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Here we present data to evaluate potential absorption of Bisphenol A through non-metabolizing tissues of the upper digestive tract. Concurrent serum and urine concentrations of d6-BPA, and its glucuronide and sulfate conjugates, were measured over a 24 h period in 10 adult male volunteers following ingestion of 30 μg d6-BPA/kg body weight in soup. The pharmacokinetic behavior of BPA and its metabolites in this cohort (rapid absorption, complete elimination, evidence against sublingual absorption) was reported. This Data in Brief article contains the corresponding individual pharmacokinetic data, reports the demographics of the cohort and provides additional details related to the analytical methods employed and is related to [4].

Physiologically based pharmacokinetic (PBPK) models integrate both chemical- and system-specific information into a mathematical framework, offering a mechanistic approach to predict the internal dose metrics of a chemical and an ability to perform species and dose extrapolations. Bisphenol A (BPA), because of its ubiquitous presence in a variety of consumer products, has received a considerable amount of attention from the public and regulatory bodies. PBPK models using deuterated BPA were developed for immature and adult rats and non-human primates and for adult humans to understand better the dosimetry of BPA. The focus of the present paper is to provide a rationale for interpreting species- and age-related pharmacokinetics of BPA. Gastrointestinal tract metabolism was an important consideration to predict unconjugated BPA serum kinetic profiles in adult and immature rats and monkeys. Biliary excretion and enterohepatic recirculation of BPA conjugates accounted for the slowed systemic clearance of BPA conjugates in rats. For monkeys, renal reabsorption was proposed as a mechanism influencing systemic clearance of BPA conjugates. The quantitative understanding of the processes driving the pharmacokinetics of BPA across different species and life stages using a computational modeling approach provides more confidence in the interpretation of human biomonitoring data and the extrapolation of experimental animal findings to humans.

A deterministic biologically based dose-response model for the thyroidal system in a near-term pregnant woman and the fetus was recently developed to evaluate quantitatively thyroid hormone perturbations. The current work focuses on conducting a quantitative global sensitivity analysis on this complex model to identify and characterize the sources and contributions of uncertainties in the predicted model output. The workflow and methodologies suitable for computationally expensive models, such as the Morris screening method and Gaussian Emulation processes, were used for the implementation of the global sensitivity analysis. Sensitivity indices, such as main, total and interaction effects, were computed for a screened set of the total thyroidal system descriptive model input parameters. Furthermore, a narrower sub-set of the most influential parameters affecting the model output of maternal thyroid hormone levels were identified in addition to the characterization of their overall and pair-wise parameter interaction quotients. The characteristic trends of influence in model output for each of these individual model input parameters over their plausible ranges were elucidated using Gaussian Emulation processes. Through global sensitivity analysis we have gained a better understanding of the model behavior and performance beyond the domains of observation by the simultaneous variation in model inputs over their range of plausible uncertainties. The sensitivity analysis helped identify parameters that determine the driving mechanisms of the maternal and fetal iodide kinetics, thyroid function and their interactions, and contributed to an improved understanding of the system modeled. We have thus demonstrated the use and application of global sensitivity analysis for a biologically based dose-response model for sensitive life-stages such as pregnancy that provides richer information on the model and the thyroidal system modeled compared to local sensitivity analysis.

The widespread usage of methylphenidate (MPH) in the pediatric population has received considerable attention due to its potential effect on child development. For the first time a physiologically based pharmacokinetic (PBPK) model has been developed in juvenile and adult humans and nonhuman primates to quantitatively evaluate species- and age-dependent enantiomer specific pharmacokinetics of MPH and its primary metabolite ritalinic acid. The PBPK model was first calibrated in adult humans using in vitro enzyme kinetic data of MPH enantiomers, together with plasma and urine pharmacokinetic data with MPH in adult humans. Metabolism of MPH in the small intestine was assumed to account for the low oral bioavailability of MPH. Due to lack of information, model development for children and juvenile and adult nonhuman primates primarily relied on intra- and interspecies extrapolation using allometric scaling. The juvenile monkeys appear to metabolize MPH more rapidly than adult monkeys and humans, both adults and children. Model prediction performance is comparable between juvenile monkeys and children, with average root mean squared error values of 4.1 and 2.1, providing scientific basis for interspecies extrapolation of toxicity findings. Model estimated human equivalent doses in children that achieve similar internal dose metrics to those associated with pubertal delays in juvenile monkeys were found to be close to the therapeutic doses of MPH used in pediatric patients. This computational analysis suggests that continued pharmacovigilance assessment is prudent for the safe use of MPH.