PBTK modeling and simulation framework to identify critical data requirements for efficient and effective pediatric risk assessment

环境污染物暴露是一个日益严重的问题，评估与这种暴露有关的人类风险仍然是一门不精确的科学。风险很大程度上是基于对动物暴露和对人类影响的推断。外推通常采取一种简单的形式，其中从动物研究中得出的阈值剂量除以调整因子（AFs），以解释毒物动力学（TK）和毒物动力学中的物种间和人类种群变异。一种有前途的改进默认AFs的方法是基于基于生理的毒物动力学（PBTK）模型。这些数学模型有助于理解暴露于化合物或摄入剂量如何转化为全身（血浆）和靶（器官）暴露，并基于生物体生理学、化合物物理化学和生化过程之间的相互作用。

Environmental contaminant exposure is an escalating concern and assessing the human risks associated with such exposure continues to be an inexact science. Risks are largely based upon the extrapolation of exposure and effect in animals to those in humans. Extrapolation customarily takes a simplistic form, wherein a threshold dose derived from animal studies is divided by adjustment factors (AFs) to account for interspecies and human population variability in toxicokinetics (TK) and toxicodynamics. One promising method to refine default AFs is based on physiologically based toxicokinetic (PBTK) models. These mathematical models facilitate the understanding of how exposure to a compound, or ingested dose, translates into systemic (plasma) and target (organ) exposure and are based on the interplay between organism physiology, compound physicochemistry and biochemical processes.