Toxicological Risk Assessment of Chemicals: A Practical Guide

438 Pages·2008·8.239 MB·English

by  Elsa Nielsen, Grete Ostergaard, John Christian Larsen

Toxicological
Risk Assessment
of Chemicals
A Practical Guide
(cid:1)2007byTaylor&FrancisGroup,LLC.
(cid:1)2007byTaylor&FrancisGroup,LLC.
Toxicological
Risk Assessment
of Chemicals
A Practical Guide
Elsa Nielsen • Grete Østergaard • John Christian Larsen
New York London
(cid:1)2007byTaylor&FrancisGroup,LLC.
Cover: Theophrastus Phillippus Aureolus Bombastus von Hohenheim, known as “Paracelsus” 1493–1541 (“the equal of
Celsus”, an early Roman physician). Paracelsus is often called “the father of toxicology.” His famous quotation forms the
central dogma of regulatory toxicology:
“All substances are poisons; there is none that is not a poison. The right dose differentiates a poison and a
remedy.”—Paracelsus
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Library of Congress Cataloging-in-Publication Data
Ostergaard, Grete.
Toxicological Risk Assessment of Chemicals : a practical guide / Elsa Nielsen, Grete Ostergaard, and
John Christian Larsen.
p. ; cm.
Includes bibliographical references and index.
ISBN-13: 978-0-8493-7265-0 (hardcover : alk. paper)
ISBN-10: 0-8493-7265-8 (hardcover : alk. paper)
1. Toxicology. 2. Toxicity testing. 3. Health risk assessment. 4. Environmental risk assessment. I.
Nielsen, Elsa. II. Larsen, John Christian. III. Title.
[DNLM: 1. Hazardous Substances--toxicity. 2. Environmental Exposure--prevention & control. 3.
Risk Assessment--methods. 4. Risk Assessment--standards. WA 670 O845p 2008]
RA1190.O88 2008
615.9--dc22 2007034227
Visit the Informa Web site at
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(cid:1)2007byTaylor&FrancisGroup,LLC.
Contents
Preface
Acknowledgment
Authors
Abbreviations and Acronyms
Chapter 1 Introduction
Reference
Chapter 2 International and Federal Bodies Involved inRisk Assessmentof Chemical
Substances
2.1 WorldHealthOrganization
2.1.1 International Programme onChemical Safety
2.1.2 Food and Agriculture Organization ofthe United Nations
2.1.3 Joint FAO=WHO Expert Committee on Food Additives
2.1.4 Joint FAO=WHO Meeting on Pesticide Residues
2.1.5 Inter-Organization Programmeforthe Sound Management of Chemicals
2.1.6 International Agency forResearch on Cancer
2.1.7 IPCS:Chemicals Assessment
2.1.7.1 Environmental Health Criteria
2.1.7.2 Concise International ChemicalAssessmentDocument
2.1.7.3 Health and Safety Guide
2.1.7.4 InternationalChemicalSafety Card
2.1.7.5 Pesticide Safety Data Sheet
2.1.7.6 The WHO RecommendedClassificationof Pesticides by Hazard
2.2 Organisation for EconomicCo-operation and Development
2.2.1 The OECDChemicals Program
2.2.2 MutualAcceptance of Data
2.2.3 The OECDExisting Chemicals Program
2.2.4 The OECDNew Chemicals Program
2.2.5 The OECDPesticides andBiocides Program
2.2.6 OECD TestGuidelines
2.3 United States of America
2.3.1 United States EnvironmentalProtection Agency
2.3.1.1 Office of PollutionPrevention and Toxics
2.3.1.2 ToxicSubstances Control Act
2.3.1.3 Existing Chemicals
2.3.1.4 High Production Volume ChallengeProgram
2.3.1.5 NewChemicals
2.3.1.6 Integrated Risk Information System
2.3.1.7 Harmonization ofUS-EPARisk Assessment
2.3.1.8 US-EPA Risk AssessmentGuidelines
2.3.1.9 US-EPA Test Guidelines
2.3.2 Agencyfor Toxic Substancesand Disease Registry
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2.3.3 National ToxicologyProgram
2.3.4 UnitedStatesFood and DrugAdministration
2.4 The European Union
2.4.1 EU Chemicals Program
2.4.1.1 Actors Involved inChemical Legislation
2.4.1.2 Current EU Regulatory Framework forChemicals
