Registration Dossier
Registration Dossier
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EC number: 204-817-5 | CAS number: 126-98-7
Basic toxicokinetics
Administrative data
- Endpoint:
- basic toxicokinetics in vivo
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- no data
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Peer reviewed literature data
Data source
Reference
- Reference Type:
- publication
- Title:
- The mammalian toxicity of methacrylonitrile
- Author:
- Pozzani UC, Kinkead ER & King JM
- Year:
- 1 968
- Bibliographic source:
- American Industrial Hygiene Association Journal, 29: 202-210
Materials and methods
- Objective of study:
- metabolism
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other: derivation of that described by Natelson S in Microtechniques of Clinical Chemistry 2nd Ed, Charles C Thomas Co, Springfield, III, pages 204-207 (1963)
- Deviations:
- yes
- Remarks:
- see below
- Principles of method if other than guideline:
- The Obrink modification of the Conway microdiffusion dish was used. Heparinized whole blood was used for preparation of standards instead of sodium hydroxide, and for preparation of unknown instead of serum. The inner chamber of the dish was filled with 1 mL of the appropriate fluid instead of 0.5 mL and the reaction time was doubled to 2 hours. The lower limit of detection for this method was 0.1 μg cyanide per mL of whole blood.
- GLP compliance:
- no
- Remarks:
- study predates GLP
Test material
- Reference substance name:
- Methacrylonitrile
- EC Number:
- 204-817-5
- EC Name:
- Methacrylonitrile
- Cas Number:
- 126-98-7
- Molecular formula:
- C4H5N
- IUPAC Name:
- 2-methylprop-2-enenitrile
- Details on test material:
- - Name of test material (as cited in study report): Methacrylonitrile
- Source: Vistron Corporation, Midland Building, Cleveland, Ohio
- Molecular weight: 67.09
- Substance type: organic, monoconstituent
- Physical state: clear, colourless liquid
- Analytical purity: minimum of 99.0 wt %
- Boiling point: 90.3 degrees Centigrade at 760 mm
- Specific gravity: d 30°/4°, 0.7896
- Solubility in water: 2.54 wt % at 30 degrees Centigrade
- Flash point (Tag open cup): 55 degrees Fahrenheit
- Vapor pressure: 65 mm at 25 degrees Centigrade
- Inhibitor (MEHQ): 35-45 ppm
- Other: Air saturated with methacrylonitrile at 25 degrees Centigrade at 760 mm contains 85,526 ppm vapour, which has a relative vapour density of 1.11 (dry air=1)
Constituent 1
- Radiolabelling:
- not specified
Test animals
- Species:
- rabbit
- Strain:
- other: albino
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- No data.
Administration / exposure
- Route of administration:
- intravenous
- Vehicle:
- physiological saline
- Remarks:
- to give a 1 % w/v solution of methacrylonitrile
- Details on exposure:
- No data
- Duration and frequency of treatment / exposure:
- Single dose
Doses / concentrations
- Remarks:
- Doses / Concentrations:
6.25 and 12.5 mg/kg
- No. of animals per sex per dose / concentration:
- Four at 6.25 mg/kg and two at 12.5 mg/kg
- Control animals:
- not specified
- Positive control reference chemical:
- No data
- Details on study design:
- No data
- Details on dosing and sampling:
- PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: blood
- Time and frequency of sampling: at various time intervals. See Figure 1 (attached) - Statistics:
- No data
Results and discussion
- Preliminary studies:
- No data
Toxicokinetic / pharmacokinetic studies
- Details on absorption:
- No data
- Details on distribution in tissues:
- No data
Transfer into organs
- Observation:
- other: no data.
- Details on excretion:
- No data
Toxicokinetic parameters
- Toxicokinetic parameters:
- other: no data.
Metabolite characterisation studies
- Metabolites identified:
- not specified
- Details on metabolites:
- No data
Any other information on results incl. tables
The blood cyanide levels were not consistently dose-related, but they all began to fall within 4 hours after injection. This latter observation indicates that rabbits can produce significant quantities of cyanide from high doses of methacrylonitrile but can metabolise the cyanide (in large part to thiocyanate) in a relatively short period of time.
Applicant's summary and conclusion
- Conclusions:
- Rabbits are able to metabolise the cyanide which is produced in the blood following methacrylonitrile administration at a concentration of 12.5 mg/kg
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