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Suggested Citation:"Front Matter." National Research Council. 2010. Review of the Environmental Protection Agency's Draft IRIS Assessment of Tetrachloroethylene. Washington, DC: The National Academies Press. doi: 10.17226/12863.
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Review of the Environmental Protection Agency’s Draft IRIS Assessment of Tetrachloroethylene

Committee to Review EPA’s Toxicological Assessment of Tetrachloroethylene

Board on Environmental Studies and Toxicology

Division on Earth and Life Studies

NATIONAL RESEARCH COUNCIL OF THE NATIONAL ACADEMIES

THE NATIONAL ACADEMIES PRESS

Washington, D.C.
www.nap.edu

Suggested Citation:"Front Matter." National Research Council. 2010. Review of the Environmental Protection Agency's Draft IRIS Assessment of Tetrachloroethylene. Washington, DC: The National Academies Press. doi: 10.17226/12863.
×

THE NATIONAL ACADEMIES PRESS

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NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the committee responsible for the report were chosen for their special competences and with regard for appropriate balance.

This project was supported by Contract 68-C-03-081 between the National Academy of Sciences and the U.S. Environmental Protection Agency. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the authors and do not necessarily reflect the view of the organizations or agencies that provided support for this project.

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Suggested Citation:"Front Matter." National Research Council. 2010. Review of the Environmental Protection Agency's Draft IRIS Assessment of Tetrachloroethylene. Washington, DC: The National Academies Press. doi: 10.17226/12863.
×

THE NATIONAL ACADEMIES

Advisers to the Nation on Science, Engineering, and Medicine


The National Academy of Sciences is a private, nonprofit, self-perpetuating society of distinguished scholars engaged in scientific and engineering research, dedicated to the furtherance of science and technology and to their use for the general welfare. Upon the authority of the charter granted to it by the Congress in 1863, the Academy has a mandate that requires it to advise the federal government on scientific and technical matters. Dr. Ralph J. Cicerone is president of the National Academy of Sciences.


The National Academy of Engineering was established in 1964, under the charter of the National Academy of Sciences, as a parallel organization of outstanding engineers. It is autonomous in its administration and in the selection of its members, sharing with the National Academy of Sciences the responsibility for advising the federal government. The National Academy of Engineering also sponsors engineering programs aimed at meeting national needs, encourages education and research, and recognizes the superior achievements of engineers. Dr. Charles M. Vest is president of the National Academy of Engineering.


The Institute of Medicine was established in 1970 by the National Academy of Sciences to secure the services of eminent members of appropriate professions in the examination of policy matters pertaining to the health of the public. The Institute acts under the responsibility given to the National Academy of Sciences by its congressional charter to be an adviser to the federal government and, upon its own initiative, to identify issues of medical care, research, and education. Dr. Harvey V. Fineberg is president of the Institute of Medicine.


The National Research Council was organized by the National Academy of Sciences in 1916 to associate the broad community of science and technology with the Academy’s purposes of furthering knowledge and advising the federal government. Functioning in accordance with general policies determined by the Academy, the Council has become the principal operating agency of both the National Academy of Sciences and the National Academy of Engineering in providing services to the government, the public, and the scientific and engineering communities. The Council is administered jointly by both Academies and the Institute of Medicine. Dr. Ralph J. Cicerone and Dr. Charles M. Vest are chair and vice chair, respectively, of the National Research Council.


www.national-academies.org

Suggested Citation:"Front Matter." National Research Council. 2010. Review of the Environmental Protection Agency's Draft IRIS Assessment of Tetrachloroethylene. Washington, DC: The National Academies Press. doi: 10.17226/12863.
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Suggested Citation:"Front Matter." National Research Council. 2010. Review of the Environmental Protection Agency's Draft IRIS Assessment of Tetrachloroethylene. Washington, DC: The National Academies Press. doi: 10.17226/12863.
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COMMITTEE TO REVIEW EPA’S TOXICOLOGICAL ASSESSMENT OF TETRACHLOROETHYLENE

