The Biocides Business: Regulation, Safety and Applications

The Biocides Business Edited by D. J. Knight and M. Cooke

The Biocides Business: Regulation, Safety and Applications. Edited by Derek J. Knight and Mel Cooke Copyright ª 2002 WILEY-VCH Verlag GmbH Co. KGaA, Weinheim ISBN: 3-527-30366-9

The Biocides Business Regulation, Safety and Applications

Edited by Derek J. Knight and Mel Cooke

The Editors of this Volume

Dr. Derek J. Knight SafePharm Laboratories LTD Shardlow Business Park London Road Derbyshire Derby DE72 2GD U.K. Dr. Mel Cooke Alchemy Compliance LTD 2 Harvey Close Ruddington Nottinghamshire NG 11 6 N3 U.K.

This book was carefully produced. Nevertheless, editors, authors and publisher do not warrant the information contained therein to be free of errors. Readers are advised to keep in mind that statements, data, illustrations, procedural details or other items may inadvertently be inaccurate. Library of Congress Card No.: Applied for. British Library Cataloguing-in-Publication Data: A catalogue record for this book is available from the British Library. Die Deutsche Bibliothek – CIP Cataloguing-in-Publication Data: A catalogue record for this publication is available from Die Deutsche Bibliothek. ª Wiley-VCH Verlag GmbH, Weinheim 2002 All rights reserved (including those of translation in other languages). No part of this book may be reproduced in any form – by photoprinting, microfilm, or any other means – nor transmitted or translated into machine language without written permission from the publishers. In this publication, even without specific indication, use of registered names, trademarks, etc., and reference to patents or utility models does not imply that such names or any such information are exempt from the relevant protective laws and regulations and, therefore, free for general use, nor does mention of suppliers or of particular commercial products constitute endorsement or recommendation for use. Printed on acid-free paper. Printed in the Federal Republic of Germany.

Cover Illustration The image used (herein) was obtained from IMSI’s Master Photos Collection, 1895 Francisco Blvd. East, San Rafael, CA 94901-5506, USA

Composition Mitterweger & Partner Kommunikationsgesellschaft mbH, Plankstadt Printing Strauss Offsetdruck GmbH, Mo¨rlenbach Bookbinding Großbuchbinderei J. Scha¨ffer GmbH & Co. KG, Gru¨nstadt ISBN 3-527-30366-9

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Contents Preface XV Editors and Authors

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1

The Political, Social, and Economic Framework

1.1 1.2 1.3 1.4 1.5

Aynsley Kellow Introduction 1 Historical, Cultural, and Economic Influences 3 National and International Regulation 6 International Organizations and Chemicals 16 Conclusion 23

2

2.1 2.1.1 2.2 2.3 2.4 2.4.1 2.4.2 2.4.3 2.5 2.6 2.6.1 2.6.2 2.7 2.8

The Biocides Market

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27

Patricia Martin Introduction 27 EC Market: End-use Applications 29 EC Market: Consumption of Biocidal Products by End Use Global Market: Consumption of Biocidal Products by Geographical Region 31 Supply Chain for Biocidal Products 32 Active-ingredient Manufacturers 32 Formulators/Service Companies 33 Distributors 34 Key Drivers for Market Development 34 History and Current Trends 36 European Community 36 United States of America 39 Impact of New Legislation 40 Conclusions 43

3

Regulatory Control of Biocides in Europe

3.1 3.2

Derek J. Knight and Mel Cooke Introduction 45 The EU Biocidal Products Directive

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The Biocides Business: Regulation, Safety and Applications. Edited by Derek J. Knight and Mel Cooke Copyright ª 2002 WILEY-VCH Verlag GmbH Co. KGaA, Weinheim ISBN: 3-527-30366-9

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3.2.1 3.2.2 3.2.3 3.2.4 3.2.5 3.3 3.4 3.4.1 3.4.2 3.4.3 3.5 3.5.1 3.5.2 3.5.3 3.5.4 3.5.5 3.5.5.1 3.5.5.2 3.5.5.3 3.6

History and Development 46 Scope of the Biocidal Products Directive 47 Approval Systems 49 Data Requirements 50 Risk Assessment and the Common Principles for the Evaluation of Dossiers 53 The Review Program for Existing Biocide Active Substances and Biocidal Products 56 European Union Chemical Control Measures 59 Scope of European Union Legislation 59 European Union Chemicals Legislation 60 Other European Controls Affecting Biocides 62 National European Biocide Authorization Schemes 63 Introduction 63 The Netherlands 64 Belgium 67 The United Kingdom 67 Scandinavia 70 Denmark 70 Finland 70 Sweden 70 Conclusion 71

4

Regulation of Biocides in the United States

4.1 4.1.1 4.1.2 4.1.3 4.2 4.2.1 4.2.2 4.3 4.3.1 4.3.1.1 4.3.1.2 4.3.2 4.3.2.1 4.3.2.2 4.3.2.3 4.3.2.4 4.3.3 4.3.4 4.4 4.4.1

Sue Crescenzi Introduction to Pesticide Regulation in the United States 75 Legal Authority 75 Federal Agencies with Responsibility for the Regulation of Biocides Information Resources 77 Regulation of Biocides in the United States 77 Regulation of Biocides Generally 77 Regulation of Antimicrobial Biocides 77 Registration of a New Active Ingredient 80 Active Ingredient Data Requirements 80 Antimicrobial Active Ingredient Data Requirements 81 Follow-on Registration of an Active Ingredient 82 Registration of End-use Product Formulations 82 Formulated Products Entitled to Formulator’s Exemption 82 Formulated Products Not Entitled to Formulator’s Exemption 82 Product-specific Data 83 Applications for Formulated Product Me-too Registrations 83 Amendments to Change Existing Registrations 83 Changes Not Requiring Amendments 84 Regulation of Biocides Used in, on, or in Contact with Food 84 EPA Regulation of Pesticide Chemicals in or on Food 84

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4.4.2 4.4.3 4.4.4 4.4.5 4.5 4.5.1 4.5.2 4.5.3 4.6 4.6.1 4.6.2 4.6.3 4.6.4 4.6.5 4.7 4.8 4.8.1 4.8.2 4.8.3 4.9 4.10 4.11 4.12 5

5.1 5.2 5.2.1 5.2.1.1 5.2.1.2 5.2.1.3 5.2.1.4 5.2.2 5.2.3 5.2.4 5.2.5 5.3 5.3.1 5.3.1.1 5.3.2

FDA Regulation of Food Additives 85 FDA Regulation of Food-contact Substances 85 Overlapping EPA and FDA Jurisdiction for Antimicrobial Food-Contact Uses 85 EPA Identification of Biocides as Food Contact 87 Pesticide Re-registration 88 Expedited Re-registration 88 Tolerance Reassessment 88 Fifteen Year Registration Review 89 Data Protection and Data Compensation Procedures 89 Procedures for Compliance with Data Protection and Compensation Requirements 90 Compensation Offers and Arbitration 91 EPA’s Role in Data Compensation 92 Data Call-ins and Offers to Jointly Develop Data 92 Data Protection and Compensability under FFDCA for Active and Inert Ingredients 93 EPA Regulation of Pesticide Inert Ingredients 93 Registrants’ Continuing Obligations 94 Data Call-ins 94 Reporting Adverse Effects Information 95 Other Reporting and Recordkeeping Requirements 96 Pesticide Import and Export Requirements 96 Cancellation and Suspension 97 EPA Enforcement Authority 98 Pesticide Licensing in Individual States 98 Regulatory Control of Biocides in Other Countries

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Sara Kirkham and Mel Cooke Introduction 103 Japan 104 Chemical Substances Control Law 104 The Inventory of Existing Substances 105 Exemptions from Notification 107 Standard Notification 108 Class I and II Specified and Designated Substances 110 The Ministry of Health, Labor, and Welfare Industrial Safety and Health Law 111 Hazard Communication 113 Other Chemical Legislation 113 Summary 115 Korea 115 The Toxic Chemicals Control Law and Ministry of Environment 115 Notification Requirements 116 Ministry of Labor Toxicity Examination 119

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5.4 5.4.1 5.4.2 5.5 5.6 5.6.1 5.6.2 5.6.3 5.7 5.7.1 5.7.2 5.8 5.8.1 5.8.2 5.8.3 5.9 5.10 5.11 5.12 5.13 5.14

China 120 Biocide Products for Pest Control (BPPC) 120 Disinfectants and General Biocidal Products (DGBP) 120 Philippines 122 Australia 124 NICNAS 124 Biocides Not Covered by NICNAS 126 Conclusion 128 New Zealand 128 Toxic Substances Act and the HSNO Act 128 Arrangements for Biocides Classified as Pesticides 130 Canada 131 Food and Drugs Act 133 Pest Control Products Act 134 Canadian Environmental Protection Act 134 Switzerland 135 South Africa 137 South America 138 India 138 Slovenia 138 Conclusion 139

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Human Health, Safety, and Risk Assessment

6.1 6.2 6.2.1 6.2.2 6.2.2.1 6.2.2.2 6.2.2.3 6.2.2.4 6.2.2.5 6.2.2.6 6.2.2.7 6.2.2.8 6.2.2.9 6.2.3 6.3 6.3.1 6.3.2 6.3.3 6.4 6.4.1 6.4.2

Roland Solecki What Is Risk Assessment? 141 Hazard Identification and Assessment 144 Information Gathering 144 Hazard Identification 146 Acute Toxic Effects 146 Irritation, Corrosivity, and Sensitization 147 Toxicokinetics and Metabolism 147 Repeated Dose Toxicity 148 Genotoxicity 149 Carcinogenicity 149 Reproductive Toxicity 150 Special Effects 150 Medical and Other Human Data 151 Dose-Response Assessment 152 Exposure Assessment 153 Characteristics of Human Exposure 153 Occupational Exposure 154 Consumer Exposure 156 Risk Characterization 157 Threshold Exposure Levels 157 Safety Margins 158

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6.4.3 6.5 6.5.1 6.5.2 6.6

Benchmark Concepts 159 Regulatory Decision-making 161 Decisions for Active Substances 161 Decisions for Products 162 Conclusions 164

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Environmental Safety and Risk Assessment

7.1 7.1.1 7.1.2 7.1.3 7.2 7.2.1 7.2.2 7.2.2.1 7.2.2.2 7.2.3 7.2.3.1 7.2.3.2 7.2.3.3 7.3 7.3.1 7.3.1.1 7.3.1.2 7.3.1.3 7.3.2 7.4 7.4.1 7.4.2 7.4.3 7.4.3.1 7.4.3.2 7.4.4

Robert Diderich What Is Risk Assessment? 167 Introduction 167 Definitions and Process 168 Risk Assessment and Data Requirements 169 Exposure Assessment 169 Release Estimation 171 Environmental Behavior 174 Transport within or between Compartments 174 Transformation and Degradation Processes 177 Environmental Concentrations 180 Surface Water and Sediment 180 The Atmosphere 182 Soil 182 Effects Assessment 184 Uncertainty Factors for Establishing PNECs 184 The Aquatic Ecosystem 185 The Sediment 186 The Terrestrial Ecosystem 186 The Statistical Extrapolation Method 187 Regulatory Decision-making 188 Risk Characterization 188 Risk Assessment of Biocidal Products 189 Other Criteria 191 Persistence, Bioaccumulation, and Toxicity 191 Comparative Assessment 192 Conclusion 192

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8.1 8.2 8.2.1 8.2.2 8.2.3 8.2.4 8.3

Wood Preservatives

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David Aston Introduction 197 Biological Degradation 197 Microbial Degradation of Timber 198 Insects and the Degradation of Timber 199 Termites and the Degradation of Timber 199 Degradation of Timber in the Marine, Brackish, and Freshwater Environments 199 Wood Preservatives-Some Characteristics 200

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8.3.1 8.3.2 8.3.3 8.4 8.5 8.5.1 8.5.2 8.5.3 8.5.4 8.5.5 8.5.6 8.5.7 8.5.8 8.6 8.7 8.8 8.9 8.9.1 8.9.1.1 8.9.1.2 8.9.2 8.10 8.10.1 8.10.2 8.10.3 8.10.4 8.10.5 8.10.6 8.11 8.11.1 8.11.2 8.11.3 8.11.4 8.12 8.13 8.14 8.14.1 8.14.2 8.15 8.16

Categorization by Function 200 Regulation of Wood Preservatives 200 Desirable Characteristics of Wood Preservatives 201 Wood Preservation at Various Stages of the Timber Transformation Process 201 Deciding on the Degree of Protection Needed 201 The Proposed End Use for the Wood Product 202 The Geographical Location in Which It Is Intended To Be Used 202 The Expected Service Life or Degree of Protection Required 202 Structural or Nonstructural Applications 202 Ease and Economics of Replacement 203 Service Factors 203 Biological Hazard Classes 203 Use Classes 204 Selection and Specification of Preventive Preservative Treatments 206 Selection and Specification of Curative Preservative Treatments 207 Wood Durability and Treatability 207 Methods of Applying Wood Preservatives 208 Treatments for Seasoned Wood 208 Pressure Treatments 208 Nonpressure Methods 209 Treatments for Unseasoned Timber 210 Types of Wood Preservatives 210 Introduction 210 Industrial Wood Preservatives 211 Remedial (Professional), Curative and Preventive Wood Preservatives 213 Amateur/Do It Yourself Wood Preservatives 213 Listing of Active Substances Currently Registered for Use in Wood Preservatives in the UK 214 European Chemicals Bureau 214 Wood Preservative Systems 215 Introduction 215 Industrial 215 Remedial 216 Amateur 216 Usage Rates 216 Disposal of Wood Commodities Containing Treated Wood and Environmental Risk 217 Mechanisms of Action 218 Microbiocides 218 Insecticides 220 Efficacy Assessment of Wood Preservatives 222 Looking Ahead 223

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Slimicides

9.1 9.2 9.3 9.4 9.5 9.6 9.7 9.7.1

Ian Gould and James Hingston Microbiological Problems Associated with the Papermaking Process Bacteria 226 Fungi 227 Algae 229 Cooling Towers 229 Control of Microbial Slimes and Deposits 230 Biocides and Their Activity 230 Examples of Biocidal Active Ingredients 231

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General Purpose Preservatives

10.1 10.2 10.3 10.3.1 10.3.2 10.3.3 10.3.4 10.3.5 10.3.6 10.3.7 10.3.8 10.3.9 10.3.10 10.3.11 10.3.12 10.3.13 10.3.14 10.3.15 10.4

Richard Elsmore Introduction 233 Biocide Selection 234 Biocide/Preservative Application Areas 235 Cooling Water Biocides 235 Cosmetic and Pharmaceutical Preservation 236 Constructional Material Preservation 237 Detergent and Household Product Preservation 238 Food Preservation 239 Fuel Preservation 240 Leather Preservation 241 Metalworking Fluid Preservation 242 Oil and Gas Exploration and Recovery 242 Plastic Preservation 243 Polymer Emulsion and Adhesive Preservation 243 Surface Coating Preservation 244 Swimming Pool and Spa Treatments 245 Textile Preservation 246 Miscellaneous Uses 246 Conclusion 247

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Disinfectants and Public Health Biocides

11.1 11.1.1 11.1.2 11.2 11.2.1 11.2.2 11.2.3 11.2.3.1 11.2.3.2 11.2.3.3

Kerys Mullen Introduction 251 Microorganisms – An Overview 251 Harmful and Nonharmful Organisms Disinfection and Disinfectants 253 Disinfection Procedure 253 Designing a Disinfectant 254 Types of Disinfectant Agents 255 Acids 255 Alkalies 255 Alcohols 255

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11.2.3.4 11.2.3.5 11.2.3.6 11.2.3.7 11.2.3.8 11.2.3.9 11.2.3.10 11.2.3.11 11.3 11.3.1 11.3.1.1 11.3.1.2 11.3.1.3 11.3.2 11.3.2.1 11.3.2.2 11.3.2.3 11.3.3 11.3.3.1 11.3.3.2 11.3.3.3 11.4 11.4.1 11.4.2 11.4.3 11.4.4 11.5

Aldehydes 255 Biguanides 255 Chlorine Active Compounds 256 Iodophores 256 Phenolic Disinfectants 256 Peroxygen Disinfectants 257 Quaternary Ammonium Compounds (QACs) 257 Amphoterics 258 Detailed Examples of Disinfectants 258 Hydrogen Peroxide 258 Mode of Action 258 Factors Affecting Performance 258 Applications 259 Quaternary Ammonium Compounds 259 Mode of Action 259 Factors Affecting Performance 260 Applications 260 Sodium Hypochlorite 261 Mode of Action 261 Factors Affecting Performance 262 Applications 262 Efficacy of a Disinfectant 264 Phase I – Biocidal Activity 264 Phase II – In-use Testing 264 Phase III – Consumer Test 264 Issues with Testing 265 Concluding Remarks 265

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Rodenticides and Insecticides

12.1 12.2 12.2.1 12.2.2 12.2.3 12.3 12.3.1 12.3.2 12.3.3 12.4 12.4.1 12.4.2 12.4.3 12.5

Alan Buckle Introduction 267 The Market for Rodenticides and Insecticides as Biocides 268 Consumer Retail Market 268 Professional Pest Management (PPM) Market 269 Municipal Market 270 Rodenticides 271 Rodenticide compounds 271 Formulations 272 Methods of Application and Patterns of Use 273 Insecticides 276 Insecticide Compounds 276 Formulations 279 Methods of Application, Equipment, and Patterns of Use 282 Conclusions 284

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13

13.1. 13.2 13.3 13.4 13.4.1 13.4.2 13.4.3 13.4.4 13.5 13.5.1 13.5.2 13.5.3 13.5.3.1 13.5.3.2 13.5.3.3 13.5.3.4 13.5.4 13.5.4.1 13.5.4.2 13.5.4.3 13.5.4.4 13.6 13.6.1 13.6.2 13.6.3 13.6.4 13.7

Antifoulants and Marine Biocides

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Carol Mackie and Graham Lloyd Introduction 287 Uses for Antifoulants 288 What Type of Organisms Are Found 288 Types of Antifoulant Used on Ships 288 Soluble Matrix 289 Insoluble Matrix 289 TBT Self Polishing Copolymer 289 Ablative (Polishing Copolymer) Tin-free 289 Active Substances Used in Antifouling Paints 289 Copper and Copper Salts 290 Tributyl Tin Oxide 292 Booster Biocides 293 4,5-Dichloro-2-n-octyl-isothiazolin-3-one (DCOI) 293 Zinc and Copper Pyrithione 293 4-tert-Butylamino-2-methylthio-6-cyclopropylaminotriazine 294 N-(Dichlorofluoromethylthio)-N,N’-dimethyl-N’-phenylsulfamide 295 Nonchemical Alternatives 295 Silicone Elastomers 295 Fibers 295 Enzymes 296 Aluminum Silicate 296 Data Requirements 296 Data Requirements for an Active Substance According to the EU Biocidal Products Directive 296 Data Requirements for Antifouling Paint 298 Leach Rates 298 Exposure Assessments and Emission Scenarios 299 What for the Future 299 Annex Directive 98/8/EC of the European Parliament and of the Council of 16 February 1998 concerning the placing of biocidal products on the market 301 Index

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Preface Why this book?

Biocides are disparate groups of chemicals often referred to as nonagricultural pesticides. The European Biocidal Products Directive (BPD) has honed this definition and given an identity to biocidal products and the industry that supplies them. Manufacturers and formulators need to combine their efforts to ensure a continued supply of their products. This new coherence has provided the impetus for us to bring together eminent professionals from industry, national authorities, and specialist consultancies to discuss issues important to them. The Biocides Business will enable the reader to get a blanced, up-to-date overview of biocides, from the commercial and technical aspects to worldwide regulatory compliance.

The Biocides Market

The worldwide biocides market has an annual sales value of up to £ 3 billion, with a growth rate currently of ca. 4 % per annum. The major user is North America, followed by Europe then Japan. The consumption is fairly evenly split between the many product types. Within the EU, the demand for industrial biocides is led by Germany, followed by the UK, France, and Scandinavia, then Italy and the Benelux region. Biocide active substances are around 12 % of the global value of all pesticides at the manufacturer level (the remainder of the sales being for agricultural and garden plant protection products). The biocides industry involves a highly varied assortment of mainly small- and medium-sized businesses. The industry delivers its final products to the end user by a complex supply and manufacture chain. Many active substances are used both in plant protection products and in biocidal products, so the leading pesticide companies are involved in the manufacture of the active ingredient for both types of product. The European BPD is the toughest legislation that the biocide industry has had to face and could cost the industry over £ 340 million to comply with. The costs are too high to maintain the existing range of products, and some products, particularly those in niche markets, will no longer be viable. Many businesses will merge or disappear completely. Manufacturers, distributors, and users of biocidal products will suffer in the new regulatory climate. Dr. Patricia Martin, the principal consultant at Product The Biocides Business: Regulation, Safety and Applications. Edited by Derek J. Knight and Mel Cooke Copyright ª 2002 WILEY-VCH Verlag GmbH Co. KGaA, Weinheim ISBN: 3-527-30366-9

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Assessment and Regulatory Compliance, draws on her extensive experience to describe the biocides market in Chapter 2.

Control of Biocides

Different regulatory jurisdictions (EU, USA, and Japan) have different definitions for biocides and varying requirements for their registration (the process which a product must undergo to be allowed to be sold). For example, some countries consider disinfectants and sanitizers as biocides, but in others they are medicines or general chemicals. As a result, the regulatory pattern is complex, with many countries having split responsibilities between different regulatory bodies for different biocide product types. This can result in barriers to trade, increased costs, and differing levels of protection of humans and the environment. Until 14 May 2000 when the BPD came info force, the European market was fragmented, with different regulatory requirements in different EU Member States. Some countries, notably Germany, had few specific control measures, and biocides were covered by the general EU chemicals legislation. Others, such as the Netherlands, had their own vigorous national approval schemes, requiring extensive testing. In the EU, the Biocidal Products Directive will gradually supersede the various current national schemes and harmonize the requirements for the registration of biocidal active ingredients and their formulations. There is also a 10-year review program to evaluate existing active substances and require authorization of formulated biocidal products containing them. The current state of the BPD is discussed in detail in Chapter 3 by Dr. Derek J. Knight of Safepharm Laboratories Ltd. and Dr. Mel Cooke of Alchemy Compliance, who was formerly at Safepharm Laboratories. Although the European Biocidal Products Directive has been a driving force in recent developments in the industry, we have taken a truly global approach, and have provided detailed information on all major economic jurisdictions. In the USA, biocides are not defined in statute, but many such products are covered by the same regulations as agricultural pesticides under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA). With the passage of the Food Quality Protection Act (FQPA) in 1996, registration of antimicrobial pesticides in the USA has become more complex. The act stipulates that any pesticide, including antimicrobials, will cause no unreasonable adverse effect on man or the environment, but also that the pesticide is safe for sensitive subpopulations, such as infants and children. Furthermore, the risk assessment also takes into account the effect of active substances with a comparable mode of action. The effect of the US FQPA, as with the European ideal of comparative assessment, is that applications for competitive products may interfere with each other in the authorization procedure and decision making. Dr. Sue Crescenzi of Steptoe and Johnson provides critical analysis of the situation in the USA in Chapter 4. The global regulatory picture is completed in Chapter 5 by Dr. Sara J. Kirkham of Safepharm Laboratories and Dr. Mel Cooke, with emphasis on the key markets of Japan, Korea, China, the Philippines, Australia, New Zealand, Canada, and Switzerland, but also covering other markets with defined chemical control regulations.

Preface

Safety and Regulation of Biocides

Biocides are intended to be toxic, but only to the target organisms to be controlled. Such biologically active chemicals could potentially pose a risk to humans or the environment. Hence biocides are one of the most tightly regulated and controlled type of chemical product. The risk from a biocide is determined from its hazardous properties and the likely exposure of humans and the environment throughout its life cycle. The intrinsic chemical, health, and environmental hazardous properties for the hazard assessment are largely determined by standardized laboratory studies, although other means of estimating and predicting hazardous properties may sometimes be used. Such an in-depth science-based risk assessment will give a realistic estimation of the potential impact of a biocide. However, this is time- and resource-consuming process that can delay regulatory approval, and such delays can be costly to industry. Dr. Roland Solecki of the German Health Ministry shows how such risk assessments are conducted relating to the impact of biocides on human health (Chapter 6), while Robert Diderich of the French Environment Ministry discusses risk assessment relating to environmental safety (Chapter 7). Both authors use the EU risk assessment procedure to illustrate the general principles of safety assessment for regulatory decision-making and product approvals. Professor Aynsley Kellow of the University of Tasmania sets the scene for the book in Chapter 1 by placing biocides and their regulation and controls within a global political and socio-economic context, and discusses the public attitude to risks from biocides.

