EnvironmEntal risk assEssmEnt EnvironmEntal risk assEssmEnt a toxicological approach second Edition Ted W. Simon CRC Press Taylor & Francis Group 6000 Broken Sound Parkway NW, Suite 300 Boca Raton, FL 33487-2742 © 2020 by Taylor & Francis Group, LLC CRC Press is an imprint of Taylor & Francis Group, an informa business No claim to original US Government works International Standard Book Number-13: 978-0-367-25097-3 (Hardback) This book contains information obtained from authentic and highly regarded sources. Reasonable efforts have been made to publish reliable data and information, but the author and publisher cannot assume responsibility for the validity of all materials or the consequences of their use. The authors and publishers have attempted to trace the copyright holders of all material reproduced in this publication and apologize to copyright holders if permission to publish in this form has not been obtained. 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Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identification and explanation without intent to infringe. Library of Congress Cataloging-in-Publication Data Names: Simon, Ted, author. Title: Environmental risk assessment : a toxicological approach / By Ted Simon. Description: Second edition. | Boca Raton : CRC Press, [2020] | Includes bibliographical references and index. | Summary: “This book explains how environmental risk assessment in particular is of increasing importance as a means of seeking to address the potential effects of chemicals in the environment in both the developed and developing world”-- Provided by publisher. Identifiers: LCCN 2019037770 (print) | LCCN 2019037771 (ebook) | ISBN 9780367250973 (hardback) | ISBN 9780429286001 (ebook) Subjects: LCSH: Environmental risk assessment. | Environmental toxicology. Classification: LCC GE145 .S56 2020 (print) | LCC GE145 (ebook) | DDC 363.73/2--dc23 LC record available at https://lccn.loc.gov/2019037770 LC ebook record available at https://lccn.loc.gov/2019037771 Visit the Taylor & Francis Web site at http://www.taylorandfrancis.com and the CRC Press Web site at http://www.crcpress.com eResource material is available for this title at https://www.crcpress.com/9780367250973 This book is dedicated to my grandchildren, Elizabeth, Charlie, Georgia and Ezra, with the hope that the world they inherit will be nurturing, beautiful, and safe. Contents Foreword .................................................................................................................xix Preface.....................................................................................................................xxi Acknowledgments ..................................................................................................xxv Chapter 1 An Introduction to Risk Assessment with a Nod to History .....................................1 1.1 Risk Assessment: Does Consistency Achieve the Goal of Fairness? .............1 1.1.1 Formaldehyde: A Cautionary Tale .....................................................4 1.1.2 A Future Look Back ..........................................................................5 1.2 Knowledge versus Fear: The Precautionary Principle and Unintended Consequences ..................................................................................................6 1.3 The History of Environmental Risk Assessment in the United States ...........7 1.3.1 Risk Assessment under NEPA ...........................................................7 1.3.2 The Events of the Late 1960s Facilitated the Passage of NEPA ........9 1.4 How Much Risk Is Enough? ..........................................................................10 1.5 Risk Assessment Recommendations from the US National Academies of Sciences and Other Government Entities .................................................12 1.5.1 The Environmental Risk Assessment Paradigm as Defined in Risk Assessment in the Federal Government: Managing the Process, the National Research Council’s 1983 “Red Book” ..........12 1.5.2 The Clean Air Act (CAA), EPA’s 1989 Risk Assessment Guidance for Superfund (RAGS), and Other Guidelines ................14 1.5.3 Science and Judgment in Risk Assessment: The National Research Council’s 1994 “Blue Book” ............................................16 1.5.3.1 EPA’s Use of Defaults per the “Blue Book” .....................16 1.5.3.2 Validation of Models, Methods, and Data........................16 1.5.3.3 Information and Data Needs ............................................18 1.5.3.4 Accounting for Uncertainty..............................................19 1.5.3.5 Understanding and Dealing with Variability ...................19 1.5.3.6 Aggregation of Risks ........................................................20 1.5.4 Framework for Environmental Risk Management: The 1997 Federal Commission Report ............................................................20 1.5.4.1 Bias and Scientific Misconduct: Another Cautionary Tale ...................................................................................21 1.5.4.2 Realism, Cost, and the Separation of Risk Assessment and Risk Management ..................................22 1.5.4.3 EPA Addresses Variability and Uncertainty ....................23 1.5.4.4 Compounding Conservatism ............................................24 1.5.5 Circular A-4 from the Office of Management and Budget ..............25 vii viii ConTenTS 1.5.6 Science and Decisions: Advancing Risk Assessment: The National Research Council’s 2009 “Silver Book” ...........................25 1.5.6.1 Improvements in Problem Formulation ...........................26 1.5.6.2 Replacing Defaults with Data ...........................................26 1.5.6.3 Controversies around “Silver Book” Recommendations for Dose–Response Assessment ........26 1.5.7 World Health Organization International Programme on Chemical Safety (WHO-IPCS) Guidance Document on Evaluating and Expressing Uncertainty in Hazard Characterization ...............................................................................28 1.6 Risk Assessment as Practiced Internationally ..............................................29 1.6.1 Will Risk Assessment in China Point the Way for the Developing World? ...........................................................................29 1.6.2 Risk Assessment in the European Union .........................................30 