Members

SAM KACEW (Chair),

University of Ottawa, Ontario, Canada

BRUCE H. ALEXANDER,

University of Minnesota School of Public Health, Minneapolis

MARGIT L. BLEECKER,

Center for Occupational and Environmental Neurology, Baltimore, MD

GARY P. CARLSON,

Purdue University, West Lafayette, IN

LINDA D. COWAN,

University of Oklahoma Health Sciences Center, Oklahoma City

MARY E. DAVIS,

West Virginia University, Morgantown

H. CHRISTOPHER FREY,

North Carolina State University, Raleigh

JOSEPH R. LANDOLPH,

University of Southern California, Los Angeles

M.E. (BETTE) MEEK,

University of Ottawa, Ontario, Canada

DAVID C. MCMILLAN,

University of Nebraska Medical Center, Omaha

M. CHRISTOPHER NEWLAND,

Auburn University, Auburn, AL

JULIA QUINT,

California Department of Public Health (retired), Berkeley

GARY L. ROSNER,

University of Texas M.D. Anderson Cancer Center, Houston

IVAN RUSYN,

University of North Carolina, Chapel Hill

ROLF SCHULTE-HERMANN,

Medical University of Vienna, Austria

IRVIN R. SCHULTZ,

Battelle Pacific Northwest Division, Sequim, WA

ROBERT SNYDER,

Rutgers, the State University of New Jersey, Piscataway

ROBERTA F. WHITE,

Boston University School of Public Health, Boston, MA

LUOPING ZHANG,

University of California, Berkeley

YILIANG ZHU,

University of South Florida, Tampa

Staff

SUSAN N. J. MARTEL, Project Director

NORMAN GROSSBLATT, Senior Editor

MIRSADA KARALIC-LONCAREVIC, Manager,

Technical Information Center

KEEGAN SAWYER, Associate Program Officer

TAMARA DAWSON, Program Associate

RADIAH ROSE, Editorial Project Manager

Sponsor

U.S. ENVIRONMENTAL PROTECTION AGENCY

Suggested Citation:"Front Matter." National Research Council. 2010. Review of the Environmental Protection Agency's Draft IRIS Assessment of Tetrachloroethylene. Washington, DC: The National Academies Press. doi: 10.17226/12863.
×

BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY

Members

ROGENE F. HENDERSON (Chair),

Lovelace Respiratory Research Institute, Albuquerque, NM

RAMÓN ALVAREZ,

Environmental Defense Fund, Austin, TX

TINA BAHADORI,

American Chemistry Council, Arlington, VA

MICHAEL J. BRADLEY,

M.J. Bradley & Associates, Concord, MA

DALLAS BURTRAW,

Resources for the Future, Washington, DC

JAMES S. BUS,

Dow Chemical Company, Midland, MI

JONATHAN Z. CANNON,

University of Virginia, Charlottesville

GAIL CHARNLEY,

HealthRisk Strategies, Washington, DC

RUTH DEFRIES,

Columbia University, New York, NY

RICHARD A. DENISON,

Environmental Defense Fund, Washington, DC

H. CHRISTOPHER FREY,

North Carolina State University, Raleigh

J. PAUL GILMAN,

Covanta Energy Corporation, Fairfield, NJ

RICHARD M. GOLD,

Holland & Knight, LLP, Washington, DC

LYNN R. GOLDMAN,

Johns Hopkins University, Baltimore, MD

JUDITH A. GRAHAM (retired),

Pittsboro, NC

HOWARD HU,

University of Michigan, Ann Harbor

ROGER E. KASPERSON,

Clark University, Worcester, MA

TERRY L. MEDLEY,

E. I. du Pont de Nemours & Company, Wilmington, DE

JANA MILFORD,

University of Colorado at Boulder, Boulder

DANNY D. REIBLE,

University of Texas, Austin

JOSEPH V. RODRICKS,

ENVIRON International Corporation, Arlington, VA

ROBERT F. SAWYER,

University of California, Berkeley

KIMBERLY M. THOMPSON,

Harvard School of Public Health, Boston, MA

MARK J. UTELL,

University of Rochester Medical Center, Rochester, NY

Senior Staff

JAMES J. REISA, Director

DAVID J. POLICANSKY, Scholar

RAYMOND A. WASSEL, Senior Program Officer for Environmental Studies

SUSAN N.J. MARTEL, Senior Program Officer for Toxicology

ELLEN K. MANTUS, Senior Program Officer for Risk Analysis

EILEEN N. ABT, Senior Program Officer

RUTH E. CROSSGROVE, Senior Editor

MIRSADA KARALIC-LONCAREVIC, Manager,

Technical Information Center

RADIAH ROSE, Manager,

Editorial Projects

Suggested Citation:"Front Matter." National Research Council. 2010. Review of the Environmental Protection Agency's Draft IRIS Assessment of Tetrachloroethylene. Washington, DC: The National Academies Press. doi: 10.17226/12863.
×