What Biocides Are and How They Are Used

Wherever there is a source of nutrition and moisture, micro-organisms and other pests will grow, even in extreme climatic conditions. Indeed, recent evidence suggests that microbial cells are found in outer space. These organisms may damage our health, our food, and our economy. The second part of The Biocides Business provides a broad overview of their main uses as disinfectants, preservatives, and pest controls. Each sector faces particular commercial and regulatory challenges. Some will see familiar registration schemes changed beyond recognition, while others will be facing for the first time rigorous regulatory control. Specialist contributors describe the chemistry, formulation, use, and specialized hazard testing for each type of biocide, and outline the important issues they are facing. Biocidal products are preparations, containing one or more active substances, that control such harmful organisms by chemical or biological means. They protect health, improve product performance, and prevent spoilage, and are increasingly important to modern life in ensuring safe, long-lasting, and effective products. Biocides encompass a wide range of applications including disinfection, preservation, and pest control. Households consume ever-increasing amounts of biocides. The assault on bacteria in the household has fuelled great interest in antibacterial products. Common household cleaners can contain simple inorganic chemicals such as sodium hypochlorite or

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hydrochloric acid. Chlorine-releasing biocides also have industrial applications in swimming pools and spas, which are prone to fouling from slime and microbe-induced corrosion. Disinfectants and public health biocides are described by Kerys Mullen of Lever Brothers Ltd. in Chapter 11. There is no doubt that the demand for biocidal products will continue to grow as the public and consumers’ awareness of the benefits of continued improvements in hygiene becomes ever more apparent. It is up to the biocides industry to developed these highly desirable products against a background of increasingly stringent legislative measures, and this will surely require openness and co-operation with other sectors of the supply chain. Related to disinfection, where the desired effect is to control a broad spectrum of micro-organisms, is preservation, where it may be sufficient to inhibit the growth of micro-organisms to prevent spoilage. Dr. Richard Elsmore of Warwick International Ltd. addresses the broad subject of general purpose preservatives in Chapter 10, covering diverse application areas such as cosmetics, food, fuel, metalworking fuels, and polymers. Wood preservatives are of enormous economic importance and are the dominant use for biocides in the EU. They include a wide range of pest control from moulds to insects in a variety of circumstances. Recently, some wood preservatives have been scrutinized because they contain heavy metals or volatile organic substances. Dr. David Aston of Arch Timber Protection discusses these issues and others in Chapter 8. Micro-organisms may interfere with manufacturing processes by causing rot or slimes to form, blocking valves and pipes, or corroding steel, plastic, and rubber. Slimicides are important in many industrial applications, as described by Ian Gould of BetzDearborn Ltd. and James Hingston of Safepharm Laboratory Ltd. in Chapter 9. The specialist area of antifouling biocides is the subject of intense debate. These products have environmental benefits in reducing fuel consumption on ships by reducing drag, but some have become notorious marine pollutants, specifically due to their ability to affect the endocrine system of some wildlife species. Dr. Graham Lloyd of Steptoe and Johnson and Dr. Carol Mackie of Compliance Services International discuss antifouling products and marine biocides in Chapter 13. Dr. Alan Buckle of Syngenta is the author of Chapter 12 on rodenticides, insecticides, and pest control agents. The control of higher order pests raises particular concerns for nontarget species, particularly wildlife and humans. The mode of action is also important as the biocide is expected to cause no undue suffering of the target species itself. We hope this book will allow our readers to appreciate the diversity of biocides, how they benefit modern life, and understand the measures taken to make sure they are safe to use. The Editors wish to acknowledge and thank the following people who have helped in the preparation for this book: Karin Sora of Wiley-VCH for advice and the invitation to edit this book; Safepharm Laboratories’ Board of Directors for permitting us the time and resources to make this book possible; Jacqueline Billing and Sara Kirkham of Safepharm Laboratories for much of the co-ordination and administration; other Safepharm staff, in particular Sheila Stokoe for word processing and Michael Andrew for editorial comments on Chapter 3, and several colleagues who gave initial advice and

Preface

suggestions; those who provided references when we first assessed the viability of the book, in particular Christina Jackson, whose suggestions led to the title of the book; and finally we give our sincere thanks to the authors, particularly those that stepped in close to the deadline, for their time, effort, and generosity in sharing their valuable expertise. Derek Knight and Mel Cooke

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Editors and Authors

Editors Dr. Derek J. Knight SafePharm Laboratories Limited PO Box 45 Derby DE1 2BT U.K. (Preface, Regulatory Control of Biocides in Europe)

Derek J. Knight is the Director of Regulatory Affairs at Safepharm Laboratories Ltd, a leading UK contract research organization specializing in safety assessment of chemicals, biocides, and agrochemical pesticides. He heads a team of regulatory affairs professionals who deal with a wide range of registration projects covering many product types for regulatory compliance in all the key markets globally. As such he has gained an overall perspective into commercial issues associated with the regulation of the biocides and chemical industry. His doctoral studies at the University of Oxford were in organosulfur chemistry.

Dr. A. Mel Cooke Alchemy Compliance Ltd. 2 Harvey Close Ruddington Nottinghamshire NG 11 6 N3 U.K. Formerly of SafePharm Laboratories Limited (Preface, Regulatory Control of Biocides in Europe and Regulatory Control of Biocides in Other Countries)

Mel A. Cooke is the founder of Alchemy Compliance Ltd. and offers independent advice on compliance issues, especially relating to biocides, notification of new chemicals, and existing chemicals programs. He gained over six years of regulatory experience at Safepharm Laboratories, reaching the position of Deputy Head of Registration Services. He has previously worked in Cambridge and Stuttgart as an editor of research journals, and gained industrial experience in the Ciba-Geigy laboratories in Basel. He researched the synthetic organic chemistry and pharmacology of inositol phosphates to gain his PhD from the University of Leicester.

Authors Dr. David Aston Arch Timber Protection Ltd. Technical Centre Wheldon Centre Castleford WF10 2JT U.K. (Wood Preservatives)

David Aston has 27 years experience in the wood preservation industry. During that time he has held technical, sales and marketing, and environmental positions in his company (formerly known as Hickson Timber Products and now as Arch Timber Protection). He has been active in the development of national and European standards and represents both his company and the industry in the interface between the regulators and industry in technical, health and safety, and environmental matters. He is currently President of the European Wood Preservative Manufacturers Group.

The Biocides Business: Regulation, Safety and Applications. Edited by Derek J. Knight and Mel Cooke Copyright ª 2002 WILEY-VCH Verlag GmbH Co. KGaA, Weinheim ISBN: 3-527-30366-9

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Editors and Authors Dr. Alan Buckle Syngenta Fernhurst Hazelmere Surrey GU27 3JE U.K. (Rodenticides and Insecticides)

Alan Buckle is Global Technical Manager for the Public Health business of Syngenta, having fulfilled similar roles in the ICI and Zeneca legacy companies. Prior to joining ICI in 1985, he held posts as a research scientist with the UK Ministry of Agriculture, Fisheries and Food, the Centre for Overseas Pest Control (now the Tropical Products Institute), and the Overseas Development Administration, during which time he completed many overseas projects and assignments for international agencies.

Dr. Sue Crescenzi Technical Specialist Environment, Health and Safety Steptoe and Johnson 1330 Connecticut Avenue, NW Washington DC 20036–1795 USA (Regulatory Control of Biocides in the United States)

Sue Crescenzi is a nonattorney regulatory specialist at Steptoe and Johnson, with almost 20 years experience in pesticide registration and regulation. She heads the firm’s pesticide registration consulting practice, working closely with clients and EPA staff on registration actions and policy issues, with an emphasis on antimicrobials. Dr. Crescenzi also assists clients in developing and presenting training programs to bring pesticide registration and compliance functions in-house. She has worked closely with the EPA on the development and implementation of a number of pesticide regulatory proposals, both individually and as a participant of industry coalitions. For example, she has worked with the EPA on tiered data requirements for antimicrobial pesticides and guidance to registrants on compliance with expanded reporting requirements on pesticide adverse effects.

Robert Diderich Institut National de l’Environnement Industriel et des Risques (INERIS) B.P. 2 60550 Verneil en Halatte France (Environmental Safety and Risk Assessment)

Robert Diderich has been involved in environmental risk assessment of chemical substances since 1992, when he joined the German Federal Environmental Agency. He has been working in France since 1995, first at the Ministry of the Environment and then at the National Institute for Industrial Environment and Risks (INERIS), where he is currently studies the environmental risks of industrial chemicals as well as biocides. He is involved in the continuous development of the EU technical guidance documents for the environmental risk assessment of industrial substances as well as biocidal substances.

Dr. Richard Elsmore Warwick International Ltd Mostyn Holywell Flintshire CH8 9HE U.K. (General Purpose Preservatives)

Richard Elsmore of Warwick International Limited has worked in the biocides industry since 1984 and has been involved with a wide range of both application areas and product chemistries. He has worked for biocidal active ingredient manufacturers and biocidal product formulators including Boots Microcheck, Coalite Chemicals, Great Lakes Water Treatment, and Robert McBride Ltd. before joining Warwick International Ltd. During this time he has been responsible for technical and regulatory management and for the marketing of biocides on a global basis. He has been responsible for the introduction of several of the commonly used biocides that are currently on the market. He holds a BSc and Doctorate in Microbiology from Cardiff University and an MBA from the University of Nottingham. He lives in North Wales with his wife Caroline, twins Morgan and Rhiannon, and an assortment of cats, dogs, and chickens.

Editors and Authors Ian Gould Business Manager Europe Microbiological Control Pulp and Paper Division BetzDearborn Ltd. Foundry Lane Widnes Cheshire WA8 8DU U.K. (Slimicides)

Ian Gould graduated from The University of Salford in 1975 with a BSc Honours Degree in Applied Chemistry. Ian went on to work as a Scientist for Bowater Technical Services, then on to Ellesmere Port (part of Bowater U.K. Paper Company) working as a Process Technician and then Mill Chemist. Joining Betz in 1980 as a Sales Representative in the Paper Industry based in Kent, he went on to hold a variety of sales and technical positions in the UK Organisation, before becoming European Technology Manager for BetzDearborn. Following the acquisition of BetzDearborn by Hercules, Ian is now European Business Manager, Microbiological Control.

James Hingston SafePharm Laboratories Limited PO Box 45 Derby DE1 2BT U.K. (Slimicides)

James Hingston is currently working as a Registration Officer with SafePharm Laboratories Ltd, specializing in the approval of biocidal products. He has previously worked for the UK’s Health and Safety Executive in the Environmental Sciences Section of the Biocides and Pesticides Assessment Unit. He has also recently completed a PhD at Imperial College, London, researching the environmental effects of wood preservative biocides in aquatic environments.

Prof. Aynsley Kellow Head, School of Government University of Tasmania Box 252–22 GPO Hobart 7001 AUSTRALIA (The Political, Social and Economic Framework)

Aynsley Kellow is Professor of Government at the University of Tasmania. He specializes in environmental politics and policy and has published several books, including most recently Transforming Power and International Toxic Risk Management (both with Cambridge University Press). He is coeditor of Globalisation and the Environment (Edward Elgar) and has published papers in many journals, including Policy Studies Journal, Natural Resources Journal, International Political Science Review, and Political Studies.

Dr. Sara. J. Kirkham Senior Registration Officer Safepharm Laboratories Ltd PO Box 45 Derby DE1 2BT U.K. (Regulatory Control of Biocides in Other Countries)

Sara Kirkham obtained her PhD in bioinorganic chemistry researching synthetic methods of biomineralization. She began working at SafePharm Laboratories in Regulatory Affairs after completing her postgraduate studies. For the past two years she has been specializing in biocide and pesticide registration, and now leads the section of the Department of Registration Services dealing with these projects as Senior Registration Officer. She enjoys gardening, shopping, drinking wine, and travelling with her family.

Dr. Graham Lloyd Senior Regulatory Specialist Steptoe and Johnson 5 Telford Gardens Brewood Staffordshire ST19 9ED U.K. (Antifouling and Marine Biocides)

Graham Lloyd has been in the biocides industry for more than 20 years. He has a degree in Microbiology and worked for Unilever Research. Graham Lloyd then moved to Sterling Industrial as Technical manager. He was Regulatory Affairs manager at Albright & Wilson and Arch Chemicals. He is now Senior Regulatory Specialist with Steptoe and Johnson. He was Vice Chairman of the Cefic sector group, the European Producers of Antimicrobial Products (EPAS), and is now on the management committee of the European Biocidal Products Forum (EBPF). He is a member of the CEPE antifoulants working group, the Chemical Industry Association Biocides Sector Group, and various working groups associated with the BPD. He represented industry on the OECD Biocides Steering group and is an industry delegate at EU competent authority meetings.

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Editors and Authors Dr. Carol Mackie Principal Consultant Compliance Services International Pentlands Science Park Penicuik Nr. Edinburgh EH26 0PZ U.K. (Antifouling and Marine Biocides)

Carol Mackie has a PhD in Microbiology. She has been a consultant to the biocide industry for 5 years and is currently principal consultant and manager of Compliance Services International, European office. Previously she worked for the UK Health and Safety Executive, Pesticides Registration Section, where she was involved in the environmental risk assessment of nonagricultural pesticides. She is a member of the CEPE anti-fouling working group and CEFIC biocides shadow working group for ecotoxicity and environmental fate and is currently the CEPE/CEFIC biocides representative at the marine risk assessment technical sub-group meetings, organized by the European Chemicals Bureau.

Dr. Patricia Martin Product Assessment and Regulatory Compliance 37 Sydney Road Cradley Heath West Midlands B64 5BA U.K. (Biocides Market)

Patricia Martin holds a PhD in biochemical toxicology. Following her academic studies she spent some nine years working both at the University of Aston in Birmingham and then Birmingham University in the Institute of Occupational Health as a Research Fellow funded by among others the UK Health & Safety Executive. Her primary interest was occupational lung cancer. Studies included an international investigation of the bichromates industry, the possible role of synergistic interactions in the causation of lung cancer, and also the UK foundry industry. She joined Albright & Wilson in 1987 as their Company Toxicologist and for the next 14 years continued to represent the widely divergent product-related safety interests of the company in both UK and CEFIC Industry Groups. During this time, Patricia was Chairperson of the CEFIC Biocides Working Group on Toxicology and Data Waiving. With the takeover by Rhodia of Albright & Wilson Patricia seized the opportunity to branch out, and in 2001 she started her own consultancy business, Product Assessment and Regulatory Compliance. The consultancy is in its first year of operation, but already the clientele includes multinational companies, who, due to internal resource shortages, have a requirement for the practical experience of a seasoned toxicologist. Patricia has maintained her links with both academia and industry, and is looking to broaden her portfolio of clients, professional services, and affiliations over the coming months.

Kerys Mullen Quality and Hygiene Centre LDC Lever Brothers Ltd Port Sunlight Merseyside CH62 42D U.K. (Disinfectants and Public Health Biocides)

Kerys Mullen is European Hygiene Claims Advisor for Unilever Home and Personal Care. She joined Lever Brothers of Port Sunlight in 1990 and obtained an honours degree in Biochemistry through sponsorship. Initially she was responsible for developing rapid methods for hygiene control in the factory. She also developed and implemented hygiene standards as a European Hygiene Systems Auditor and spent some time responsible for product preservation. In 1998, she became the European Hygiene Claims Advisor principally responsible for developing claims and defining laboratory methods. She is a representative on UK and international bodies, including BACS Microbiological Committee and Work Group 3 for Comite´ Europe´en de Normalisation (CEN TC 216-Antiseptics and Disinfectants), which has been established to produce harmonized European test methods for antiseptics and disinfectants in the fields of food and institutional hygiene. She is also an expert advisor to the British Standards Panel TCI/80/-/5 Testing Of Anti-Microbial Treated Textiles.

Editors and Authors Dr. Roland Solecki BgVVBerlin Bundesinstitut f. gesundheitlichen Verbraucherschutz Und Veterina¨rmedizin Thielallee 88–92 D-14195 Berlin Germany (Human Health, Safety and Risk Assessment)

Roland Solecki was born in 1954 and was educated (1973 to 1978) at the University of Leipzig in animal physiology and neuro-endocrinology. From 1978 to 1991, he worked in the Institute for Plant Protection Research in Kleinmachnow as toxicopathologist in experimental toxicology studies of pesticides on rats, mini-pigs, and Japanese quails. After his doctorate, he worked for a year at the Pathological Institute of the Charite´ in Berlin. Then he undertook postdoctoral study at the „Academy for physicians further education“ from 1983 to 1986, and finished as toxicologist. Since 1991, he has worked in the Pesticides and Biocides Division of the Federal Institute for Health Protection of Consumers and Veterinary Medicine (BgVV) in Berlin. As branch head, he is responsible for coordination and management of health evaluations of pesticides and biocides. As a toxicologist, he is engaged in the human health risk assessment of active substances for the evaluation of pesticides at national and European level. As a temporary adviser, he is participating in several toxicological expert groups for pesticides and biocides of the European Union, OECD, and WHO. His experimental work in the last 10 years has concentrated on the investigation of reproductive effects of biocides and pesticides in birds.

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The Political, Social, and Economic Framework Aynsley Kellow

1.1

Introduction

Biocides are chemical agents which have come under increasing regulatory scrutiny. Yet, as Guy Eisenberg (Product Integrity Director at producer Rohm and Haas) put it, “Most people don’t even know what a biocide is” [1]. The term “biocides”, following the OECD approach, is taken here to refer to nonagricultural pesticides. There are seven broad groups of biocides: disinfectants/sanitizers; preservatives/microbiocides; antifouling products; wood preservatives and structural treatments; microbiocides for waste disposal and strip mine sites; products used in aquatic nonfood sites (molluscicides, lampricides, algicides, disinfectants); products used for vertebrate and invertebrate pest control [2]. Mention the word pesticides and most people probably think of agricultural pesticides, yet nonagricultural uses of biocidal agents are everywhere. Biocides are used in hospitals and medical establishments, in eating establishments, mortuaries, laundries, bathrooms, kitchens, air-conditioning ducts and cooling towers, on boats and marine structures, to preserve wood, in swimming pools, in oils and cutting fluids, and to kill or repel pests such as rodents and insects. They are also used to control microbes in strip mine acid, and in sewage disposal, and paper and textile mills. They have widespread uses in households or industry. As one would expect, the use of products which possess economic value courtesy of their toxic effects on living organisms also carries risks to the environment and human health, and such risks have to be managed so as to minimize the possibility of unintended biological damage. To manage such risks, most countries have adopted various regulatory regimes. These tend to reflect different histories, uses, and cultures, and this gives rise to a number of issues at the international level. Different regulatory regimes in different countries can result in barriers to trade and increase the costs of product registration. But such regimes (like any regulatory sysThe Biocides Business: Regulation, Safety and Applications. Edited by Derek J. Knight and Mel Cooke Copyright ª 2002 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN: 3-527-30366-9

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tem) can also provide advantages for some economic actors, and in an age of increasing trade liberalization, regulation can be a way of re-erecting national borders. On the other hand, attempts to harmonize regulations across jurisdictions provide opportunities for some actors to seek to impose regimes which advantage them. For example, if domestic regulatory measures have favored particular chemicals and producers, the export of regulations exports advantage for domestic producers and exports disadvantage for those who have not been required to meet the standards in question. In addition to the political, economic, and social factors which influence the making of domestic risk-management policy, the relationship between domestic and international politics and policy is thus significant for the regulation of biocides. One central problem relates to the very definitional ambiguity which arises with deciding what is a biocide and what is not. Definition of the object of regulatory activity is a necessary part of any regulatory regime, because what cannot be defined cannot be regulated. How definitional terms are applied can also mean that the subjects of regulation are allocated to different agencies, each of which can have different cultures and approaches to risk. Biocides are sometimes defined and regulated as pesticides, sometimes as drugs, and sometimes as industrial chemicals. One consequence of this is that it will often be necessary here to discuss regulation of chemical products more generally, but it is an issue which also impacts upon regulation per se. The problem of definition is important because there is no single regulatory approach among OECD members, with disinfectants and sanitizers (for example) regulated as pesticides in some jurisdictions, as medicines or drugs in others, and as industrial chemicals in others. Antifouling products are regulated as pesticides in some jurisdictions and as industrial chemicals in others. As a result, the regulatory pattern is complex, with many countries having split responsibilities between different ministries and different agencies within ministries for both different biocide product types and even for the same product type. While there are few national authorities involved, there is often considerable complexity at lower administrative levels. Active ingredients have to be approved first in some jurisdictions, such as under the European Union Biocidal Products Directive, where they are placed on a “positive list” before they can be used in all products. In most countries, however, data on the active ingredients and formulated end-use product are considered together as an integrated package, but approval is only given to the end-use product (approval is then given for between four and ten years, and is often subject to conditions relating to use). Regulation of biocides is mostly aimed at ensuring safety. There is some, though little, regulation of biocides for efficacy, both in terms of initial effectiveness and the development of any resistance by target organisms. Most jurisdictions require labeling, which is taken to include hazard warnings, uses, target species, warnings or restrictions based on risk, and directions or instructions. Approval can be denied on the basis of lack of efficacy, or on the grounds that the product presents an unacceptable

1.2 Historical, Cultural, and Economic Influences

risk to humans or the environment. Human exposure assessments take into account user characteristics and formulation types and application methods. Data is usually required to be kept on usage so that monitoring can occur, so that risk assessment can incorporate “field experience”. Most countries require the storage of data on: chemical identity, physical/chemical properties, function, mode of action and handling, analytical methods, and toxicology. These different regulatory approaches reflect the differing histories and cultures of countries using chemicals. They are differences which can give rise to wishes to harmonize regulatory approaches in order to prevent the use of regulatory differences as disguised barriers to trade. These social, economic, and political factors influence the regulation of biocides and other chemicals at both the domestic and international levels, and add complexity to the risk-management process. Especially at the international level, focusing on science might be thought to be helpful in developing shared appreciations of risk, but this is inherently problematic. To understand why science does not yield identical perceptions of risk and risk-management decisions, we must understand the way in which social, economic, and political factors affect the question of risk. That is the purpose of the present chapter.

1.2

Historical, Cultural, and Economic Influences

The modern chemical manufacturing industry developed out of the munitions and dyestuffs industries [3 – 7]. Because of links between the chemical and pharmaceutical industries much of the chemical industry had had experience with regulation through pharmaceutical registration [8], when attention turned to pesticides in the 1970s. Many of the early pesticidal agents were metal salts – such as copper sulfate, calcium arsenate, lime sulfur, and lead arsenate. DDT, the first synthetic pesticide, was not developed commercially (by Geigy) until 1939. Many of the synthetic pesticides were seen as providing considerable advantages over the metal salts, many of which were known to pose acute toxicity risks to humans. Concern over synthetic chemical products developed after the publication of Silent Spring in 1962 [9], and by the 1980s the industry faced an increasingly hostile public, despite the fact that most of the serious instances of chemical hazard were acute catastrophic emergencies (at Seveso, Flixborough, and Bhopal) rather than chronic poisoning of humans or the environment through the use of synthetic chemicals [10]. The most notable cases of chronic chemical toxicity involved heavy metals (methyl mercury with Minimata disease and cadmium with itai itai). Most of the dangerous metal salts were replaced by synthetic pesticides, and initial domestic regulation focused on the safety of new products.

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Worldwide usage of pesticides doubled every decade after 1945 until the mid-1980s, when a slowdown occurred as a result of both changes in applications and environmental concerns, which effectively stabilized usage in volume terms [11]. Economies became substantially less chemical-intensive, with pesticide use in kilograms per dollar of GDP declining by half over the two decades from 1980. The costs of developing and marketing new chemical products have encouraged substantial concentration of ownership. By the mid-1990s, the top nine producers accounted for half of the world production. These were Ciba-Geigy, Zeneca, Monsanto, Bayer, DuPont, Dow Elanco, Rhone-Poulenc, BASF, and American Cyanamid. AgrEvo, a joint venture of Hoechst and Schering was the tenth largest, followed by “second-tier” companies such as Sumitomo, Sandoz, FMC, and Rohm and Haas, with sales below $ 1 billion [11]. The growing importance of biotechnology to the chemical industry has also resulted in considerable reorganization. For example, Clariant was the former specialty chemicals division of Sandoz, which later merged with the specialty chemicals division of Hoechst. Creanova Inc., formerly Huls America Inc., includes the worldwide colorants and biocides business of the North American operation of the specialty chemical business of Creanova Spezialchemie GmbH. Rhone-Poulenc has formed Merial, a joint venture with Merck in animal health, while forming a specialty chemicals subsidiary called Rhodia. Solutia is the former chemicals unit of Monsanto, while its biotechnology interests have been moved into Pharmacia (for further details of industry structure, see Chapter 2). Critical mass in the chemical industry is thought to be reached at a level of annual sales of $ 1 – 1.5 billion, which is thought to be necessary to be able to afford higher R&D costs and regulatory burdens. Producers endeavor to develop product portfolios, ideally with a flagship product, such as Monsanto’s Roundup, with estimated sales of $ 1 billion per annum. However, typically only two flagship products are likely to appear in a decade and they dominate for a while, and then when patent protection lapses, a replacement is developed. Niche products, which solve specific problems, are more common, with ten to twenty developed per decade. Substitute pesticides, marketed as supplements or alternatives, are introduced at the rate of about five to ten every decade. The chemical industry is technology driven. When patent protection expires, generic competition arises, but large firms can counter this by quickly introducing new products. Lax enforcement of patent rights is one factor which has limited investment in developing nations, such as India. As a result, production is concentrated in Canada, the US, Western Europe, and Japan. The biocides business differs from that of the large agricultural pesticides sector. In the biocides sector, smaller players have been more numerous than with agricultural chemicals, with many smaller chemical specialties companies in existence, often trading at substantially less than global scale. The biocides business is much smaller than other businesses in the chemical industry, perhaps only a tenth of the size of the plant

1.2 Historical, Cultural, and Economic Influences

protection market [12]. The sector is diverse with many small to medium companies, with some operating only on a national or regional basis. This reflects in part the small tonnages involved with specialty chemicals, but it also reflects the lower levels of regulatory scrutiny for biocides compared with agricultural chemicals, because the costs of chemical registration favor larger, global players, which can afford to meet registration costs and which can pursue international harmonization. Harmonization of registration means that the costs of registration can be spread over a larger market. The growth of biocides regulation (as we shall see below) has added to the pressures for concentration of ownership. The pattern of ownership and distribution of manufacturing capacity has meant that the chemical industry overall is dominated by transnational corporations, and this is a feature which has been important in the politics of regulation. The existence of transnational corporations larger than many small states gives rise to concerns about their power and accountability. They are feared, disliked, and mistrusted on these grounds alone, and the risks associated with their products and their manufacture provide a useful point of attack for their critics. Thus, in addition to any concerns over risks for human health or the environment, campaigns which draw attention to risks and call for their regulation become a means of weakening disliked organizations. This concern has been marked where operations have involved Developing Countries, and it has helped bring about change both as a result of regulation and from within. Ironically, the regulation of chemical risk has been driven by politics involving attacks on excessive concentration of capital, and yet this has served to produce further concentration. The disaster at Bhopal, India, where an explosion in a pesticide factory owned by Union Carbide released substantial amounts of the toxic intermediate product methyl isocyanate into a heavily populated district helped create internationally a new level of concern with toxic chemicals, and prompted the industry to develop its “Responsible Care” program to raise standards for behavior. There were complex causes in the Bhopal disaster, including the insistence of the Indian government that local staff be employed, and the intrusion of residential development into the buffer zone around the factory [13, 14]. But the Bhopal tragedy was widely interpreted as the fault of the company, and focused transnationals on the issues of liability which existed even despite the absence of effective regulation in the host country. Most resolved to demand fuller control over the staffing, design, and equipment of their foreign plants, since they would be exposed to liability in the US courts [14]. Whether or not they had previously sought to locate factories where environmental standards were lax, chemical companies were reluctant to do so after Bhopal. A UN study by the Center on Transnational Corporations shortly after found that multinational investment in hazardous industries had gravitated chiefly toward countries with advanced industrial economies and firm pollution controls [14]. Despite this, there has

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been much talk of “toxic colonialism” since Bhopal, aided by concerns over the export to Developing Countries of some chemical products no longer licensed in “Northern” nations. This is a highly complex area. During the negotiation of the Rotterdam Treaty (on prior informed consent for trade in chemicals), Developing Countries such as Malaysia floated the idea of restrictions on exports of chemicals from OECD countries into Developing Countries, relying upon the “toxic colonialism” rhetoric, but clearly with the aim of providing mechanisms which might encourage investment in such countries to circumvent the trade barrier thus created. Even the issue of the export of “obsolete” chemicals to the developing world is not a simple one. The negotiation of a treaty on persistent organic pollutants (POPs, concluded in Johannesburg in December 2000) ultimately permitted the continued use of DDT in Developing Countries, acknowledging that it was cheap and effective in combating malaria, although it had passed out of patent and was able to be made cheaply by generic chemical manufacturers in Developing Countries. The elimination of malaria in Europe and North America came as the result of various social and economic changes, but most significantly only after the development of DDT [15]. Only in the 1970s was Europe considered malaria free, and even the World Wide Fund for Nature acknowledged the strength of the claim for exemptions from Developing Countries from proposals to phase out DDT. The risk-benefit calculus of DDT is different for poor tropical countries, which are less concerned over effects on wildlife than are affluent countries. These characteristics of the chemical industry, especially the prominence of transnational corporations and issues involving the Third World, such as differing perceptions of environmental risk resulting from different stages of development and questions of the export of chemicals which might still be accepted for use in some countries, affect the way in which risks of chemicals are perceived (in ways we shall examine below). There are many complex issues here, including matters relating to patents, since many “obsolete” chemicals can be made cheaply as generics, and calls to restrict exports serve to provide market protection for new, patented chemicals, to the advantage of the transnationals.

