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Title: Databases applicable to quantitative hazard/risk assessment-Towards a predictive systems toxicology

Abstract

The Workshop on The Power of Aggregated Toxicity Data addressed the requirement for distributed databases to support quantitative hazard and risk assessment. The authors have conceived and constructed with federal support several databases that have been used in hazard identification and risk assessment. The first of these databases, the EPA Gene-Tox Database was developed for the EPA Office of Toxic Substances by the Oak Ridge National Laboratory, and is currently hosted by the National Library of Medicine. This public resource is based on the collaborative evaluation, by government, academia, and industry, of short-term tests for the detection of mutagens and presumptive carcinogens. The two-phased evaluation process resulted in more than 50 peer-reviewed publications on test system performance and a qualitative database on thousands of chemicals. Subsequently, the graphic and quantitative EPA/IARC Genetic Activity Profile (GAP) Database was developed in collaboration with the International Agency for Research on Cancer (IARC). A chemical database driven by consideration of the lowest effective dose, GAP has served IARC for many years in support of hazard classification of potential human carcinogens. The Toxicological Activity Profile (TAP) prototype database was patterned after GAP and utilized acute, subchronic, and chronic data from the Office of Air Qualitymore » Planning and Standards. TAP demonstrated the flexibility of the GAP format for air toxics, water pollutants and other environmental agents. The GAP format was also applied to developmental toxicants and was modified to represent quantitative results from the rodent carcinogen bioassay. More recently, the authors have constructed: 1) the NIEHS Genetic Alterations in Cancer (GAC) Database which quantifies specific mutations found in cancers induced by environmental agents, and 2) the NIEHS Chemical Effects in Biological Systems (CEBS) Knowledgebase that integrates genomic and other biological data including dose-response studies in toxicology and pathology. Each of the public databases has been discussed in prior publications. They will be briefly described in the present report from the perspective of aggregating datasets to augment the data and information contained within them.« less

Authors:
 [1];  [2]
  1. ILS, Inc., P.O. Box 13501, Research Triangle Park, NC 27709 (United States), E-mail: mwaters@ils-inc.com
  2. ILS, Inc., P.O. Box 13501, Research Triangle Park, NC 27709 (United States)
Publication Date:
OSTI Identifier:
21180466
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 233; Journal Issue: 1; Conference: 2007 TRAC: 2007 toxicology and risk assessment conference: Emerging issues and challenges in risk assessment, West Chester, OH (United States), 23-26 Apr 2007; Other Information: DOI: 10.1016/j.taap.2007.12.036; PII: S0041-008X(08)00277-9; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; AIR QUALITY; BIOASSAY; CARCINOGENS; CLASSIFICATION; DOSES; DRUGS; EVALUATION; HEALTH HAZARDS; NEOPLASMS; RISK ASSESSMENT; RODENTS; TOXICITY; WATER

