Computational modeling of paclitaxel diffusion into arterial tissue. Developed a finite-element model of paclitaxel diffusion from a drug-coated balloon catheter into surrounding arterial tissue for prevention of restenosis. Model was developed in COMSOL and accurately explained paclitaxel diffusion and residence in deep tissue layers.
Modification of existing VOC PBPK models to include micturition and multiple exposure routes. Existing VOC PBPK models were extended to include representation of chemical elimination through renal clearance and subsequent appearance in urine. Concentration in urine was modeled by taking urine production and bladder elimination schedule into account for purposes of dose inference. Models were also extended to support additional exposure routes..
Development and analysis of PBPK model for predicting nicotine kinetics. A published PBPK model of nicotine and cotinine kinetics was extended by adding exposure routes, tissue compartments and a PD model. Model parameters were estimated from published data using Bayesian/MCMC techniques. Model accurately predicts nicotine kinetics for exposure via IV, PO (gum), oral spray and smoking routes. PD model accurately predicts nicotine effects on heart rate, including tolerance effects. Sensitivity analysis and variability analysis were performed to determine confidence in parameter estimates.o.
Development of a platform for human health risk assessment of engineered nanomaterials. An proof-of-concept integrated platform for risk assessment of engineered nanomaterials was developed by integrating in vitro dosimetry, dose-response model, and inhaled deposition models. Resulting platform can produce hazard ranking of inhaled nanoparticle exposure by 1) estimating delivered in vitro dose to cells by accounting for diffusion and sedimentation effects; 2) producing BDM estimates of safe cellular exposure using the dose information computed in (1); and 3) extrapolating the safe cellular exposure to a corresponding equivalent human exposure by using an inhaled particle deposition dosimetry model..
PBPK modeling and population calibration of organophosphates (chlorpyrifos) PBPK model. A whole-body PBPK/PD model for ADME of organophosphate pesticides was extended and calibrated using data collected from Egyptian agriculture workers in 2010. Modeling efforts included addition of improved exposure and metabolism models. Sensitivity and uncertainty analysis of the model were performed to study population variability.
Model development and support for PBPK model of polychlorinated biphenyls and related breast cancer correlation study. Collaborated with subject matter experts to reconstruct lifetime toxicokinetic PCB profiles using PBPK models and completed a large-scale Monte-Carlo based study based on 2134 individuals. Developed framework to leverage large CLUMEQ cluster to significantly reduce runtime of massive Monte Carlo study.o.
Development of a probabilistic (Bayesian) approach to infer internal exposures from biomarkers and calculate biological limit values for lipophilic volatile organic compounds Developed a generic population PBPK model for volatile organic compounds (VOCs) in end-exhaled air. Model was calibrated using MCMC techniques and human data from controlled exposures. MCMC chains from the calibrated compounds can be used to generate predictions for other VOCs.
Evaluation of techniques for identifying uncertainty and variability in dose reconstruction for carbaryl exposures using a PBPK model of carbaryl kinetics in humans. Conducted study comparing the effectiveness of several dose-reconstruction techniques for carbaryl. Performed configuration and execution of Carbaryl dose-reconstruction using MCMC and other methods on 500 individuals.