Contribution of toxicokinetic modeling to the adjustment of exposure limits to unusual work schedules.

This study compared two toxicokinetic approaches for determining correction factors to be applied to occupational exposure limits (ELs) for unusual exposure scenarios: a classic one-compartment toxicokinetic approach and the physiologically based toxicokinetic (PBTK) approach. The approaches were applied to three typical unusual exposure scenarios: four consecutive 10-hour workdays followed by 3 days of recovery; three consecutive 12-hour workdays followed by 4 days of recovery; and a 4/3 work schedule. Results indicate that use of an adjustment method for ELs based on contaminant toxicokinetics generates less protective correction factors (i.

Physiologically-based pharmacokinetic modeling of pyrene in the rat.

The objective of the present study was to develop a physiologically-based model to simulate the oral and i.v. pharmacokinetics of pyrene in the rat.

Physiologically-based pharmacokinetic modeling of a mixture of toluene and xylene in humans.

A physiologically-based pharmacokinetic (PBPK) model for a mixture of toluene (TOL) and xylene (XYL), developed and validated in the rat, was used to predict the uptake and disposition kinetics of TOL/XYL mixture in humans. This was accomplished by substituting the rat physiological parameters and the blood:air partition coefficient with those of humans, scaling the maximal velocity for hepatic metabolism on the basis of body weight0.75, and keeping all other model parameters species-invariant.

Effect of various exposure scenarios on the biological monitoring of organic solvents in alveolar air. II. 1,1,1-Trichloroethane and trichloroethylene.

The purpose of the present study was to investigate the influence of different exposure scenarios on the elimination of trichloroethylene (TRI) and 1,1,1-trichloroethane (1,1,1-TRI) in alveolar air and other biological fluids in human volunteers. In addition, it was sought to establish an interactive process between experimental data gathering and simulation modeling in an attempt to predict the influence of the different scenarios of exposure to TRI and 1,1,1-TRI on their respective biological monitoring indices and thus to establish the flexibility and validity of simulation models. Two adult male and two adult female Caucasian volunteers were exposed by inhalation, in a dynamic controlled exposure chamber, to various concentrations of TRI (12.

Ethanol induced modification of m-xylene toxicokinetics in humans.

This study was undertaken to determine whether previous subacute treatment with ethanol could modify the kinetics of m-xylene in humans. A group of six volunteers was exposed twice to either 100 or 400 ppm of m-xylene during two hours (between 0800 and 1000). Ethanol was given orally in the early evening on each of two consecutive days before exposures (total ethanol intake of 137 g).