Chemical Risk Assessment

Dr Peter Fisk, Managing Director, is a chemist, with 15 years experience in industrial research and development, and over 13 years as a consultant working for regulatory authorities, industry and publishers. He has a background in laboratory science, and methods of chemical property prediction, as well as wide knowledge of chemical regulation.

• List of Figures xv List of Tables xviiList of Contributors xixIntroduction xxi1. Introduction: Policy and Scientific Context of Chemicals Risk and Risk Management 11.1 Overview of the Risk Assessment of Chemical Substances 41.2 Chemical Hazard and Risk Programmes 51.2.1 REACH Overview 51.2.2 Registration 61.2.3 Evaluation 81.2.4 Authorisation and Restriction 111.2.5 Hazard and Risk Communication 141.2.6 Hazards 161.2.7 Overview of Types of Exposure 171.2.8 Overview of Risk Characterisation 191.2.9 Successful Interaction with REACH: Registration, Evaluation and Authorisation 211.2.10 Regulation and Assessment of Hazardous Chemicals Outside of the European Union 242. Roles and Responsibilities in REACH 392.1 The Structure and Responsibilities of the Authorities 392.1.1 Role of the ECHA 392.1.2 The Role of the Member State Committee (MSC) 402.1.3 The Role of the Member State Competent Authorities (MSCA) 402.2 Forum Enforcement Project – REACH-EN-FORCE-1 412.3 Future Aims of the HSE (an Example of a ECHA-Related Authority Acting in the UK) 412.4 What Does REACH Require as Regards Enforcement? 412.5 What Powers Do Enforcing Authorities Have? 422.6 The Responsibilities of Industry 422.6.1 Responsibilities of the Manufacturer 422.6.2 Responsibilities of the Importer 432.6.3 The Only Representative 432.6.4 Responsibilities of the Downstream User 432.7 Communication in the Supply Chain and with Regulators 442.7.1 Use Descriptor System 443. Control of Chemicals – Legislative and Policy Context 573.1 How EU Chemical Legislation Evolved 573.2 Air Quality Regulations 633.3 Water Framework Directive 643.4 Carcinogens at Work 653.5 Cosmetics 663.6 Biocidal and Plant Protection Products 673.7 Nationally (UK)-Implemented Legislative and Policy Frameworks 683.7.1 Workplace Exposure 683.7.2 Control of Substances Hazardous to Health Regulations (COSHH) 2002 693.7.3 Dangerous Substances and Explosive Atmospheres Regulations (DSEAR) 2002 723.8 UK Environmental Regulation 743.8.1 Overview and IPPC 743.8.2 Waste (England and Wales) Regulations 2011 SI 988 753.8.3 Water Legislation in the UK 753.8.4 Directive 2006/118/EC on the Protection of Groundwater against Pollution and Deterioration 773.8.5 Groundwater (England and Wales) Regulations 2009 (SI 2009 No. 2902) 773.8.6 Air Legislation in the UK 774. Identification of Substances for REACH – Practicalities 814.1 Substance Identification 814.1.1 Types of Substances 824.1.2 Mono-Constituent Substances 824.1.3 Multi-Constituent Substances (MCSs) 824.1.4 Substances with Unknown or Variable Composition, or of Biological Origin (UVCBs) 824.1.5 Nanomaterials 834.1.6 Articles 844.1.7 EC Number 844.2 Sameness 854.3 Essentially-Pure Substances 854.4 Approaching the Substance Data Set – Understanding the Substance 865. Physico-Chemical Properties for REACH – Purpose and Practicalities 895.1 Physico-Chemical Properties 895.2 Strategy in Physico-Chemical Testing Plans 915.2.1 Tier 1 Tests 915.2.2 Tier 2 Tests 925.2.3 Tier 3 Tests 935.3 Difficult-to-Measure Substances 945.3.1 Multiconstituent or UVCB Substances (Mixtures) 945.3.2 Poorly Soluble Substances 945.3.3 Volatile Substances 945.3.4 Unstable Substances Either by Hydrolysis, Photolysis or Oxidation 945.3.5 Ionisable Substances 955.3.6 Surface Active Substances 955.4 Hazardous Physico-Chemical Data 955.5 Relationship between Physico-Chemical Tests 955.6 Application of Physico-Chemical Test Data 965.7 Can Physico-Chemical Tests Be Omitted? 