1.3

National and International Regulation

Environmental regulation of toxic chemicals began at the domestic level and focused initially on pesticides. The US Environmental Protection Agency (EPA) was given authority to register pesticides in 1972, and these powers were soon mirrored in other industrial countries, particularly Japan, and the European Community (now European Union), and Nordic countries [16, 17]. Industry feared that it would suffer the costs of

1.3 National and International Regulation

having to register its products separately in each jurisdiction, and pushed for international harmonization. It was supported in this by the US food industry and agricultural exporters such as Australia and Canada, which feared that the European Union would use internal pesticide regulations as nontariff barriers to trade [18]. The Codex Alimentarius Commission in The Hague, a joint Food and Agriculture/World Health Organization (FAO/WHO) body, was established to address this issue, and established a system designed to harmonize the basis for national regulation of food (see below). There have been three waves of concern which have driven the regulation of biocides and other chemicals. The first was the set of issues highlighted by Rachel Carson. Prior to Silent Spring, modern chemical agents were considered relatively safe. They lacked the acute toxicity of the metal salts and other agents they replaced. As a result, they were used with little care and in copious quantities. DDT, for example, was widely employed to attack mosquitoes in much of Europe and the United States, where malaria was endemic until the latter half of the Twentieth Century [15, 19]. Things which are perceived to constitute small hazards often become large risks because our risk perceptions cause us to behave in ways which increase the probability of harm, and this was the case with DDT. Silent Spring fostered concern which eventually drove regulation, the development of nonpersistent chemicals, and the development of integrated pest management, but its most immediate result was that it encouraged greater caution in the application of chemicals. The second wave of concern was the “War on Cancer” declared by President Nixon in the US. It is important to note, however, that cancer concerns and regulation had been around for a decade previously. The 1958 Delaney Amendment to the Food, Drug, and Cosmetics Act required that processed foods must not contain residues of any pesticides which induce cancer in laboratory animals. This included 36 pesticides including: mancozeb, a fungicide used on cereals and grapes; dicofol, an insecticide used on fruits; and captan, a fungicide used on plums, grapes, and tomatoes. The modern concern over cancer stemmed from a conclusion at a 1968 conference that as many as 80 percent of malignant cancers might be attributable to “environmental” causes. There followed a popular misinterpretation of what the term “environmental” means. In medical and scientific idiom, “environmental” means anything not genetic – stress, diet, and so on. In fact, the research upon which the conference statement was based specifically included dietary differences as variables, and therefore included all the natural dietary carcinogens discussed by Bruce Ames et al. [20], who have pointed out just how elusive a quest for a world free from chemical risk is likely to be if we were to eschew the use of chemicals known to cause cancer in laboratory rats. As they demonstrate, the greatest human exposure to pesticides comes not through exposure to anthropogenic pesticide residues, but from the ingestion of naturally occurring pesticides present in the food we eat.

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This 1968 attribution of cancer to “environmental causes” suggested cancer was avoidable, if only environmental exposures could be identified and managed. It coincided with the rise of environmental politics, and “environmental” was widely interpreted in a different sense than its technical application in epidemiology. The result was Nixon’s declaration of war on cancer in which the imperative was to identify which carcinogens to avoid. In 1967, there were about 500 animal carcinogens, but this had grown by 1976 to 2400 after a great deal of expensive testing. Then, Epstein’s The Politics of Cancer [21] was published and became a best seller, fuelling popular concern over chemical carcinogens. Scientific advances since then have made the task of chemical regulation more, rather than less, difficult. For example, the US Food Quality Protection Act of 1996 attempted to deal with inconsistencies arising from the fact that the Delaney Clause applied to processed foods but not raw commodities, together with the fact that testing had indicated that many chemicals could breach Delaney if found in trace amounts [22]. Its impact provides some insight into chemical regulation. A National Academy of Sciences Report [23] estimated that 60 percent of the herbicide, 90 percent of fungicide, and 30 percent of insecticide use by weight consisted of materials classified by the EPA as carcinogenic to laboratory animals or potentially so to humans. FQPA reflected the impossibility of applying Delaney in practical terms when test protocols turned up numerous rodent carcinogens among existing products, and it had become possible to detect residues at levels of one part per quadrillion. There are problems in relying on the use of results tests involving massive doses of chemicals on laboratory species as a proxy for carcinogenicity in humans. Not only does the sensitivity of species vary markedly – even between rats and guinea pigs, let alone between those species and humans – but such tests typically involve the administration of massive doses administered in ways which often do not reflect probable exposure paths. Test protocols for examining the effects of chemicals on animals were developed as a means of screening new chemicals, and doses given to laboratory animals can be as much as 35 000 times those likely to be found in typical human exposures and are often introduced directly into tissues. If a new synthetic chemical is found to be carcinogenic or teratogenic in laboratory test species, that is a very good reason for restricting its use, subject to further testing, but many things proved to be carcinogenic in massive doses, and there is little point in banning substances long in use solely on the basis of a screening test. Nor does this approach guarantee protection, for chemicals might be human carcinogens even though they have no effect on laboratory species (as is the case with a species of arsenic). The difficulties of chemical testing have been exacerbated by ethical considerations, with animal rights concerns creating pressures for less reliance on animal testing. Animal rights campaigners in the United Kingdom have targeted the testing company Huntingdon Life Sciences with a number of violent actions, and thus created political

1.3 National and International Regulation

pressures which might result in greater reliance having to be placed in future on in vitro techniques which are even more unrealistic as means of assessing hazards. The third wave of concern has centered on the possible endocrine-disrupting effects of very small amounts of some chemicals, either alone or synergistically with other chemicals [24]. These claims are controversial, with sceptical scientists quick to point out that there are many naturally occurring chemicals which mimic endocrines, including phytoestrogens in many foods, such as coffee and soy products. The process of evaluating chemical risks is difficult and expensive. In the US, a typical pesticide is put through more than 100 tests, and approval can take more than three years [11].Brian Wynne once noted that there were (then) approximately 7 000 000 known chemicals, 80 000 of which were in commercial circulation. Approximately 1000 new chemicals entered commercial use each year. Using total world laboratory resources, about 500 chemicals could be tested each year. One test for carcinogenicity can involve 800 test animals, 40 different tissue specimens per animal, and a cost of $ 500 000 over three and a half years [25, pp.48 – 49] (the costs have inevitably risen). What gets chosen for toxicity testing, by whom, and by what methods are crucial political questions. Only about 7000 chemicals had been tested for carcinogenicity, and only about 30 had been demonstrated to reasonable standards of proof to cause cancer in human populations. Much of our work in managing chemical risk thus takes place in at least partial ignorance. More recently, the focus has shifted from new to existing chemicals, often with some attempt to more complete assessments of risks, not just to human health, but to the natural environment. The costs of moving from toxicity testing to a full-blown risk assessment, which considers actual exposures and pathways, are even greater than those for toxicity testing. The growing importance of environmental risk has thus added to the task of evaluating chemicals, because complex ecological factors cannot be satisfactorily explored by following laboratory testing, be it in vitro or in vivo. But detailed environmental risk analysis is very costly, and these costs are having an impact on the nature of the market in both agricultural pesticides, where product runs are large, and (especially) biocides, where markets are often too small to justify the expense of re-registering many existing chemicals. With the addition of ecological complexities, there is an inevitable temptation to either “let the toxicity do the talking” or to engage in some “quick and dirty” risk analysis via some formula, which will approximate a risk analysis. Both these alternatives result in the reduction of chemical risk policy to a technical level which is likely to privilege technical specialists since they remove the evaluative and economic dimensions from the risk-management process and leave the toxicity specialists firmly in control. Such specialists are more likely to operate on a technical rather than cultural theory of risk, and are likely to be somewhat myopic towards the social, economic, and political dimensions, which are the realm of the subjective risk professionals, but the

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result – especially when combined with the moralistic and highly charged politics generated by the environmental movement – is potentially a contamination of the “science” of toxicity and ecotoxicity by evaluative processes which are implicit rather than explicit [26]. Chemical risk management can never be undertaken solely on the basis of scientific knowledge of toxicity. In theory, all chemicals are toxic. In practice, risk management must consider the ways in which people or other living things can be exposed to such toxic substances in amounts that can cause harm, the probability of such exposure occurring, and the hazards they pose. To manage or reduce the risks associated with hazardous chemicals requires consideration of the costs as well as the benefits of such an action, where costs include opportunity costs as well as any risks associated with the use of any substitute or pursuit of any alternative practice. This requires an understanding of hazard identification, risk estimation, risk evaluation, and risk management. Most models for risk assessment and risk management commence with some form of hazard identification, using scientific research to establish the nature of some adverse effect [27]. The notion of risk involves both the hazard and the probability of its occurrence, and risk estimation thus involves probabilities. Hazard identification and risk estimation involve primarily the use of toxicological and epidemiological data as their primary sources of knowledge, although structure/activity analysis may also be used in the case of chemical hazards. Risk estimation must also involve some consideration of human activities, the uses to which chemicals are put, the form in which they are used, and so on. Risk evaluation inevitably involves the social science disciplines, with public policy considerations becoming paramount in the evaluation of advisory, economic, or regulatory options using the formal tools of program evaluation, “tempered by the public’s perception of the risk involved as well as prevailing socio-political factors” [27, p.404]. Finally, risk management involves the implementation of the control strategy selected – again, a process which has more to do with the social sciences than the natural sciences. As Krewski and Birkwood [27, p.405] note, “Hazard identification and risk estimation are clearly in the scientific realm, whereas risk evaluation and risk management fall within the domain of social decision-making”. Risk evaluation inevitably involves both the notion of risk as a social construct and the consideration of economics. Importantly, trade-offs must be considered. We cannot live in a risk-free world, and any alternatives we might consider also carry risks. Economics addresses this point neatly with its notion of opportunity cost – what we have to give up in order to choose a particular course of action – although economics itself cannot provide an objective science of risk management. A risk-management approach calls for the following steps to be taken:

1.3 National and International Regulation

1. Before taking action to regulate an environmental problem, an objective assessment of scientific knowledge must indicate that exposure to the pollutants of concern may represent a significant danger to human health or the environment. 2. To make efficient use of resources, environmental problems should be ranked in order of priority by some formal or informal “comparative risk” process. 3. The proposed actions should reduce the risks of targeted pollutants by a greater degree than they increase other risks to public health and the environment. 4. The economic costs of the action must be balanced against the expected benefits of risk reduction. Such balancing might be quantitative or monetary (where possible) but might be in many cases more qualitative and judgmental [28, pp.1 – 2]. Politics often drives risk regulation, so that these principles are not followed, at considerable cost. For example, Tengs et al [29] examined the cost effectiveness of 587 lifesaving interventions, including conventional medical intervention, injury reduction measures, and toxic chemical regulations. While it ignored any environmental benefits of chemical regulation, this analysis revealed just how powerful the political pressures for chemical regulation were, and how great the costs were of regulating so rigorously. Overall, the median intervention cost $ 42 000 per life year saved. The median medical intervention cost $ 19 000/life year; injury reduction $ 48 000/life year; and toxic chemical regulation $ 2 800 000/life year. Put another way, studies of the relationship between societal income and mortality in the US indicate that a reduction of income of about $ 12 million may cost one statistical life. Since many regulations cost more than this per life saved, they literally cost more lives than they save [30]. Despite the fact that the Reagan administration in the US imposed a benefit-cost test requirement on regulations, the US Office of Management and Budget (which oversees risk-regulation agencies) has never rejected a regulation with a cost under $ 100 million per life saved. This fact reflects the subjective elements in risk management. To a very large extent, risk-management approaches reflect the methodologies employed to estimate risks and evaluate them, as well as various institutional and social factors. One of the more farcical examples of the result of different institutional factors embodying differing risk-management approaches concerned the US Department of Agriculture and the US EPA. The USDA had responsibility for regulating permissible levels of pesticide residues on agricultural produce, and its standards were understandably more sympathetic to its agricultural clients than were those of the EPA, which had responsibility for setting limits for chemicals disposed in solid waste dumps. The result was that at one time a sprayed apple which could be sold for human consumption under USDA regulations could not be disposed of in a landfill under US EPA regulations [25, p.49]. Another example can be used to show how different methodological approaches followed by different agencies produced substantially different assessments of

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what level of risk was socially acceptable. Radiation hazards frequently arouse considerable anxiety on the part of the public, yet risk-management processes followed in the United States produced regulatory outcomes markedly different for radiation hazards and chemical hazards, and this difference was an artefact of the methodologies employed. Permissible occupational exposure to radiation in the United States would lead to an additional lifetime probability of death of well in excess of one in 100; typical limitations on exposure to chemical carcinogens corresponded to an increased probability of about one in 1000. This order of magnitude difference reflected the histories of the two regulatory approaches. Radiation risk management evolved under the assumption that risks should be balanced against the benefits of radiation and radiation-producing technologies and “taking into account the unavoidable natural sources of background radiation” [31, p.2336]. Chemical risk management developed from a different background and embodied different assumptions. It was assumed that public health could be completely protected, and assumed (because the program was dealing primarily with screening new chemicals for registration) there were no significant natural sources of the chemicals – an assumption which Ames et al have shown cannot be safely made. Moreover, rather than dealing with epidemiological observations in humans, chemical risk management was based upon projections from experiments performed on laboratory animals. The differences between the two approaches went largely unnoticed until the US EPA began treating radiation risks in the same context as chemical risks, and found that applying standard chemical risk-management criteria to radionuclides produced limitations on excess radiation doses that were unworkably small in comparison to natural background radiation. Chemical risk assessments were likely to produce overestimates of human risk thanks to two factors. First, because of the uncertainty in predicting risks at low doses based on risks observed at high doses, most regulatory agencies used the upper confidence limit of risk measures, feeling that they are erring on the side of caution. Second, some agencies (including the EPA) further used a conservative “surface area scaling rule” to predict human responses from animal bioassays. Moreover, as the first chemical risk assessments were conducted for synthetic carcinogens, there was assumed to be no naturally occurring background level to be subtracted from additional exposures in risk assessments, so background risks came to be seen as irrelevant. This has consequences for the application to existing chemicals (including naturally occurring chemicals) of techniques developed to detect any carcinogenic potential associated with new substances. This outcome was facilitated by political factors and legal judgments, which underscores the point that risk assessment is a highly political process. Political institutions, political culture, power, and interests all affect the development and implementation of risk-management processes [32 – 34].

1.3 National and International Regulation Table 1.1.

Activities increasing probability of death by one chance in a million (Source: [35, p.219])

Smoking 1.4 cigarettes Spending one hour in a coal mine Living two days in New York or Boston (air pollution) Travelling 300 miles by car Travelling 10 miles by bicycle Flying 1000 miles by jet Living two months with a cigarette smoker One chest X-ray in a good hospital Eating 40 tablespoons of peanut butter (aflatoxin) Drinking 30 cans of diet soda (saccharin) Living 150 years within 20 miles of a nuclear power plant (low-level radiation) Living within five miles of a nuclear reactor for 50 years (accidental release of radiation).

Risk perception is influenced by all manner of influences. The way in which evaluations of risk affect our perceptions can be illustrated by reference to various kinds of risks to which we are commonly exposed. The activities set out in Table 1.1 have the same probability of causing death. This list shows how our perceptions of risk vary. Few people would think twice about driving 300 miles in a car, yet some of these refuse to fly. Most environmentalists would happily ride ten miles to work on a bicycle, but would refuse steadfastly to live near a nuclear reactor. Probability theory cannot explain this. People engage in risky activities all the time, but our perception of those risks, and our willingness to accept them, varies greatly. The distribution of risks is also important: car deaths occur disproportionately with young males, so a fear of flying among females and the middle aged is not as irrational as it might seem. Chemicals pose hazards which have been estimated epidemiologically, but such an estimate depends upon many social factors which might affect exposure and probabilities, so it cannot be taken as a substitute for a risk assessment – at least not without some risks. Drinking water chlorinated to the maximum level permitted by the US EPA carries an annual probability of death of 0.8 per 100 000, largely from bladder cancer. But the risks of unchlorinated water are usually considered higher, and (to put the risk in perspective) the annual rate of death from all causes is 1000 per 100 000 [35, p.218]. There are serious dangers in trying to reduce risk assessment of chemicals to toxicological science and ignoring the social and economic context. One example of this comes from the use of a US EPA risk assessment for chlorinated water in Peru. Peruvian officials decided to follow the lead of the US EPA and not chlorinate the water from many wells. In the ensuing cholera epidemic, more than 3500 people were saved from bladder cancer by an early death [36]. General public

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health conditions in the United States make the probability of cholera remote, and cancer is likely to loom larger in a risk assessment of chlorinated water there than in Peru. The figures in Table 1.1 do not tell us why some risks are accepted, while others with a lower probability of occurrence are deemed unacceptable. To put it simply, it matters how we die, not just whether and when. We know some of the factors which affect the assessment of various kinds of risks by individuals, and these are shown in Table 1.2, which indicates factors found to result in risk perceptions being amplified or reduced. These assessments reflect broader cultural and political forces which are driving the politics of risk. Anthropologist Mary Douglas [26, p.15] sees the environmentally based preoccupation with risk as having to do with blame, and as, at least partly, a public backlash against the large corporations. According to this view, the almost obsessive preoccupation with avoiding dangers, which are (objectively) much more remote than those we are exposed to every day, is a reaction to the vulnerability and loss of control we feel in an era of globalization, especially with chemicals which are made by the transnational corporations that engender many of these fears. The last pair of factors in Table 1.2 points to a vexed problem with chemical safety and thus to chemical and drug registration (and, more recently, with the products of genetic engineering). Most of the research is conducted by the scientists of the appliTable 1.2.

Factors in risk assessment (Source: Adapted from [37, p.18]).

Risk considered greater

Risk considered less

Man-made risks

natural risks

High loss of life accidents

low fatality accidents

Immediate effects

delayed effects

Risks to nonbeneficiaries (residents near industry)

risks to beneficiaries (workers in industry)

Involuntary risks (contaminated food)

voluntary risks (smoking)

Uncontrollable risks

controllable risks

Unfamiliar risks

familiar risks

Imposed risk (budget cuts lowering safety)

self-chosen risk (using a vaccine)

Risk from secret activities (waste from a secret lab)

risk from open activities (waste from a mine)

Risks to children

risks to adults

Known victims

“faceless” victims

Irreversible effects

reversible effects

Scientific uncertainty

scientific certainty

Untrusted institution

trusted institution

Risks evaluated by industry

risk evaluated by unbiased groups

1.3 National and International Regulation

cant company, or under research contracts let by the applicant. Some details, often including the formula of the substance, are kept confidential in order to protect intellectual property rights. Regulatory authorities have reached accommodations with industry, and regulatory systems including audit processes are in place, but the tensions between open science and confidentiality facilitate claims that regulators and contract researchers – if not the whole scientific process – have been corrupted by the economic power of industry [38]. Dismissing scientific findings because they were produced by a scientist who has at some stage “worked for industry” is thus a powerful weapon for amplifying risk perceptions, even though it commits the genetic fallacy (the validity of science is not determined by its origins), and is somewhat meaningless, since most scientists will be “guilty” by some tenuous association. But, at a time when government scientific regulatory institutions are falling into distrust, this can be damaging. Levels of trust are one of many things which are likely to vary across nations. and are possible sources of variation in risk assessments and thus management policies. Given the inevitable variation among risk assessments performed at the national level, how do we secure international agreement for action or inaction at that level? How can we gain the advantages harmonized approaches can bring, while allowing inevitable (and sometimes desirable) national variations in approach, and at the same time preventing national standards from being used as disguised barriers to trade? One temptation is to resort to scientific reductionism, to regulate on the basis of toxicity testing alone, but this will ignore questions of bioavailability as well as differing national uses, exposures, and values. The recent prominence given to the precautionary principle is an example of this phenomenon. While the precautionary principle properly interpreted is a reasonable injunction not to allow residual scientific uncertainty to serve as a reason for delaying preventative action (though it does not and cannot tell us how much precaution is prudent), it is often misinterpreted as meaning that a single piece of scientific evidence is sufficient to then place the burden of proof on a chemical producer to show that a chemical is safe. There are differences between the US and the EU over how the precautionary principle is interpreted, but even within the US there are legislative enactments which differ in the way in which they impose the burden of proof. For example, the burden of proof lies with the Food and Drug Administration over food ingredients, but the producer bears the burden of proof with the licensing of new pharmaceuticals. The proponents of the Toxic Substances Control Act initially assigned the burden of proof to producers, but as enacted, TSCA placed the burden of proof on the EPA [39, p.171]. These factors have given rise to various regulatory approaches in different countries, but trade matters have also affected the response. The US saw the international focus on the registration of new chemicals as uneven in its impact, since this was an area

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where its chemical industry enjoyed advantage. It therefore pushed for international regulation to be extended to existing chemicals, an area where the chemical industry in the European Union was seen as having advantage [40]. It worked for regulation to be extended to existing chemicals in international arenas such as the OECD Chemicals Program (see below), but it also undertook a process of re-registration of existing chemicals at the domestic level, including biocides, which had the effect of disadvantaging imported biocides. There are numerous intergovernmental organizations which deal with international matters related to the regulation of chemicals, and we shall now examine these briefly before looking at the different trajectories followed by biocides regulation in the US and the EU.

1.4

International Organizations and Chemicals

The Codex Alimentarius Commission (mentioned above) was established in 1962 jointly by the UN World Health Organization and the UN Food and Agricultural Organization. Its current membership is over 160 countries, and its official mandate is to implement the Joint FAO/WHO Food Standards Program, among the aims of which are to protect the health of consumers and to ensure fair practices in the food trade. Members adhere to the Codex voluntarily. The Codex volumes cover specific food areas, or methods of analysis and sampling, and may also contain general principles, definitions, codes, methods, and recommendations. The Codex contains food standards for commodities, pesticide residue limits, codes of hygienic or technological practice, guidelines for contaminants and evaluations of pesticides, food additives, and veterinary drugs. While Codex has more relevance for agricultural pesticides, it thus has the potential to affect biocides which might be present as contaminants in foods. In many ways Codex is a model for the integration of risk management in other areas into international agreements, including the WTO agreements because it is science-based and sets out agreed hazard information, while leaving risk management to national authorities. This is an approach which is finding favor in the evolving trade regime – for example, the Sanitary and Phytosanitary (SPS) Agreement governing quarantine matters [41]. Such approaches limit arbitrary decision-making to use risk-management decisions as disguised barriers to trade while preserving the sovereign capacity of governments to exercise discretion within prescribed rules. The OECD, as we shall see, has played an important role in harmonizing chemical risk management, but there are, however, developments within the UN system which both limit sovereignty and allow scope for trade-restrictive action.

1.4 International Organizations and Chemicals

The Organization for Economic Cooperation and Development (OECD) is an intergovernmental organization established in 1960 with democracies with advanced market economies as its members [42]. Its aims and responsibilities are to promote sustainable economic growth and employment, to promote economic and social welfare, and to stimulate and harmonize the efforts of its members in assisting developing countries. Much of its work is aimed at achieving harmonized policy approaches between member states, and its standards have assisted the development of internationally accepted test protocols and laboratory practices, allowing both reduced costs through mutual recognition approaches and transparency of national risk-management decisions which might serve as trade barriers. The OECD has numerous specialist committees and subsidiary groups in which representatives of member governments participate. In 1970 the OECD established an Environment Policy Committee (EPOC), serviced by an Environment Directorate, to promote the integration of environmental and economic policies, reduce pollution, assess environmental performance, develop environmental protection tools, and improve international data and information on environmental issues. It has a number of activity areas in divisions, including an Environmental Health and Safety Division, within which is located the OECD Chemicals Program. The Chemicals Group was first established by the OECD in 1971, and its work was expanded in 1978 with the creation of a Special Program on the Control of Chemicals. This development of the group’s activity in the 1970s took place within the dramatic context provided by events such as the chemical works explosion at Flixborough in 1974, and that at Seveso in 1976 [43]. The Program commenced by dealing primarily with safety issues relating to specific chemicals such as PCBs, mercury, and CFCs, but it developed to take on a role in creating and harmonizing chemical testing and hazardassessment procedures. This was aimed not only at allowing risk assessments of new chemicals before they were introduced, but at ensuring some degree of standardization, to ensure that differences in national legislation did not create barriers to trade. To these ends, the Program established Test Guidelines (1981), Principles of Good Laboratory Practice (1981), Mutual Acceptance of Data generated in accordance with these practices and guidelines (1981), and a Decision on the Minimum Pre-marketing set of Data (MPD) required for the licensing of new chemicals (1982). All of this activity can be seen as ensuring that regulation of chemical products did not interfere with trade, and was able to proceed on a basis which delivered some economies through scale and avoidance of duplication. International concern then began to develop over the risks of existing chemicals, and in 1987 the OECD Council adopted a decision to strengthen and harmonize existing policies to bring about the systematic investigation of existing chemicals. As a result, the OECD commenced the cooperative investigation of high-volume chemicals (those produced at rates in excess of 10 000 tpa in one country or more than 1000 tpa by more

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than one company). The OECD developed the Screening Information Data Set (SIDS), closely resembling MPD, to share the burden of assembling the minimum data for determining whether a chemical was sufficiently hazardous to require further investigation. These data were then forwarded to various UN bodies such as the International Program on Chemical Safety (IPCS). This move to deal with existing chemicals was the result of political action by the United States, which saw itself as disadvantaged by the focus on new chemicals. As a former USEPA official has noted, during the 1970s in the OECD the US was continuously confronted by European requests for agreement on more restrictions on the development of new chemicals, an area where the US had an edge: The same countries opposed efforts to review the possible hazards associated with chemicals which were already on the market. These chemicals had found their niches in Europe, and the European governments were not eager to sacrifice them. While representatives of all countries were presumably motivated by environmental concerns, priorities were surely influenced by economic interests [44, p.239]. Industry played, and continues to play, a significant role in this process, with the Business and Industry Advisory Council, national chemical industry associations, and individual companies assisting with the promotion of data collection and ensuring the expeditious completion of testing. Again, the test results, if performed in accordance with OECD Test Guidelines and GLP, are accepted throughout the OECD. The International Program on Chemical Safety was established in the aftermath of the United Nations Conference on the Human Environment (UNCHE) in Stockholm in 1972. In 1980, the World Health Organization (WHO), International Labor Organization (ILO), and United Nations Environment Program (UNEP) agreed to cooperate in the program to coordinate work on health, labor, and environmental aspects of chemicals. IPCS has worked closely with the OECD and provides evaluated data which are intended to form a basis on which relevant national authorities can establish policy. These include Environmental Health Criteria (EHC) documents, essentially peer-reviewed statements of hazard designed to assist risk evaluation for human health and the environment at the national level. EHCs have been completed for many chemicals. IPCS Health and Safety Guides (HSGs) are short documents summarizing toxicity information in nontechnical language and providing advice on safe handling and storage, first aid, and so on. There has been long-standing cooperation between IPCS and scientific bodies such as the International Life Sciences Organization (strongly supported by the food industry), the chemical industry, professional scientific and technical societies, and workers’ federations and associations.

