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Design of Developmental Toxicity Studies for Assessing Joint Effects of Dose and Duration

机译:用于评估剂量和持续时间的联合效应的发育毒性研究设计

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In the assessment of developmental and reproductive effects, the timing and duration of exposures to chemical compounds or other environmental contaminants are of particular interest, as the gestational cycle is known to have periods of increased sensitivity. The goal of this research is to identify optimal experimental designs for conducting developmental toxicity studies when the effects of both exposure level and duration of exposure are of interest. The elements of the study design considered in this evaluation are the allocation of animals to dose‐duration exposure groups and the determination of the most efficient intermediate exposure levels. The optimality of various designs is assessed via the accuracy of the estimated excess risk as well as testing criteria. Simulation studies are conducted to compare these criteria and determine optimal design strategies under various underlying dose‐response patterns. Asymptotic results are also derived to lend support to the simulation stud
机译:在评估发育和生殖影响时,特别令人感兴趣的是暴露于化合物或其他环境污染物的时间和持续时间,因为已知妊娠周期具有敏感性增加的时期。本研究的目的是确定在暴露水平和暴露持续时间的影响都令人感兴趣时进行发育毒性研究的最佳实验设计。本评估中考虑的研究设计要素是将动物分配到剂量持续时间暴露组以及确定最有效的中间暴露水平。通过估计的超额风险和测试标准的准确性来评估各种设计的最佳性。进行模拟研究以比较这些标准并确定各种潜在剂量反应模式下的最佳设计策略。此外,还推导了渐近结果,为仿真螺柱提供了支持

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