Experimental Design and Statistical Analysis of Studies to Demonstrate a Threshold in Genetic Toxicology : A Mini-review
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概要
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A mechanistic understanding of genotoxicity is important for the risk assessment of the exposure of human populations to chemicals. The nature of the dose response relationship at low doses is valuable information in the evaluation of the biological importance of such exposures. A range of mathematical and statistical approaches have been used to try to characterize responses at these low doses. Methods include mathematical models which do or do not include thresholds and statistical methods which try to identify No-observable effect levels (NOELs). It is important to appreciate that determination of an NOEL is not evidence for a threshold. There is an increasing appreciation of the potential to identify 'pragmatic' thresholds using experimental systems with a range of biomarkers. The accurate characterization and estimation of these dose-response relationships requires careful experimental design which can improve the accuracy of the estimates of the response while avoiding the introduction of artifactual effects. Statistical approaches such as Design of Experiment (DoE) methodology, which builds on the traditional factorial design, can provide efficient approaches for the description and estimation of dose-response relationships of both individual and combinations of agents. Estimation approaches such as the benchmark dose methodology and the concept of thresholds of toxicological concern provide practical methods for addressing the threshold problem.
- 2008-11-20
著者
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Lovell David
Postgraduate Medical School, University of Surrey
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Lovell David
Postgraduate Medical School University Of Surrey