1.4 International Organizations and Chemicals

A call for greater activity and coordination of risk management of chemicals was made at the United Nations Conference on Environment and Development (UNCED) in Rio de Janiero in 1992, through Chapter 19 of Agenda 21. This work increasingly has moved outside the OECD to the International Program on Chemical Safety (IPCS), the Intergovernmental Forum on Chemical Safety (IFCS), and to UNEP. Chapter 19 of Agenda 21 identified six work programs: expanding and accelerating the international assessment of chemical risks; harmonization of classification and labeling of chemicals; information exchange on chemicals and chemical risks; establishment of risk-reduction programs; strengthening of national capabilities and capacities for management of chemicals; prevention of illegal international traffic in toxic and dangerous products. UNCED also decided international work on chemicals should be strengthened and better coordinated. WHO, UNEP, and the ILO were to be the focus, but the work of the OECD, FAO, and the European Community was also to be coordinated. Finally, intergovernmental mechanisms should be established where chemicals could be dealt with in an intersectoral manner. In response to this last point, an international conference was held in Stockholm at the end of April 1994, at which was established the Intergovernmental Forum on Chemical Safety. There was representation from 114 governments and over 20 NGOs. Sweden was elected president, and an intersessional group (ISG) was established with a membership of 26. This Forum was to identify priority actions in order to carry out the UNCED strategy. Specified actions were to be completed by the 1997 UN General Assembly special session to review the results of UNCED. On an interim basis, the secretariat of the IFCS was co-located with the IPCS and administered through WHO. The Commission on Sustainable Development established to oversee implementation of Agenda 21 gave the IFCS initiative strong support and called for a close association between IPCS and the Forum [45, p.23]. It was seen as very important that the work of IPCS should be the best possible science, and that only the IFCS should consider policy considerations. Every attempt was thus made to keep the technical work separate from the policy work. While there were advantages in co-locating the two secretariats, therefore, there was a case for trying to ensure that the outside world saw the IPCS as independent in its technical evaluations, removed from any commercial considerations. IPCS had had problems in the past with the United States National Institute of Occupational Health and Safety (NIOSH) because of strong lobbying by industry, and there was a perception that much of what has happened in US chemical regulation resulted from advocacy rather than consultation and consensus. IPCS had tried unsuccessfully to involve the WTO in consultations over the trade implications of its activities. The UNEP governing Council approved the commencement of negotiations to develop a convention on Prior Informed Consent for trade in toxic chemicals in May 1995. Such a convention (the Rotterdam Convention) has been concluded, as has an-

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other to phase out persistent organic pollutants (POPs). Trade restrictions under these conventions will prevail in any conflict with WTO rules (where all parties are members of both) because the subsequent agreement prevails in international law. These developments are therefore important, as are the IPCS and IFCS. Restrictions on chemical trade have already begun to appear under the Rotterdam Convention. In 2000, the European Commission approved the implementation of import restrictions on 13 hazardous chemicals under the Rotterdam Convention, requiring prior informed consent of authorities in importing countries. Five of these substances were already banned or severely restricted: binapacryl, captafol, hexachlorobenzene, and toxaphene. The eight others (lindane, 2,4,5-T, chlorobenzilate, methamidophos, methylparathion, monochrotophos, parathion, and phosphamidon) were being reviewed under EU legislation on pesticides and biocides. The European Crop Protection Association supported the restrictions because most were old and obsolete [46]. It is not just explictly chemical conventions which are important for biocides, however, as regulation can occur under other regimes. For example, the International Maritime Organization (IMO) agreed in December 1999 to ban the use of tributyl tin (TBT) biocides in antifouling paints for ships. A ban of painting ships with TBT antifouling paints was to come into effect on 1 January 2003, and a ban on the presence of TBT on ships hulls was instituted from 1 January 2008. This ban was opposed by the Organotin Environmental Program Association (ORTEPA) which represented TBT producers, including Elf Atochem and CK Witco, but benefitted those companies which had developed alternatives, such as Ciba, Rohm and Haas, Arch Chemicals, and Azko Nobel, again highlighting the way in which regulation creates winners and losers [47]. As indicated above, the US and EU have different histories of chemical regulation, with each seeking advantage through regulation. This applies both for crop protection chemicals and biocides, and the differences in approaches have impacted upon the economics and structure of both sectors of the chemical industry. As a result of the EPA call-in for data review after the US EPA first required biocide registration in 1987 and 1988 amendments to the Federal Fungicide, Insecticide, and Rodenticide Act, about 100 of the 300 active ingredients called in were removed from the market, and the number of players was reduced [48]. It was feared that the development of a new product could escalate in cost to the extent that it would be well beyond the capacity of small producers, although actual costs were only estimated to be $ 2 – 5 million, with a time of 3 – 5 years from drawing board to market. By 1994, almost half the products which had been on the market in 1987 had been withdrawn. The number of registered active ingredients in biocide applications dropped from about 1600 in 1976 to about 400 in 1993 [49]. The 1988 FIFRA amendments alone are estimated to have resulted in 232 existing chemicals being withdrawn

1.4 International Organizations and Chemicals

from the market [22]. There was a general trend away from heavy metals in biocides and towards chemistries which used less chlorine and released less formaldehyde. A similar impact flowed from the US FQPA, which dealt with cumulative risk from all currently licensed uses, meaning that if risks from current uses exceeded the overall standard, a chemical would have to be withdrawn from some uses. There were industry concerns that this would create an incentive to cancel some current uses in order to keep residue tolerances below the standard or permit new uses, and that there were thus incentives to cancel uses for small-market crops in order to minimize the impact on sales. The withdrawal of products had implications for the implementation of re-registration, because it had been intended that the process be self-financing. The review of existing pesticides in the US under the 1988 amendment to FIFRA ran into resource problems because it was to be funded by a one-off fee and annual maintenance fees on registered products. But the revenue base shrank because the regulatory effort resulted in the withdrawal of substances from the market, leaving a shortfall of $ 35 – 40 million in the funds needed to undertake the re-registration of products by the 1997 deadline [50]. This was also to mean that when the EU moved later to re-register existing pesticides and biocides, there were substances still on the European market which had been withdrawn from the US market rather than having been evaluated there. Many of these were then withdrawn in Europe rather than their producers paying the costs of registration, so the lack of international harmonization has resulted in the loss of products which might have been retained on the market had registration costs been spread over both the US and Europe. The EU Biocidal Products Directive (98/8/EC) came into force on 14 May 2000 (it was adopted on 16 February 1998, but the deadline for integrating the Directive into the national law of member countries was 14 May 2000; see Chapter 3) [51]. Existing registration procedures in Canada and the US, being harmonized through the OECD Biocides Steering Group, were ignored in formulating the BPD in the EU, which opted for its own system with higher data requirements. Industry would have welcomed a single risk-assessment procedure [1]. One estimate of the costs for additional data required for a risk assessment and therefore to support an active substance under the EU Biocidal Product Directive is $ 2.25 – 5.3 million. If 500 active substances are supported, the total cost to the sector will be $ 1162 – 2656 million. These costs will mean that small-market active substances are likely to be withdrawn from the market regardless of whether they are environmentally preferable to others simply on cost grounds. Further, the directive is likely to limit innovation as R&D budgets are diverted to regulatory purposes [12]. Many of the 1500 – 2000 biocides currently on the European market were never registered in the US, where some of the necessary data would have been gener-

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ated [1]. Among the beneficiaries of the BPD were therefore expected to be companies such as Huntingdon Life Sciences which specializes in safety, health, and environmental testing. It was expected that the costs of registering an existing biocide would cost around $ 6 million, and a new biocide around $ 9 million, a sum which would take 25 years to recover for most products. As a result of the BPD, attention was likely to turn to new formulations using existing active substances in synergistic combinations, rather than attempting to develop new active substances. Ironically, it was expected that the BPD would expand the markets for halogenated and phenolic biocides, with annual growth rates of 3.5 and 2 percent, respectively, forecast [52]. The BPD provides for a ten year transition period for registering products, but critics have argued that this is inadequate and have pointed to the experience with the Plant Protection Products Directive (91/414/EEC) implemented in 1991 with a similar implementation period for 600 pesticides. After seven years, only one product had been registered [1]. The PPPD came into force fully in July 1993, with the first stage of the PPPD process covering 90 active substances. Producers had to officially notify the European Commission of their support for a specific active substance, and then had 12 months to produce complete technical dossiers containing a series of safety studies. Of 90 active substances covered, 86 were notified. A dossier was also required on at least one PPP containing the active substance in the context of a real situation, a task which was particularly onerous and costly, with the expense running into millions of dollars. Several active substances were supported by several producers, and the intention was that they would cooperate in generating the missing studies and submit a joint dossier for the full review, but this rarely happened, and rapporteur competent authorities were required to pool separate dossiers and evaluate the complete data package produced [50]. There were also free-rider problems with the provision of data. Limited periods of data protection mean that those carrying out the work would be penalized compared those that did not produce data. It was intended to complete the PPP process by July 2003. By 2000, only two existing active substances had been fully assessed and listed in Annex I as approved substances. As a result, the Second Review Regulation for the PPP Directive abandoned separate rounds and attempted to deal with all the remaining existing active substances together [50]. The experience with the PPP does not augur well for the BPD, with indications that the timetable is unrealistic, that it will result in removal of products from the market and assist further concentration of capital in the industry, ironically, a factor which heightens risk perceptions. Further, inasmuch as it appears to be enhancing the market prospects of halogenated and phenolic biocides, it could be counterproductive in terms of its effects, because chlorinated chemicals in particular are the subject of intense opposition from groups such as Greenpeace.

1.5 Conclusion

There is evidence, therefore, of a failure to secure the advantages of harmonization of the regulation of biocides. The BPD is also reflective of the priorities of the “vanguard” states in Europe, particularly the members of the Nordic Council. The Common Principles for reviewing and authorizing biocides were developed by the Danish Environmental Protection Agency [50]. The Netherlands played a similar lead role in developing the measures to implement the Regulation on the evaluation and control of the risks of existing substances (EC793/93) covering high production volume (HPV) chemicals [54]. But the Biocides Directive (98/8/EEC) implements the substitution principle, which requires that products should no longer be authorized for use if there is in existence an alternative product less harmful to human health and the environment. This was first developed in Sweden as part of its “Sunset Program” in 1991 [55], and it subsequently sought to have it adopted in the OECD chemicals program approach to existing chemicals [56]. It is one of several ways in which Sweden and its Nordic Council allies have sought to “harmonize” EU chemicals policy to its own [57]. The dangers of substituting one substance for another without considering carefully any problems which might arise as a result are exemplified by the case of detergents containing phosphates, which contributed to eutrophication of waterways, often resulting in toxic algal blooms. Environmentally conscious industry and consumers in the 1980s were quick to move to new “green” detergents, but in 1996 Bryn Jones, the former head of Greenpeace in the United Kingdom, who led the worldwide campaign by for a phase-out, admitted it had been a mistake, with the substitution for phosphate detergents causing more problems than they solved. The German company Henkel developed phosphate substitutes – such as zeolites and polycarbonates – and licensed them internationally, but they caused rivers to foam in Switzerland where phosphates had been banned and possibly exacerbated algal blooms because of their toxicity for Daphnia water fleas which ate algae and thus helped prevent algal blooms. Another example of substitution without adequate risk assessment provides an even more salutary lesson: CFCs were developed in 1928 as substitutes for inflammable and noxious refrigerants [58]; their threat to the ozone layer was not identified until 1974. 1.5

Conclusion

The regulation of biocides has historically been of less salience than that of agricultural pesticides, but has come more to the fore as progress has been made on agricultural products, and attention has turned to smaller volume chemicals. As we have seen in this chapter, regulation of chemicals generally is affected by numerous political, social, and economic factors, and, in turn, has consequences

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1 The Political, Social, and Economic Framework

for these factors. Regulation is not just driven by concerns over efficacy or safety, but by the economic impact of regulation, which always creates winners and losers, at the company or national levels. This is a consideration which is made all the more important by the importance of intellectual property in the chemical industry. Patents are a form of licensed limited monopoly, and restrictions on competing products which are out of patent can enhance their value. Regulation of biocides also impacts by raising the costs of keeping existing products on the market and has helped assist the withdrawal of several active substances. It advantages companies which are global in character and products which enjoy larger markets, because registration costs can be recovered more readily in these circumstances. Much of the political concern the chemical industry has faced has been the result of concern over the size and power of the transnational corporations which dominate the industry. The biocides sector has traditionally seen a much more fragmented industry structure, but ironically the recent moves to increase regulation in most jurisdictions are likely to accentuate capital concentration in the sector. Different approaches have been taken in the US and the EU, and this has meant that the later EU regulation under the Biocidal Products Directive has been more costly than it might have been if harmonization of regulatory approaches had been achieved. Chemical regulation must reflect risk evaluations which vary from one situation to the next, and this poses a dilemma, since it makes sense for variation to exist in risk regulation between jurisdictions as risk-benefit calculations vary. This creates opportunities for national differences in regulatory approaches to be exploited for economic advantage. The Biocidal Products Directive has placed new demands on chemical testing. As we have seen, this is but one stage in the risk-management process which must inevitably involve the consideration of political, social, and economic factors, as well as the science of toxicity. But the rise in importance of ethical concerns, as evidenced by the rise of the animal rights lobby, has made even science a subject of increasing politicization.

References

References

[1] C. Hume, S. K. Moore, European Directive Will Push Up Costs, Chemical Week. 1999, September, 46. [2] OECD, Pesticide Programme Biocides – Non-agricultural Pesticide: A Report of the Survey of OECD Member Countries’ Approaches to the Regulation of Biocides Environmental Health and Safety Publication (No. 9 in Series OECD Pesticides Publications); 1999, June.

[3] L. N. Davis, The Corporate Alchemists: The Power and Problems of the Chemical Industry, Temple Smith, London, 1984. [4] B.G. Rueben, M.L. Burstall, The Chemical Economy, Longman, London, 1973. [5] G. C. Hufbauer, Synthetic Materials and the Theory of International Trade, Duckworth, London, 1966.

References [6] E. de Ghellinck, The Chemical and Pharmaceutical Industries, in The European Challenge, ed D.G. Mayes, Harvester Wheatsheaf, London, 1992. [7] W. Grant, W. Paterson, C. Whitston, Government and the Chemical Industry: A Comparative Study of Britain and West Germany, Clarendon Press, Oxford, 1989. [8] W. S. Comaner, The Political Economy of the Pharmaceutical Industry, Journal of Economic Literature. 1986, 24, 1178 – 1217. [9] R. Carson, Silent Spring, Houghton Mifflin, Boston, 1962. [10] M. K. Tolba, O. A. El-Kholy, The World Environment 1972 – 1992: Two Decades of Challenge, Chapman & Hall/UNEP, London, 1992. [11] L. Young, S. Ram Rao, S. G. Cort, Industry Corner: The Pesticide Market and Industry: A Global Perspective, Business Economics. 1996, 31(1), 56 – 61. [12] G. Lloyd, The Biocides Directive and Innovation: A Model of Over-Regulation? Paper presented at the joint European Commission CEFIC conference The Impact of New Regulatory Requirements on the Chemical Industry and its Competitiveness, Brussels, 2000, 5 October. [13] P. Shrivastava, Bhopal: Anatomy of a Crisis, Ballinger, Cambridge, Mass., 1987. [14] F. M. Bordewich, The Lessons of Bhopal: The Lure of Foreign Capital is Stronger Than Environmental Worries, Atlantic Monthly. 1987, March, 30 – 34. [15] P. Reiter, From Shakespeare to Defoe: Malaria in England in the Little Ice Age Emerging Infectious Diseases. 2000, 6(1), January–February. [16] K. Reichelderfer, M. Kuwano Hinkle, The Evolution of Pesticide Policy, in The Political Economy of US Agriculture, ed C. S. Kramer, Washington, D.C., Resources for the Future, 1989. [17] R. Boardman, Pesticides in World Agriculture: The Politics of International Regulation, New York, St Martin’s Press, 1986. [18] R. L. Paarlberg, Managing Pesticide Use in Developing Countries, in Institutions for the Earth: Sources of Effective International Environmental Protection, eds P. M. Haas, R. O. Keohane, and M. A. Levy, Cambridge, Mass., MIT Press, 1993.

[19] M. J. Dobson, Contours of Disease and Death in Early Modern England, Cambridge, Cambridge University Press, 1997. [20] B. N. Ames, R. Magaw, L. Swirsky Gold, Ranking Possible Carcinogenic Hazards, Science. 1987, 236 (17 April): 271 – 280. [21] S.S. Epstein, The Politics of Cancer, Sierra Club Books, San Francisco, 1978. [22] E. S. Mintzer, C. Osteen, New Uniform Standards for Pesticide Residues in Foods, Food Review. 1997, 20(1), 18 – 27. [23] National Academy of Sciences Regulating Pesticides in Food: The Delaney Paradox, National Academy Press, 1987. [24] T. Colborn, J. Peterson Myers, D. Dumanoski, Our Stolen Future: Are We Threatening Our Own Fertility, Intelligence, and Survival? A Scientific Detective Story, ed E. P. Dutton, New York, 1996. [25] B. Wynne, Risk Management and Hazardous Waste: Implementation and the Dialectics of Credibility, Springer-Verlag, Berlin, 1987. [26] M. Douglas, Risk and Blame, Routledge, London, 1992. [27] D. Krewski, P. L. Birkwood, Risk Assessment and Risk Management: A Survey of Recent Models, in Risk Assessment and Risk Management, ed L. Lave, Plenum Press, 1987. [28] J. D. Graham, J. Kassalow Hartwell, The Risk Management Approach, in The Greening of Industry: A Risk Management Approach, eds J. D. Graham and J. Kassalow Hartwell, Harvard University Press, Cambridge, Mass., 1997. [29] T. O. Tengs, M. E. Adams, J. S. Pliskin, D. G. Safran, J. E. Siegel, M. C. Weinstein, J. D. Graham, Five-Hundred Life-Saving Interventions and Their Cost-Effectiveness. Risk Analysis, 1995, 15(3), 369 – 390. [30] R. J. Zeckhauser, W. Kip Viscusi, The Risk Management Dilemma, Annals of the American Academy of Political and Social Sciences. 1996, 545, 144 – 155. [31] S. L. Brown, Harmonizing Chemical and Radiation Risk Management Environmental Science and Technology. 1992, 26, 2336 – 2338. [32] R. Brickman, S. Jasanoff, T. Ilgen, Controlling Chemicals: The Politics of Regulation in Europe and the United States, Cornell University Press, Ithaca, NY, 1985.

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1 The Political, Social, and Economic Framework [33] B. Fischoff, S. Lichtenstein, P. Slovic, S. Derby, R. Keeney, Acceptable Risk, Cambridge University Press, New York, 1981. [34] S. Jasanoff, Risk Management and Political Culture, Russell Sage Foundation, New York, 1986. [35] J. V. Rodricks, Calculated Risks: Understanding the Toxicity and Human Health Risks of Chemicals in Our Environment, Cambridge, Cambridge University Press, 1992. [36] C. Anderson, Cholera Epidemic Traced to Risk Miscalculation, Nature. 1991, 354, 255. [37] P. H. Barnes, Conflicting Notions of Risk: The Chasm of Conflict Between Institutional Regulators and the Public, in Integrated Risk Assessment: Current Practice and New Directions, eds R. E. Melchers and M. G. Stewart, Balkem, Rotterdam, 1995. [38] S. Beder, Global Spin: The Corporate Assault on Environmentalism, Scribe, Melbourne, 1997. [39] R. G. Noll, Reforming Risk Regulation, in Annals of the American Academy of Political and Social Sciences, 1996, 545, 165 – 175. [40] G. E. Schweitzer, Toxic Chemicals: Steps Towards Their Evaluation and Control, in Environmental Protection: The International Dimension, eds D. A. Kay and H. Jackson, Allanheld, Osmun, Totowa, NJ, 1983. [41] D. Robertson, A. Kellow, Globalisation and the Environment: Risk Assessment and the WTO, Edward Elgar, Aldershot, 2001. [42] H. Somsen, The European Union and the OECD, in Greening International Institutions, ed J. Werksman, Earthscan, London, 1996. [43] OECD, The OECD Chemicals Programme, OECD, Paris, 1993. [44] G. E. Schweizter, Borrowed Earth, Borrowed Time; Healing America’s Chemical Wounds, Plenum Press. New York, 1991. [45] C. Mensah, The United Nations Commission on Sustainable Development, in Greening International Institutions, ed J. Werksman, Earthscan, London, 1996.

[46] J. Brown, EU Restricts Chemical Imports, Chemical Week. 2000, 1 November. [47] A. Scott, IMO Agrees on Tributyl Tin Ban, Chemical Week. 1999, 8 December. [48] H. Tilton, Biocide Makers Deep in Regulatory Waters; Chemical Marketing Reporter. 1989, 24 April. [49] R.Westervelt, Biocide Market Pared Down by Environmental Regulations: Producers Look Overseas to Maintain Margins, Chemical Week. 1994, 27 July. [50] R. Begley, E. Chynoweth, Pesticide Registration: High Anxiety in the US and Europe: EPA Cries Poor Again While EC Starts Its Program, Chemical Week. 1992, 9 September. [51] D. Knight, Active Control for Biocides, Chemistry and Industry. 2000, 7 August. [52] K. Walsh, S. K. Moore, European Directives Will Kill Some Actives, Chemical Week. 1998, 21 October. [53] K. Walsh, S. K. Moore, European Directives Will Kill Some Actives, Chemical Week. 1998, 21 October. [54] P. McCutcheon, Risk Management of Chemical Substances in the European Union, in The Politics of Chemical Risk: Scenarios for a Regulatory Future, eds R. Bal and W. Halffman, Kluwer, Dordrecht, 1998. [55] Swedish National Chemicals Inspectorate and Swedish Environmental Protection Agency, Risk Reduction of Chemicals, KEMI Report No 1/91, 1991. [56] A. Kellow, International Toxic Risk Management: Ideals, Interests and Implementation, Cambridge University Press, Cambridge, 1999. [57] R. Nillson, Integrating Sweden into the European Union, in The Politics of Chemical Risk: Scenarios for a Regulatory Future, eds R. Bal and W. Halffman, Kluwer, Dordrecht, 1998. [58] D. L. Downie, UNEP and the Montreal Protocol, in International Organizations and Environmental Policy, eds R. V. Bartlett, P. A. Kurian and M. Malik, Greenwood Press, Westport, 1995.

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2

The Biocides Market Patricia Martin

2.1

Introduction

Wherever there is a source of nutrition and moisture micro-organisms, such as bacteria, viruses, algae, moulds, and yeasts, will grow, even in extreme climatic conditions. The growth of these micro-organisms may impact on human health by causing spoilage of food products. Alternatively, they may interfere with manufacturing processes by causing rot or slimes to form or by blocking valves and pipes. Man’s principal defence against these micro-organisms is the use of a biocidal product. Biocidal products are supplied in a wide variety of forms and range from the inexpensive bulk commodity chemical material to the high-priced niche formulation designed to target a specific micro-organism(s). There are a number of chemical classes of material which comprise today’s biocidal products, and these are marketed with distinct efficacy (or performance) profiles against a range of micro-organisms. What this range of biocidal products has in common is the ability to kill (or control the proliferation of) these deleterious micro-organisms under a given set of conditions. It is this property which makes biocidal products commercially viable in the divergent global environmental marketplace.

Definitions

In the European Community (EC) legislation, within the body text of the Biocidal Products Directive (98/8/EC), there is a rather complex definition of a biocidal product [1]: Active substances and preparations containing one or more active substances, put up in the form in which they are supplied to the user, intended to destroy, deter, render harmless, prevent the action of, or otherwise exert controlling effects on any harmful organism by chemical or biological means. The Biocides Business: Regulation, Safety and Applications. Edited by Derek J. Knight and Mel Cooke Copyright ª 2002 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN: 3-527-30366-9

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2 The Biocides Market

A “harmful organism” is further defined as: Any organism which has an unwanted presence or a detrimental effect for humans, their activities or the products they use or produce, or for animals, or for the environment. The situation regarding regulation of those products which by chemical (or biological) means prevent the adverse effects of micro-organisms (or control pests) in Europe and the parallel regulation of plant protection products (which are commonly referred to as pesticides) is somewhat different to the legislative regimes which exist in the United States of America. Here regulatory control of both crop and noncrop protection products is administered by the USA Environmental Protection Agency (EPA) Office of Pesticide Programs (OPP). However, in the USA noncrop pesticides or biocidal products are usually referred to as antimicrobial pesticides. Antimicrobial pesticides, such as disinfectants and sanitizers, are pesticides defined in the USA legislation as being those that are intended to: *

*

disinfect, sanitize, reduce, or mitigate growth or development of microbiological organisms, or protect inanimate objects (for example, floors and walls), industrial processes or systems, surfaces, water, or other chemical substances from contamination, fouling, or deterioration caused by bacteria, viruses, fungi, protozoa, algae, or slime.

