Measurement of steady-state blood concentrations in B6C3F1 mice exposed by inhalation to vinylidene fluoride.
The purpose of this study was to obtain data on blood concentrations of vinylidene fluoride (VDF), an important plastics monomer in B6C3F1 mice during inhalation exposure. A new method for sampling blood from mice during the exposures was developed. The technique used a pernasal exposure tube with an outer, sliding cylinder that allowed access to the heart through the thorax. Blood was removed from an anesthetized mouse via heart-puncture while the animal was being exposed to VDF. Concentrations of VDF were measured in blood of mice during 6-h exposures to nominal concentrations of 250, 3750, or 15,000 ppm VDF. A physiological model developed to simulate blood levels of VDF in rats was adapted for mice by incorporating physiologically realistic parameters for mice where appropriate (alveolar ventilation, cardiac output, blood flow to organs, and organ volumes) and by assuming that chemical-specific parameters such as tissue/blood partition coefficients determined for rats could also be applied to mice. Measured steady-state levels of VDF in blood of mice increased with increasing exposure concentration. For both the 15,000 and 3750 ppm VDF exposures, the experimentally determined data fell within the 95% confidence interval predicted by the physiological model. For the 250 ppm VDF exposure, the experimentally determined values for VDF in blood were lower than what was predicted by the model. Model predictions indicated that for mice, as observed for rats, levels of VDF would rise very rapidly, reaching steady-state within minutes of exposure, and that at the end of exposure, blood levels will decline rapidly. At the two lowest exposure concentrations, we were unable to detect VDF in blood taken 15 min or longer after cessation of exposure, suggesting that the post-exposure levels were at or below our limit of detection which was 4 ng VDF/ml blood. For the 15,000 ppm exposure VDF could be detected in blood up to 15 min post exposure.
Medinsky
M A
MA
Inhalation Toxicology Research Institute, Lovelace Biomedical and Environmental Research Institute, Albuquerque, NM 87185.
Bechtold
W E
WE
Birnbaum
L S
LS
Henderson
R F
RF
D000280:Administration, Inhalation; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002849:Chromatography, Gas; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D014018:Tissue Distribution; D014753:Vinyl Compounds / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D014753:Vinyl Compounds; C007384:1,1-difluoroethylene