Biologically Based Methods for Cancer Risk Assessment


Book Description

"Biologically Based Methods for Cancer Risk Assessment", an Advanced Research Workshop, (ARW) sponsored by the North Atlantic Treaty Organization (NATO) was held in Corfu, Greece in June, 1989. The intent of the workshop was to survey available pharmacokinetic and pharmacodynamic methods in cancer risk assessment and identify methodological gaps and research needs for biologically based methods in cancer risk assessment. Incorporation of such methods represents one of the most challenging areas for risk assessment. The workshop included an international group of invited experts in the field and provided for a dynamic exchange of ideas and accomplishments. Some of the major topics discussed were: * Inventory of available pharmacokinetic and pharmacodynamic methods for cancer risk assessment. * Identification of methodology gaps and research needs in biologically based methods in cancer risk assessment. * Development of a general framework to guide future cancer risk assessment research. This book is a compilation of the papers presented at the workshop and is intended to provide guidance for future research to reduce uncertainties in the cancer risk assessment process. The primary sponsorship of this ARW by NATO and the advice and cooperation of Dr. C. Sinclair of the Scientific affairs Division are gratefully acknowledged. Acknowledgement is also given to the National Science Foundation for its support. The organization of the ARW and the preparation of this book have required considerable help from many other sources.




Perspectives on Biologically Based Cancer Risk Assessment


Book Description

The first meeting of the NATO/CCMS Pilot Study "Dose-Response Analysis and Biologically-Based Risk assessment for Initiator and Promoter Carcinogens" was held in Rome, Italy, in the spring of 1991, and was followed by annual or bi-annual meetings held in Germany, Greece, Netherlands, Portugal, USA, up to the end of 1995; in large part supported by NATO/CCMS grants or fellowships, and organized by Pilot Study participants. The Pilot Study activity has been characterized by a higly collaborative atmosphere, which was essential for a deep and detailed analysis of a problem on which different points of view, methodological approaches and regulations exist in the various member countries. The Pilot Study was aimed at proposing a carcinogenic risk assessment procedure which is based on a detailed analysis of the relevant biological processes, and may also consent the verification of hypotheses. The specific form of theoretical and mathe matical models is identified by considering and using the whole set of objective data available. The multidisciplinary approach of the pilot study is reflected by the struc ture of this book. Each chapter is the result of the cooperation of several authors from to produce a comprehensive manual that includes different countries; its objective was both theoretical and practical information.




Volume 159: Biologically Based Methods for Cancer Risk Assessment


Book Description

Research Needs for Biologically Based Risk Assessment; Multistage Models for Cancer Risk Assessment; Understanding Multistage Carcinogenesis at the Molecular Level - Notes on Recent Progress; The Use of Enzyme-Altered Foci for Risk Assessment of Hepatocarcinogens; Pathogenic Interrelationship of Focal Lesions, Nodules, Adenomas and Carcinomas in the Multistage Evolution of Azaserine-Induced Rat Pancreas Carcinogenesis; Phenotypic Cellular Changes in Multistage Carcinogenesis; Interspecies Extrapolation; Comparative Carcinogenesis, Is There a Theoretical Approach to Interspecies Similarity; Biological Basis for Interspecies Extrapolation of Halogenated Solvents and of 1,3-Butadiene; Species Specific Inhalation Pharmacokinetics of 2-Nitropropane, Methyl Ethyl Ketone, and n-Hexane; Overview of Promotion as a Mechanism in Carcinogenesis; Hepatocarcinogenesis by Non-Genotoxic Compounds; The Role of Inhibited Intercellular Communication in Carcinogenesis - Implications for Risk Assessment From Exposure to Chemicals; Comparative Analyses of the Timing and Magnitude of Genotoxic and Nongenotoxic Cellular Effects in Urinary Bladder Carcinogenesis; Alterations in Gene Expression in Mouse Hepatocarcinogenesis; Medium Term Bioassay Models for Environmental Carcinogens - Two - Step Liver and Multi-Organ Carcinogenesis Protocols; The Use of Aldh Induction as a Carcinogenic Risk Marker in Comparison With Typical in Vitro Mutagenicity System; Expression of Inducible Cytochrome P-450 mRNAs During Promotion of Experimental Chemical Hepatocarcinogenesis; An In Vitro Approach for Interspecies Extrapolation Using Animal and Human Airway Epithelial Cell Culture; Assessment of Low-Exposure Risk from Carcinogens, Implication of the Knudson-Moolgavkar Two-Critical Mutation Theory; A Biological Data Base for Methylene Chloride Risk Assessment; Computer Simulation of Chemical Carcinogenesis; Determination of Carcinogen Exposure by Immunological Techniques; Risk Estimation for Leukemogenic Drugs.




Health Risks from Exposure to Low Levels of Ionizing Radiation


Book Description

This book is the seventh in a series of titles from the National Research Council that addresses the effects of exposure to low dose LET (Linear Energy Transfer) ionizing radiation and human health. Updating information previously presented in the 1990 publication, Health Effects of Exposure to Low Levels of Ionizing Radiation: BEIR V, this book draws upon new data in both epidemiologic and experimental research. Ionizing radiation arises from both natural and man-made sources and at very high doses can produce damaging effects in human tissue that can be evident within days after exposure. However, it is the low-dose exposures that are the focus of this book. So-called “late” effects, such as cancer, are produced many years after the initial exposure. This book is among the first of its kind to include detailed risk estimates for cancer incidence in addition to cancer mortality. BEIR VII offers a full review of the available biological, biophysical, and epidemiological literature since the last BEIR report on the subject and develops the most up-to-date and comprehensive risk estimates for cancer and other health effects from exposure to low-level ionizing radiation.