965.8 (Q)SAR and Physico-Chemical Tests 975.9 (Quantitative) Structure-Activity Relationships ((Q)SAR) 976. Assessing and Documenting the Intrinsic Properties of Substances in REACH 1036.1 Introduction to REACH Data Requirements 1036.1.1 Strictly Controlled Conditions 1046.2 Hazards 1086.3 PBT 1086.4 Equivalent Concern 1096.4.1 Adversity 1096.4.2 Mode of Action 1106.5 Test Proposal Rule 1106.6 Availability of Existing Data and Rights of Access 1116.7 Data Reliability 1116.8 Data Gaps – Options for Surrogate Data for Description of Hazard and Risk – Including Read-Across 1116.9 Read-Across 1137. Assessing Environmental Properties Data 1157.1 Environmental Properties Data 1157.1.1 PNECs 1157.1.2 Classification and Labelling (C&L) 1167.1.3 PBT 1167.2 Environmental Fate 1167.2.1 Degradation 1177.2.2 Bioaccumulation 1207.2.3 Adsorption 1217.3 Ecotoxicology 1237.3.1 Introduction 1237.3.2 Hazard Assessment and Risk Characterisation 1237.3.3 Data Review 1277.3.4 Testing of Difficult Substances 1277.3.5 (Q)SARs, Data Waiving and EPM 1287.3.6 Further Testing 1297.3.7 Toxicity to Sewage Treatment Plant Microorganisms 1297.4 Turning Intrinsic Properties into ‘No-Effect’ Concentrations 1307.4.1 Selecting a Suitable Starting Point for a PNEC Calculation 1317.4.2 Calculating a PNEC Using Assessment Factors 1317.4.3 Calculating a PNEC Using Sensitivity Distribution 1337.4.4 Calculating a PNEC Using Equilibrium Partitioning 1337.4.5 Intermittent versus Continuous Releases 1348. Environmental Exposure 1378.1 Substance Identity and Approach to Exposure Assessment 1378.2 Characterising Releases 1388.2.1 Evaluating Use Pattern 1388.3 Evaluating Releases 1398.3.1 Reality Checking – Top Down and Bottom Up 1418.4 Documentation for the Registration 1428.4.1 Uncertainty 1428.5 Local Scale Releases 1428.5.1 Site Size 1428.5.2 Site Inspections 1438.6 Exposure Assessment – Models or Measurements? 1438.6.1 Using Measurements 1438.6.2 Using Models 1458.6.3 Models or Measurements – Recommended Approach 1458.6.4 Tools 1458.7 Water 1468.7.1 Release via Waste-Water 1468.7.2 River Environment 1488.7.3 Marine Environment 1498.7.4 Sediments 1498.8 Soil 1498.8.1 WWTP Sludge and Agricultural Soil 1498.8.2 Deposition 1498.8.3 Biodegradation in Soil 1508.8.4 Crops and Grassland 1508.8.5 Industrial Soil 1508.9 Air 1508.9.1 Air in the Standard PEC Models 1508.9.2 Ozone Depletion and Other Specific Effects 1508.9.3 Long Range Pollutants 1518.10 The Food Chain 1518.10.1 Biomagnification 1518.10.2 Secondary Poisoning 1519. Assessing the Hazards to Human Health from Chemicals 1539.1 Mammalian Toxicology 1539.2 Exposure Routes and Local/Systemic Effect Types 1539.3 Acute and Chronic Effects 1549.4 Influences on Toxicity 1549.5 How Chemicals Cause Harm 1559.5.1 Asphyxiants 1559.5.2 Narcotics 1559.5.3 Irritants and Corrosives 1559.5.4 Sensitisation (Allergic Reactions) 1569.5.5 Carcinogenicity 1569.5.6 Genotoxic Effects 1579.5.7 Reproductive and Developmental Effects 1579.5.8 Target Organ Effects 1579.6 Toxicokinetics 1579.7 Toxicological Testing 1589.7.1 Data Gaps 1599.7.2 Data Waiving 1599.7.3 Acute Toxicity Studies 1599.7.4 Short-Term, Repeated Dose Studies 1609.7.5 Long-Term (Chronic) Studies 1609.7.6 Other Systemic Effects 1619.7.7 Local Effects 1629.8 Genetic Toxicology 1629.8.1 Introduction 1629.8.2 Hazard Assessment 1639.8.3 Risk Assessment 1669.9 Turning Intrinsic Properties into ‘No-Effect’ Levels 1669.9.1 Special Cases 16910. Human Exposure to Chemicals 17110.1 Exposure 17110.2 Exposure to Chemicals in the Workplace 17310.2.1 First Tier Models 17310.2.2 Higher Tier Models 17410.2.3 Risk Management Measures 17410.2.4 Exposure in the Professional Use Setting 17510.2.5 Models 17610.2.6 Measurements 17810.3 Risk Management Measures 17910.4 Consumer Exposure 17910.4.1 General Considerations for Exposure Estimation for Consumers 18010.4.2 Tier 1 Models 18010.4.3 Refinement of Initial Exposure Estimates, Higher Tier Models and Measurements 18110.4.4 Risk Management Measures – Consumers 18110.5 Indirect Exposure (Humans via the Environment) 18210.6 Risk due to Physico-Chemical Hazard 18211. Managing Hazard and Risk 18511.1 Characterisation, Assessment and Management of Risk 18511.2 What Is ‘Risk’ under REACH? 