Uptake of vinylidene fluoride in rats simulated by a physiological model

The purpose of this study was to develop a physiological model to simulate the uptake of vinylidene fluoride (VDF), an important plastics monomer, in laboratory animals. Male Fischer 344/N rats were exposed nose-only for 6 hr to concentrations of VDF ranging from 27 to 16,000 ppm. Tidal volume (mean, 1.51 ml/breath) and respiratory frequency (mean, 132 breaths/min) were not influenced by exposure concentration. Experimentally determined, steady-state blood levels of VDF, obtained by gas chromatography-head space analysis of samples from rats with indwelling jugular cannulas, increased linearly with increasing exposure concentration up to 16,000 ppm. VDF tissue/air partition coefficients were determined experimentally to be 0.07, 0.18, 0.8, 1.0, and 0.29 for water, blood, liver, fat, and muscle, respectively. These values and calculated constants for total body elimination of VDF, Km and Vmax were incorporated into the physiological model. Model predictions agreed with the experimentally determined data. Time to reach steady-state blood levels of VDF was less than 15 min for all concentrations. After cessation of exposure, blood levels of VDF decreased to 10% of steady-state levels by 1 hr. Simulation of the metabolism of VDF indicated that although blood levels of VDF increased linearly with increasing concentration the amount of VDF metabolized per 6-hr exposure period approached a maximum at about 2000 ppm VDF.