The USA definition does not include certain antimicrobial pesticides intended for food use, nor does the legislation apply to personal health care disinfectants, which are regulated as “drugs” under the Food and Drugs Administration (FDA). Thus, there is likely to be continuing confusion and uncertainty for global suppliers of these biocidal products with respect to which regulatory authority has to be adhered to. The major determinants are: * *

the end-use application of the antimicrobial/biocidal product, and the specific nation for which the biocides will be marketed.

It appears that despite the recent efforts of the Organization for Economic Cooperation and Development (OECD) on various aspects of harmonization [2], there is still some way to go before the major countries/trading blocks are prepared to compromise and set a uniform standard to ensure mutual acceptance of data packages for the prior approval of biocidal products on a global basis.

2.1 Introduction

2.1.1

EC Market: End-use Applications

According to the EC Directive (98/8/EC) the biocidal products industry may usefully be considered as being composed of four major areas with some 23 different product types encompassed therein. These are further illustrated below: *

*

*

*

Main area 1: Disinfectant and general biocidal products Product Type: (1) Human hygiene biocidal products (2) Private area/Public health area disinfectants and other biocidal products (3) Veterinary hygiene biocidal products (4) Food and feed area disinfectants (5) Drinking water disinfectants Main area 2: Preservatives Product Type: (6) In-can preservatives (7) Film preservatives (8) Wood preservatives (9) Fiber, leather, rubber; and polymerized materials preservatives (10) Masonry preservatives (11) Preservatives for liquid-cooling and processing systems (12) Slimicides (13) Metal working-fluid preservatives Main area 3: Pest control Product Type: (14) Rodenticides (15) Avicides (16) Molluscicides (17) Piscicides (18) Insecticides, acaricides, and products to control other arthropods (19) Repellents and attractants Main area 4: Other biocidal products Product Type: (20) Preservatives for food or feedstocks (21) Antifouling products (22) Embalming and taxidermist fluids (23) Control of other vertebrates

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Despite the above categorization and the statement in the body text of the Directive (98/8/EC) which specifically excludes products which are covered under the scope of other existing Community legislation, there remain a number of “gray areas” yet to be finally resolved to allow suppliers to understand if their products are in, or out of, scope of the Biocidal Products Directive and hence strive for compliance with this legislation. It is understood that the EC Commission may document decisions on scope issues in a written form similar to the “Manual of Decisions”, which is associated with the notification of new substances legislation [3] under the 7th Amendment to the Dangerous Substances Directive (67/548/EEC).

2.2

EC Market: Consumption of Biocidal Products by End Use

The following data relates to the use of specialty biocides and excludes commodity chemical data on substances such as chlorine and hypochlorite. The latter chemicals have many other functionalities besides that of antimicrobial use. According to a survey conducted by the Biocides Information Services [4], the western and central European consumption of specialty biocides was in excess of US $ 850 million at manufacture level during 2000. Figure 2.1 illustrates the divisions by main end-use application area. As might be expected, the single largest end use in western and central Europe for biocidal products is that related to wood preservation and timber treatment applications. This is coincidentally also the product type with the greatest existing controls legislation in a number of member states governing the use of these treated products

Fig. 2.1. European consumption of specialty biocidal products by main end-use application for the year 2000

2.3 Global Market: Consumption of Biocidal Products by Geographical Region

and is therefore expected to be an application area where industry have a wealth of both hazard and exposure data. For these reasons, primarily, this product type, (PT8), formed the first of two end uses to be called in under the First Review Regulation [5], the other being rodenticides, (PT14), which were formerly controlled under crop pesticides legislation in the majority of EC Member States with existing laws. The European market for biocidal products in 1999 – 2000 was valued at some US $ 850 million by various international marketing consulting companies, including Frost and Sullivan [6]. The latter forecast a total market revenue rise to US $ 984 million by 2006 with a compound annual growth rate of some 2.1 %.

2.3

Global Market: Consumption of Biocidal Products by Geographical Region

It has been variously estimated that the global consumption of biocidal products in recent years accounts for some US $ 3200 – 3500 million. The single largest consumer is undoubtedly the North American region (43 %) with Europe (ca. 27 %) being the second largest consumer [4]. An illustration of the global market consumption by regions is given in Figure 2.2. According to figures released by the market research company, Directed Research/ Agricultural Information Services (DR/AIS), noncrop pesticides or biocidal products constituted some 12 % of the global pesticide market for active substances (AIS) at manufacturer level in 1997 [7]. DR/AIS has been tracking the use of biocidal products since 1992 and ascertained that this area was the fastest growing of all pesticide segments, and during the period 1995 – 1997 it actually achieved an average growth rate of almost 4 % (excluding the flower and over-the-counter home and garden market uses). Within Western Europe it is generally accepted that the demand for industrial biocides, based upon country or region is led by Germany (ca. 25 % market). The United

Fig. 2.2.

Consumption of biocidal products by geographical region

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Kingdom, France, and the Nordic countries (Denmark, Finland, Norway, and Sweden) are the second largest markets (15 %), followed by Italy (9 %), then the Benelux countries (8 %) together with Spain and Portugal (8 %), and finally Austria, Ireland, Greece, and Switzerland (4 %). According to a report from the Freedonia Group [8], global demand for biocidal products is forecast to increase 5.6 % p. a. to US $ 5.8 billion in 2004 (statement issued in early 2001). North American demand is expected to grow by 5 % p. a. to US $ 2.6 billion with Western Europe markets growing by a similar rate to US $ 1.4 billion and usage in Asia Pacific increasing at the rate of 6.8 % p. a. to US $ 1.2 billion. Demand from the rest of the world is expected to grow at 6.7 % p. a. to US $ 580 million.

2.4

Supply Chain for Biocidal Products

The European biocides industry is a highly varied assortment of small businesses. The introduction of the Biocidal Products Directive (98/8/EC) brings into focus, probably for the first time for many, the wide ranging potential problems which might adversely affect our domestic lifestyle and health, as well as industrial products and processes, caused by the effects of “pests” ranging from micro-organisms to mammals. This variety of causative agents leads to the supply of counteracting products, biocidal products, to effect control of these pests from a highly fragmented, but often highly specialized industry. The biocidal products industry operates globally to deliver its products and services from manufacture to end user by way of a supply chain that might usefully be categorized into three distinct groups as listed below: * * *

active-ingredient manufacturers formulators of biocidal products/service companies distributors.

The manner in which the supply of biocidal products reaches the market is illustrated in Figure 2.3.

2.4.1

Active-ingredient Manufacturers

These companies manufacture the substance(s), which have the ability to kill or otherwise control deleterious micro-organisms or affect pest control. Data to evaluate the potential health, safety, and environmental effects of these substances as well as their

2.4 Supply Chain for Biocidal Products

Fig. 2.3.

Supply chain scenario for the biocides industry

efficacy are collected as part of the costs for developing and marketing the active substances. It is seldom the case that companies involved in the biocides industry act solely as manufacturers of active ingredients, more often than not they are also involved in formulation of the specialty biocidal products for the various end-use applications. Active-ingredient manufacturers’ major route for supply is direct sales to companies that prepare formulations, the formulators or service companies. This route probably accounts for up to 60 % of their distribution. In addition, they may sell the active ingredient direct to the end user and/or use distributors. Both routes are likely to account for some 20 % each of the supply chain movement for active ingredients. The leading active-ingredients manufacturers include companies such as: Akzo Nobel, Arch, Avecia, Bayer, BASF Microcheck, Ciba, Clariant, Dow, Great Lakes, Lonza, Rohm and Haas, and Troy.

2.4.2

Formulators/Service Companies

The strengths of this component of the supply chain for biocidal products are intimately related to their customer-care approach to problem-solving and the provision of on-site services. Using these attributes has enabled the formulators to achieve a significant market penetration for their custom-based products based upon the active ingredients purchased. The formulator is able to put together specific customerblends, at relatively low costs, to meet niche requirements.

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The know-how and skills of providing these formulated products (with often a broader spectrum of micro-organism(s) control) to meet specific end-user requirements afford the formulator the opportunity to pass on a significant charge for the product and service in excess of the cost of the ingredients in the biocidal formulation. The leading formulators include such companies as: Buckman, Creanova, DiverseyLever, Ecolab, Henkel, Hercules BetzDearborn, Nalco, Rentokil, Suez Lyonnais des Eaux, Sanitised, and Schulke and Mayr.

2.4.3

Distributors

Distributors are the “middlemen” in the supply chain acting as agents for both the active-ingredient manufacturer and the formulator to enable speedy and competitive delivery of, often small, volumes of biocidal products to end-use customers globally. The distributor is a popular means for supply since they tend to market a range of chemical additives to end users and are often already involved in a supply chain relationship outside of the biocides industry. Simply adding biocidal products onto an already existing delivery schedule enables the distributor to be competitive. The leading distributors for biocidal products include: Ashland, Brenntag, Biesterfeld, Ellis and Everard, Kloeckner, Quimidroga, and Univar.

2.5

“Key Drivers” for Market Development

Undoubtedly the paramount influence on the European biocides market for the next ten-years or so will be the Biocidal Products Regulation and any associated “daughter” legislation. The principal impacts of the legislation are expected to be: *

*

*

*

Reduction in product development activity Associated with the increased costs for registration and leading to fewer new products on the market. Not all the currently listed “active substances” presently available will be subsequently “approved” and be listed in Annex 1 (1A) Support through the “approval” procedures will depend upon “profitability” and willingness of manufacturer (and others) to fund data collection. Registration/approval processes favor large companies Large companies expected to be “data-rich”. Expected changes include extension of existing product range to new applications and to new formulations.

2.5 „Key Drivers“ for Market Development *

Expected changes include further company mergers and/or acquisitions and divestments from noncore activities.

A conservative estimate of expected growth of the European biocide industry is some 2 % per year up to 2005 [4]. A number of factors will impinge on this forecast and include: * * * * * *

developing countries population demographics “safer” alternatives technological change awareness of “hygiene” new uses.

Developing Countries – the use of biocidal products is likely to increase in concert with rising living standards. It may also be expected that there will be a fundamental change away from the older active ingredients, such as the organochlorine chemicals, in these areas as they are progressively phased-out in other more developed regions based, hopefully, on a thorough assessment of risk rather than simply their intrinsic hazardous properties. Population Demographics – people are retiring earlier and/or have more leisure time, and with this there will be an expected increase in leisure time and activities. It is expected that “the gardening population” will significantly increase, and hence use of biocidal products associated with this pursuit. “Safer Alternatives” – some traditional biocidal active ingredients are already being “substituted” as the result of other legislative pressures i.e. ban on the use of mercurials, pentachlorophenol, and triorgano tin compounds. These bans and other prospective restrictions on the marketing and use of the “older” biocidal products, as a result of their risk assessment under the new Directive (98/8/EC) will lead to less choice for the end user. Technological Change – the most obvious example is in the shift away from solventbased paints to aqueous-based systems over the last ten years as a result of the hazards associated with solvent-neuropathies perceived to be caused as a direct result of (chronic) inhalation exposure (or dermal contact) to the off-gases – known as volatile organic carbons (VOCs). “Hygiene” Awareness – over the past three to five years, the use of biocidal products as hygiene aids in household products, personal care, and textiles has escalated aided by media presentations. Hardly any member of the shopping public can have failed to observe the upsurge in advertising associated with products marketed under the MICROBAN name in the general grocery and supermarket chains. Despite the claims

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made, the active ingredient, a chlorinated phenolic compound, is not all that efficacious against certain commonly occurring bacterial pathogens found in various domestic environments. It seems the public are not interested in “efficacy” per se, if that means they loose out on available products, which provide at least some degree of perceived “safety” with respect to actions against unwanted micro-organisms. New Uses – human research and innovation proceeds in line with the quest for sustainability of finite resources at the same time as re-use/recycling continues, and, as part of this evolutionary process the use of biocidal products, to address these new situations, will abide as new applications and end uses demand. New, or novel, biocidal active ingredients are unlikely to be at the forefront of the research and development plans of many global companies due to the high costs associated with gaining entry to the market (especially in the EC with the Biocidal Products Directive) and the relatively long recovery times for recouping these costs. The volumes of supply of biocidal active ingredients are coupled to the low inclusion levels in the formulated products, and hence the time to recover initial development costs (and associated hazard and efficacy data) can be greater than ten years, by which time there will be no data protection. Second suppliers, “me too” products, can enter the market place with none of the development costs of the original developer/manufacturer.

2.6

History and Current Trends 2.6.1

European Community

The first step in the EC towards a comprehensive regulatory framework for biocidal products was initiated in 1991 when an “early unofficial” draft [9] of a proposed Biocidal Products Directive appeared and this was subsequently followed in 1993 by the official first proposal [10]. The premise of the European Commission in 1993 was to establish a single European market in biocidal products by the introduction of a harmonized authorization scheme based upon the assessment of risks to humans and the environment, coupled with a consideration of efficacy. Before the introduction of the Biocidal Products Directive (98/8/EC), the European market for these products was something of a “jig-saw” insofar as being able to identify those member states with any forms of regulation, and which particular end uses this applied to, prior to being able to supply products to customers. A variety of regulatory practices were utilized in the various member states, and these were reviewed under an OECD initiative in 1997 using a questionnaire survey

2.6 History and Current Trends

approach [2]. It appeared that those countries surveyed had an approval system for wood preservatives, and most also had a system for products used in vertebrate and invertebrate pest control (specifically for rodenticides, repellents, and insecticides/acaricides for direct use on humans, clothes, and/or pets). In the UK, the only legislation covering biocidal products prior to enactment of the EC Directive (98/8/EC) into UK law was that of the Control of Pesticides Regulations (COPR) 1986, and this covered wood preservatives, public hygiene insecticides, masonry biocides, and antifouling paints. Approval schemes administered by other authorities in the UK did consider the nature and properties of the chemicals to be used in areas such as, for example, swimming pools and off-shore applications. The Biocidal Products Directive aims to ensure harmonization of the European market for biocidal products and their active substances and at the same time will guarantee a high level of protection for humans and the environment. This harmonization of the internal market is likely to be of more immediate benefit to those industries where controls already exist. However, the removal of the barriers to trade will not be at the expense of lowering health or environmental protection. The Directive will work by ensuring that only those biocidal products which contain an active ingredient(s) listed in Annex I of the Directive will be authorized for use. In parallel with the Directive, the Commission will be utilizing various other legislative instruments, such as Regulations, to require Industry to submit data on “existing active ingredients” over a ten year timetable. The first of these Regulations [5] “called in” data for all active ingredients used as wood preservatives and rodenticides for evaluation at Commission level and possible inclusion in Annex I. During the intervening period of this evaluation, existing national rules in the various member states continue to apply to any biocidal product containing an existing active ingredient until such time as it is listed in, or refused listing in, Annex I. Once an active ingredient is listed in Annex I, biocidal products containing this active substance may be authorized for marketing at individual member-state level by the national competent authorities. Once a product is authorized in the first member state it will be possible for it to be mutually recognized and hence authorized by other member states. Despite the laudable aims of the introduction of the Directive, which are supported by the European biocides industry, there are still doubts about the implementation and running of this very complex legislation being voiced even at this late stage by the industry. Consistently the biocides industry has stated that the Directive will seriously inhibit innovation. Industry has illustrated this concern by reference to the following facts [11] gathered against the background of the current nonharmonized schemes for biocidal products in existence across the member states:

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* *

one to two new active ingredients for biocidal products per year in the EC (22 new active substances since 1984 in the USA) seven to eight new active molecules for plant protection products 250 new industrial chemicals per year in the EC.

According to an industry spokesperson, the Directive is likely to replace the USA EPA as the “major hurdle” to worldwide research on new biocides [12]. The European Chemical Industry Federation, CEFIC, believes that few, if any, companies will carry out targeted speculative research on new biocide active substances in the near future, and thus it is difficult not to envisage that the already low rate of innovation in this area will become even lower. According to the EC Commission, the introduction of the Directive in this area was the “simplest legislative instrument and also the least costly [option], which ensures a high level of health and environmental protection” [13]. The EC Biocides Industry has always disagreed on this aspect related to industrial competitiveness and at open meetings have given examples to attempt to provide an insight for the regulators and the public of the real costs associated with this Directive. There can be little doubt among industry and regulators that the Directive will significantly increase the costs of compliance as a consequence of the following expenses: * * * * *

regulatory studies, eco-/toxicology, environmental fate efficacy studies dossier preparation competent authority review charges legal costs for forming/running task forces

Industry will pass these additional costs on to the European consumer of these biocidal products as they do not have the necessary resources available to absorb the costs involved. An “average” EC manufacturer of active ingredients for specialty biocidal products is likely to have an annual turnover of less than ECU/euro 20 million (ca. US $ 17.5 million) generated from the sales of eight active substances in a total market of between ECU/euro 300 – 500 million (ca. US $ 260 – 440 million) p.a. [11]. The annual profit, some ECU/euro 2.5 million (ca. US $ 2.2 million) per company (based on 30 companies) is less than the predicted costs for compiling the data set for one existing active substance, ECU/euro 2.8 – 4.2 million (ca. US $ 2.5 – 3.7 million). Thus it is not difficult to visualize the impact on innovation. During the ten year review period (assuming that the active ingredient is not called-in “early” via a Regulation) the “average” EC manufacturer of active ingredients for specialty biocidal products will have a maximum income of less than ECU/euro 200 million (ca. US $ 175

2.6 History and Current Trends

million). If the average investment in research and development is say 5 % of income, then this equates to some ECU/euro 10 million (ca. US $ 8.8 million). ECU/euro 10 million (ca. US $ 8.8 million) would only support three to four active substances, and yet the “average EC manufacturer” needs to support twice that number of active-ingredient materials before considering investment in new novel active-ingredient chemistries!

2.6.2

United States of America

The system administered in the United States by the Environmental Protection Agency (EPA), commonly known as the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), has been in situ for a number of years and has both similarities and differences, in approach and application, for the control of biocides to that now proposed in the EC. FIFRA registration procedures apply to both crop and noncrop pesticides. The EC Biocides Industry had hoped that the regulators, when considering harmonization of legislation for the control of biocidal products in the EC, would look to improve on, and learn from, the experiences of the operation of the FIFRA process. Following minor revisions to the FIFRA registration process in 1984 with significant revisions in 1988 (see later chapter for greater detail) which required the intervention of the President, the EPA saw a substantial increase in its workload, and with that a realization that the review procedures (and re-registration) would not be completed until sometime after the nine year period allowed for by the changes in the law. At the start of this FIFRA process, there were approximately 420 active ingredients classified for use in noncrop pesticides, however as the review program began to take effect this number was reduced to 261. The EC biocides industry was therefore rightly concerned that if the significant resources available to the EPA were strained by review of 261 active substances, then it does not take a mathematical genius to comprehend the difficulties likely to be faced by the EC Commission and the national competent authorities with respect to the >900 active substances on the European list. The costs to US industry for the FIFRA ’88 program were estimated at £ 225 million; recently the EPA informed registrants that the funds were nearly used up and requested industry to contribute additional funds to this re-registration procedure. Again, this must raise doubts for the European biocides industry and their ability to fund the newly introduced legislation especially when one considers that there have been a number of measures introduced in the US legislation to streamline the process and keep costs commensurate with likely exposure and risks, such as:

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2 The Biocides Market * *

a “tiered approach” for the submission of hazard data efficacy data only required with the dossier for those products used to control pests, which pose a threat to health.

Such measures have not been forthcoming with respect to the development and implementation of the Biocidal Products Directive, despite all the scientific and commercial presentations from industry since 1991. Indeed the recent Commission White Paper on a future chemicals policy [14] is at odds with this Directive. The White Paper advocates a “tiered approach to testing” commensurate with risk and it also seeks to promote innovation and competitiveness of the EC industry. How then does the Commission reconcile their proposed strategy with Directive 98/8/EC?

2.7

Impact of New Legislation

The introduction of the Biocidal Products Directive in Europe will undoubtedly lead to the loss of the small- and medium-sized enterprises/companies (SMEs), which until now have been responsible for many of the formulations on the European market supplied into niche application areas. The costs for generation of the EC dossier required to register these small volume products will be prohibitively expensive for the SMEs. However, there may be a glimmer of hope afforded in the legislation if the following concepts are utilized: * * *

low-risk products frame formulations task forces.

Low-Risk Product – is one which under the conditions of use is considered to pose only a low risk to humans, animals, and the environment and contains as active substance(s) one or more of those listed in Annex 1A of the Directive and does not contain any substance(s) of concern. The legislation instructs that decisions on low-risk products will be made within 60 days, and that they will be “registered” on receipt of a simplified dossier containing the following elements: * * *

applicant details identity of the biocidal product intended uses

2.7 Impact of New Legislation * * *

efficacy data analytical methods classification, packaging and labeling data, and a safety data sheet

Frame Formulation – is considered to be a “specification” for a group of biocidal products having the same end-use and user type. These products contain the same active substance (not necessarily purchased from the same manufacturer, but at least the active substance must have the same product/chemical specification). This concept of frame formulations is similar to the proposal introduced by the EPA for the “Clustering of Products” following the 1988 review of FIFRA to facilitate the increased workload associated with the re-registration process. In PR Notice 88 [15], Clustering of Quaternary Ammonium Compounds, the EPA placed all 211 registered quaternary (“quats”) ammonium compounds classified as active substances into one of four groups depending upon the alkyl chain length and the percentage carbon distribution within the chain. The frame-formulation concept allows for small variations in the composition of the chemical substances present in a frame formulation provided: * *

these variations do not affect the level of risk, nor affect the efficacy of the product.

For example, the legislation allows for: * * *

a reduction in the percentage of the active ingredient, and/or a variation in the percentage of nonactive substances, and/or the replacement of colors and perfumes.

Under the existing terms of the draft Technical Notes for Guidance (Finland) [16], the process would then be: *

*

*

The “mother formulation” representative of many like-products would be authorized following assessment by the normal procedure. Subsequent formulations, from applicants with rights to the dossier of the “mother product”, and which are a “fit” for the frame concept, would only require a simplified dossier for submission and assessment. The “simplified” assessment dossier should lead to registration within 60 days.

The “ownership” of the dossier associated with the “mother product” and subsequent “frame groups” may rest with individual companies, groups of loosely associated companies, or may be more formalized under a Task-Force sharing agreement.

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Task Force (TF) – is essentially a coalition of competitor companies with a (hopefully) defined purpose: for example, achieving Annex I listing, under Directive 98/8/EC, for a specific active ingredient used in a number of different biocidal products marketed by the companies (or their supply chain contemporaries). The EC Directive does not contain any specific stated provisions on task forces, although it does encourage data sharing. Such alliances have worked successfully in the context of the re-registration of antimicrobials under the USA FIFRA legislation and also in Canada, and have prevented the unnecessary suffering of animals (by reducing duplicate testing) and thereby also saved the associated costs for these studies. Lately, TFs have been used in relation to the EC pesticides legislation under 91/ 414/EEC (17). Typically a document, often referred to as a “Memorandum of Understanding” [MoU] defines the purpose of the task force, names the member companies, and describes an agreed limit for the capital expenditure. A TF generally operates with at least two tiers: 1. a business/commercial committee, and 2. a technical-scientific/regulatory committee. The MoU should also incorporate the following parameters: * *

* *

* *

which end uses are to be defended define the provisions for late joining and early departure from the TF or “takeovers” between members the terms for the financial compensation for data already held by members the mechanism of cost-sharing for new studies i.e. based on market-share, equal share, or a combination thereof default provisions in the event of nonpayment by a member “ownership of the data” and its availability for use outside of the EC 98/8/EC provisions by members and/or affiliates

One also needs to keep the obligations of compliance with EC competition law paramount when considering setting up and entering into a task force arrangement. The EC competition law prohibits agreements or concerted practices amongst competitors, which may restrict competition (for example, agreements on pricing, territorial allocations etc.). In addition the legislation requires that there must be no exclusion of competitors from joining on equal conditions. Failure to comply with this EC legislation may result in a financial penalty, for each member of the task force, which may be up to 10 % of a company’s turnover.

References

2.8

Conclusions

The extensive cost of the Biocidal Products Directive to the EC biocides market will inevitably cause further slowing down in terms of both the research and development of innovative chemistries for new active ingredients. As a way of overcoming this, manufacturers and formulators will be forced to work together in a closer manner than perhaps hitherto to introduce new products onto the market, possibly by elucidating synergies between the dwindling supported active substances available on Annex 1, that have not yet been discovered. The supply chain will most probably consolidate, and we may see more mergers and acquisitions in a similar manner to that which has occurred over the past two years in the general industrial chemicals area. Some limited evidence in support of this is available with Clariant’s takeover of BTP and Rhodia’s acquisition of Albright and Wilson in March 2000. The formulators, under the CEFIC sector group, EPFP (European Producers of Formulated (Biocidal) Products), have already researched alternate suppliers for their active ingredients, and unless the Commission adopts further measures we may well see an explosion of non-EC manufactured biocidal products entering the market place. These imports can easily out-price domestic products as they do not have to be manufactured under the existing legislative strictures for human or environmental wellbeing that form the cornerstone of the European legislation. There is no doubt that the demand for biocidal products will continue to grow as the public and consumers awareness of the benefits of continued improvements in hygiene become ever more apparent. It is open to the biocides industry to successfully implement a strategy to develop these highly desirable products against a background of increasingly stringent legislative measures, and that probably is predicated on more openness and co-operation with other sectors of the supply chain.

References

References

[1] Directive 98/8/EC of the EU Parliament and Council of 16th February 1998 concerning the placing of biocidal products on the market. Official Journal publication L123, 24th April, 1998. [2] OECD Report to Pesticides Forum, 16 – 17 June, 1997. ENV/MC/CHEM/PEST/RD (97)3. Biocides/Nonagricultural pesticides: Preliminary results of the survey on the regulation of biocides in OECD member countries.

[3] Council Directive 92/32/EEC of 30th April, 1992 amending for the seventh time Directive 67/548/EEC on the approximation of the laws, regulations, and administrative provisions relating to the classification, packaging, and labeling of dangerous substances. Official Journal publication L154, 5th June, 1992. [4] Biocide Information Services (BIS), Ireland (2000). Personal communication from N D’Arcy concerning an executive summary of global biocides data, 2000.