2.4.1.3 New EURegulatory Framework forChemicals
2.4.1.4 Existing Substances
2.4.1.5 New Substances
2.4.1.6 International Uniform ChemicaL InformationDatabase
2.4.1.7 Biocidesand Plant Protection Products
2.4.1.8 Classification and Labeling of ChemicalSubstances
2.4.1.9 EUTestGuidelines
2.4.2 Harmonizationof Risk Assessment inDG SANCO
2.4.2.1 Scientific Committee on Health and EnvironmentalRisks
2.4.2.2 Scientific Committee on ConsumerProducts
2.4.2.3 Scientific Committee on Emerging and Newly Identified
Health Risks
2.4.2.4 EFSA Committees
2.5 Globally HarmonizedSystem ofClassificationand Labeling ofChemicals
2.6 Precautionary Principle
References
Chapter 3 Data forHazard Assessment
3.1 Introduction
3.2 HumanData
3.2.1 CaseReports
3.2.2 Clinicaland Physiological Investigations
3.2.3 Studies inVolunteers
3.2.4 Occupational Experience
3.2.5 Epidemiological Studies
3.2.6 Meta-Analysis
3.3 Datafrom Studies inExperimentalAnimals
3.3.1 Animal ToxicityStudies
3.3.2 TestGuidelinesfor Animal Toxicity Studies
3.3.3 Good LaboratoryPractice
3.3.4 OECDTest Guidelines
3.3.5 US-EPA TestGuidelines
3.3.6 EU Test Guidelines
3.3.7 Nonguideline Animal Toxicity Studies
3.4 In Vitro Methods
3.4.1 UnitedStatesInteragency Coordinating Committee onthe Validation
of Alternative Methods
3.4.2 UnitedStatesNational ToxicologyProgram Interagency Center
for theEvaluation ofAlternative Toxicological Methods
3.4.3 ICCVAM Review Process
3.4.4 In Vitro TestsUndergoing Validationby ICCVAM
3.4.5 EuropeanCenter for theValidationof Alternative Methods
3.4.6 In Vitro TestsUndergoing Validationby ECVAM
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3.4.7 In Vitro Test Guideline Methods
3.4.7.1 OECD In Vitro Test GuidelineMethods
3.4.7.2 EUIn Vitro Test GuidelineMethods
3.5 NontestingData
3.5.1 Physico-Chemical Properties
3.5.2 Use of Structure–ActivityRelationships
3.5.3 Quantitative Structure–Activity Relationship
3.6 Data Collection
3.6.1 Criteria Documents andMonographs from International Bodies
3.6.1.1 Environmental Health Criteria
3.6.1.2 Monographsfrom the International Agency forResearch on Cancer
3.6.1.3 Monographsfrom the Joint FAO=WHOExpert Committee
onFoodAdditives and from theJoint FAO=WHO Meeting
onPesticide Residues
3.6.1.4 WHOGuidelines forDrinking-WaterQuality
3.6.1.5 WHOAirQuality Guidelines for Europe
3.6.1.6 Toxicological Profiles from Agency forToxicSubstances
andDisease Registry
3.6.1.7 EURisk AssessmentReports on Existing Chemicals
3.6.1.8 Publicationsfrom theInternational Life Sciences Institute
3.6.1.9 Publicationsfrom theEuropean Centre forEcotoxicology
andToxicology of Chemicals
3.6.1.10 BUA Reports from theGerman ChemicalSociety
3.6.1.11 AmericanConference on Governmental IndustrialHygienists
3.6.1.12 Criteria Documentsfrom the Nordic Expert Group
3.6.2 Databases
3.6.2.1 IPCS INCHEM
3.6.2.2 International Uniform ChemicaL InformationDatabase
3.6.2.3 US-EPA Integrated Risk InformationSystem
3.6.2.4 U.S.National Library of Medicine TOXNET
References
Chapter 4 Hazard Assessment
4.1 Introduction
4.2 General Aspects
4.2.1 SystemicEffects versus Local Effects
4.2.2 AdverseEffects versus Non-Adverse Effects
4.2.3 Dose–Response Relationships
4.2.4 No-Observed-Adverse-Effect Level, Lowest-Observed-Adverse-Effect Level
4.2.5 The Benchmark DoseConcept
4.2.6 Toxicological Modes ofAction
4.2.7 Critical Effects
4.3 Toxicokinetics
4.3.1 Definitions
4.3.2 Objectivesfor Assessingthe Toxicokinetics ofa Substance
4.3.3 Test Guidelines
4.3.3.1 InVivo Tests
4.3.3.2 InVitro Tests
4.3.4 Guidance Documents
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4.3.5 Use of Toxicokinetics inHazard Assessment