18611.3 What Are Risk Reduction and Risk Management? 18711.3.1 Risk 18711.3.2 How Can Risks Be Controlled Adequately? 18911.4 Where Safe Levels Cannot Be Established – CMRs and PBTs (and vPvBs) 19011.5 Responsibilities in the Supply Chain – Introduction 19011.6 Regulatory Requirements 19111.7 Guidance 19311.8 The Extended Safety Data Sheet 19311.8.1 Current issues surrounding the use of eSDS by DUs 19411.9 When Communication Is Difficult 19411.10 Exposure Measurements in the Workplace – Occupational Hygiene 19511.11 Control of Environmental Releases – Abatement Techniques 19611.11.1 Engineering Controls 19611.11.2 Enclosure and Containment 19711.11.3 Bunding 19711.11.4 Dedicated Equipment 19711.11.5 Investment and Scale of Use – Economic Viability 19711.11.6 Waste Stream Treatments 19711.11.7 WWTP Treatments 19811.11.8 Custom and Practise 19811.11.9 Handling Standards 19811.11.10 Clean-Down Practises 19811.12 Effectiveness of Risk Reduction – Risk Management Options 20011.13 Types of Risk Management – in the Workplace 20111.13.1 Options Overview 20211.13.2 Understanding Assumptions and Critical Issues 20211.13.3 Risk Management Measures 20211.14 Types of Risk Management – for the Environment 20311.14.1 Unacceptable Risk 20311.14.2 Options Overview 20311.14.3 When a Data Set Is Not Complete 20411.14.4 When a Data Set Is as Complete as It Can Be 20411.14.5 Understanding Assumptions and Critical Issues 20411.14.6 Strategies to Reduce the Amount of Substance Released to the Environment 20411.15 Consumer Protection 20512. Avoiding the Use of Hazardous Substances: Substitution and Alternatives 20712.1 Properties That Contribute to Hazard and Risk for Human Health and the Environment 20912.2 Assessment of Alternatives – Replacement of Use 21012.3 What Is an Alternative? 21112.4 Analysis of Alternatives 21112.5 Substitution – Replacement with Substances of Reduced Hazard 21112.5.1 Examples of Voluntary Substitution 21212.5.2 Regulation-Led Substitution – Case Studies 21312.6 Sustainability and Green Chemistry 21812.7 What Is Green Chemistry in Practice? Principles and Concepts 21912.7.1 Why Is Green Chemistry Important? 22012.7.2 Research in Green Chemistry 22012.7.3 Substance Design 22012.7.4 Process Design 22213. Hazards, Risks and Impacts – The Development and Application of Frameworks for the Assessment of Risk 22513.1 Policy Context – Risk, Hazard and the Precautionary Principle 22613.1.1 Assessment Frameworks – Hazard and Risk and Impacts 23013.1.2 Precaution – Where No Safe Level Can Be Established 23213.1.3 Application of Assessment Frameworks to Human Health and Environmental Protection 23413.2 From Hazards to Risks to Impacts – Understanding the Implications of Exposure to Dangerous Chemicals 23513.2.1 Introduction: The Need for a Culture of Safety 23613.2.2 Responsible Care® 23813.2.3 Standards and Management Tools 23913.2.4 Risk Control and Management 24113.2.5 Risk Control and Management in REACH 24113.3 Risk Management Options – REACH Processes for Control of Hazardous and Risky Substances 24413.3.1 Restrictions and Authorisations in REACH 24413.3.2 Restrictions 24613.3.3 Authorisations 24714. Socio-Economic Analysis in REACH 25114.1 Background – the Need for and Development of Socio-Economic Analysis in the Regulation of Chemicals 25314.2 What Is SEA and Why Is It Needed and Applied in REACH? 