Physiologically based pharmacokinetic toolkit to evaluate environmental exposures: Applications of the dioxin model to study real life exposures

ABSTRACT Chlorinated dibenzo‐p‐dioxins (CDDs) are a series of mono‐ to octa‐chlorinated homologous chemicals commonly referred to as polychlorinated dioxins. One of the most potent, well‐known, and persistent member of this family is 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD). As part of translational research to make computerized models accessible to health risk assessors, we present a Berkeley Madonna recoded version of the human physiologically based pharmacokinetic (PBPK) model used by the U.S. Environmental Protection Agency (EPA) in the recent dioxin assessment. This model incorporates CYP1A2 induction, which is an important metabolic vector that drives dioxin distribution in the human body, and it uses a variable elimination half‐life that is body burden dependent. To evaluate the model accuracy, the recoded model predictions were compared with those of the original published model. The simulations performed with the recoded model matched well with those of the original model. The recoded model was then applied to available data sets of real life exposure studies. The recoded model can describe acute and chronic exposures and can be useful for interpreting human biomonitoring data as part of an overall dioxin and/or dioxin‐like compounds risk assessment. HIGHLIGHTSThe best available dioxin PBPK model for interpreting human biomonitoring data is presented.The original PBPK model was recoded from acslX to the Berkeley Madonna (BM) platform.Comparisons were made of the accuracy of the recoded model with the original model.The model is a useful addition to the ATSDR's BM based PBPK toolkit that supports risk assessors.The application of the model to real‐life exposure data sets is illustrated.