiosulphate, which may be only available in the body in small amounts depending on the nutritional status (Schulz et al, 1982). No major polymorphisms have been identified to date. A rare hereditary disease, Leber’s optic atrophy has been linked by some authors to a deficiency in rhodanese activity (Cagianut et al, 1984; Wilson, 1965, 1983; Poole and Kind, 1986), but this was not confirmed by other authors (Pallini et al, 1987; Berninger et al, 1989; Whitehouse et al, 1989). Protein deficient populations are more susceptible to cyanide intoxication as thioamino acid levels are reduced."
Low-dose cyanide metabolim under normal physiological conditions
Cyanide is presend and metabolised under normal physiolgical conditions as referred in the rationale of Acute Exposure Guideline Levels (AEGLs) established by AEGL-Committee (US-NAC, Acetone Cyanohydrin, Interim Acute Exposure Guideline Levels (AEGLs), Interim final draft, 2005; in the following cited as AEGL):
"With regard to the metabolism of cyanide, it is important to distinguish between low-dose cyanide metabolism, which occurs under circumstances in which cyanide is present in physiological concentrations, and high-dose cyanide disposition, in which there are amounts of cyanide far in excess of those present under normal physiological conditions. Low-dose cyanide metabolism involves incorporation via vitamin B12-dependent enzymes of cyanide into the C1-metabolite pool from which it can be eliminated as carbon dioxide. Under physiological conditions, the normal capacity of rhodanese to handle cyanide is not overwhelmed and circulating cyanide remains in metabolic equilibrium with the C1-metabolic pool (DECOS, 1995; ATSDR, 1997)" (quotation from AEGL).
Mode of action
“Cyanide poisoning is caused by complex formation with the iron in cytochrome oxidase which is present in tissues at cellular level. The complex formation inhibits oxygen from receiving electrons from the cytochrome oxidase and a so-called intracellular or cytotoxic anoxia occurs, i.e. oxygen is present but cannot be utilised by the cell.
Because neurons and cardiac myocytes are highly dependent on aerobic metabolism they are extremely sensitive to the deprivation of oxygen. If aerobic metabolism fails due to the inactivated cytochrome oxidase by cyanide, the neuron immediately loses its capacity to conduct nervous pulses properly and the brain fails to function with consequent loss of consciousness. If this stage continues for some minutes, the damage becomes irreversible and the neurons die. For these reasons, prolonged hypoxia, regardless of its cause, often results in injury to the brain. Toxicants that inhibit aerobic cell respiration like HCN and hydrogen sulphide have the same effect (Anthony and Graham, 1991)" (quotation from ECETOC).
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.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.