Toxicogenomic Technologies And Risk Assessment Of Environmental Carcinogens

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.

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 book provides a timely overview of toxicogenomics, with special emphasis on the practical applications of this technology to the risk assessment process. Introductory sections are followed by a series of chapters highlighting practical and systematic applications of toxicogenomics in informing the risk assessment process – including the areas of mutagenicity, carcinogenicity, endocrine toxicity, organ-specific toxicity, population monitoring, and ecotoxicology. The book concludes with approaches for the integration of this technology in safety evaluation studies, and an outlook on how toxicogenomics and complementary technologies can reframe the current risk assessment paradigm.

Research over the past decade has demonstrated that TGx methods of various types can be used to discriminate modes of mutagenesis as a function of dose. TGx can quickly inform safety evaluation regarding potential mechanisms of conventional outcomes and can provide essential dose-response information. This can then be used to ascertain the sequence of key events in a putative mode of action as may apply in quantitative cancer risk assessment. With the increasing complexity of research in mode of action investigations it is important to gain a better understand of approaches to data integration and health risk assessment. Furthermore, it is essential to consider how novel test systems and newer methods and approaches may be used in future to gain a better understanding of mechanisms. Toxicogenomics in Predictive Carcinogenicity describes toxicogenomics methods in predictive carcinogenicity testing, mode of action and safety evaluation, and cancer risk assessment. It illustrates these methods using case studies that have yielded significant new information on compounds and classes of compounds that have proven difficult to evaluate using conventional methods alone. This book additionally covers current and potential toxicogenomic research using stem cells as well as new bioinformatics methods for drug discovery and environmental toxicology. This publication is an indispensable tool for postgraduates, academics and industrialists working in biochemistry, genomics, carcinogenesis, pathology, pharmaceuticals, food technology, bioinformatics, risk assessment and environmental toxicology.

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.

In 2007, the National Research Council envisioned a new paradigm in which biologically important perturbations in key toxicity pathways would be evaluated with new methods in molecular biology, bioinformatics, computational toxicology, and a comprehensive array of in vitro tests based primarily on human biology. Although some considered the vision too optimistic with respect to the promise of the new science, no one can deny that a revolution in toxicity testing is under way. New approaches are being developed, and data are being generated. As a result, the U.S. Environmental Protection Agency (EPA) expects a large influx of data that will need to be evaluated. EPA also is faced with tens of thousands of chemicals on which toxicity information is incomplete and emerging chemicals and substances that will need risk assessment and possible regulation. Therefore, the agency asked the National Research Council to convene a symposium to stimulate discussion on the application of the new approaches and data in risk assessment. The symposium was held on May 11-13, 2009, in Washington, DC, and included presentations and discussion sessions on pathway-based approaches for hazard identification, applications of new approaches to mode-of-action analyses, the challenges to and opportunities for risk assessment in the changing paradigm, and future directions.

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.

Beginning in the early 1980s, new technologies, began to permit evaluation of the expression of individual genes. Recent technological advances have expanded those evaluations to permit the simultaneous detection of the expression of tens of thousands of genes and to support holistic evaluations of the entire genome. The application of these technologies has enabled researchers to unravel complexities of cell biology and, in conjunction with toxicologic evaluations, the technologies are used to probe and gain insight into questions of toxicologic relevance. As a result, the use of the technologies has become increasingly important for scientists in academia, as well as for the regulatory and drug development process.