Methyl vinyl ether

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Meets generally accepted scientific standards (restrictions: no details about test substance)

Data source

Reference

Reference Type:

publication

Title:

Determination of the kinetic constants for metabolism of inhaled toxicants in vivo using gas uptake measurements.

Author:

Andersen ME, Gargas ML, Jones RA, Jenkins LJ

Year:

1980

Bibliographic source:

Toxicol Appl Pharmacol 54: 100-116.

Materials and methods

Objective of study:

toxicokinetics

Principles of method if other than guideline:

Saturable inhalation uptake in rats measured

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Methyl vinyl ether

EC Number:

203-475-4

EC Name:

Methyl vinyl ether

Cas Number:

107-25-5

Molecular formula:

C3H6O

IUPAC Name:

methoxyethene

Details on test material:

commercially available in pressurized cylinders
no further details

Radiolabelling:

no

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male

Details on test animals or test system and environmental conditions:

body weight 180-280 g
water and diet ad libitum
acclimatisation: several days
no further data

Administration / exposure

Route of administration:

inhalation

Vehicle:

other: air

Details on exposure:

rats exposed in 31-liter battery jar chambers origin; whole body exposure.
Analytical control every 5 min starting 10 min after initiation of exposure

Duration and frequency of treatment / exposure:

3 h; single exposure

Doses / concentrations

Remarks:

Doses / Concentrations:
100, 300, 1000, 3000 ppm (240, 720, 2400, 7200 mg/m³)

No. of animals per sex per dose / concentration:

9

Details on study design:

gas uptake and metabolism in a whole body inhalation chamber measured

Details on dosing and sampling:

percentage loss of initial concentration versus time was measured every 10 min adjusted for the unoccupied chamber loss rate.

Statistics:

means calculated
kinetic parameters calculated

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

The uptake of MVE was saturable. The plot uptake rate vs. ambient concentration resembled a theoretical Michaelis-Menten-plot. The data were plotted according to a modified Eadie-Hofstee plot. The best fit straight line (correlation r²= 0.99) gave the following results:
Michaelis constant Km = 462 ppm (i.e. the concentration of MVE at which uptake proceeds at half maximal velocity)
Vmax. (the maximal rate of gas uptake from the 31-l inhalation chamber used) was 176 ppm/kg bw/hr, equivalent to 12.9 mg MVE/kg bw/hr.

Details on distribution in tissues:

no data

Details on excretion:

no data

Metabolite characterisation studies

Details on metabolites:

no data

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): other: uptake of MVE is depending on the velocity of the enzymatic metabolism
Saturable inhalation uptake in rats was reported.

Executive summary:

The saturable inhalation uptake in male F344 rats was measured during 3 h exposure in a 31-liter battery jar chambers (100, 300, 1000, 3000 ppm [240, 720, 2400, 7200 mg/m³] for 180 min; whole body exposure). Data were transformed by modified Eadie-Hofstee plots to calculate the kinetic parameters. The concentration at which the uptake proceeds at half maximal velocity was Km = 462 ppm; the maximal gas uptake was Vmax= 176 ppm/kg bw/hour, i.e. 12.9 mg/kg bw/hour.