OTHER REPORTS OF THE BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY

Contaminated Water Supplies at Camp Lejeune—Assessing Potential Health Effects (2009)

Review of the Federal Strategy for Nanotechnology-Related Environmental, Health, and Safety Research (2009)

Science and Decisions: Advancing Risk Assessment (2009)

Phthalates and Cumulative Risk Assessment: The Tasks Ahead (2008)

Estimating Mortality Risk Reduction and Economic Benefits from Controlling Ozone Air Pollution (2008)

Respiratory Diseases Research at NIOSH (2008)

Evaluating Research Efficiency in the U.S. Environmental Protection Agency (2008)

Hydrology, Ecology, and Fishes of the Klamath River Basin (2008)

Applications of Toxicogenomic Technologies to Predictive Toxicology and Risk Assessment (2007)

Models in Environmental Regulatory Decision Making (2007)

Toxicity Testing in the Twenty-first Century: A Vision and a Strategy (2007)

Sediment Dredging at Superfund Megasites: Assessing the Effectiveness (2007)

Environmental Impacts of Wind-Energy Projects (2007)

Scientific Review of the Proposed Risk Assessment Bulletin from the Office of Management and Budget (2007)

Assessing the Human Health Risks of Trichloroethylene: Key Scientific Issues (2006)

New Source Review for Stationary Sources of Air Pollution (2006)

Human Biomonitoring for Environmental Chemicals (2006)

Health Risks from Dioxin and Related Compounds: Evaluation of the EPA Reassessment (2006)

Fluoride in Drinking Water: A Scientific Review of EPA’s Standards (2006)

State and Federal Standards for Mobile-Source Emissions (2006)

Superfund and Mining Megasites—Lessons from the Coeur d’Alene River Basin (2005)

Health Implications of Perchlorate Ingestion (2005)

Air Quality Management in the United States (2004)

Endangered and Threatened Species of the Platte River (2004)

Atlantic Salmon in Maine (2004)

Endangered and Threatened Fishes in the Klamath River Basin (2004)

Cumulative Environmental Effects of Alaska North Slope Oil and Gas Development (2003)

Estimating the Public Health Benefits of Proposed Air Pollution Regulations (2002)

Biosolids Applied to Land: Advancing Standards and Practices (2002)

The Airliner Cabin Environment and Health of Passengers and Crew (2002)

Page viii Cite
Suggested Citation:"Front Matter." National Research Council. 2010. Review of the Environmental Protection Agency's Draft IRIS Assessment of Tetrachloroethylene. Washington, DC: The National Academies Press. doi: 10.17226/12863.
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Arsenic in Drinking Water: 2001 Update (2001)

Evaluating Vehicle Emissions Inspection and Maintenance Programs (2001)

Compensating for Wetland Losses Under the Clean Water Act (2001)

A Risk-Management Strategy for PCB-Contaminated Sediments (2001)

Acute Exposure Guideline Levels for Selected Airborne Chemicals (seven volumes, 2000-2009)

Toxicological Effects of Methylmercury (2000)

Strengthening Science at the U.S. Environmental Protection Agency (2000)

Scientific Frontiers in Developmental Toxicology and Risk Assessment (2000)

Ecological Indicators for the Nation (2000)

Waste Incineration and Public Health (2000)

Hormonally Active Agents in the Environment (1999)

Research Priorities for Airborne Particulate Matter (four volumes, 1998-2004)

The National Research Council’s Committee on Toxicology: The First 50 Years (1997)

Carcinogens and Anticarcinogens in the Human Diet (1996)

Upstream: Salmon and Society in the Pacific Northwest (1996)

Science and the Endangered Species Act (1995)

Wetlands: Characteristics and Boundaries (1995)

Biologic Markers (five volumes, 1989-1995)

Science and Judgment in Risk Assessment (1994)

Pesticides in the Diets of Infants and Children (1993)

Dolphins and the Tuna Industry (1992)

Science and the National Parks (1992)

Human Exposure Assessment for Airborne Pollutants (1991)

Rethinking the Ozone Problem in Urban and Regional Air Pollution (1991)

Decline of the Sea Turtles (1990)


