skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Approaches to cancer assessment in EPA's Integrated Risk Information System

Abstract

The U.S. Environmental Protection Agency's (EPA) Integrated Risk Information System (IRIS) Program develops assessments of health effects that may result from chronic exposure to chemicals in the environment. The IRIS database contains more than 540 assessments. When supported by available data, IRIS assessments provide quantitative analyses of carcinogenic effects. Since publication of EPA's 2005 Guidelines for Carcinogen Risk Assessment, IRIS cancer assessments have implemented new approaches recommended in these guidelines and expanded the use of complex scientific methods to perform quantitative dose-response assessments. Two case studies of the application of the mode of action framework from the 2005 Cancer Guidelines are presented in this paper. The first is a case study of 1,2,3-trichloropropane, as an example of a chemical with a mutagenic mode of carcinogenic action thus warranting the application of age-dependent adjustment factors for early-life exposure; the second is a case study of ethylene glycol monobutyl ether, as an example of a chemical with a carcinogenic action consistent with a nonlinear extrapolation approach. The use of physiologically based pharmacokinetic (PBPK) modeling to quantify interindividual variability and account for human parameter uncertainty as part of a quantitative cancer assessment is illustrated using a case study involving probabilistic PBPK modeling formore » dichloromethane. We also discuss statistical issues in assessing trends and model fit for tumor dose-response data, analysis of the combined risk from multiple types of tumors, and application of life-table methods for using human data to derive cancer risk estimates. These issues reflect the complexity and challenges faced in assessing the carcinogenic risks from exposure to environmental chemicals, and provide a view of the current trends in IRIS carcinogenicity risk assessment.« less

Authors:
 [1];  [2];  [1];  [1];  [2];  [1]
  1. U.S. Environmental Protection Agency, Office of Research and Development, National Center for Environmental Assessment, 1200 Pennsylvania Ave NW, Washington, DC 20460 (United States)
  2. U.S. Environmental Protection Agency, Office of Research and Development, National Center for Environmental Assessment, Research Triangle Park, NC 27711 (United States)
Publication Date:
OSTI Identifier:
21587782
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 254; Journal Issue: 2; Conference: TRAC 2008/2009 meeting: 2008 Toxicology and Risk Assessment Conference;2009 Toxicology and Risk Assessment Conference, West Chester, OH (United States);West Chester, OH (United States), 14-17 Apr 2008;27-30 Apr 2009; Other Information: DOI: 10.1016/j.taap.2010.10.019; PII: S0041-008X(10)00412-6; Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CARCINOGENS; CHRONIC EXPOSURE; GLYCOLS; HAZARDS; METHYLENE CHLORIDE; MONTE CARLO METHOD; NEOPLASMS; RECOMMENDATIONS; SIMULATION; US EPA; ALCOHOLS; CALCULATION METHODS; DISEASES; HYDROXY COMPOUNDS; NATIONAL ORGANIZATIONS; ORGANIC CHLORINE COMPOUNDS; ORGANIC COMPOUNDS; ORGANIC HALOGEN COMPOUNDS; POLLUTION CONTROL AGENCIES; US ORGANIZATIONS

Citation Formats

Gehlhaus, Martin W., E-mail: Gehlhaus.Martin@epa.gov, Gift, Jeffrey S., E-mail: Gift.Jeff@epa.gov, Hogan, Karen A., E-mail: Hogan.Karen@epa.gov, Kopylev, Leonid, E-mail: Kopylev.Leonid@epa.gov, Schlosser, Paul M., E-mail: Schlosser.Paul@epa.gov, and Kadry, Abdel-Razak, E-mail: Kadry.Abdel@epa.gov. Approaches to cancer assessment in EPA's Integrated Risk Information System. United States: N. p., 2011. Web. doi:10.1016/j.taap.2010.10.019.
Gehlhaus, Martin W., E-mail: Gehlhaus.Martin@epa.gov, Gift, Jeffrey S., E-mail: Gift.Jeff@epa.gov, Hogan, Karen A., E-mail: Hogan.Karen@epa.gov, Kopylev, Leonid, E-mail: Kopylev.Leonid@epa.gov, Schlosser, Paul M., E-mail: Schlosser.Paul@epa.gov, & Kadry, Abdel-Razak, E-mail: Kadry.Abdel@epa.gov. Approaches to cancer assessment in EPA's Integrated Risk Information System. United States. doi:10.1016/j.taap.2010.10.019.
Gehlhaus, Martin W., E-mail: Gehlhaus.Martin@epa.gov, Gift, Jeffrey S., E-mail: Gift.Jeff@epa.gov, Hogan, Karen A., E-mail: Hogan.Karen@epa.gov, Kopylev, Leonid, E-mail: Kopylev.Leonid@epa.gov, Schlosser, Paul M., E-mail: Schlosser.Paul@epa.gov, and Kadry, Abdel-Razak, E-mail: Kadry.Abdel@epa.gov. Fri . "Approaches to cancer assessment in EPA's Integrated Risk Information System". United States. doi:10.1016/j.taap.2010.10.019.
@article{osti_21587782,
title = {Approaches to cancer assessment in EPA's Integrated Risk Information System},
author = {Gehlhaus, Martin W., E-mail: Gehlhaus.Martin@epa.gov and Gift, Jeffrey S., E-mail: Gift.Jeff@epa.gov and Hogan, Karen A., E-mail: Hogan.Karen@epa.gov and Kopylev, Leonid, E-mail: Kopylev.Leonid@epa.gov and Schlosser, Paul M., E-mail: Schlosser.Paul@epa.gov and Kadry, Abdel-Razak, E-mail: Kadry.Abdel@epa.gov},
abstractNote = {The U.S. Environmental Protection Agency's (EPA) Integrated Risk Information System (IRIS) Program develops assessments of health effects that may result from chronic exposure to chemicals in the environment. The IRIS database contains more than 540 assessments. When supported by available data, IRIS assessments provide quantitative analyses of carcinogenic effects. Since publication of EPA's 2005 Guidelines for Carcinogen Risk Assessment, IRIS cancer assessments have implemented new approaches recommended in these guidelines and expanded the use of complex scientific methods to perform quantitative dose-response assessments. Two case studies of the application of the mode of action framework from the 2005 Cancer Guidelines are presented in this paper. The first is a case study of 1,2,3-trichloropropane, as an example of a chemical with a mutagenic mode of carcinogenic action thus warranting the application of age-dependent adjustment factors for early-life exposure; the second is a case study of ethylene glycol monobutyl ether, as an example of a chemical with a carcinogenic action consistent with a nonlinear extrapolation approach. The use of physiologically based pharmacokinetic (PBPK) modeling to quantify interindividual variability and account for human parameter uncertainty as part of a quantitative cancer assessment is illustrated using a case study involving probabilistic PBPK modeling for dichloromethane. We also discuss statistical issues in assessing trends and model fit for tumor dose-response data, analysis of the combined risk from multiple types of tumors, and application of life-table methods for using human data to derive cancer risk estimates. These issues reflect the complexity and challenges faced in assessing the carcinogenic risks from exposure to environmental chemicals, and provide a view of the current trends in IRIS carcinogenicity risk assessment.},
doi = {10.1016/j.taap.2010.10.019},
journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 2,
volume = 254,
place = {United States},
year = {2011},
month = {7}
}