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2 The Biocides Market [5] Commission Regulation 1896/2000 on the first phase of the program referred to in Article 16(2) of Directive 98/8 of the European Parliament and of the Council on biocidal products. Official Journal publication L228, 8th September, 2000. [6] Frost and Sullivan, Report: Strategic Review of the Impact of the European Biocidal Directive, 2000. [7] S. Watkins, World Nonagricultural Pesticide Markets; Agrow Reports publication, 2000. [8] Freedonia Group Report 1257, Biocides to 2004, 2000. [9] Proposal for a Council Directive of 1991 concerning the placing of nonagricultural pesticides and the active substances thereof on the market. Document XI/III/ 563/91. Brussels, 9th August, 1991. [10] Proposal for a Council Directive of 1993 concerning the placing of biocidal products on the market COM (93) 351 final–SYN 465 (27/7/93). Official Journal publication C239, Vol. 36, 3rd September, 1993. [11] B. Backhouse, M. Burt, Current Issues for Industry: Time for Reappraisal. Paper at the 1997 IBC International Conference on the Biocidal Products Directive, Brussels, 1997.

[12] B. Backhouse, Biocidal Products Directive 98/8/EC: Impact on Industry. European Safety Newsletter June/July, 1998. [13] European Commission, An Industrial Competitiveness Policy for the European Chemical Industry: An Example. COM (96) 187 final, Brussels, 30th April, 1996. [14] European Commission, White Paper: Strategy for a Future Chemicals Policy. COM(2001) 88 final, Brussels 27th February, 2001. [15] Pesticide Registration Notice PR Notice 88-2 Clustering of Quaternary Ammonium Compounds, EPA, 26-2-88. [16] Data Requirements for Biocidal Product Types, Project No. 96/720/3040/DEB/E2 Finnish Environmental Institute, Draft Proposal Version 4, June, 1999. [17] Council Directive 91/414/EEC of 15th July, 1991 concerning the placing of plant protection products on the market. Official Journal publication L230, 19th August, 1991.

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3

Regulatory Control of Biocides in Europe Derek J. Knight and Mel Cooke

3.1

Introduction

The biocides industry transformed dramatically with the implementation of the Biocidal Products Directive (BPD) [1]. The Directive took years to formulate and will impact on manufacturers, distributors, and users of biocides. The BPD is tougher than any prior legislation, either within Europe or in the rest of the world, and may cost the industry over £ 350 million. Active substance suppliers will have to co-operate with distributors to get biocidal products registered. The industry has serious concerns over the cost of testing of active substances, particularly if the full data specified in the BPD are needed in all cases. However, the data requirement issue is likely to be resolved, at least in part, through published guidance and also by precedent during the transitional period from national regulation of biocides to the European BPD (“learning by doing”). Industry must therefore invest in keeping up-to-date with regulatory advances as the authorities grow in experience and the state-of-the-art evolves. The BPD filled a gap that existed in current legislation of chemical substances, although some prior EU legislation had already been in force for some biocides: the Marketing and Use Directive [2] [76/769/EEC (as amended) restricting the marketing and use of certain dangerous substances]; the Dangerous Substances Directive [3] (67/548/EEC), and its 7th Amendment [4] (92/32/EEC) covering notification of new chemical substances and classification, packaging, and labelling of dangerous substances; and the Dangerous Preparations Directive [5] (Council Directive 88/379/ EEC, as amended) covering hazard communication of dangerous preparations. Belgium, Denmark, Finland, the Netherlands, Sweden, and the UK had systematic and comprehensive national controls of some types of biocidal products. The BPD harmonizes the authorization of biocidal products within each Member State, while the active substances are evaluated at EU level by the European Commission.

The Biocides Business: Regulation, Safety and Applications. Edited by Derek J. Knight and Mel Cooke Copyright ª 2002 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN: 3-527-30366-9

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3 Regulatory Control of Biocides in Europe

3.2

The EU Biocidal Products Directive

3.2.1

History and Development

The European Commission first drafted legislation to answer the concern of the Council of Ministers that there was a lack of harmonized EU provisions for biocidal products, and to ensure a more uniform and higher level of health and environmental protection throughout the EU without compromising the internal market. Hence, on 27 July 1993, the Commission submitted a proposal to the Council for a Directive concerning the placing of biocidal products on the market. This initial proposal was amended by the Commission to satisfy European Parliament and Council opinion that guidance on risk assessment and authorization should be an integral part of the Directive. The Commission therefore submitted a revised version to the Council on 20 July 1995, which incorporated a set of Common Principles covering this as Annex VI to the Directive. The European Parliament and the Economic and Social Committee examined the proposed new Directive and delivered their opinions on 18 April 1996 and 27 March 1996, respectively. The Commission then forwarded a second amended proposal to the Council on 24 June 1996, culminating in the Council adopting its Common Position on the new Directive on 20 December 1996. After a second reading of this Common Position by the European Parliament and further consultations under the auspices of the Conciliation Committee to resolve remaining differences with the Commission and Council during 1997, a final text for the Directive was adopted by the Council and Parliament Decisions of 18 December 1997 and 14 January 1998, respectively. This Biocidal Products Directive [1], Directive 98/8/EC of the European Parliament and Council of 16 February 1998, was published on 24 April 1998 and entered into force 20 days thereafter. Each Member State appointed an agency to deal with the new legislation: the so-called competent authority. There was a two year period for the member states to transcribe the BPD into their own national legislation. Hence the scheme was scheduled to come into force in each Member State by 14 May 2000, although in practice this target date was not met in many countries. The BPD contains a timetable for the transition to the new authorization scheme, so existing national or other EU provisions continue to apply until the various aspects of the BPD come into force. The BPD is comparable to Plant Protection Products Directive [6] (Council Directive 91/414/EEC), and also incorporates principles already being used to assess chemical substances. The Directive itself had to be agreed by the Environment Ministers of all the member states. It also had to be agreed by the European Parliament, with directly elected

3.2 The EU Biocidal Products Directive

members from individual regions across Europe. Hence the Directive is a compromise between the various parties. It is also somewhat idealistic, in that some of the provisions are impractical and place unnecessary burden on European industry. Fortunately, however, the BPD gives the operation of the scheme to the European Commission and national competent authorities. There has been much debate amongst industry and the national competent authorities about how to operate the scheme, within the idealistic legal framework of the Directive. Some competent authorities themselves are considered by some to take an idealistic approach, whereas others are more pragmatic and give higher priority to the needs of industry and biocide users.

3.2.2

Scope of the Biocidal Products Directive

The BPD defines biocidal products as preparations containing one or more active substances that are intended to control harmful organisms by either chemical or biological, but not physical, means. This encompasses a wide range of products including disinfectants, insect repellents, and antifouling paints. Annex V of the BPD classifies biocidal products into four main groups: disinfectants and general biocides, preservatives, pest controls, and other biocides, which are further broken down into 23 separate categories (see Table 3.1). Table 3.1.

Products defined as biocides within the BPD

Main Group 1: Disinfectants and general biocides Product types: 1. Human hygiene products 2. Private and public health area disinfectants 3. Veterinary hygiene biocides 4. Food and feed area disinfectants 5. Drinking water disinfectants Main Group 2: Preservatives Product types: 6. In-can preservatives 7. Film preservatives 8. Wood preservatives 9. Fiber, leather, and polymerized materials preservatives 10. Masonry preservatives 11. Preservatives for liquid cooling systems and processing 12. Slimicides 13. Metal-working fluid preservatives

Main Group 3: Pest control Product types: 14. Rodenticides 15. Avicides 16. Molluscicides 17. Piscicides 18. Insecticides, acaricides and products to control other anthropods 19. Repellants and attractants Main Group 4: Other biocides Product types: 20. Preservatives for food or feedstocks 21. Antifouling products 22. Embalming and taxidermist fluids 23. Control of vertebrates

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The BPD interfaces with several other EU schemes for controlling various types of chemical product which can be grouped into four categories: product authorization schemes; general industrial chemicals legislation; classification and labeling Directives; and others such as worker protection and water Directives. Because of the wide variety of products defined in the BPD as biocides, careful delineation of certain products must be made to avoid making them subject to two authorization schemes. Biocidal products encompass medicines, veterinary medicines, cosmetics, and plant protection products. Where these products are already subject to EU authorization schemes, they are generally not intended to be subject to authorization under the BPD, but the borderline between the schemes needs to be carefully clarified. For example the interface between the BPD and the Plant Protection Products Directive [6] is clarified by the following examples: 1. Products applied directly or indirectly to crops in order to protect plants from organisms harmful to them are plant protection products, but those used as general hygiene disinfectants in empty structures, where it is not clear which products will be stored in the structure and the target organisms are not specifically plant pathogens, are biocidal products. 2. Algicides applied to soil or water to protect crops are plant protection products, whereas if intended to control on nonsoil surfaces (e.g. greenhouses), they are biocidal products. 3. Wood preservatives used up to the saw-mill stage to protect trees and felled timber are regulated as plant protection products; in the saw-mill and thereafter they are biocidal products (so called “saw-mill gates” principle). 4. Rodenticides used in the field to protect crops and plant products temporarily stored outside are plant protection products, but generally they qualify as biocidal products if used in buildings, including farm buildings. 5. When used to control plant pests, anthropod growth regulators are considered as plant protection products. However, pheromones and semiochemicals used in traps to monitor pest populations are outside the scope of both Directives, and only come under the BPD if the use is biocidal. Another area of dispute concerning scope is the regulation of in situ generated biocides. These include substances that are mixed together or otherwise generated by the consumer to create the biocidal active ingredient. The European Commission and member states have agreed that the in situ generation of ozone is not covered. The BPD applies only to biocidal products placed on the EU market, and since ozone is generated at the site of use, it is not regulated by the BPD.

3.2 The EU Biocidal Products Directive

3.2.3

Approval Systems

To obtain authorization for the marketing of a biocide, the applicant must submit two data packages: the first on the active substance, and the second on the formulated product. Also, the BPD makes a pragmatic but arbitrary distinction between those biocidal active substances on the market before 14 May 2000 (“existing” active substances) and those placed on the market for the first time after this date (“new” active substances). To gain authorization for a new active substance, the applicant should address all the data points for the active substance (given in Annex IIA, with some additional data points from Annex IIIA of the BPD) and at least one formulated product (Annex IIB, with additional data points from Annex IIIB). The member states and the Scientific Committee on Biocidal Products review the scientific content of the dossier and make an appropriate recommendation to the Commission. If the recommendation is favorable, the Commission will enter the active substance in an approved list (Annex I of the BPD). A review program is established in the BPD to assess systematically during a ten year period all the existing active substances. The data requirements are the same as for new active substances. Existing biocidal products can continue to be marketed while their active substances are reviewed under the ten year program. As with new biocides, once the data on the existing active substance have been evaluated and approved by the European Commission and the member states, the substance will be entered in Annex I of the Directive. A Technical Notes for Guidance (TNG) [7] covers the evaluation process and criteria for listing active substances in Annex I. The inclusion of an active substance in Annex I will be restricted to product use types listed in Annex V of the BPD (see Table 3.1) for which adequate data have been submitted. Annex I comprises three sections. Annex I itself lists regular active substances. Annex IA contains “low risk” active substances. Such Annex IA active substances cannot be carcinogenic, mutagenic, toxic for reproduction, sensitizing, or both bioaccumulative and not readily biodegradable. Annex IB contains “basic” active substances, the major use of which is not biocidal but which have a minor biocidal role. Substances entered in Annex I will initially be listed for up to ten years, and then be reviewed. The applicant can apply for ten year renewals as necessary. Somewhat controversially, under the principle of comparative assessment, the BPD (Article 10, para. 5) also gives the Commission the power to remove an active substance from Annex I if there is a comparable, alternative substance that presents “significantly less risk to health or to the environment”. Authorization of the formulated biocidal products is the responsibility of the individual member states. Full authorization under the BPD may only be granted if the active substance of the product is listed in Annex I.

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Standard biocidal products containing active substances in Annex I of the BPD require a full dossier of information (see Section 3.1.2 4), and applications for authorization are evaluated by the national competent authority without undue delay. Biocidal products containing only low risk active substances from Annex IA of the BPD can be registered with much reduced information, and the competent authority has to reach a decision on the registration application within 60 days. Biocidal products containing a new active substance for which a decision for Annex 1 listing is pending may be provisionally authorized for up to three years. New products containing existing active substances can be authorized under existing national schemes for up to ten years during the review program. The previous national schemes continue to apply to biocidal products containing existing active substances until the Commission makes a decision on whether to include that active substance into Annex I. If the listing in Annex I is not approved, the biocidal products containing them will be subject to a phase-out period. If the active substance is approved the existing biocidal product will have to be re-authorized by the member states. Under the BPD, applicants may use the concept of frame formulation to facilitate authorization of re-branded biocidal products. Frame formulations are groups of biocidal products with the same active substance of the same technical specification and use, which differ only in minor details of the formulation composition, such as the color and perfume ingredients, and hence have the same risk and efficacy. New biocidal products within a frame formulation can be authorized within 60 days. Once one Member State approves a biocidal product, all other member states must approve the product, subject to certain safeguards, according to the principle of mutual recognition. Thus a Member State receiving an application for approval of a biocidal product which has been already authorized or registered (if a low-risk biocidal product) in another Member State must authorize or register that product within 120 or 60 days respectively. The Member State can refuse the application only if the target species does not exist in that country, there is proven unacceptable resistance to the active substance, or if the circumstances (e.g. climate or breeding period) differ significantly from the lead country. The Standing Committee on Biocidal Products will resolve dispute between the member states. Member states may opt out of the mutual recognition procedure for avicide, piscicide and vermin-control biocidal products. 3.2.4

Data Requirements

Under the BPD [1], each biocidal product must have a dossier that contains information on its biocidal efficacy, physical and chemical properties, environmental effects and, where appropriate, any effects it has if brought into contact with food. The dossier should establish that the biocide is sufficiently effective without having unacceptable

3.2 The EU Biocidal Products Directive

effects on the target organisms or on the environment, including nontarget organisms. There must also be no adverse effects, direct or indirect, on human or animal health or groundwater from the residues of the substance. The BPD itself gives rules on data requirements (especially in Article 8). Annexes IIA and IIB specify detailed core data requirements common to all active substances and standard biocidal products, respectively. Note that much of the Annex IIB data are not needed for registration of a biocidal product containing only low-risk (Annex IA listed) active substances. In addition, specific additional data requirements apply for each of the 23 product types, and these are to be established on the basis of Annexes IIIA and IIIB, which contain indicative lists of tests for active substances and biocidal products, respectively. The specification of the additional data requirements takes into account the use characteristics of each biocidal product type. The common core data requirements in Annex II together with the specific data requirements in Annex III constitutes the complete set of data on which to base an adequate risk assessment. In principle, the data requirements are the same throughout the EU. They are intended, according to the BPD, to be the minimum necessary, but sufficient to conduct a proper risk assessment and make regulatory decisions. Due to the diverse exposure and potential risks associated with different biocidal products and the general nature of the rules given in the Directive, a Technical Notes for Guidance document (TNG) [8] gives detailed and practical guidance on which studies and other data are required when applying for authorization. This TNG also ensures efficient and harmonized day-to-day implementation of the Directive. However, expert judgement by the applicant and the competent authority is normally necessary in order to compile a satisfactory dossier. Member States and applicants negotiate the data requirements and identify, preferably at an early stage, any additional studies required. The Member State may request at any time additional information or studies necessary for the adequate assessment and decision making. The Member State may justify such additional studies either by the properties of the chemical (i.e. hazard) or by the predicted exposure. In addition to the core and specific data required, the applicant has to submit any additional available data, relevant to the risk assessment. The Member State also takes into consideration for the evaluation of the dossier any other relevant technical or scientific information available to them on the biocidal product, its components, metabolites, or residues. A high priority is to minimize the amount of animal testing. This means that all unnecessary testing of active substances and biocidal products must be avoided, and ideally existing data should be shared between applicants. In principle, studies should be compliant with the principles of Good Laboratory Practice (GLP) [9] and, conducted to the EU methods of Annex V [10] of the Dangerous Substances Directive or internationally recognized methods where appropriate (e.g. OECD guidelines [11]). New studies should be conducted to these methods. However, existing studies con-

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ducted to other methods may be adequate, and they have to be evaluated before conducting new tests, taking into account, amongst other factors, the need to minimize animal testing. To fulfil the data requirements without excessive costs, ways of reducing the amount of testing are very important, and there are several means to address a particular data requirement without testing. Information that is not necessary owing to the nature of the biocidal product or of its proposed uses need not be supplied. The same applies where it is not scientifically necessary or technically possible to supply the information. In such cases, the applicant must submit a justification acceptable to the competent authority. Such justifications for data waivers are evaluated on a case-by-case basis and, once there has been some experience in this area, the Commission will publish a compilation of cases in a Manual of Decisions. As a general rule, tests on an active substance should be carried out on the technical grade, including any essential additives (stabilizers etc) and impurities. However, certain specified physico-chemical testings are performed on a purified active substance. For the biocidal product approval, data may also be required on co-formulant substances if they are hazardous (i.e. substances of concern). Also, in certain cases, information on metabolites or environmental transformation products of the active substance may be needed. The information on active substances and biocidal products is summarized and interpreted in a standard format, according to Practicality Guidelines [12] for the preparation and presentation of complete dossiers for active substances and biocidal products and the subsequent competent authority reports. The guidance emphasizes how the dossier and reports should be prepared and structured, and covers the formatting of subdocuments and study summaries. The approach reduces the workload by harmonizing the format of the applicant’s summary dossier and the competent authority report derived from this, with the minimum number of subdocuments, and a clear demarcation between study summaries and the risk assessment. The structure of the dossier includes study summaries, summary tables, and completeness checks to make the assessment process easier. The standard formats have been designed in such a way that the competent authority can adapt the study summaries submitted by the applicant in an all-in-one approach without having to rewrite them for their evaluation report. The level of detail used in study summaries needs to be reasonably high, so that the competent authority can make an assessment without having to go back to the full report.

3.2 The EU Biocidal Products Directive

3.2.5

Risk Assessment and the Common Principles for the Evaluation of Dossiers

The Common Principles for the Evaluation of Dossiers are presented in Annex VI to the BPD, and give guidance on the approval of biocidal products. An important aspect of this is risk assessment both for the intended use and a reasonable worst-case situation. A further TNG detailing the risk assessment and decision-making processes for approval of biocidal products [13] supplements the framework of Annex VI. This is consistent with the Technical Guidance Document on risk assessment of existing and notified new chemical substances [14]. Risk assessment forms an important part of the regulatory process. The risk from a chemical substance is determined from its intrinsic hazardous properties and the likely exposures of humans and the environment throughout its life-cycle. The intrinsic chemical, health, and environmental hazardous properties can be quantified as a hazard assessment. The hazard of the biocide is assessed predominantly through toxicological testing in animal models. Under the BPD, these tests are prescribed in the Common Core Data set (Annex IIA for the active substance, Annex IIB for the biocidal product). Good quality human data may also be available, perhaps from epidemiological studies. The hazard assessment is combined with an exposure assessment to produce a risk assessment. If the outcome of the risk assessment is favorable, the substance will be recommended for Annex 1 listing. However, an unfavorable risk assessment may lead the assessor to ask for further information on toxicity or exposure in order to refine the risk assessment. If the risk assessment remains unfavorable a regulatory decision may be taken to implement risk management requirements, such as additional labeling or restrictions on use, to permit product approval. Exposure assessment is a more complex issue, because the biocidal product may be used in several of the 23 product types given in Table 3.1, and exposure from each type of application must be assessed. There are two basic options for exposure assessment, measuring (i.e. determining the exposure by direct measurement) or modeling. Modeling can be carried out using generic data for chemical release. Estimates of environmental release are improved by gathering information on the release of biocides from specific processes to develop EU biocide environmental emission scenarios (referred to as EUBEES). There is a corresponding project on emission scenarios and predictive models for human health. The risks from the proposed use of a biocidal product must be identified, and a decision made whether they are acceptable. Each active substance in the biocidal product requires assessment, as does any other substances of concern in the product. A substance of concern is a co-formulant that is classified as dangerous according to the Dangerous Substances Directive [4] (67/548/EEC) and present at above the concentration limits leading to classification (given in the Dangerous Preparations Direc-

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tive, 88/379/EEC, as amended, [5]). The results of these risk assessments on the component substances are integrated to give an overall assessment for the biocidal product itself, thereby determining the measures necessary to protect humans, animals and the environment during both the proposed use and in a realistic worst-case situation. The regulatory outcomes available to the assessor are as follows: the biocidal product cannot be authorized; it can be approved subject to specified restrictions and conditions; or that further information is needed to reach a decision. The decision-making process also takes into account the nature and severity of the adverse effects, the proposed risk management measures, and also the efficacy and potential benefits of the biocidal product. Biocidal products can only be approved if, when used as prescribed, they do not present unacceptable risks to man, animals, or the environment, are efficacious and use permitted active substances. Approval of biocidal products requires that they are used properly at an effective but minimized application rate. The regulatory authority also assesses the packaging, labeling, and accompanying safety data sheet. Risk characterization is also conducted regarding animals kept and used by humans. The humaneness of biocidal products targeted at vertebrates is also considered. The Danish and Finnish Competent Authorities evaluated full review dossiers on the active substances tebuconazole (as a wood preservative) and glutaraldehyde (as a paper slimicide and preservative for cooling-water systems) as pilot projects to validate the risk assessment procedures. All member states were involved, with workshops to facilitate discussion and learning. The hazardous properties of acute and repeat-dose toxicity, irritation and corrosivity, sensitization, mutagenicity, carcinogenicity, toxicity for reproduction and the physicochemical properties of each active substance or substance of concern in the biocidal product are identified and quantified, if possible, in terms of a dose-response effect. The repeat-dose and reproduction toxicity yields the no-observed-adverse-effect level (NOAEL), which is the highest dose level at which no adverse effects are realized. For acute toxicity, the LD50 value (or discriminating dose) partially quantifies the hazard. For irritation, corrosivity, skin and respiratory sensitization, mutagenicity, and carcinogenicity, the hazard is simply identified, in the absence of practical or theoretical means of evaluating a dose-response effect. The assessor estimates the exposure of professionals, nonprofessionals, and man exposed indirectly via the environment to each active substance or substance of concern in the biocidal product from use during its lifecycle. Exposure may be calculated using appropriate models, or estimated using measured data for existing or analogous products. Risk characterization involves comparison of the predicted exposure with the estimated effect level, qualitatively if necessary. Only as a last resort can the assessor take into account the use of personal protective equipment to enable a biocidal product to be used safely. Preferred measures include replacement of the hazardous

3.2 The EU Biocidal Products Directive

substance with a nonhazardous one, engineering solutions, such as local exhaust ventilation, and isolation techniques. Biocidal products containing category 1 or 2 carcinogens, mutagens or substances toxic to reproduction at above the classification limit for corresponding classification of the preparation (see Dangerous Preparations Directive, [5]) cannot be approved for use by the general public. The environmentally hazardous properties of the active substance and substances of concern are identified on the basis of test results or reasonable grounds for concern (i.e. bioaccumulation potential, persistence, shape of the ecotoxicity/time curve, indications of long-term adverse human health effects or structure-activity relationships, SAR). Full risk characterization is needed for each component if the biocidal product is classified as dangerous on the basis of that component, according to the Dangerous Preparations Directive (88/379/EEC, [5], as amended to include criteria for “dangerous for the environment”). The assessor evaluates the concentration-effect relationship to quantify the hazardous property in terms of a predicted-no-effect concentration (PNEC), or a qualitative estimation if appropriate. The PNEC can be derived from acute toxicity studies by dividing the LC50 in the most sensitive species by an assessment factor. With three acute studies (fish, Daphnia, and algae) the assessment factor is normally 1000. The assessment factor gives a margin of safety to account for inter- and intra-species variation and extrapolation to long-term exposures. If long-term toxicity studies are available, the PNEC is derived from the no-observed-effect level (the lowest dose in a particular test at which no effects are seen) in the most sensitive species by dividing by a lower assessment factor: perhaps 100 if two long-term studies are available, or 10 if there are three or more. The assessor estimates the predicted environmental concentration (PEC) for each environmental compartment (water, including sediment, soil, and air). Risk characterization entails calculating the PEC/PNEC ratio, or instead doing a qualitative evaluation, for each compartment, and then combining the results to find the overall conclusion. A biocidal product cannot be approved if one of the active substances, substances of concern, or a metabolite or breakdown product, is predicted to exceed the EU permitted concentration limits in ground water or surface water, which is intended for abstraction for drinking water. The user of the biocidal product must take measures to reduce accidental contamination of water. Products that contaminate soil and are expected to be persistent will not be approved, unless the applicant demonstrates that there is no unacceptable accumulation. Also, the applicant must address other unacceptable effects, such as the target species developing resistance to the biocidal product. The applicant must also substantiate the claimed efficacy of the biocidal product and in principle the product should be at least as efficacious as any existing products.