Copies of these reports may be ordered from the National Academies Press

(800) 624-6242 or (202) 334-3313

www.nap.edu

Suggested Citation:"Front Matter." National Research Council. 2010. Review of the Environmental Protection Agency's Draft IRIS Assessment of Tetrachloroethylene. Washington, DC: The National Academies Press. doi: 10.17226/12863.
×

Preface

In June 2008, the U.S. Environmental Protection Agency (EPA) released its draft Toxicological Review of Tetrachloroethylene (Perchloroethylene) (CAS No. 127-18-4) in Support of Summary Information on the Integrated Risk Information System (IRIS). The assessment provided estimates of cancer and noncancer effects, which will be used to establish air and water quality standards to protect public health and set cleanup standards for hazardous-waste sites. EPA requested that the National Research Council review the scientific evidence on the adverse health effect of tetrachloroethylene and the agency’s application of such data in quantifying human health risks. The review was sought to ensure that the draft IRIS assessment was consistent with current EPA guidance on conducting risk assessments and that it reflected sound scientific analysis and judgment.

In response to EPA’s request, the National Research Council convened the Committee to Review EPA’s Toxicological Assessment of Tetrachloroethylene, which prepared this report. The members of the committee were selected for their expertise in pharmacokinetics, liver toxicology, kidney toxicology, neurotoxicology, hematopoietic toxicology, reproductive toxicology, developmental toxicology, genotoxicity, carcinogenesis, epidemiology, physiologically based pharmacokinetic modeling, biostatistics, and risk assessment. Biographic information on the committee members is provided in Appendix A.

To help the committee in its review, public meetings were held in November 2008 and January and April 2009 to gather information from EPA, academic and industry researchers, state public-health departments, and the general public. The committee is grateful to those who gave presentations on research related to tetrachloroethylene or on topics relevant to the committee’s task, including Judith Schreiber, Office of the New York State Attorney General; Philip Bushnell, EPA; Thomas Burke, Johns Hopkins Bloomberg School of Public Health; Andy Salmon, California Environmental Protection Agency; and Harvey Clewell III, Hamner Institutes for Health Sciences. The committee also thanks Peter Preuss, Kathryn Guyton, and Karen Hogan for providing background information and responding to questions throughout the study.

One committee member, Rolf Schulte-Hermann, disagreed with the committee’s support of EPA’s conclusion that the mode of action of tetrachloroethylene in inducing liver cancer in rodents is unknown. He judges that the induction of liver cancer in mice can be fully explained by a mode of action that involves the activation of the peroxisome proliferator-activated receptor-alpha. The basis of his judg-

Suggested Citation:"Front Matter." National Research Council. 2010. Review of the Environmental Protection Agency's Draft IRIS Assessment of Tetrachloroethylene. Washington, DC: The National Academies Press. doi: 10.17226/12863.
×

ment and of his dissent from the committee’s position is detailed in Appendix B, where it is followed by the committee’s rebuttal.

This report and the dissenting statement have been reviewed in draft form by persons chosen for their diverse perspectives and technical expertise in accordance with procedures approved by the National Research Council’s Report Review Committee. The purpose of the independent review is to provide candid and critical comments that will assist the institution in making its published report as sound as possible and to ensure that the report meets institutional standards of objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the deliberative process. We thank the following for their review of this report: A. John Bailer, Miami University; Lucio Costa, University of Washington; Scott E. Bowen, Wayne State University; Wolfgang Dekant, University of Würzburg; Adnan Elfarra, University of Wisconsin; Jeffrey Fisher, University of Georgia; David H. Garabrant, University of Michigan; Bernard D. Goldstein, University of Pittsburgh; David G. Hoel, Medical University of South Carolina; Ronald Melnick, National Institute of Environmental Health Sciences; Dorothy Patton, Environmental Protection Agency (retired); David Richardson, University of North Carolina School of Public Health; and Lauren Zeise, California Environmental Protection Agency.

Although the reviewers listed above provided many constructive comments and suggestions, they were not asked to endorse the conclusions or recommendations, nor did they see the final draft of the report before its release. The review of the report was overseen by the review coordinator, David Eaton, University of Washington, and review monitor, Mark Cullen, Yale University. Appointed by the National Research Council, they were responsible for making certain that an independent examination of the report was carried out in accordance with institutional procedures and that all review comments were carefully considered. Responsibility for the final content of the report rests entirely with the author committee and the institution.