Genetic Toxicology and Cancer Risk Assessment


Book Description

Presents state-of-the-art regulatory cancer risk assessment models including a biologically based model for two-hit carcinogenesis and cell proliferation! This book comprehensively reviews the various roles of genetic toxicology in human cancer risk assessment conducted by United States and worldwide regulatory agencies-discussing hazard identification, dose-response relationships, exposure assessment, and current practices of risk characterization. Examines predictive values of mutagenicity tests, mechanisms of carcinogenesis, and conventional genotoxicity tests required by the International Conference on Harmonization and the Organization for Economic Cooperation and Development/Environmental Protection Agency guidelines! Comprised of contributions from prominent experts and risk assessors and including nearly 1200 references to facilitate further study, Genetic Toxicology and Cancer Risk Assessment reviews contemporary human cancer genetics as related to the mutagenic nature of carcinogenesis calculates acceptable exposure levels based on a carcinogenic threshold dose for nongenotoxic carcinogens reveals the rationale and methodology of quantitative estimation of human cancer risks using mathematical models discusses the threshold concept of carcinogenesis demonstrates how bacterial mutagenicity assays are the most reliable for predicting rodent carcinogens considers structural activity relationship (SAR) analysis of chemical carcinogenicity describes the emergence of the mouse lymphoma microwell and in vitro micronucleus assays illustrates the use of genetic biomarkers for dosimetry analysis and more! Linking human cancer genetics, mutagenicity assays, mechanisms of carcinogenesis, carcinogenic thresholds, molecular epidemiology, mathematical modeling, and quantitative cancer risk analysis, Genetic Toxicology and Cancer Risk Assessment is a must-have reference for toxicologists; oncologists; geneticists; biostatisticians; reproductive, developmental, cell, and molecular biologists; endocrinologists; biochemists; and upper-level undergraduate, graduate, and medical school students in these disciplines.




Recent Advances in Quantitative Methods in Cancer and Human Health Risk Assessment


Book Description

Human health risk assessment involves the measuring of risk of exposure to disease, with a view to improving disease prevention. Mathematical, biological, statistical, and computational methods play a key role in exposure assessment, hazard assessment and identification, and dose-response modelling. Recent Advances in Quantitative Methods in Cancer and Human Health Risk Assessment is a comprehensive text that accounts for the wealth of new biological data as well as new biological, toxicological, and medical approaches adopted in risk assessment. It provides an authoritative compendium of state-of-the-art methods proposed and used, featuring contributions from eminent authors with varied experience from academia, government, and industry. Provides a comprehensive summary of currently available quantitative methods for risk assessment of both cancer and non-cancer problems. Describes the applications and the limitations of current mathematical modelling and statistical analysis methods (classical and Bayesian). Includes an extensive introduction and discussion to each chapter. Features detailed studies of risk assessments using biologically-based modelling approaches. Discusses the varying computational aspects of the methods proposed. Provides a global perspective on human health risk assessment by featuring case studies from a wide range of countries. Features an extensive bibliography with links to relevant background information within each chapter. Recent Advances in Quantitative Methods in Cancer and Human Health Risk Assessment will appeal to researchers and practitioners in public health & epidemiology, and postgraduate students alike. It will also be of interest to professionals working in risk assessment agencies.




Cancer Risk Assessment


Book Description

With a weight-of-the-evidence approach, cancer risk assessment indentifies hazards, determines dose-response relationships, and assesses exposure to characterize the true risk. This book focuses on the quantitative methods for conducting chemical cancer risk assessments for solvents, metals, mixtures, and nanoparticles. It links these to the basic toxicology and biology of cancer, along with the impacts on regulatory guidelines and standards. By providing insightful perspective, Cancer Risk Assessment helps researchers develop a discriminate eye when it comes to interpreting data accurately and separating relevant information from erroneous.







Cancer Risk Evaluation


Book Description

An overview of the different approaches to cancer risk assessment of environmental factors - including "-omics" technologies, discussing the strengths and weaknesses of the methods in different fields. The main focus is on the carcinogenic effects of ionizing and non-ionizing radiation, demonstrating the difficulties in accurately assessing those factors that may or may not pose a significant cancer risk. The book extends the view to a broader context of risk assessment, highlighting various aspects of risk management. Written by leading experts in the field, this is a resource for policy makers and professionals in health risk assessment, and public health workers, as well as oncologists and researchers in academia. This title is also available as a mobile App from MedHand Mobile Libraries. Buy it now from Google Play or the MedHand Store.




Biologically Based Models in Risk Assessment


Book Description

Dose-response characterization in the risk assessment process for chemical carcinogens entails extrapolation of tissue dosimetry and tumor response seen at high exposure concentrations in test animals to humans exposed to much lower concentrations. The difficulty in predicting the potential human tumor incidence arises from interspecies differences in tissue susceptibility and from the dose, species, and/or exposure-route dependency of chemical disposition. These extrapolations are usually conducted with 'mandated' models, a linearized, multistage, cancer model for low-dose extrapolation and a body surface or body weight correction for interspecies extrapolation. In recent years, there have been several attempts to provide an increasing level of biological realism to these extrapolation models. Biologically based dosimetry and response modeling approaches enable identification and characterization of critical determinants of chemical disposition and tissue response and form a mechanistic basis for dose, species and exposure-route extrapolations. This paper briefly outlines the utility of biologically based models in predicting tissue dosimetry and response and provides an example of the use of biologically based dosimetry models in cancer risk assessment for methylene chloride.