A Compartmental Model for the Prediction of Breath Concentration and Absorbed Dose of Chloroform After Exposure While Showering

摘要

In order to predict the exhaled breath concentration of chloroform in individuals exposed to chloroform while showering, an existing physiologically based pharmacokinetic (PB‐PK) model was modified to include a multicompartment, PB‐PK model for the skin and a completely mixed shower exposure model. The PB‐PK model of the skin included the stratum corneum as the principal resistance to absorption and a viable epidermis which is in dynamic equilibrium with the skin microcirculation. This model was calibrated with measured exhaled breath concentrations of chloroform in individuals exposed while showering with and without dermal absorption. The calibration effort indicated that the expected value of skin‐blood partitioning coefficient would be 1.2 when the degree of transfer of chloroform from shower water into shower air was 61. The stratum corneum permeability coefficient for chloroform was estimated to be within the range of 0.16‐0.36 cm/hr and the expected value was 0.2 cm/hr. The estimated ratio of the dermally and inhaled absorbed doses ranged between 0.6 and 2.2 and the expected value was 0.75. These results indicate that for the purposes of risk assessment for dermal exposure to chloroform, a simple steady‐state model can be used to predict the degree of dermal absorption and that a reasonable value of skin permeability coefficient for chloroform used in this model would be 0.2 cm/hr. Further research should be conducted to compare the elimination of chloroform via exhaled breath when different exposure routes are being compared. The model results from this study suggest that multiple measurements of exhaled breath concentrations after exposure may be necessary when making comparisons of breath concentrations that involve different expo