1.6.3 Risk Assessment in Canada .............................................................32 1.7 What Happens When Things Go Right ........................................................32 1.7.1 The Sangamo-Weston Superfund Site .............................................33 1.7.2 Good Communication Is the Reason Things Go Right ...................36 1.8 Perception Is Reality: Risk Communication and Stakeholder Participation ..................................................................................................36 1.8.1 Public Perception of Hexavalent Chromium: A Cautionary Tale ...................................................................................................38 1.8.2 Why the Movie Erin Brockovitch Changed the Public’s View of Chromium ....................................................................................40 1.9 Association versus Causation ........................................................................40 1.10 Key Concepts in Modern Risk Assessment ..................................................43 1.10.1 Mode of Action ................................................................................43 1.10.2 Point of Departure ...........................................................................43 1.10.3 Adverse Outcome Pathway (AOP) ...................................................44 1.10.4 Biomarker.........................................................................................44 1.10.5 Biomonitoring Equivalent (BE) .......................................................44 1.10.6 Physiologically Based Pharmacokinetic (PBPK) Modeling ..........................................................................................44 1.10.7 New Approach Methods (NAMs) ....................................................45 1.11 Emerging Risks .............................................................................................45 1.11.1 Climate Change ...............................................................................46 1.11.2 Perfluorinated Chemicals (PFCs).....................................................46 1.12 Exercises for Thought and Discussion ..........................................................47 1.12.1 The Current Debate about Chemical Safety ....................................47 1.12.2 Risk Assessment History: Robert F. Kennedy’s Speech at the University of Kansas ........................................................................48 1.12.3 Animal and Human Carcinogens ....................................................48 Further Reading .......................................................................................................48 References ................................................................................................................48 ConTenTS ix Chapter 2 Perception, Planning, and Scoping, Problem Formulation, and Hazard Identification: All Parts of Risk Assessment ...........................................................63 2.1 What Is Risk, and How Can We Estimate Risk? ..........................................63 2.1.1 Three Types of Risk: Aleatory, Epistemic, and Ontological ...........64 2.1.2 Risk of Being Struck by Lightning ..................................................64 2.1.2.1 Frequentist or Actuarial Risk of Lightning ......................64 2.1.2.2 Predicted Risk of Lightning: Using a Model ...................65 2.1.2.3 Perceived Risk of Lightning .............................................67 2.1.2.4 Predicted Risk of Lightning While Swimming in an Indoor Pool ..................................................................67 2.2 Designing Risk Assessments: Planning and Scoping versus Problem Formulation ...................................................................................................68 2.2.1 History of Problem Formulation ......................................................69 2.2.2 The Need for Problem Formulation Is Not Limited to Ecological Risk Assessment ............................................................70 2.2.3 The Importance of Problem Formulation for All Risk Assessments .....................................................................................72 2.3 Hazard versus Risk .......................................................................................76 2.3.1 What Is Hazard Identification? ........................................................77 2.3.2 Uncertainty Classifications Used in Hazard Identification ..............78 2.3.3 Weight of Evidence ..........................................................................80 2.4 Epidemiologic Studies for Hazard Identification ..........................................82 2.4.1 Biomonitoring and the Use of Biomarkers ......................................82 2.4.2 Biomarkers of Exposure and Biomarkers of Effect .........................83 2.4.3 Historical Reconstruction of Exposure ............................................85 2.4.3.1 False Positives in Epidemiologic Studies .........................85 2.4.3.2 Quantiles and Statistical Power ........................................86 2.4.3.3 Reverse Causation ............................................................87 2.4.4 Example of Hazard Identification from Epidemiology ....................88 2.5 Animal Bioassays as the Basis for Hazard Identification .............................89 2.6 In Vitro Testing and Informatics as the Basis for Hazard Identification ......90 2.6.1 Toxicity Pathways, Adverse Outcome Pathways, and Mode of Action (MOA) ..................................................................................91 2.6.2 Implementing Toxicity Testing in the 21st Century (TT21C) ..........92 2.6.3 Can in Vitro Assays Cover All Toxicity Pathways? .........................92 2.6.4 In Vitro Assays May in Time Be Useful for Hazard Characterization ...............................................................................93 2.6.5 What Do in Vitro Assays Actually Measure, and How Should They Be Used? .................................................................................93 2.6.6 High-Throughput Exposure for Selecting Chemicals ......................94 2.7 In Silico Prediction Models as the Basis for Hazard Identification ..............94 2.7.1 Quantitative Structure–Activity Relationship ..................................95 2.7.2 Read-Across: Using What Is Already Known .................................96