25414.2.1 What Is SEA within REACH? 25414.3 Role, Purpose and Performing an SEA in REACH 25514.3.1 Role and Purpose of an SEA in REACH 25514.3.2 Doing an SEA in REACH 25614.4 The Difficulties of Moving from Risks to Impacts 25614.5 Regulatory Processes – Who Are the Decision Makers and What Are Their Roles? 26514.6 The Wider Benefits of Performing an SEA 26514.7 Developments and the Future 26715. REACH: How It Is Working and May Develop 26915.1 Introduction 26915.2 Experiences and Observations 26915.2.1 Observations 27015.3 Basics of Successful Submission 27115.4 Testing, Prediction and Read-Across 27115.5 The Community Rolling Action Plan 27215.6 EU and National Responsibilities 27215.7 Risk-Based Regulation and the Precautionary Approach 27215.8 Higher Tiers of Assessment 27315.9 REACH Developments 27415.9.1 Methods of Operation and Constant Change 27415.9.2 Improved Efficiency of Operation 27515.9.3 Increased Scope 27515.9.4 Policy Development on the Control of Chemicals – EU and Global Perspectives 27615.10 Rationalising Overlap with Other Legislation 27615.11 Scientific Developments and Challenges 27815.12 Impact on Industry 27815.12.1 Manufacturers and Importers 27815.12.2 Downstream Users and Consumers 27815.12.3 Innovation 27915.13 ECHA Evaluation Report 2012 27916. Resources, Official Guidance, Further Reading and Centres of Expertise 28316.1 Introduction to Resources and Organisations 28316.1.1 Official Journal 28316.1.2 ECHA and REACH-IT 28416.1.3 CEFIC and Sector Groups 28516.1.4 IUCLID Guidance 28516.1.5 ECETOC 28616.1.6 OECD 28616.1.7 EU JRC 28616.2 Facts and Statistics 286Appendix A Substance Classification and Labelling under REACH 317A.1 Important Differences 319A.1.1 Physico-Chemical Hazards 320A.1.2 Health Hazards 320A.1.3 Environmental Hazards 321A.1.4 Supplementary Labelling Requirements under the CLP Regulations 321A.2 CLP Symbols 322A.2.1 Comparison of DSP/DPD with CLP 2008 325A.3 Specific Target Organ Systemic Toxicity – Single Exposure 334A.3.1 Carcinogenic Substances 335A.3.2 Mutagenic Substances 337A.3.3 Effect during Lactation 337A.3.4 Aquatic Environment 338A.3.5 Ozone 338A.4 Harmonised Classification and Labelling 339Appendix B Further Discussion of Substance Identification and Sameness 341B.1 Substance Identifiers 341B.1.1 EC Name 341B.1.2 CAS Registry Number (CAS# or CAS No.) 341B.1.3 SMILES 341B.1.4 InChI 342B.2 Substance Analysis 342B.2.1 Sameness 343B.2.2 Impurities 344B.2.3 Departures from the Agreed Norm 344B.3 Straightforward Organic Substances 345B.3.1 Identity 345B.3.2 Purity and Characterisation 346B.4 Complex Organic Substances 347B.5 Inorganic Substances 348B.5.1 Structure 349B.5.2 Elemental Quantification 349B.6 Analysis of UVCBs 349Appendix C Tools for REACH Compliance: IUCLID, Chesar and In-House Databases 351C.1 International Uniform Chemical Information Database (IUCLID) 351C.2 IUCLID and PPORDs 354C.3 Submission of PPORD to ECHA 354C.3.1 IUCLID Submission 354C.3.2 Notification by REACH-IT 355C.4 Chesar 356C.4.1 Introduction 356C.4.2 Chesar Functionalities or Organisation of the Tool 356C.4.3 Assessment workflow of Chesar 358C.5 Advice on Storing of Data Outside of the IUCLID 358C.5.1 Structure 359C.5.2 Identifiers 360C.5.3 Mechanistic Issues 360C.5.4 Identification and Expression of Substance Identity 361C.5.5 Result Values 361C.5.6 SMILES and Textual Representations of Structure 361C.5.7 Modifications to the Data Set 361C.5.8 Composited Fields and Repeated Processes 361C.5.9 Duplicates 362C.5.10 Validation 362C.5.11 Checking 363C.5.12 Study Reports and Cataloguing 363C.5.13 Snapshots and Backups 364Appendix D Glossary 365Index 383