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3.3

The Review Program for Existing Biocide Active Substances and Biocidal Products

Existing active substances, i.e. those on the market before the implementation of the BPD on 14 May 2000, shall be reviewed at EU level for possible addition to Annex I (which currently is empty). The BPD (Article 16) contains the framework for this review program, and the Commission will carry out the review through a series of regulations. The European Chemicals Bureau (ECB) has produced a nonexhaustive indicative list of existing active substances [15]. Active substances on the final list and products containing them will benefit from the transitional arrangements of the BPD. Any substance not included on the final list of existing active substances will be considered as “new” and, together with biocidal products containing it, will have to meet the various provisions of the BPD before they can be marketed in the EU. Hence it is important for industry to ensure the final list is complete. The first Review Regulation [16] implements the first phase of the work program to evaluate existing active substances. This was not ready for 14 May 2000, but it was adopted as Commission Regulation (EC) Number 1896/2000 on 7 September 2000 and published in the Official Journal of the European Communities on 8 September 2000 and came into force 20 days later on 28 September 2000. Its purpose is to establish the definitive list of existing active substances, determine which of these will be supported through the full review procedure, begin the full review of the active substances for wood preservatives and rodenticides and provide a framework for phasing out unsupported active substances and the biocidal products containing them. A second Review Regulation, perhaps in force for mid 2003, will give the definitive list of existing active substances, and will list which have been notified, in accordance with the requirements of the first review regulation, as supported for subsequent full review. This second Review Regulation, and subsequent Regulations, will describe the priorities for the systematic review of the rest (other than rodenticides and wood preservatives) of the supported existing active substances. The deadlines for the full review dossiers for the second, third and final phases of the review may be mid 2006, mid 2007 and late 2008 respectively. There will be specific decisions on nonsupported active substances, detailing phase-out arrangements for them and biocidal products containing them. The first review regulation explains how manufacturers or formulators (or their solerepresentatives) can “identify” existing active substances for inclusion of the official list. Industry must submit the data given in Annex I of the first review regulation [16] by 28 March 2002, using the electronic form available from the ECB Website. Annex I data consist of commercial, technical and administrative data . The ECB will provide member states with a list of “identified” active substances (within an unspecified time). The member states are allowed three months to add further active substances

3.2 The EU Biocidal Products Directive

to the list, if they consider, for instance, that a particular unsupported active substance is important to their country. The Commission (again within an unspecified time) produces the definitive list of existing (identified) active substances, which is to be made public electronically. Active substances not on the list can no longer be used, but those on the list but not notified (see below) are allocated a reasonable phase-out period of up to three years. The first review regulation also establishes which of the existing active substances are to be supported for full review. Manufacturers, formulators, their sole-representatives, or associations do this by making a notification by supplying data given in Annex II to the regulation to the ECB, again by 28 March 2002. The information consists essentially of the Annex I identification data plus summaries of the physico-chemical, toxicological, and ecotoxicological studies corresponding approximately to the EU “Base Set” for notification of a new chemical substance (i.e. in Annex VIIA of the Seventh Amendment, [4]). Importantly, as part of the notification, the applicant (notifier) undertakes to complete the testing specified in Annexes IIA and IIIA of the BPD to support the active substance, either alone or as part of a task force, during the full review. IUCLID (version 3.2 or higher) which is modified for use with biocide active substances, has to be used to make the notification. A high proportion of European existing active substances will have inadequate data. Suppliers of active substances should gather available information (e.g. from existing studies and literature searching), and obtain expert regulatory advice in evaluating existing information, the use of surrogate data, conducting the outstanding studies, and preparing the dossier. Again member states have three months from receiving the list of notified active substances to notify other substances. The definitive list of existing active substances will specify by product types those active substances that have been notified. The notified existing active substances can continue to be marketed until they undergo full review (i.e. once all the necessary data in Annexes IIA and IIIA of the BPD are available), but only for the product types notified. Member states can indicate possible basic substances within six months, and anyone may notify a basic substance within 18 months of the first review regulation coming into force. Member states then have a further three months to notify further candidates. If the notification of the potential basic substance is accepted, the notifier is committed, unless exceptional circumstances apply, to submit all the information needed for full review and subsequent entry of the basic substance in Annex IB of the BPD. A draft of the first Review Regulation required industry to provide full data for review on an active substances in the first list within 18 months, which would have been impractical since some studies take up to four years. The final version, however, avoids this problem, yet still enables the full review program to begin, by dealing first with active substances that are likely already to have extensive test data from earlier national

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authorizations (the so-called twin-track approach). Hence applicants whose notifications are accepted for active substances of wood preservatives and rodenticides have to submit a full dossier to the designated rapporteur Member State by 28 March 2004. The Commission will use the notification data to decide the priority in which active substances will undergo full review, by product type. All successfully notified existing active substances will systematically be evaluated in full according to a timetable prescribed in subsequent review regulations. The time limit for the review of all existing active substances is ten years from transcription of the BPD in member states’ national law (i.e. by 14 May 2010). The applicant must have the rest of the BPD Annex IIA common core data, with any additional data from Annex IIIA which may be needed for an adequate assessment of the active substance. The applicant also has to include a dossier for at least one biocidal product containing the active substance. Once existing substances have been reviewed and approved at European level, all biocidal products containing them have to be registered (or re-registered) in each country of supply. The procedure for obtaining authorizations in multiple member states is facilitated by the mutual recognition agreement (Article 4 of the BPD). The UK Health and Safety Executive (HSE, the UK competent authority) has produced a Regulatory Impact Assessment, which was part of the drafting of the Biocidal Products Regulations to implement the BPD in the UK [17], in order to assess the commercial impact of BPD. They report that the UK Chemical Industry Association (CIA) estimate the cost of full testing for each active substance is between £ 2.1 million and £ 3.1 million, plus £ 0.16 million to £ 0.31 million for regulatory and administrative costs to compile dossiers, form task forces, etc. The industry is expected to support ca. 400 existing active substances during the review process. The HSE assumed that sufficient data are already available on 150 of these 400 active substances, because they are already registered under other schemes broadly equivalent to the BPD. For the remaining 250 active substances, assuming costs at the low end of the CIA ranges (i.e. £ 2.1 million plus £ 0.16 million), and also that for each of these active substances £ 0.78 million of data are already available (based upon the typical cost of registration in the USA), an overall cost of £ 1.48 million per active substance is derived, and a total cost of £ 370 million for the whole EU review program for active substances. Data will also have to be supplied for the first authorization or registration of each biocidal product. The HSE estimate that 800 products per year across the EU will require authorization or registration once their active substance has been reviewed and added to Annex I. However, it is estimated that for 200 of these sufficient information will already be available, because the products will have been registered under national approval schemes. The cost of providing data will vary substantially for different biocidal products. Some products will be very similar in formulation, and hence most of the information can be transferred between products, but for others substan-

3.4 European Union Chemical Control Measures

tial new testing will be needed. The HSE estimated the cost to industry would be between £ 10000 and £ 131000 to test each product, with an average of £ 78000. The biocides industry is structured differently to the agrochemical industry. Instead of each active substance being developed, and hence registered, by a single innovator company, many biocide active substances are likely to be supported by several producers, each with a partial set of safety studies. The sales value of biocides is much lower, so there are less resources available for review of existing biocides. The cost of conducting studies can constitute a considerable proportion of the development costs of a new biocide, so the periods during which these data are protected from unauthorized use by competitors is of key importance. A major problem for biocide companies in deciding whether to support their active substances in the EU review is the high degree of uncertainty in the cost of the studies needed. The experience gained in the various European national review program for biocides and pesticides, and indeed in the USA under the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA), can be brought to bear in operating the EU BPD. Many of the concerns expressed by industry during drafting of the BPD have been resolved, or will be addressed in the practical operation of the scheme, so that in general industry accept the BPD, in spite of the cost implications.

3.4

European Union Chemical Control Measures 3.4.1

Scope of European Union Legislation

There are 15 countries in the EU, or European Community (EC) as it is often referred to, and Austria, Finland, and Sweden are the most recent members. All the European Free Trade Association (EFTA) countries except Switzerland had entered into an agreement with the EU to form the European Economic Area (EEA). Only Iceland, Liechtenstein, and Norway are part of the EEA but not the EU. Although there were transitional arrangements and some differences are permitted, the 18 countries of the EEA constitute a single chemical market with essentially harmonized chemical safety measures and controls. Chemical control legislation in Switzerland is different to that of the EU. In practice products can normally be approved for Switzerland using the available EU information, or with only a little extra testing, although separate submissions to the Swiss regulatory authorities may be necessary. In due course chemical legislation in Switzerland will become more fully harmonized with the EU, but there does not seem to be any immediate likelihood of Switzerland joining the EU, or even the EEA, although the country is still part of EFTA.

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Finally, the relationship between Western Europe and the Central and Eastern European countries should be noted. Generally chemicals are not currently well regulated in these latter states, although some countries have compulsory certification or registration procedures. Many of these countries have applied for EU membership, however, and have entered into Association Agreements, which allow for existing chemical control measures to be harmonized with the EU.

3.4.2

European Union Chemicals Legislation

Many EU countries regulated biocides as general chemicals before the introduction of the BPD. Until the various facets of the BPD scheme come into operation, the previous national provisions continue in force. Hence it is useful to understand the EU controls for general chemicals. Chemical control in the European Union (EU) is based on a network of legislation for hazard communication and safety assessment. The framework is established by means of Council (or Council and Parliament) Directives or Regulations, with implementation by the Commission as Adaptations to Technical Progress or Commission Regulations, respectively, and associated guidance documents on working practices and administrative provisions. EU legislation is brought into force in individual member states by national laws, regulations and administrative procedures and hence, although chemical control is fundamentally harmonized, there can be minor differences between countries. All “dangerous” substances have to be classified, packaged, and labeled according to the requirements of the so-called Dangerous Substances Directive [3] (67/548/EEC), as amended [4]. Substances officially classified as dangerous are listed in Annex I of the Dangerous Substances Directive (67/548/EEC), which is updated by the Commission periodically by means of Adaptations to Technical Progress. The criteria to enable substances to be classified and labeled are given in Annex VI of this Directive [18]. Substances are classified for labeling by evaluation of their physical, toxicological, and ecotoxicological properties. There are 15 “dangerous” classifications: explosive, oxidizing, flammable, highly flammable, extremely flammable, harmful, toxic, very toxic, irritant, corrosive, sensitizing, carcinogenic, mutagenic, toxic for reproduction, and dangerous for the environment. Labeling consists of appropriate hazard symbols and information on potential hazards and safety precautions in the form of standard phrases (R- and S-phrases, respectively). The EU scheme for classification, packaging, and labeling of dangerous “preparations” (i.e., formulated products consisting of a mixture of substances) is specified in the Dangerous Preparations Directive [5] (88/379/EEC), which is updated from 30 July 2002 by Directive 1999/45/EC.

3.4 European Union Chemical Control Measures

Industrial users of dangerous chemical substances or preparations must be supplied with a safety data sheet (SDS), according to Commission Directive 93/112/EEC [19]. The classification, packaging, and labeling of biocidal products is the same as for chemicals, except that insecticide, acaricide, rodenticide, avicide, and molluscicide products are covered by the provisions of Council Directive 78/631/EEC [20]. Therefore, the active substance will generally be classified and labeled according to Annex VI [18] of the Dangerous Substances Directive (67/548/EEC) on the classification, packaging, and labeling of dangerous substances. The Dangerous Preparations Directive [5] also applies to biocidal products. Safety data sheets are also required for biocide active substances and products as for chemicals. New chemical substances must be notified according to the Seventh Amendment [4] (92/32/EEC) of the Dangerous Substances Directive before being placed on the EU market. The physico-chemical, toxicological, and ecotoxicological studies required depend on the supply level. Chemicals controlled under separate EU legislation, such as those for exclusive use in medicinal products, are exempt from notification, as are “existing” chemical substances, which are defined as those listed in the European Inventory of Existing Commercial Chemical Substances (EINECS) [21]. The Existing Chemicals Regulation [22] (793/93) on the evaluation and control of the risks of existing substances applies to all EU manufacturers or importers of existing chemical substances. The available data on substances supplied at above 1000 tonnes per annum has been reported and used for priority setting to select particular existing substances for thorough review with full “base-set” data (corresponding Annex VIIA of Directive 92/32/EEC, [4]). Commercial and technical data of substances supplied at above 10 tonnes per annum has also been reported. Risk assessment is conducted on notified new substances according to the general principles of Commission Directive 93/67/EEC [23]. Of the many reported existing chemicals, a priority-setting scheme is used to determine which require full risk assessment according to the general principles of Commission Regulation Number 1488/94 [24]. Risk assessment of new and priority existing chemicals involves hazard identification, hazard characterization by assessing the effect of dose (or concentration), or response (or effect) then comparison of this with an exposure assessment to produce a risk characterization covering both human health and environmental effects. These risk assessments are subsequently combined in an overall integration of conclusions. Assessors reach a conclusion after risk characterization of each of the identified hazardous properties, and those for which there are other reasonable grounds for concern, for each appropriate human population and environmental compartment. The risk assessment, after any necessary refinement, could include recommendations for risk reduction. The necessary risk reduction measures are adopted at EU level using existing provisions; for existing chemicals those measures already applied are

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taken into account. Recommendations may include modification of the classification, packaging, or labeling of the substance, the SDS, or the recommended emergency procedures. Alternatively, the relevant control authorities may be advised to consider controls for the protection of man and the environment by means of, for example, occupational exposure or environmental discharge limits. Very occasionally, restrictions on marketing and use under the Marketing and use Directive (Council Directive 76/769/EEC, as amended) [2] may be necessary, but only after a risk-benefit analysis. Note that under the BPD, in cases where active substances are evaluated and refused listing on Annex I, the Commission must bring forward proposals under the Marketing and Use Directive to restrict their use.

3.4.3

Other European Controls Affecting Biocides

Biocides, whether new products approved under the BPD, or existing products covered under the transitional arrangements by the previous national measures, are also subject to other control measures which affect them at all stages of their life cycle. Chemical control legislation, including the degree of its practical enforcement, varies between countries, as does the associated official advice and voluntary industry codes of practice. These systems for chemical control are being developed and improved, sometimes with a view to international harmonization. Chemicals have to be classified, packaged, and labeled according to the United Nations (UN) scheme for safe transport [25], i.e., by ship, inland waterways, air, rail, and road. Advice on emergency action to take following accidental spillage has to be available, e.g., from Transport and Emergency (TREM) cards, poison centers, or other information sources. Safe transport of marine pollutants is ensured by MARPOL 73/78 [26], which is in effect a supplement to the International Maritime Dangerous Goods Code of the International Maritime Organization. Discharge of pollutants to air and water are controlled by suitable means [27], to enforce the appropriate national environmental quality standards or internationally agreed pollution control targets, such as the release of ozone-depleting chemicals according to the Montreal Protocol [28]. The disposal of waste chemicals, including absorbed spillages and contaminated containers, is also regulated to ensure pollution is minimized [29], and recycling and the use of safer or less polluting chemicals is encouraged. Biocides have to be used safely in the workplace, in compliance with EU [30] and national worker safety legislation and any applicable occupational exposure limits or standards. Also, the necessary emergency measures to be taken following accidental spillage or poisoning have to be assessed, and national fire control legislation will also apply. Exceptional risks to the community surrounding a chemical plant may have to

3.5 National European Biocide Authorization Schemes

be evaluated under major accidents hazards legislation, such as the EU Seveso Directive [31]. Chemical products have to be fit for their intended purpose and may be covered by mandatory or advisory product standards. They will certainly be subject to civil legislation on product liability. Industry association voluntary codes of practice may apply, or alternatively a manufacturer may decide it is commercially undesirable to sell a product containing chemicals with certain properties (e.g., those that are positive in an Ames test for mutagenicity) even though there is no legal or ethical restriction. The choice of chemicals to use in the manufacturing process may be governed by the desire to have an environmental (ECO) label for the finished product, to obtain a competitive advantage in retail sales. Finally, the packaging of the finished product might be chosen with a consideration of packaging waste legislation, such as the EU Scheme [32] or national schemes (notably in Germany). Some countries, such as Finland, Norway, and Sweden, require chemicals to be reported to commercial product inventories. Furthermore, the appropriate national Customs requirements have to be fulfilled before chemicals can be imported. There may also be restrictions on the export of substances banned or restricted in the country of manufacture, because of the UN Prior Informed Consent program [33]. Some products may be used in such a way that they are regulated not only by general chemical or biocide legislation, but also as other chemical products, such as detergents [34], or offshore chemicals under the OSPAR harmonized offshore chemical notification scheme [35] of the Oslo and Paris Commissions.

3.5

National European Biocide Authorization Schemes 3.5.1

Introduction

Before the BPD, provisions for controlling biocidal products in individual EU member countries were very diverse, and in many cases there were no specific provisions. Where formal arrangements existed, they ranged from EU notification procedures under general chemical legislation described previously, to specific approval or registration schemes for certain categories of perceived higher risk biocides (e.g. wood preservatives). Regulation of such chemical products varied considerably between countries, and it was not uncommon for the same chemical to be defined as an industrial chemical in one country, as a biocide in another, and to be covered by both categories in a third. The more strictly controlled biocides tended to be those used for wood preservation, vertebrate and invertebrate pest control, and as disinfectants espe-

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cially in food or animal feed areas. However, such approval schemes invariably fell short of the rigorous registration required for plant protection products, and there were marked inconsistencies in regulatory procedures and data requirements between countries. Until existing active substances are reviewed, and the biocidal products containing them registered under the BPD, the previous national authorization measures continue to apply. It is even possible to have new biocidal products containing an existing active substance approved under these existing arrangements. Hence some of the most important European national biocide authorization schemes are described briefly. More detailed summaries of national regulations for biocides worldwide, including EU countries, are to be found in an OECD survey [36]. The BPD was based on these national schemes, and the practical aspects for its implementation developed within the culture of these existing systems. Regulators, industry, and politicians responsible for developing the BPD were clearly influenced by what had gone before.

3.5.2

The Netherlands

The primary legislation controlling the authorization, sale, and use of pesticides (including biocides) in the Netherlands is the Pesticide Act of 1962 [37], which stipulates the registration procedure that allows a pesticide to be sold, stored, or used. The Act has been implemented through Regulations [38] covering: limitation of use to specified applications or user categories; professional training and licensing, with environmental requirements such as controls on the distance of fumigated object from surrounding buildings; publicity and advertising; waste disposal of pesticides and containers; surveillance; and residues in foodstuffs. The same basic regulatory principles apply as for plant protection products. Trade and use of these pesticide products is permitted only after authorization. The applicant provides a full dossier that includes physical and chemical information, efficacy, toxicology, residues, and environmental data. Data requirements are specified for each product category. From these data the efficacy is judged by the Competent Authority, as well as the risks for public health, operators, and the environment. The Dutch regulations for biocidal products encompass a very broad range of products, including disinfectants, pesticides for domestic and industrial use, wood preservatives, antifouling paints, fumigants for stored products, ectoparasiticides, and human-skin insect repellants. All herbicides, however, are considered as plant protection products. In principle all 23 product types of the BPD are covered, except for products used on animals. According to the Dutch Pesticide Act, a biocidal product is any substance or preparation containing one or more active substances intended for use in the following:

3.5 National European Biocide Authorization Schemes *

*

*

*

controlling or repelling organisms which may cause injury to plant products or to designated animal products; controlling or repelling animal or plant organisms in or on: – buildings and other premises, not used to house animals or as nurseries for plants; – water-supply services, swimming baths, and waters used for bathing and swimming as well as camping sites, caravans and tents; – refuse dumps; – vehicles, ships, and aircraft, not used for the transport of animals; – materials, apparatus, and utensils; controlling or repelling animals, which may cause diseases in or transmit diseases to man, (except products separately regulated as medicinals); controlling or repelling animals, other than those referred to under the above point, for the prevention of nuisance to man.

Before authorization is granted, the product must be established as: * *

*

sufficiently active; producing no harmful side effects when used as prescribed, including: – harming plants or plant products; – endangering humans, directly or indirectly; – harming animals, directly or indirectly; – endangering the person applying the product; – endangering those coming into contact with residues of the product; – harming the quality of foodstuffs; – unnecessarily damaging vertebrates to be controlled; – harming the quality of ground water; – harming the environment, considering the product’s distribution in soil and water and effect on nontarget species. complying with the requirements for classification, packaging, and labeling.

The information needed for approval is specified in the Dutch Regulations, which distinguish between plant protection products and biocides. The biocides are given a Classification Group according to the use-category, which determines which data are required. For example, industrial biocides for use in cooling water and in liquids during production processes in the paper industry are in Classification Group D5. Wood preservatives applied outdoors, or for wood to be used outdoors, are in Classification Group C1; those applied indoors, or for use indoors, are in Classification Group C2. The applicant should submit all data unless: * *

public data are concerned (e.g. published material); the data have previously been submitted to the Dutch competent authority by some-

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*

*

*

one else who has given written permission to use them in the current application; the data have been submitted to the Dutch competent authority in support of another application, and the authorization is more than ten years old; the data have been submitted by someone else in support of an application for extension or amendment of a registration, and five years have passed since the extension or amendment was granted; the data have been submitted before 5 February 1994 by someone else in support of an application for registration, or extension or amendment or a registration.

The information on a biocidal product is summarized in Application Form A, which contains the following sections: Section A, data concerning the applicant; Section B, information on the product; Section C, composition of the product; Section D, information on the active ingredient; Section E, information on the toxicity of the formulated product and the active products and its metabolites; Section F, information on the metabolism in the plant, and on residues; Section G, behavior of the product and its metabolites in soil, water, and air; and Section H, toxicity to organisms present in the environment. In many cases, the guidelines recommend relevant international or national test guidelines as the appropriate test methods, especially for Sections C, D, E, and H, such as OECD [11], or EU Annex V [10] guidelines. The Dutch competent authority is the Board for the Authorization of Pesticides (College voor de Toelating van Bestrijdingsmiddelen, CTB). Fees are payable to the CTB. Anyone intending to conduct or commission animal testing is obligated to ask the CTB whether the studies have previously been submitted. The enquiry is made on a form available from the CTB, which establishes the bone fide intention of the applicant. The CTB will divulge whether the product has been registered and the identity of those holding the data. The application procedure in principle follows a defined timetable. Within two weeks of receipt of the form, the CTB issues an application number. The application is checked for completeness, including all the appendices and declarations, and within twelve weeks the applicant is informed of any deficiencies. Thirty-four weeks after the CTB have declared the application to be complete and have received the fees for summarizing and evaluation, they inform the applicant of additional data requirements. Within 48 weeks after either receipt of the fees or any additional data requested, the CTB will make a decision on the application based on efficacy and safety. An authorization is valid until a specified expiry date, up to a maximum of ten years, and can be extended by the holder upon application, and after it has been demonstrated that the criteria for authorization are still being met.

3.5 National European Biocide Authorization Schemes

3.5.3

Belgium

The royal decree of 5 June 1975 [39] concerning conservation, trade, and the utilization of pesticides and for nonagricultural use covers nearly all groups of biocidal products. The decree regulates an extensive range of product use: antimicrobials used in buildings, transport, waste sites, swimming baths; preservatives to prevent decay or damage to animal or plant products; insecticides to combat or eliminate ectoparasites of small domestic animals; and disinfectants used to treat plants, water, or soil used to prevent illnesses to man or to animals. Notable exemptions include substances and preparations used as antiseptics or disinfectants for surgical material, additives for food and feeding stuffs, and biocidal products used for research and scientific trials. The detailed requirements are contained in a comprehensive explanatory document “La Mise sur le Marche d’un Pesticide a Usage Non-Agricole”, issued by the Conseil Superieur d’Hygiene in November 1995 [40]. This document explains the need for either a full dossier (especially mammalian toxicology), or a reduced dossier if the active ingredient is already registered in Belgium, including for other uses such as in a plant protection product. The appraisal procedure and timing is as follows. The applicant provides a dossier and fees to the Ministry of Public Health. The Ministry checks the administrative aspects of the dossier within a deadline of 14 days, and then send copies to the Scientific Secretariat to evaluate the completeness of the dossier, within a deadline of one month. The Scientific Secretariat will contact a company directly if more information is needed, and any additional data are sent directly to the Scientific Secretariat. When a dossier is judged to be complete, it is then evaluated by the Human Health Council, who are expected to give a verdict within four months. If more information is needed, the Human Health Council requests the information through the Administration Department of the Ministry of Public Health, who approaches the applicant.

3.5.4

The United Kingdom

Prior to 1985, pesticides were controlled in the UK by the nonstatutory Pesticides Safety Precaution Scheme, which was formally agreed between the British government and the agrochemical industry. This scheme was not directly concerned with the efficacy of pesticides, but a separate arrangement, the Agricultural Chemicals Approval Scheme, covered this for products used in agriculture, horticulture, forestry, home gardens, and for control of insect and mite pests on farm-stored grain. The Control of Pesticides Regulations (COPR) [41] which were established under Part III of the Food and Environment Protection Act 1985, came into force

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on 6 October 1986. The Pesticide Safety Precautionary Scheme and the Agricultural Chemicals Approval Scheme effectively lapsed on this date, but statutory approvals were granted to all products that had at least provisional clearance under these nonstatutory arrangements. The COPR define in detail those types of pesticides which are subject to control, prescribe the approvals required before any pesticide may be sold, stored, supplied, used, or advertised, and allow for general requirements on use, including aerial application. They apply with certain exemptions to pesticides and to any substance, preparation, or organism prepared or used for any of the following purposes: (a) protecting plants or wood or other plant products from harmful organisms; (b) regulating the growth of plants; (c) giving protection against harmful creatures; (d) rendering such creatures harmless; (e) controlling organisms with harmful or unwanted effects on water systems (including sewage works), buildings or other structures, or on manufactured products; and (f) protecting animals against ectoparasites. The applicant submits the dossier for the nonagricultural pesticide to the HSE. The Interdepartmental Secretariat (IDS) considers more complex applications, which are to be evaluated by the Committee Procedure. This procedure is used if the active ingredient in the new product has not been considered for approval previously, for pesticides with novel means of application, or other proposals that appear to offer a new hazard. The IDS is part of the Advisory Committee on Pesticides (ACP), which is an independent body whose function is to advise government ministers on the level of approval that should be granted. For the registration of nonagricultural pesticides that contain recognized active ingredients there are three routes of approval: *

*

*

Secretariat. This type of application applies when precedents already exist for the type of product required, i.e. where the active ingredient levels are below the maximum approved for the areas of use, application method, and user group. Approval takes up to 90 days. Departmental. This type of application applies when the product is without precedent in the area of use, the amount of active ingredient, or formulation type. The application requires a risk assessment, based on all previous data, which is evaluated by the IAS. The approval takes 6 to 12 months, and there is no guarantee of success. Committee. This application is required when the use pattern of the product is radically changed, for example from professional to amateur use. The applicant must submit information on efficacy, and mammalian and environmental toxicology. The IPS and the ACP evaluate the data. The application takes typically 18 months to three years to complete, again with no guarantee of success.

3.5 National European Biocide Authorization Schemes

There are three levels of approval: experimental permit for research and development purposes on the applicants own premises; provisional approval, once the HSE is satisfied that the product may be safely used; and full approval when all data requirements have been fulfilled. The data required for approval consists of a core set for all biocidal products, with additional data required according to the type of product and its area of use. For general biocides, applicants are referred to the Non-Agricultural Pesticides Registration Handbook [42]. The ACP and IDS have data requirements for active substances and their products for each end-use covered by COPR, and, although some of the data requirements are specific to the particular end use, the basic core data are common to all areas. All testing should be performed on representative batches of the active substance or formulation in accordance with internationally acceptable guidelines (preferably EU Annex V Methods [10] or OECD guidelines [11]) and, where appropriate, to GLP [9]. The data requirements also depend on the label claim, areas of use, and methods of application, and user category. The user-categories for nonagricultural pesticide are: (a) industrial, with the product only used in a factory situation (currently applied only to wood preservatives); (b) professional, with the product applied by trained or experienced operators; and (c) amateur, with the product available to the general public. Where use of the product may result in significant operator, consumer or environmental exposure to the substance, additional data will be required. Also, some of the additional data may be required if the core-package data is inadequate for risk assessment. Data for active substances and product-related data submitted in support of applications for the first commercial approval are protected for ten years. Active substance data subsequently required to support continued approval, or for review of the pesticide, are protected for five years. All active substances are subject to a full scientific review regarding safety ten years from the date of the first commercial approval of the products containing them. The review involves evaluating the safety of all products containing the substance. Reviews are then to be repeated at ten year intervals, although an emergency review can be undertaken if concerns are expressed about a pesticide. Hence the HSE have comprehensive data packages on certain active ingredients. Companies wishing to use these active ingredients may buy from a “recognized source”, who will supply the HSE with a letter of authorization allowing access to the data with regards to the application for the formulated product.