The committee is grateful for the assistance of National Research Council staff in preparing the report, in particular Susan Martel, who served as project director and contributed to the report. Other staff members who contributed are James Reisa, director of the Board on Environmental Studies and Toxicology; Keegan Sawyer, associate program officer; Norman Grossblatt, senior editor; Mirsada Karalic-Loncarevic, manager of the Technical Information Center; Radiah Rose, editorial projects manager; and Tamara Dawson, program associate.

Finally, I thank all the members of the committee for their time and efforts throughout the development of this report.


Sam Kacew, Chair

Committee to Review EPA’s Toxicological Assessment of Tetrachloroethylene

Suggested Citation:"Front Matter." National Research Council. 2010. Review of the Environmental Protection Agency's Draft IRIS Assessment of Tetrachloroethylene. Washington, DC: The National Academies Press. doi: 10.17226/12863.
×

Abbreviations

AUC area under the curve

BMC benchmark concentration

BMCL benchmark concentration with its lower confidence limit

BMD benchmark dose

BuChE butyrylcholinesterase

CCI color-confusion index

CFU colony-forming unit

CHO Chinese hamster ovary

CI confidence interval

CNS central nervous system

CYP cytochrome P-450

DCA dichloroacetic acid

DEHP diethylhexylphthalate

EBV Epstein Barr virus

8-OHdG 8-hydroxydeoxyguanosine

EPA U.S. Environmental Protection Agency

FDA Food and Drug Administration

FMO flavin-containing monooxygenase

GJIC gap junctional intercellular communication

GSH glutathione

GST glutathione S-transferase

HD Hodgkin disease

IARC International Agency for Research on Cancer

IRIS Integrated Risk Information System

JEM job-exposure matrix

JISA Japan Industrial Safety Association

JTEM job-task exposure matrix

LGLL large granular lymphocytic leukemia

LOAEL lowest observed-adverse-effect level

MCL mononuclear-cell leukemia

MOA mode of action

N-Ac-TCVCS N-acetyl-S-(1,2,2-trichlorovinyl)-L-cysteine

Suggested Citation:"Front Matter." National Research Council. 2010. Review of the Environmental Protection Agency's Draft IRIS Assessment of Tetrachloroethylene. Washington, DC: The National Academies Press. doi: 10.17226/12863.
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NCI National Cancer Institute

NES Neurobehavioral Evaluation System

NHL non-Hodgkin lymphoma

NK natural-killer

NOAEL no-observed-adverse-effect level

NRC National Research Council

NTP National Toxicology Program

OECD Organisation for Economic Co-operation and Development

OR odds ratio

PBPK physiologically based pharmacokinetic modeling

PCO palmitoyl-CoA oxidation

POD point of departure

PPARα peroxisome proliferator-activated receptor-alpha

RCC renal-cell carcinoma

RfC reference concentration

RfD reference dose

RfV reference value

SAB Science Advisory Board

SCE sister-chromatid exchange

SIR standardized incidence ratio

SMR standardized mortality ratio

TCA trichloroacetic acid

TCVC S-(1,2,2-trichlorovinyl)-L-cysteine

TCVCS S-(1,2,2-trichlorovinyl)-L-cysteine sulfoxide

TCVG S-(1,2,2-trichlorovinyl) glutathione

TWA time-weighted average

VCS visual-contrast sensitivity

VEP visual evoked potential

WHO World Health Organization

Page xiii Cite
Suggested Citation:"Front Matter." National Research Council. 2010. Review of the Environmental Protection Agency's Draft IRIS Assessment of Tetrachloroethylene. Washington, DC: The National Academies Press. doi: 10.17226/12863.
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Suggested Citation:"Front Matter." National Research Council. 2010. Review of the Environmental Protection Agency's Draft IRIS Assessment of Tetrachloroethylene. Washington, DC: The National Academies Press. doi: 10.17226/12863.
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 Evidence for Indirect Genotoxicity,

 

55

   

 Formation of Reactive Metabolites in Animals and Humans,

 

56

   

 Cell-Transformation Assays,

 

56

   

 Findings and Recommendations,

 

57

6

 

HEPATIC TOXICITY AND CANCER

 

59

   

 Hepatotoxicity,

 

59

   

 Hepatocarcinogencity,

 

61

   

 Summary,

 

66

7

 

RENAL TOXICITY AND CANCER

 

68

   

 Human Studies,

 

68

   

 Animal Studies,

 

70

   

