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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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
Description of key information
Data for acute oral, dermal and inhalation toxicity are available. The substance is very toxic by all these exposure routes which is reflected in the legally binding harmonised classification as given in REGULATION (EC) No 1272/2008 Annex VI Table 3.1 (GHS):
Acute tox 2* H330 (oral)
Acute tox 1 H310 (dermal)
(Acute tox 2* H300 (inhalation, vapour)) Based on the actual data this classification in annex VI, EU GHS, is too low. Data indicate the following:
Acute tox 1 H300 (inhalation, vapour)
and Table 3.2 (Annex I of Directive 67/548/EEC):
T+; R26/27/28
Key value for chemical safety assessment
Acute toxicity: via oral route
Endpoint conclusion
- Dose descriptor:
- LD50
- Value:
- 17 mg/kg bw
Acute toxicity: via inhalation route
Endpoint conclusion
- Dose descriptor:
- discriminating conc.
- Value:
- 223 mg/m³ air
Acute toxicity: via dermal route
Endpoint conclusion
- Dose descriptor:
- LD50
- Value:
- 16 mg/kg bw
Additional information
2-hydroxy-2-methylproanenitril has been the subject of an assessment report of the European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC report, JACC No. 53, Volume I, 2007; in the following cited as ECETOC). Furthermore Acute Exposure Guideline Levels (AEGLs) have been established by AEGL-Committee (US-NAC, Acetone Cyanohydrin, Interim Acute Exposure Guideline Levels (AEGLs), Interim final draft, 2005; in the following cited as AEGL). In these reports 2-hydroxy-2-methylproanenitril is designated as acetone cyanohydrin (ACH). Data for acute oral, dermal and inhalation toxicity are available.
Acute toxicity oral:
One key study has been identified, Smith et al 1962. In this acute oral toxicity study groups of five male Carworth Wistar rats (four to five weeks old, weight: 90 to 120 g) were given a single oral dose of 2-hydroxy-2-methylproanenitrile (a.i. and % dilution unstated) in a suitable vehicle. The dosages were arranged in a logarithmic series differing by the factor of two. Animals were then observed for 14 days.
Oral LD50 Males = 17 mg/kg bw (11 – 26 mg/kg bw 95% C.I.)
Supporting data are available from literature and IUCLID 4 database, which fit very well with the observations of this study. Data reported from AEGL committee are presented in the following table. The same data are reported in the ECETOC report.
Summary of oral LD50 data for acetone cyanohydrin |
||
Species |
LD50 (mg/kg) |
References |
Rat |
17 |
Smyth et al., 1962 |
Rat |
13.3 |
Shkodich, 1966 |
Rat |
17.8 |
Marhold, 1972 |
Mouse |
14 |
Marhold, 1972 |
Mouse |
15 |
Hamblin, 1953 |
Mouse |
2.9 |
Shkodich, 1966 |
Guinea pig |
9 |
Shkodich, 1966 |
Rabbit |
13.5 |
Shkodich, 1966 |
Acute toxicity inhalation:
Only one study from literature could be selected as reliable. This is in compliance with ECETOC and AEGL. “The AEGL Committee found that hardly any data exist on inhalation for ACH. They relied on a range-finding study of Smyth et al (1962)” (quotation from ECETOC). The study was described in the AEGL as follows:
“Smyth et al. (1962) exposed groups of 6 albino rats to acetone cyanohydrin vapors that were produced by passing a 2.5-l/min-air stream through a fritted glass disc immersed in 50 ml acetone cyanohydrin. Doses were logarithmically distributed, differing by a factor of two (doses were not stated explicitly). The observation period was 14 days. After exposure for 4 hours, 2/6 rats were killed at 62.5ppm and 6/6 rats were killed at 125 ppm. The maximum time rats could be exposed to saturated vapor (about 1300 ppm) without producing any deaths was 5 minutes. No other signs of toxicity were reported.”
Concentration(mg/m³) (ppm) |
Exposure time (h) |
Number of deaths/exposed |
Observation period (d) |
62.5 (221) |
4 |
2/6 |
14 |
125 (442) |
4 |
6/6 |
14 |
Acute toxicity dermal:
The study of Carreon has been identified as reliable from available literature in compliance with ECETOC.