4.3.5.1 Human and Animal Data
4.3.5.2 InVitro Data
4.3.5.3 Other Data
4.3.6 PBPK=PBTK Models
4.4 AcuteToxicity
4.4.1 Definitions
4.4.2 Objectives forAssessing theAcute Toxicity of a Substance.
4.4.3 TestGuidelines
4.4.3.1 InVivo Tests
4.4.3.2 InVitro Tests
4.4.4 GuidanceDocuments
4.4.4.1 WHO
4.4.4.2 OECD
4.4.4.3 US-EPA
4.4.4.4 EU
4.4.5 Use of Acute Toxicity Datain Hazard Assessment
4.4.5.1 Human Data
4.4.5.2 Animal Data
4.4.5.3 InVitro Data
4.4.5.4 Other Data
4.5 Irritation andCorrosion
4.5.1 Definitions
4.5.1.1 OECD
4.5.1.2 US-EPA
4.5.1.3 EU
4.5.2 Objectives forAssessing Irritation and Corrosion of aSubstance
4.5.3 TestGuidelines
4.5.3.1 InVivo Tests
4.5.3.2 InVitro Tests
4.5.4 GuidanceDocuments
4.5.5 Use of Information onIrritation andCorrosion inHazardAssessment
4.5.5.1 Human Data
4.5.5.2 Animal Data
4.5.5.3 InVitro Data
4.5.5.4 Other Data
4.6 Sensitization
4.6.1 Definitions
4.6.2 Objectives forAssessing Sensitization of aSubstance
4.6.3 TestGuidelines
4.6.3.1 InVivo TestsforSkin Sensitization
4.6.3.2 InVivo TestsforRespiratory or Oral Sensitization
4.6.3.3 InVitro Tests
4.6.4 GuidanceDocuments
4.6.4.1 WHO
4.6.4.2 OECD
4.6.4.3 US-EPA
4.6.4.4 EU
4.6.5 Use of Information onSensitization inHazardAssessment
4.6.5.1 Human Data
4.6.5.2 Animal Data
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4.6.5.3 InVitro Data
4.6.5.4 Other Data
4.7 Repeated DoseToxicity
4.7.1 Definitions
4.7.1.1 OECD
4.7.1.2 US-EPA
4.7.1.3 EU
4.7.2 Objectivesfor Assessingthe Repeated Dose Toxicityof a Substance
4.7.3 Test Guidelines
4.7.3.1 InVivo Tests
4.7.3.2 InVitro Tests
4.7.4 Guidance Documents
4.7.4.1 WHO
4.7.4.2 OECD
4.7.4.3 US-EPA
4.7.4.4 EU
4.7.5 Use of Informationon Repeated DoseToxicity inHazardAssessment
4.7.5.1 Human Data
4.7.5.2 Animal Data
4.7.5.3 InVitro Data
4.7.5.4 Other Data
4.7.6 Immunotoxicity
4.7.6.1 Definitions
4.7.6.2 TestGuidelines
4.7.6.3 Guidance Documents
4.7.6.4 Use ofInformation from Repeated Dose Toxicity Studies
intheHazard Assessmentof Immunotoxicity
4.7.7 Neurotoxicity
4.7.7.1 Definitions
4.7.7.2 TestGuidelines
4.7.7.3 Guidance Documents
4.7.7.4 Use ofInformation from Repeated Dose Toxicity Studies
intheHazard Assessmentof Neurotoxicity
4.7.8 NasalToxicity
4.8 Mutagenicity
4.8.1 Definitions
4.8.1.1 OECD
4.8.1.2 US-EPA
4.8.1.3 EU
4.8.2 Objectivesfor Assessingthe Mutagenicity of a Substance
4.8.3 Test Guidelines
4.8.3.1 InVivo Tests
4.8.3.2 InVitro Tests
4.8.4 Guidance Documents
4.8.4.1 WHO
4.8.4.2 OECD
4.8.4.3 US-EPA
4.8.4.4 EU
4.8.5 Use of Informationon Mutagenicity inHazardAssessment
4.8.5.1 Human Data
4.8.5.2 Animal Data
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4.8.5.3 In Vitro Data
4.8.5.4 Other Data
4.9 Carcinogenicity
4.9.1 Definitions
4.9.2 Objectives forAssessing theCarcinogenicityof aSubstance
4.9.3 TestGuidelines
4.9.3.1 In VivoTests
4.9.3.2 In Vitro Tests
4.9.4 GuidanceDocuments
4.9.4.1 WHO
4.9.4.2 OECD
4.9.4.3 US-EPA
4.9.4.4 EU
4.9.4.5 IARC
4.9.5 Use ofInformation onCarcinogenicity in Hazard Assessment
4.9.5.1 Human Data
4.9.5.2 Animal Data
4.9.5.3 In Vitro Data
4.9.5.4 Other Data
4.9.6 Effects inExperimentalAnimalsof Disputed Relevance forHumans
4.9.6.1 Leukemia (Mononuclear Cell Type)in theFischer Rat
4.9.6.2 Kidney Tumors inMale Rats
4.9.6.3 Liver Tumors in Mice and Rats
4.9.6.4 Leydig Cell Tumors inRats
4.9.6.5 Thyroid Tumors in theRat
4.9.6.6 Urinary Bladder Tumorsinthe Rat and Mouse
4.9.6.7 Forestomach Tumors inMice andRats
4.9.6.8 Other Types ofTumors
4.9.7 Categorization for Carcinogenicity
4.9.7.1 IARC
4.9.7.2 US-EPA
4.9.7.3 EU
4.9.8 The Carcinogenic Potency Database
4.10 Reproductive Toxicity
4.10.1 Definitions
4.10.2 Objectives forAssessing theReproductive Toxicityof aSubstance
4.10.3 TestGuidelines
4.10.3.1 In VivoTests
4.10.3.2 In Vitro Tests
4.10.4 GuidanceDocuments
4.10.4.1 WHO
4.10.4.2 OECD
4.10.4.3 US-EPA
4.10.4.4 EU
4.10.5 Use ofInformation onReproductiveToxicityin Hazard Identification
4.10.5.1 Human Data
4.10.5.2 Animal Data
4.10.5.3 In Vitro Data
4.10.5.4 Other Data
4.11 Endocrine Disrupters
4.11.1 Definitions
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