Linking a PBPK model for chloroform with measured breath concentrations in showers: implications for dermal exposure models.
Four issues are addressed in this paper. First, both dermal uptake models and a revised PBPK model are developed and combined into a form appropriate for simulating chloroform breath levels in individuals exposed in showers by inhalation and dermal routes and by the inhalation route only. Second, experimentally measured and previously reported ratios of chloroform concentrations in air and breath to tap-water concentration are used to evaluate the model predictions. Particular attention is given to the implied dermal uptake as measured by these experiments and to whether this is consistent with the recommended value for skin uptake of chloroform that is calculated using EPA guidance. This analysis indicates that the ratio of chloroform dermally absorbed in the shower relative to tap-water concentration is between 0.25 and 0.66 mg per mg/L and that the effective permeability of the skin during a 10-min. shower exposure is between 0.16 and 0.42 cm/hr. Third, the model is used to assess the relationship of dermal and inhalation exposure to metabolized dose in the liver. It is found that, for dermal and inhalation exposures in the shower and under conditions of linear metabolism, the ratio of metabolized dose to water concentration is on the order of 0.41 mg per mg/L. Fourth, the model is used to determine the chloroform concentration at which dermal and inhalation exposures to chloroform would begin to result in nonlinear metabolism. This concentration is found to be in the range of 60 to 100 mg/L.
McKone
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Lawrence Livermore National Laboratory, Livermore, California.
D001944:Breath Tests; D002725:Chloroform / Q000032:analysis / Q000493:pharmacokinetics*; D004781:Environmental Exposure / Q000032:analysis*; D006801:Humans; D008099:Liver / Q000378:metabolism; D008954:Models, Biological; D012119:Respiration; D012869:Skin Absorption; D014881:Water Supply / Q000032:analysis*
D002725:Chloroform