Use of factorial designs in combination toxicity studies
Use of factorial designs in combination toxicity studies
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DOI：
10.1016/s0278-6915(97)00078-1
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发表时间：
1996-11-01
影响因子：
4.3
通讯作者：
Feron, VJ
中科院分区：
文献类型：
--
作者：
Groten, JP;Schoen, ED;Feron, VJ
使用析因设计，其中n种化学品在x（n）剂量水平（x处理组）进行了研究，已被提出作为一个有价值的统计方法的危险性评估的化学混合物。最近，一项"2（5）研究"描述了五种多环芳烃的致癌活性之间的相互作用，一项"5（3）研究"用于确定三种化合物对发育毒性的非累加效应。然而，全因子设计导致非常昂贵的实验，并且即使仅使用两个剂量水平，也不总是能够使用2（n）个测试组进行常规毒性测试以确定所有感兴趣的化学品之间可能的相互作用。处理这个问题的一种方法是使用部分析因设计。这些分级设计仍然识别化合物之间的大部分相互作用，并确定哪些化合物在引起效应方面是重要的，但具有测试组数量可管理的优点。部分因子设计已被证明是一种有效的（即成本效益）的方法：（a）确定七种微量元素和镉在体内积累之间的相互作用;和（B）描述的情况下，在一个为期4周的毒性研究中测试的九种化学品的混合物的非加和性。版权所有（C）1997 Elsevier Science Ltd.
The use of factorial designs, in which n chemicals are studied at x(n) dose levels (x treatment groups), has been put forward as one of the valuable statistical approaches for hazard assessment of chemical mixtures. Very recently a '2(5) study' was presented to describe interactions between the carcinogenic activity of five polycyclic aromatic hydrocarbons and a '5(3) study' was used to identify the non-additive effects of three compounds on developmental toxicity. Full factorial designs, however, lead to very costly experiments and, even if only two dose levels are used, it is not always possible to perform conventional toxicity tests using 2(n) test groups to identify possible interactions between all chemicals of interest. One way to deal with this problem is the use of fractionated factorial designs. These fractionated designs still identify most of the interactions between the compounds and determine which compounds are important in causing effects, but have the advantage that the number of test groups is manageable. Fractional factorial designs have been shown to be an efficient (i.e. cost-effective) approach to: (a) identify interactive effects between seven trace elements and cadmium accumulation in the body; and (b) describe cases of non-additivity in a mixture of nine chemicals tested in a 4-wk toxicity study in rats. Copyright (C) 1997 Elsevier Science Ltd.