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

PBTK 建模和模拟框架，用于确定高效且有效的儿科风险评估的关键数据要求

• 批准号: RGPIN-2017-05056
• 负责人: Edginton, Andrea
• 金额: $ 2.04万
• 依托单位: University of Waterloo
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=630188
• 关键词: PBTK; modeling; simulation; framework; identify

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.

环境污染物暴露是一个日益令人关切的问题，评估与这种暴露相关的人类风险仍然是一门不精确的科学。风险在很大程度上是基于对动物的暴露和影响与人类的接触和影响的推断。外推通常采取一种简单的形式，即从动物研究中得出的阈值剂量除以调整因子(AFs)，以考虑毒物动力学(TK)和毒物动力学(TK)中的物种间和人类种群变异性。一种很有前途的方法是基于生理毒代动力学(PBTK)模型来精炼缺省AFS。这些数学模型有助于理解接触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、化合物物理化学和生化过程之间的相互作用。