Citation Formats

Waters, Michael, and Jackson, Marcus. Databases applicable to quantitative hazard/risk assessment-Towards a predictive systems toxicology. United States: N. p., 2008. Web. doi:10.1016/j.taap.2007.12.036.
Waters, Michael, & Jackson, Marcus. Databases applicable to quantitative hazard/risk assessment-Towards a predictive systems toxicology. United States. doi:10.1016/j.taap.2007.12.036.
Waters, Michael, and Jackson, Marcus. 2008. "Databases applicable to quantitative hazard/risk assessment-Towards a predictive systems toxicology". United States. doi:10.1016/j.taap.2007.12.036.
@article{osti_21180466,
title = {Databases applicable to quantitative hazard/risk assessment-Towards a predictive systems toxicology},
author = {Waters, Michael and Jackson, Marcus},
abstractNote = {The Workshop on The Power of Aggregated Toxicity Data addressed the requirement for distributed databases to support quantitative hazard and risk assessment. The authors have conceived and constructed with federal support several databases that have been used in hazard identification and risk assessment. The first of these databases, the EPA Gene-Tox Database was developed for the EPA Office of Toxic Substances by the Oak Ridge National Laboratory, and is currently hosted by the National Library of Medicine. This public resource is based on the collaborative evaluation, by government, academia, and industry, of short-term tests for the detection of mutagens and presumptive carcinogens. The two-phased evaluation process resulted in more than 50 peer-reviewed publications on test system performance and a qualitative database on thousands of chemicals. Subsequently, the graphic and quantitative EPA/IARC Genetic Activity Profile (GAP) Database was developed in collaboration with the International Agency for Research on Cancer (IARC). A chemical database driven by consideration of the lowest effective dose, GAP has served IARC for many years in support of hazard classification of potential human carcinogens. The Toxicological Activity Profile (TAP) prototype database was patterned after GAP and utilized acute, subchronic, and chronic data from the Office of Air Quality Planning and Standards. TAP demonstrated the flexibility of the GAP format for air toxics, water pollutants and other environmental agents. The GAP format was also applied to developmental toxicants and was modified to represent quantitative results from the rodent carcinogen bioassay. More recently, the authors have constructed: 1) the NIEHS Genetic Alterations in Cancer (GAC) Database which quantifies specific mutations found in cancers induced by environmental agents, and 2) the NIEHS Chemical Effects in Biological Systems (CEBS) Knowledgebase that integrates genomic and other biological data including dose-response studies in toxicology and pathology. Each of the public databases has been discussed in prior publications. They will be briefly described in the present report from the perspective of aggregating datasets to augment the data and information contained within them.},
doi = {10.1016/j.taap.2007.12.036},
journal = {Toxicology and Applied Pharmacology},
number = 1,
volume = 233,
place = {United States},
year = 2008,
month =
}
  • A minimal approach to risk assessment in reproductive toxicology involves four components: hazard identification, hazard characterization, exposure characterization, and risk characterization. In practice, risk assessment in reproductive toxicology has been reduced to arbitrary safety factors or mathematical models of the dose-response relationship. These approaches obscure biological differences across species rather than using this important and frequently accessible information. Two approaches that are formally capable of using biologically relevant information (pharmacokinetics and expert system shells) are explored as aids to risk assessment in reproductive toxicology.
  • Hepatic systems toxicology is the integrative analysis of toxicogenomic technologies, e.g., transcriptomics, proteomics, and metabolomics, in combination with traditional toxicology measures to improve the understanding of mechanisms of hepatotoxic action. Hepatic toxicology studies that have employed toxicogenomic technologies to date have already provided a proof of principle for the value of hepatic systems toxicology in hazard identification. In the present review, acetaminophen is used as a model compound to discuss the application of toxicogenomics in hepatic systems toxicology for its potential role in the risk assessment process, to progress from hazard identification towards hazard characterization. The toxicogenomics-based parallelogram is usedmore » to identify current achievements and limitations of acetaminophen toxicogenomic in vivo and in vitro studies for in vitro-to-in vivo and interspecies comparisons, with the ultimate aim to extrapolate animal studies to humans in vivo. This article provides a model for comparison of more species and more in vitro models enhancing the robustness of common toxicogenomic responses and their relevance to human risk assessment. To progress to quantitative dose-response analysis needed for hazard characterization, in hepatic systems toxicology studies, generation of toxicogenomic data of multiple doses/concentrations and time points is required. Newly developed bioinformatics tools for quantitative analysis of toxicogenomic data can aid in the elucidation of dose-responsive effects. The challenge herein is to assess which toxicogenomic responses are relevant for induction of the apical effect and whether perturbations are sufficient for the induction of downstream events, eventually causing toxicity.« less
  • The rate of chemical synthesis and use has outpaced the development of risk values and the resolution of risk assessment methodology questions. In addition, available risk values derived by different organizations may vary due to scientific judgments, mission of the organization, or use of more recently published data. Further, each organization derives values for a unique chemical list so it can be challenging to locate data on a given chemical. Two Internet resources are available to address these issues. First, the International Toxicity Estimates for Risk (ITER) database ( (www.tera.org/iter)) provides chronic human health risk assessment data from a varietymore » of organizations worldwide in a side-by-side format, explains differences in risk values derived by different organizations, and links directly to each organization's website for more detailed information. It is also the only database that includes risk information from independent parties whose risk values have undergone independent peer review. Second, the Risk Information Exchange (RiskIE) is a database of in progress chemical risk assessment work, and includes non-chemical information related to human health risk assessment, such as training modules, white papers and risk documents. RiskIE is available at (http://www.allianceforrisk.org/RiskIE.htm), and will join ITER on National Library of Medicine's TOXNET ( (http://toxnet.nlm.nih.gov/)). Together, ITER and RiskIE provide risk assessors essential tools for easily identifying and comparing available risk data, for sharing in progress assessments, and for enhancing interaction among risk assessment groups to decrease duplication of effort and to harmonize risk assessment procedures across organizations.« less
  • Scientific and technological developments bring unprecedented stress to our environment. Society has to predict the results of potential health risks from technologically based actions that may have serious, far-reaching consequences. The potential for error in making such predictions or assessment is great and multiplies with the increasing size and complexity of the problem being studied. Because of this, the availability and use of reliable data is the key to any successful forecasting effort. Scientific research and development generate new data and information. Much of the scientific data being produced daily is stored in computers for subsequent analysis. This situation providesmore » both an invaluable resource and an enormous challenge. With large amounts of government funds being devoted to health and environmental research programs and with maintenance of our living environment at stake, we must make maximum use of the resulting data to forecast and avert catastrophic effects. Along with the readily available. The most efficient means of obtaining the data necessary for assessing the health effects of chemicals is to utilize applications include the toxicology databases and information files developed at ORNL. To make most efficient use of the data/information that has already been prepared, attention and resources should be directed toward projects that meticulously evaluate the available data/information and create specialized peer-reviewed value-added databases. Such projects include the National Library of Medicine`s Hazardous Substances Data Bank, and the U.S. Air Force Installation Restoration Toxicology Guide. These and similar value-added toxicology databases were developed at ORNL and are being maintained and updated. These databases and supporting information files, as well as some data evaluation techniques are discussed in this paper with special focus on how they are used to assess potential health effects of environmental agents. 19 refs., 5 tabs.« less