In this acute dermal toxicity study equivalent to OECD TG 402 (1981), 3 groups of New Zealand White rabbits (2 males and 2 females per dose level) were dermally exposed to 2-hydroxy-2-methylpropionitrile (10 % aq.) for 24 hours at doses of 6, 25, 40 mg/kg bw. Animals then were observed for 14 days.
Dermal LD50 Combined = 16 mg/kg bw (95% C.I. 8 - 28).
Lethargy (at 6, 25, 40 mg/kg bw), labored breathing (at 25 and 40 mg/kg bw), and convulsions (at 25 mg/kg bw) were clinical signs of toxicity observed after treatment. There were no treatment related necropsy findings. Slight (4/5 animals) to moderate (1/5 animals) redness, slight swelling in 3/5 animals, and slight necrosis in 1/5 animals were found after 24 hours post treatment in the surviving animals.
One additional study has been identified by ECETOC as follows:
Skin condition |
LD50 (mg/kgbw) |
Reference |
Intact |
16.0 |
Carreon et al, 1981 |
Intact |
850 |
Sterner and Chibanguza, 1980 |
Abraded |
150 |
Sterner and Chibanguza, 1980 |
Discussion:
“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)" (quotation from ECETOC).
"On a molar basis, there is no significant difference in acute toxicity between HCN, or its alkali salts, and ACH. This is consistent with the molar decomposition of ACH into acetone and HCN (US-NAC, 2000a,b)” (quotation from ECETOC).
"All cyanides ingested will be present, at the physiological pH of the stomach, as HCN. The HCN will be absorbed in the blood via the stomach wall and in the intestines. Before the blood enters the systemic circulation it has to pass the liver with a relatively high content of the enzyme rhodanese. A considerable part of cyanide is detoxified in the liver. This is apparent from comparison of the oral LD50 value for rabbits (0.092 mmol/kgbw) with those obtained by intravenous (i.v.) injection or inhalation for 5 minutes (0.022 or 0.019 mmol/kgbw, respectively) (Ballantyne, 1987a), indicating a first-pass effect via ingestion" (quotation from ECETOC).
“The difference between the two dermal LD50 values reported for ACH is remarkable since both studies were carried out according to the OECD 402 protocol, the only apparent difference being that Sterner and Chibanguza (1980) clipped the hair of only 150 cm² on the back, whereas – Carrion et al (1981) clipped the hair from the full trunk of the rabbits. This suggests that the area of skin contact and integrity of the skin areas very important in case of ACH. Abrasion of the skin enhances the dose rate and increases the toxicity of ACH” (quotation from ECETOC).
"In the humid air and the moist mucosa of the respiratory tract, acetone cyanohydrin decomposes to yield its molar equivalent in hydrogen cyanide and acetone. This reaction is a result of the physical chemistry of acetone cyanohydrin (Stewart and Fontana, 1940) and it is not known to be enzyme catalyzed in animals or humans (DECOS, 1995; Kaplita and Smith, 1986)" (quotation from AEGL).
"In mammals, cyanide is rapidly absorbed in the form of HCN following oral, dermal or inhalation exposure. Cyanides are very toxic by all routes of entry. The mechanism of toxicity is by inhibition of oxygen utilisation by tissues; the most sensitive organs are those with the greatest oxygen demand such as brain, heart and testes. In humans, the acute lethal dose is approximately 1.5 mg/kgbw following oral uptake. The acute inhalation toxicity is a function of the body weight and the time of exposure. Using probit analysis of the acute inhalation data in different species, a human LC50 value of 202 mg/m³ (180 ppm) and an LC01 of 88 mg/m³ (78 ppm) were derived, both following 60 minutes of exposure. The lethal dose by the dermal route will depend upon the area of skin exposed. A dose of approximately 100 mg/kgbw is lethal even if only a small area of skin is contacted. Acutely toxic levels might also be achieved following eye contact" (quotation from ECETOC).
Justification for classification or non-classification
Legally binding harmonised classification as given in REGULATION (EC) No 1272/2008 Annex VI Table 3.1 (GHS):
Acute tox. 2* H330
Acute tox. 1 H310
Acute tox. 2* H300
and Table 3.2 (Annex I of Directive 67/548/EEC):
T+; R26/27/28
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.