Preface

The concept for this book grew out of an Applied Symposium presented in two parts by many of the chapter authors on September 19, 2014, at the 45th Anniversary Annual Meeting of the Environmental Mutagenesis and Genomics Society in Orlando (FL, USA): “Toxicogenomics in the Assessment of Mutagenicity and Carcinogenicity: Implications for Risk Assessment (Parts 1 and 2)”; chairs: Michael Waters, Russell Thomas and Francina Webster.

In attempting to address the topic of the book, predictive carcinogenicity, we have followed essentially the same format as the symposium. The earlier chapters document the status of toxicogenomics methods as they have been applied in the fields of predictive carcinogenicity testing from the year 1999 to the present. These chapters describe the development and application of toxicogenomics in vitro and in vivo in ways that recapitulate the 45 year history of genetic toxicology bioassays in the screening and identification of genotoxic and nongenotoxic substances. With the recognition of the full power of genomic and bioinformatics technologies, toxicogenomics applications have rapidly expanded to include both safety and health risk assessment. Thus, subsequent chapters address toxicogenomics dose–response analysis as well as mode of action—all of which are subjects of major regulatory significance for drugs and environmental chemicals. To further represent the breadth and depth of coverage of the applications of toxicogenomics, there are chapters on the effects of xenobiotics on the genome and epigenome of stem cells, and the use of toxicogenomics data by the International Agency for Research on Cancer in the evaluation of carcinogenic hazards to humans. In three additional chapters, we have included extensive details of research to evaluate chemicals to which humans are widely exposed (the conazoles, benzene, and furan), so that the scope and extent of knowledge that has been and can be gained from toxicogenomics research may be fully appreciated. Finally, there are two concluding chapters, one representing the parallelogram approach applied to acetaminophen (paracetamol), an extrapolation concept from the past that continues to be useful in this toxicogenomics-based instance, and a broad and heavily illustrated survey of the use bioinformatics of genomics in the assessment of cancer.

Throughout the book we have tried to emphasize best-of-class investigations that point the way to future scientific developments. With all of this, we hope to bring the reader up to date on progress in the field of predictive carcinogenicity that has resulted from the application of toxicogenomics since its inception just over 15 years ago. We would like to acknowledge the pioneering work of the National Center for Toxicogenomics at the National Institute of Environmental Health Sciences in Research Triangle Park (NC, USA), where the word “toxicogenomics” was coined, many important early studies were performed, and the first public toxicogenomics knowledgebase (Chemical Effects in Biological Systems) was built. What has resulted from these beginnings and other pioneering research efforts worldwide is truly remarkable.

Michael D. Waters,

Michael Waters Consulting, North Carolina, USA

Russell S. Thomas,

National Center for Computational Toxicology, US EPA, North Carolina, USA