Editor's Choice Article for October 2014

Environmental and Molecular Mutagenesis (EMM) Editor's Choice - October 2014

The Editor's Choice for October is "Derivation of Point of Departure (PoD) Estimates in Genetic Toxicology Studies and Their Potential Applications in Risk Assessment” by George E. Johnson, Lya G. Soeteman-Hernandez, B. Bhaskar Gollapudi, Owen G. Bodger, Kerry L. Dearfield, Robert H. Heflich, J. Gregory Hixon, David Pl. Lovell, James T. MacGregor, Lynn H. Pottenger, Chad M. Thompson, Liz Abraham, Veronique Thybaud, Jennifer Y. Tanir, Errol Zeiger, Jan van Benthem, and Paul A. White.

Identifying a Point-of-Departure (PoD) within a chemical dose response is standard practice in many areas of applied toxicology, and PoD metrics are routinely employed to assess and manage the human health risks associated with toxic chemicals.  Under the auspices of the Quantitative Analysis Workgroup of the Genetic Toxicology Technical Committee (GTTC, HESI/ISLI), the authors of October's Editor's Choice article sought to systematically evaluate different statistical approaches for identifying a PoD from genetic toxicology dose-response data.  Johnson and co-authors collected and analyzed 45 data sets from studies that analyzed the induction of gene mutation or chromosomal damage (micronucleus formation) induced by two model mutagens (1-ethyl-1-nitrosourea and 1-methyl-1-nitrosourea). They evaluated the performance of four different statistical approaches for calculating a PoD and concluded that the benchmark dose approach is the most pragmatic for analyzing continuous genetic toxicity data.  In addition, their analysis identified aspects of genetic toxicology study design that are necessary for effective PoD determination. The article includes a number of other important recommendations and insights for investigators in the field.  Finally, the article describes how the recommended methodology for dose-response analysis could be used to set regulatory limits for genotoxic chemicals. Environ. Mol. Mutagen. 55:609–623, 2014. © 2014Wiley Periodicals, Inc.

 

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