The new field of toxicogenomics presents a potentially powerful set of tools to better understand the health effects of exposures to toxicants in the environment. At the request of the National Institute of Environmental Health Sciences, the National Research Council assembled a committee to identify the benefits of toxicogenomics, the challenges to achieving them, and potential approaches to overcoming such challenges. The report concludes that realizing the potential of toxicogenomics to improve public health decisions will require a concerted effort to generate data, make use of existing data, and study data in new waysâ€"an effort requiring funding, interagency coordination, and data management strategies.

This detailed book provides an accessible compendium of up-to-date methods in the fields of environmental toxicology, molecular toxicology, and toxicogenomics. Organized into four major sections, the volume examines methods utilizing model animal species, such as nematode, fruit fly, mice, chicken, and amphibians, methods using plants to study chemical toxicity, applying the Ames assay to chemical mutagenicity study, as well as methods for environmental chemical analysis. Although this book is divided into these parts, the methods can be used across species. Written for the highly successful Methods in Molecular Biology series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Environmental Toxicology and Toxicogenomics: Principles, Methods, and Applications serves as a valuable resource for the scientific community, particularly for young scientists and graduate and undergraduate students, inspiring more research in the vitally important field of environmental toxicity, molecular toxicology, and toxicogenomics.

Some of what we know about the health effects of exposure to chemicals from food, drugs, and the environment come from studies of occupational, inadvertent, or accident-related exposures. When there is not enough human data, scientists rely on animal data to assess risk from chemical exposure and make health and safety decisions. However, humans and animals can respond differently to chemicals, including the types of adverse effects experienced and the dosages at which they occur. Scientists in the field of toxicogenomics are using new technologies to study the effects of chemicals. For example, in response to a particular chemical exposure, they can study gene expression ("transcriptomics"), proteins ("proteomics") and metabolites ("metabolomics"), and they can also look at how individual and species differences in the underlying DNA sequence itself can result in different responses to the environment. Based on a workshop held in August 2004, this report explores how toxicogenomics could enhance scientists' ability to make connections between data from experimental animal studies and human health.

"Traditional toxicity testing methods rely on exposing whole organisms to chemicals and observing high-level responses such as mortality and reproduction. These methods are too slow, expensive, and ethically concerning to assess the tens of thousands of legacy and novel substances in need of testing, and do not provide much biological insight into the toxicity mechanism. There has been a growing push to develop new approach methods for toxicity testing that do not use animal exposures. One major objective of this movement is to conduct exposures in vitro, measure comprehensive molecular outcomes, and use the molecular data to predict and manage risk to whole organisms. This not only promises to make toxicity testing faster, less expensive, and more humane, but also promises to generate more informative data. Toxicogenomics, the measurement of 'omics data such as transcriptomics, proteomics, and metabolomics in the context of toxicology, is key to realizing this goal. However, toxicogenomics data is extremely complex and the lack of computing resources, programming skills, advanced statistical training, and knowledge of bioinformatics databases presents barriers to many researchers and regulators. The barriers are particularly pronounced for environmental toxicologists using ecologically relevant species, as there are few bioinformatics resources outside of a small number of model organisms. The objective of this thesis is to design new statistical methods and corresponding software for analyzing and visualizing toxicogenomics data to support decision-making in the context of environmental toxicology. Many of the additional barriers to using transcriptomics data in ecologically relevant non-model organisms are related to raw data processing and annotation. Chapter 3 presents a set of computational tools (EcoOmicsAnalyst, ExpressAnalyst, EcoOmicsDB) for producing and analyzing annotated counts tables from raw RNA-seq data from any species, regardless of whether there is a reference genome. Traditional transcriptomics results such as lists of impacted genes and pathways are difficult to integrate into regulatory decision-making processes. Chapter 4 presents EcoToxModules, custom gene sets for summarizing and communicating transcriptomics data that are focused on toxicologically relevant biological processes. Chapter 5 presents FastBMD, software for performing rapid transcriptomics dose-response modeling. Since dose-response results such as benchmark dose values and points-of-departure are already familiar to the toxicology community, this type of analysis is useful because it translates unfamiliar toxicogenomics data into the familiar dose-response framework. Finally, while the cost of acquiring whole-transcriptome data has decreased tremendously over the last few decades, it is still outside the scope of many research programs. EcoToxChips are qPCR arrays with 384 genes for six ecologically relevant species that address this issue because qPCR technology is cost-effective with widespread availability. Chapter 6 presents EcoToxXplorer, software focused on EcoToxChip data processing, analysis, and interpretation. Together, the chapters in this thesis aim to support the use of toxicogenomics data in decision-making processes by making it more usable and understandable to individual members of the toxicology community, while also enabling standardized workflows that can be easily accessed by many different people in different locations. One important aspect of this is that all software presented in this thesis are web-based, which means that they do not require users to have substantial computing resources or programming skills, and do not require local installation. Throughout statistical method and software development, a design-thinking framework was used to continuously obtain and incorporate feedback from a large group of stakeholders and potential end-users from academia, government, and industry"--

Toxicogenomics is a discipline that combines expertise in toxicology, genetics, molecular biology, and environmental health to help understand the response of living organisms to stressful environments. The National Research Council convened a workshop to discuss how toxicogenomic data could be applied to improve risk assessments, particularly cancer risk from environmental exposure to chemicals. Risk assessments serve as the basis of many public-health decisions in environmental, occupational, and consumer protection from chemicals. The workshop provided a forum for communities of experts, including those working in "-omics" and those in the policy arena, to discuss where their fields intersect, and how toxicogenomics could address critical knowledge gaps in risk assessments.

Toxicogenomics, the study of how genomes respond to exposure to toxicants, may ultimately hold the promise of detecting changes in the expression of a person's genes if he or she is exposed to these toxicants. As the technology rapidly develops, it is critical that scientists and the public communicate about the promises and limitations of this new field. Communicating technical information to the public about a developing science can be challenging, particularly when the applications of that science are not yet well understood. Communicating Toxicogenomics Information to Nonexperts is the summary of a workshop designed to consider strategies for communicating toxicogenomic information to the public and other non- expert audiences, specifically addressing the communication of some key social, ethical, and legal issues related to toxicogenomics and addressing how information related to the social implications of toxicogenomics might be perceived by nonexperts.

The new field of toxicogenomics presents a potentially powerful set of tools to better understand the health effects of exposures to toxicants in the environment. At the request of the National Institute of Environmental Health Sciences, the National Research Council assembled a committee to identify the benefits of toxicogenomics, the challenges to achieving them, and potential approaches to overcoming such challenges. The report concludes that realizing the potential of toxicogenomics to improve public health decisions will require a concerted effort to generate data, make use of existing data, and study data in new waysâ€"an effort requiring funding, interagency coordination, and data management strategies.