Detecting interaction(s) and assessing the impact of component subsets in a chemical mixture using fixed-ratio mixture ray designs
Detecting interaction(s) and assessing the impact of component subsets in a chemical mixture using fixed-ratio mixture ray designs
复制标题
DOI：
10.1198/108571104x3406
复制
发表时间：
2004-09-01
影响因子：
1.4
通讯作者：
Simmons, JE
中科院分区：
文献类型：
--
作者：
Casey, M;Gennings, C;Simmons, JE
一个重要的环境和监管问题是保护人类健康免受累积接触多种化学品的潜在不利影响。早期文献建议将推理限制于特定的感兴趣的固定比率射线。基于适当的加和性定义，使用单一化学数据来预测零相互作用情况下化学物质之间的关系。可加性模型与沿固定比率射线拟合的模型之间的参数比较用于检测与可加性的偏离。沿着减少的固定比率射线收集数据，其中感兴趣的化学物质的子集从混合物中去除，并且剩余的化合物具有与完整射线中考虑的相同的相对比率，使研究人员能够推断所去除的化学物质的影响。开发了用于拟合关于最佳拟合模型与可加性下预测的模型之间差异的同时置信带的方法，以识别沿着射线发生显着相互作用的区域。这种通用方法称为“所需单一化学品”(SCR) 分析方法。第二种方法称为“不需要单一化学品”(SCNR) 分析方法，它基于有关响应面参数化的基本假设。在一般假设下，沿着固定比率射线拟合的模型的多项式项与相互作用项相关联。考虑仅沿混合射线的数据可用的情况。还开发了假设检验，其中考虑了化学物质子集造成的相互作用。
An important environmental and regulatory issue is the protection of human health from potential adverse effects of cumulative exposure to multiple chemicals. Earlier literature suggested restricting inference to specific fixed-ratio rays of interest. Based on appropriate definitions of additivity, single chemical data are used to predict the relationship among the chemicals under the zero-interaction case. Parametric comparisons between the additivity model and the model fit along the fixed-ratio ray(s) are used to detect departure from additivity. Collection of data along reduced fixed-ratio rays, where subsets of chemicals of interest are removed from the mixture and the remaining compounds are at the same relative ratios as considered in the full ray, allow researchers to make inference about the effect of the removed chemicals. Methods for fitting simultaneous confidence bands about the difference between the best fitting model and the model predicted under additivity are developed to identify regions along the rays where significant interactions occur. This general approach is termed the "single chemicals required" (SCR) method of analysis. A second approach, termed "single chemicals not required" (SCNR) method of analysis, is based on underlying assumptions about the parameterization of the response surface. Under general assumptions, polynomial terms for models fit along fixed-ratio rays are associated with interaction terms. Consideration is given to the case where only data along the mixture rays are available. Tests of hypotheses, which consider interactions due to subsets of chemicals, are also developed.