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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:
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

Reference
Name:
Unnamed
Type:
Constituent
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 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:
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.