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Toxicological information

Basic toxicokinetics

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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:
1968
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

Constituent 1
Chemical structure
Reference substance name:
Methacrylonitrile
EC Number:
204-817-5
EC Name:
Methacrylonitrile
Cas Number:
126-98-7
Molecular formula:
C4H5N
IUPAC Name:
methacrylonitrile
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)

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