Design of developmental toxicity studies for assessing joint effects of dose and duration.
Design of developmental toxicity studies for assessing joint effects of dose and duration.
复制标题
设计发育毒性研究以评估剂量和持续时间的联合效应。
DOI：
10.1111/j.1539-6924.1994.tb00076.x
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
Williams,PL
中科院分区：
文献类型：
--
作者：
Scharfstein,DO;Williams,PL
在评估对发育和生殖的影响时，特别关注接触化合物或其他环境污染物的时间和持续时间，因为众所周知，妊娠周期的敏感期会增加。这项研究的目标是确定当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。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。进行了模拟研究，以比较这些标准，并确定在各种潜在剂量-反应模式下的最优设计策略。给出了渐近结果，为仿真研究提供了支持。
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 studies.