 Summary and Recommendations,

 

73

8

 

HEMATOPOIETIC EFFECTS

 

75

   

 Animal Studies,

 

75

   

 Human Studies,

 

78

   

 Mode of Action,

 

78

   

 Summary,

 

80

9

 

GENERAL REVIEW OF EPIDEMIOLOGIC EVIDENCE PERTAINING TO CANCER

 

81

   

 Esophageal Cancer,

 

83

   

 Lymphoid Cancers,

 

84

   

 Other Cancers,

 

84

   

 General Comments on the Environmental Protection Agency’s Presentation on Epidemiologic Evidence on Cancer,

 

85

   

 Research Recommendations,

 

85

10

 

REFERENCE VALUES FOR TETRACHLOROETHYLENE

 

86

   

 Selection of Critical End Point and Studies,

 

86

   

 Dose Metrics,

 

89

   

 Route-to-Route Extrapolation,

 

89

   

 Characterization of Uncertainties,

 

90

   

 Graphical Presentation of Reference Values,

 

93

11

 

CANCER RISK ESTIMATES FOR TETRACHLOROETHYLENE

 

98

   

 Cancer Classification,

 

98

   

 Selection of Tumor Type for Quantitative Assessment,

 

101

   

 Mode of Action Analysis,

 

102

   

 Age-Dependent Adjustment Factor,

 

103

   

 Low-Dose Extrapolation,

 

104

   

 Physiologically Based Pharmacokinetic Models, Dose Metrics, and Interspecies Scaling,

 

106

   

 Uncertainty,

 

112

12

 

MOVING BEYOND THE CURRENT STATE OF PRACTICE

 

114

   

 Organization and Approach,

 

114

   

 Uncertainty Assessment,

 

116

Suggested Citation:"Front Matter." National Research Council. 2010. Review of the Environmental Protection Agency's Draft IRIS Assessment of Tetrachloroethylene. Washington, DC: The National Academies Press. doi: 10.17226/12863.
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BOXES, FIGURES, AND TABLES

BOXES

11-1

 

EPA Cancer Guidance for Concluding a Chemical is Likely to be Carcinogenic to Humans (EPA 2005),

 

99

FIGURES

S-1

 

Distribution of sample reference values,

 

7

2-1

 

Simplified illustration of the metabolic pathways of tetrachloroethylene,

 

26

10-1

 

Distribution of sample reference values,

 

94

TABLES

3-1

 

Estimated Meana Neuropsychologic Test Results by Lifetime Exposure to Tetrachloroethylene in Study by Echeverria et al. (1995),

 

35

11-1

 

Summary of Data on Hepatic Metabolism of Tetrachloroethylene and Urinary Excretion of Glutathione-Pathway Metabolites,

 

110

Suggested Citation:"Front Matter." National Research Council. 2010. Review of the Environmental Protection Agency's Draft IRIS Assessment of Tetrachloroethylene. Washington, DC: The National Academies Press. doi: 10.17226/12863.
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Tetrachloroethylene is a volatile, chlorinated organic hydrocarbon that is widely used as a solvent in the dry-cleaning and textile-processing industries and as an agent for degreasing metal parts. It is an environmental contaminant that has been detected in the air, groundwater, surface waters, and soil. In June 2008, the U.S. Environmental Protection Agency released its draft Toxicological Review of Tetrachloroethylene (Perchloroethylene) (CAS No. 127-18-4) in Support of Summary Information on the Integrated Risk Information System (IRIS). The draft IRIS assessment provides quantitative estimates of cancer and noncancer effects of exposure to tetrachloreothylene, which will be used to establish airquality and water-quality standards to protect public health and to set cleanup standards for hazardous waste sites.

At the request of EPA, the National Research Council conducted an independent scientific review of the draft IRIS assessment of tetrachloroethylene from toxicologic, epidemiologic, and human clinical perspectives. The resulting book evaluates the adequacy of the EPA assessment, the data and methods used for deriving the noncancer values for inhalation and oral exposures and the oral and inhalation cancer unit risks posed by tetrachloroethylene; evaluates whether the key studies underlying the draft IRIS assessment are of requisite quality, reliability, and relevance to support the derivation of the reference values and cancer risks; evaluates whether the uncertainties in EPA's risk assessment were adequately described and, where possible, quantified; and identifies research that could reduce the uncertainty in the current understanding of human health effects associated with tetrachloroethylene exposure.

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