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3.5.5

Scandinavia Denmark The current approval system for pesticides [43] was set up in Denmark with the entry into force of the Chemical Act in 1980. The approval system is applicable to both plant protection products and biocidal products. Approval by the Danish National Agency of Environmental Protection (EPA) is subject to proof by the applicant that the product is not considered dangerous to health or to the environment. With the amendment of the Chemical Act in 1987, stricter provisions were made for hazard assessment of pesticides. The EPA have designated a framework for the assessment of pesticides. The Chemicals Act was amended in 2000 in order to implement the BPD. In the transitional period, before the EU BPD scheme comes fully into force, the biocidal products regulated under the current Danish scheme are products to control fungus attacking wood, algae, slimicides for pulp, vermin on domestic animals, pests in textiles, pests in timber and woodwork, insects, snails, mites and products to control rabbits, water voles, mice, and rats. Also, registration is needed for chemical repellant products to control the above mammals and lower animals. 3.5.5.1

3.5.5.2 Finland

In Finland, wood preservatives and slimicides are “protective chemicals” which must not be manufactured, imported, delivered for sale, or used without advance approval according to the Chemicals Act 744/1989 as amended [44], the Decree on Wood Preservatives and Slimicides (123/1994) [45] and the Decision (256/1994) of the Ministry of the Environment [46]. Applications are made to the Finnish Environmental Institute (FEI). Prior approval is not needed for reported protective chemicals or products for wood-preserving paints, and instead these are notified to the FEI. The Amended Chemicals Acts 1198/2000 [44] requires registration of antifouling products. Finally, premarketing approval is needed for rodenticides, molluscicides, insecticides, and repellents under the Pesticides Act (327/69) [47] from the Pesticide Board of the Plant Protection Center. Standard EU [10] or OECD [11] GLP-compliant [9] studies are required.

3.5.5.3 Sweden

Miljo¨balken 1998:808 (Chapter 8) in the Swedish Environmental Code [48] makes general provisions for testing and authorization of plant protection products and a number of biocidal product types. Ordinance SFS2000:338 [49] covers biocidal products. The term “pesticide” in the Ordinance is taken to mean a chemical product

3.6 Conclusion

that is intended for use to protect against damage to property, sanitary nuisances or other comparable nuisances caused by plants, animals, or microorganisms. Authorization is normally for five years, but in some cases can be for ten years. The Swedish National Chemicals Inspectorate (referred to as KEMI) is the competent authority. Note that KEMI also practice comparative assessment, so that inclusion on the national approved list may be refused, or existing approvals may be withdrawn, if another chemical is considered safer (considering health, environmental, efficacy, and practical and economic aspects), or if nonchemical substitutes are available.

3.6

Conclusion

The EU is one of the three main biocide markets, together with the USA and Japan. Until the BPD came into force, the European market was fragmented, with different regulatory requirements in different EU Member States. Some countries, notably Germany, had no specific control measures, and biocides were covered by the general EU chemicals legislation. Others, such as the Netherlands, had their own vigorous national approval schemes, requiring extensive testing. Hence the level of protection of humans and the environment from the possible adverse effects of biocidal products varied across Europe. The disharmony in regulatory obligations also resulted in nontariff barriers to trade in biocidal products within the EU. The BPD rectified both these problems, by introducing a harmonized scheme for appraisal of biocidal products within EU countries, using active substances evaluated at EU levels, to ensure a high level of safety for humans and the environment. The BPD is the legal framework for the new EU Scheme for authorization of biocidal products and evaluation of active substances. It took many years to finalize, with extensive debate with stakeholders and a great deal of political compromise from the EU and national law-making bodies involved in the complex EU legislative development process. The BPD is clearly influenced by previous EU schemes, especially for general chemicals and plant protection products, and the various national approval schemes for biocidal products. The practical implementation of the scheme is left to the European Commission, the ECB and the national competent authorities. The diverse background, experience, and interest of these diverse parties has meant further compromise in developing the practical aspects for operating the BPD. Industry, academics, the public, and environmental pressure groups have also had input into the technical guidance documents which are pivotal to the smooth operation of the scheme. Many of the early concerns of industry with the BPD seem to have been resolved, for example regarding comparative risk assessment.

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For worldwide marketing of a biocidal product, the regulatory hurdle used to be the US FIFRA. Now, generally, the cost of testing for the EU BPD is higher, and the time to get EU approval is likely to be at least as long as for the USA. The biocides industry may not be able to support such extensive testing, especially for certain less profitable markets. Hence development of new products may be adversely affected. The problem may be especially acute for existing biocide active substances, because in principle the same amount of data are needed for the ongoing 10-year EU review program, it is virtually certain there will be far fewer biocidal products on the market, with a reduced selection of active substances.

References [1] Directive of the European Parliament and Council of 16-2-98 concerning the placing of biocidal products on the market (98/8/EC), Off. J. Eur. Communities, L123, 24-04-98. [2] EC Council Directive 76/769/EEC of 29-4-75 relating to restrictions on the marketing and use of certain dangerous substances and preparations (76/769/EEC), Off. J. Eur. Communities, L262, 27-9-76, as amended. [3] Council Directive 67/548/EEC, as amended and adopted to technical progress, as partly published up to January 1997 as “Classification, packaging, and labeling of dangerous substances in the European Union”, European Commission, Luxembourg, 1997. [4] EC Council Directive of 30-4-92 amending for the seventh time Directive 67/548/EEC on the approximation of the laws regulations and administrative provisions relating to the classification, packaging, and labeling of dangerous substances (92/32/EEC), Off. J. Eur. Communities, L154, 05-06-92. [5] EC Council Directive of 31-5-99 amending the Directive 88/379/EEC on the approximation of the laws, regulations, and administrative provisions of the member states relating to the classification, packaging, and labeling of dangerous preparations (99/45/EC), Off. J. Eur. Communities, L200, 30-07-99. [6] EC Council Directive of 15-7-91 concerning the placing of plant protection products on the market (91/414/EEC), Off. J. Eur. Communities, L230, 19-08-91, as amended. [7] Technical Notes for Guidance on the inclusion of active substances in Annexes I, IA, and IB of the Biocidal Products Direc-

References

[8]

[9]

[10]

[11] [12]

[13]

tive, European Commission document, in preparation. Technical Notes for Guidance on data requirements, European Commission document, in preparation. Council Directive 87/18/EEC of 18-12-86 on the harmonization of the laws, regulations, and administrative provisions relating to the application of the principles of GLP and the verification of their application for tests on chemical substances, Off. J. Eur. Communities, L15, 17-1-87, as adapted to technical progress by Commission Directive 1999/11/EC of 8-3-99, Off. J. Eur. Communities, L77, 23-3-99. Annex V of Council Directive 67/548/EEC, as adopted to technical progress by Commission Directive 92/69/EEC of 31-7-92, Off. J. Eur. Communities, L383A,. 29-12-92, Commission Directive 96/54/EC of 30-70-96, Off. J. Eur. Communities, L24I, 30-9-96, Commission Directive 98/73/EC of 18-9-98, Off. J. Eur. Communities, L305, 16-11-98, Commission Directive 2000/32/EC of 19-5-00, Off. J. Eur. Communities, L136, 8-6-00 and Commission Directive 2000/33/EC of 25-4-00, Off. J. Eur. Communities, L136, 8-6-00. OECD Guidelines for the Testing of Chemicals, OECD, Paris, 1993, as updated. Guidelines for the Practical Implementation of Directive 98/8/EC, European Commission document, in preparation. Technical Notes for Guidance in support of Annex VI of the Directive, European Commission document, in preparation.

References [14] Technical Guidance Documents in support of the EC Commission Directive on risk assessment for new notified substances (93/67/EEC) and the Commission Regulation on risk assessment for existing substances ((EC)1488/94), European Commission document, April 1996. [15] Biocidal Products Directive: The Provisional List of Existing Active Substances (98/8/EC), http://ecb.ei.jrc.it/biocides. [16] EC Commission Regulation of 7-9-00 on the first phase of the program referred to in Article 16(2) of Directive 98/8/EC of the European Parliament and of the Council on biocidal products (No. 1896/2000), Off. J. Eur. Communities, L228, 8-9-00. [17] Proposals for the Biocidal Product Regulations (BPR) and approved Code of Practice on test methods for data submitted under the BPR. Consultative Documents 1999, CD149 C40 7/99, HSE books, Sudbury, UK. [18] Annex VI of Council Directive 67/548/ EEC, as adapted to technical progress by Commission Directive 93/21/EEC of 27-4-93, Off. J. Eur. Communities, L110, 4-5-93, Commission Directive 96/54/EC of 30-7-96, Off. J. Eur. Communities, L248, 30-9-96, Commission Directive 97/69/EC of 5-12-97, Off. J. Eur. Communities, L343, 13-12-97, Commission Directive 98/98/EC of 15-12-98, Off. J. Eur. Communities, L355, 30-12-98, as corrected by Commission Decision 2000/368/EC of 19-5-00, Off. J. Eur. Communities, L136, 8-6-00, and Commission Directive 2000/32/EC of 195-00, Off. J. Eur. Communities, L136, 8-6-00. [19] EC Commission Directive of 10-12-93 on Safety Data Sheets (93/112/EC), Off. J. Eur. Communities, L314, 16-12-93. [20] EC Council Directive of 26-6-78 on the approximation of the laws of the member states relating to the classification, packaging, and labeling of dangerous preparations (pesticides) (78/631/EEC), Off. J. Eur. Communities, L206, 29-7-78. [21] Notice No 90/C 146 A/01 Commission communication pursuant to Article 13 of Council Directive of 27 June 1967 on the approximation of the laws, regulations, and administrative provisions relating to the classification, packaging, and labeling of dangerous substances, as amended

[22]

[23]

[24]

[25]

[26]

[27]

[28]

[29] [30]

[31]

by Directive 79/831/EEC–Einecs (European Inventory of Existing Commercial Chemical Substances) (67/548/EEC), Off. J. Eur. Communities, C146, A.15-6-90. Vol. 33. EC Council Regulation No. 793/93 of 23-3-93 on the evaluation and control of risks of existing substances (793/93/EEC), Off. J. Eur. Communities, L84, 5-4-93. Commission Directive 93/67/EEC of 20-7-93 laying down the principles for the assessment of risks to man and the environment of substances notified in accordance with Council Directive 67/548/EEC, Off. J. Eur. Communities, L227, 8-9-93. Commission Regulations (EC) No. 1488/ 94 of 28-6-94 laying down the principles for the assessment of risks to man and the environment of existing substances in accordance with Council Regulation (EEC) No. 793/93, Off. J. Eur. Communities, L161, 29-6-94. United Nations Recommendations on the Transport of Dangerous Goods Model Regulations, Eleventh revised edition, United Nations, New York and Geneva, 2000. International Convention for the Prevention of Pollution from Ships adopted 1973, modified by Protocol of 1978 (MARPOL 73/78). Chapters 4 and 6 of “Manual of Environmental Policy: the EU and Britain”, ed. N. Haigh, Elsevier Science, Oxford, 2000. Council Regulation (EC) No. 3093/94 of 15-12-94 on substances that deplete the ozone layer, Off. J. Eur. Communities, L333, 22-12-94, as amended. Chapter 5 of ref [27]. Council Directive 89/391/EEC of 12-6-89 on the introduction of measures to encourage improvements in the safety and health of workers at work, Off. J. Eur. Communities, L183, 29-6-89, and the individual Directives and their amendments within the meaning of Article 16(1) of Directive 89/391/EEC. EC Council Directive of 26 January 1994 on the control of major accident hazards involving dangerous substances (92/82/EC), Off. J. Eur. Communities, L10, 14-1-97.

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3 Regulatory Control of Biocides in Europe [32] EC Council Directive of 9-9-93 on packaging and packaging waste (94/62/EC), Off. J. Eur. Communities, L365, 31-12-94. [33] Decision 18/12; Development of an international legally binding instrument for the application of the prior informed consent procedure for certain hazardous chemicals in international trade, and consideration of further measures to reduce the risks from hazardous chemicals. Adopted 18th Session of Governing Council of United Nations Environment Program, Nairobi, 15 – 26 May 1995. [34] EC Council Directive of 16-6-71 on detergents (73/404/EEC), Off. J. Eur. Communities, L347, 17-12-73, as amended. [35] a) Offshore Chemical Notification scheme: PARCOM Decision 96/3 on a harmonized mandatory control system for the use and reduction of the discharge of off-shore chemicals; b) Harmonized Mandatory Control System for the Use and Reduction of the Discharge of Offshore Chemicals: OSPAR Decision 2000/2. [36] OECD Series on Pesticides, Number 9; Report of the Survey of OECD Member Countries’ Approaches to the Regulation of Biocides, ENV/JM/MONO(99)11 28 April 1999, http://www.oecd.org/ehs). [37] Bestrijdingsmiddelenwet, 1962. [38] Regeling Toelating bestrijdingsmiddlelen, 5 February 1994. [39] Arrt royal du 5 June 1975 relatif la conservation, au commerce et l’utilisation des pesticides et des produits phytopharmaceutiques, moniteur belge, 4.11.1975 p.13864 (as amended). [40] La Mise sur le marche d’un pesticide a usage non-agricole Project, Conseil Superieur d’hygiene, November 1995.

[41] Control of Pesticide Regulations (COPR) 1986, as amended, Statutory Instrument Number 1510. [42] The Non-Agricultural Pesticides Registration Handbook, HSE, latest version. [43] Statutory order from the Ministry of the Environment Act, No. 212 of 23-5-79 on chemical substances and products, as amended by Act No. 68 of 20-2-80, by Act No. 285 of 13-5-87, and by Act No. 791 of 10-12-87 on Chemical pesticides, the Consolidated Act from Ministry of Environment and Energy No 21 of 16-1-96 on Chemical substances as amended by Act No 256 of 12 April 2000, and products and the Statutory Orders from The Ministry of Environment and Energy No 722 of September 1997, No 241 of April 1998 and No 313 of 5 May 2000. [44] The Finnish Chemicals Act 744/1989, as amended by 1198/2000. [45] Decree on Wood Preservatives and Slimicides (123/1994) (Chemical preservatives). N:o 123 Suojauskemikaaliasetus, Annettu Helsingissa II pa¨iva¨na¨ helmikuuta 1994, p.335. [46] Decision 256/94, Ministry of the Environment, 1-5-94, No. 256 Ympa¨risto¨ministerio¨n pa¨a¨to¨s, suojauskemikaalien ennakkohyva¨ksymis – ja ilmoitusmenettelysta¨. Annettu Helsingissa 5 pa¨iva¨na¨ huhti kuuta 1994. [47] The Finnish Pesticides Act 327/69. [48] Chapter 14 of Miljo¨bakan 1988:808 in “The Swedish Environmental Code”, Fritzes Offentliga, latest version. [49] Swedish Ordinance SFS 2000:338.

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Regulation of Biocides in the United States Sue Crescenzi

4.1

Introduction to Pesticide Regulation in the United States 4.1.1

Legal Authority

In the United States, there are two different statutes that provide the basis for the regulation of all pesticides including biocides and agricultural (plant protection) products: the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA)[1] and the Federal Food, Drug, and Cosmetic Act (FFDCA) [2]. FIFRA is the principal statute regulating pesticides. It focuses on the safety of products and their labeling. FIFRA authorizes the US Environmental Protection Agency (EPA) to register (license) a pesticide prior to marketing [3]; to regulate the labeling of all pesticide products, including technical active ingredients and formulated end-use products [4]; to re-evaluate (re-register) pesticides registered prior to 1984[5]; to evaluate pesticides every 15 years [6]; to regulate all aspects of the sale, distribution and use of pesticides [7]; to impose post-registration obligations, including various reporting requirements [8] and the generation of additional data to support continued registration [9]; and to regulate pesticide exports and imports [10]. FFDCA sets forth the requirements for the establishment of legal pesticide limits (residues) for pesticides used in or on food or feed crops [11]. FFDCA also provides the basis for the regulation of pesticides with uses that may result in contact of the pesticide with food (food additive and food-contact substances) [12]. FFDCA is administered in part by EPA, and in part, by the Food and Drug Administration (FDA). FIFRA was first enacted in 1947 and has been amended on a number of occasions. The two most recent amendments are the Food Quality Protection Act (FQPA) of 1996 [13] and the Antimicrobial Reform Technical Corrections Act (ARTCA) of 1998 [14]. The Biocides Business: Regulation, Safety and Applications. Edited by Derek J. Knight and Mel Cooke Copyright ª 2002 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN: 3-527-30366-9

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4 Regulation of Biocides in the United States

FQPA, discussed in Section 4.5.2, has revolutionized the manner in which EPA assesses potential risks associated with pesticide residues which may be present on food. FQPA also has impacted the manner in which food-contact biocides in the United States are assessed and regulated. FQPA and ARTCA also have altered the jurisdiction for food-contact antimicrobial pesticides in the United States and is discussed more fully in Section 4.4.4.

4.1.2

Federal Agencies with Responsibility for the Regulation of Biocides

EPA’s Office of Pesticide Programs (OPP) administers FIFRA and also administers the FFDCA requirements for pesticide residues in food. FDA regulates the use of pesticides, primarily antimicrobials, as food additives* or food-contact substances**. Both are handled by FDA’s Center for Food Safety and Applied Nutrition (CFSAN), Office of Food Additive Safety. FDA regulated all chemical substances used as food additives or food-contact substances. However, when used to mitigate, kill or otherwise act against pests***, these compounds also are regulated by EPA as pesticides. Antimicrobial registrations are handled primarily by the Antimicrobial Division within OPP. OPP’s Registration Division generally handles registrations and responsibilities for “conventional” chemical pesticides. Details on antimicrobial and conventional pesticide registrations and other regulatory procedures are discussed in more detail in the following sections. (There is a separate OPP division for “biopesticide” products, which are not addressed in this discussion.) “Re-registration” actions are handled by the OPP Special Review and Reregistration Division (SRRD) and are discussed in more detail in Section 4.5.

*

A „food additive“ is defined as „any substance, the intended use of which results or may reasonably be expected to result, directly or indirectly, in its becoming a component or otherwise affecting the characteristics of any food....“ FFDCA § 201(s); 21 U.S.C. 321(s). See Section 4.4.2 for additional information on the FDA regulation of food additives. ** A „food-contact substance“ is defined as „any substance intended for use as a component of materials used in manufacturing, packing, packaging, transporting, or holding food if such use is not intended to have any technical effect in such food.“ FFDCA § 409(h)(6); 21 U.S.C. 348(h)(6). See Section 4.4.3 for additional information on the regulation of foodcontact substances by FDA.

*** A „pest“ is defined as „(1) any insect, rodent, nematode, fungus, weed, or (2) any other form of terrestrial or aquatic plant or animal life or virus, bacteria, or other micro-organism (except viruses, bacteria, or other micro-organisms on or in living man or other living animals)“. FIFRA § 2(t); 7 U.S.C. 136(t). EPA’s regulations further qualify the term „pest“ as excluding any „fungus, bacterium, virus or other microorganisms ... on or in processed food or processed animal feed, beverages, drugs (as defined in FFDCA sec. 201(g)(1)) and cosmetics (as defined in FFDCA sec. 201(i)).“ A „pesticide“ is defined, in part, as „any substance or mixture of substances intended for preventing, destroying, repelling, or mitigating any pest ...“. FIFRA § 2(u); 7 U.S.C. 136(u).

4.2 Regulation of Biocides in the United States

4.1.3

Information Resources

EPA has promulgated a series of regulations on pesticide regulatory procedures and requirements, found at 40 Code of Federal Regulations (C.F.R.) Parts 150 through 186. EPA also has developed numerous guidance materials, much of which can be accessed through the OPP Internet Home Page, www.epa.gov/pesticides/. FDA regulations governing food additives are published at 21 C.F.R. Parts 170 through 189. Additional FDA guidance on its regulation of biocides used as food additives and food-contact substances can be accessed through the CFSAN Internet Home Page, www.cfsan.fda.gov/.

4.2

Regulation of Biocides in the United States 4.2.1

Regulation of Biocides Generally

The term “biocides,” as used herein, refers to pesticides covered by the European Union’s Biocides Product Directive (BPD). In the US, there is no formal recognition of biocides as a distinct group of pesticides with separate authorizing legislation, regulations, or regulatory authority. It is important to know the specific use to which a biocidal product will be put to determine the statutory and regulatory scheme(s) that will apply. Table 4.1 is a listing of the BPD product categories and provides a brief description of the manner in which each category is regulated in the US.

4.2.2

Regulation of Antimicrobial Biocides

One section of the FQPA amendments to FIFRA in 1996 [15] required EPA to establish review time frames or “goals” for the completion of action by EPA on applications for antimicrobial registrations and amendments [16], and to establish registration procedures [16a] and data requirements specific to antimicrobials [16b]. There are no statutory review time goals for registration actions for other types of biocides, except that EPA action on a “me-too” application, discussed in detail in Section 4.3.2.4, is to be completed within 90 days [17]. An “antimicrobial pesticide” is defined as “a pesticide (A) that is intended to (i) disinfect, sanitize, reduce, or mitigate growth or development of microbiological organisms; or (ii) protect inanimate objects, industrial processes or systems, surfaces,

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4 Regulation of Biocides in the United States Tab. 4.1.

EU BPD biocide categories and US regulatory equivalents

EU Product Category

US Regulatory Status

1. Human hygiene biocidal products (for use on the human body)

Regulated as cosmetics and/or drugs by the FDA under FFDCA

2. Private area and public area disinfectants, and other biocides (nonfood contact)

Regulated as antimicrobial pesticides by EPA under FIFRA

3. Veterinary biocidal products (for use in housing, transport, etc.)

Regulated as antimicrobial pesticides by EPA under FIFRA

4. Food and food area disinfectants and sanitizers

Jointly regulated by EPA under FIFRA as pesticides and by FDA under FFDCA as food additives, when used in process waters in food processing facilities Regulated solely by EPA as pesticides under FIFRA and FFDCA Section 408 when used on food-contact surfaces in food processing facilities. Regulated solely by EPA as pesticides under FIFRA when used on food-contact surfaces in residences (however, EPA might apply requirements consistent with FFDCA Section 408). (See Section 4.4.5 for discussion.)

5. Drinking water disinfectants

Jointly regulated by EPA Office of Pesticide Programs as antimicrobial pesticides under FIFRA and by EPA Office of Drinking Water under Safe Drinking Water Act

6. In-can preservatives

Regulated by EPA under FIFRA as antimicrobial pesticides; if used in materials potentially in contact with food (for example, preservative in adhesives used in food packaging), also regulated by FDA under FFDCA Section 409 as indirect food additives (See Section 4.4.4 for discussion.)

7. Film preservatives

Regulated by EPA as antimicrobial pesticides

8. Fiber, leather, and polymerized materials preservatives

Regulated by EPA as antimicrobial pesticides; if used as preservatives in components of articles in contact with food (for example, conveyor belt in food processing plant), also regulated by FDA as indirect food additives (See Section 4.4.4 for discussion.)

9. Wood preservatives

Regulated by EPA under FIFRA as antimicrobial pesticides or conventional pesticides, depending on target pest

10. Masonry preservatives

Regulated by EPA under FIFRA as antimicrobial pesticides

11. Preservatives for liquid-cooling and processing systems

Regulated by EPA under FIFRA as antimicrobial pesticides

12. Slimicides

Regulated by EPA under FIFRA as antimicrobial pesticides; if used in the production of food-contact paper or paperboard, also regulated by FDA under FFDCA Section 409 as indirect food additives (See Section 4.4.4 for discussion.)

13. Metalworking fluid preservatives

Regulated by EPA under FIFRA as antimicrobial pesticides

14. Rodenticides

Regulated by EPA under FIFRA as conventional pesticides

4.2 Regulation of Biocides in the United States Tab. 4.1.

EU BPD biocide categories and US regulatory equivalents (Cont.)

EU Product Category

US Regulatory Status

15. Avicides

Regulated by EPA under FIFRA as conventional pesticides

16. Molluscicides

Regulated by EPA under FIFRA as conventional pesticides

17. Piscicides

Regulated by EPA under FIFRA as conventional pesticides

18. Insecticides, acaricides

Regulated by EPA under FIFRA as conventional pesticide.

19. Repellants and attractants

Regulated by EPA under FIFRA as conventional pesticides

20. Preservatives for food and feedstocks

Regulated by FDA under FFDCA Section 409 as direct food additives

21. Anti-fouling products

Regulated by EPA under FIFRA as antimicrobial pesticides or conventional pesticides, depending on target pest

22. Embalming and taxidermy fluids

Not federally regulated in US

23. Vertebrate control products

Regulated by EPA under FIFRA as conventional pesticides

water, or other chemical substances from contamination, fouling, or deterioration caused by bacteria, viruses, fungi, protozoa, algae, or slime....” [18]. However, there are important exceptions to the types of antimicrobials that are subject to the antimicrobial reform provisions. All antimicrobials used in food or in contact with food are excluded from the definition. Moreover, wood preservatives and antifoulants that make claims against pests other than, or in addition to, microorganisms are excluded*. Applications for registration of antimicrobials that meet the statutory definition are to be reviewed within specified time frames. * * * *

* *

540 days for a new antimicrobial active ingredient; 270 days for a new antimicrobial use of a previously registered active ingredient; 120 days for any other new antimicrobial product; 90 days for substantially similar or identical (“me-too”) products (discussed in more detail in Section 4.3.2.4); 90 days for amendments that do not require scientific review of data; and 90 to 180 days for other types of amendments. [19]

No other pesticides are subject to review time goals. *

FIFRA § 2(mm)(1)(B); 7 U.S.C. 136(mm)(1)(B) [18a], excludes from the definition any antimicrobial subject to FFDCA § 408 [11] or § 409 [12]. FIFRA § 2(mm)(2); 7 U.S.C. 136(mm)(2) [18b] excludes wood preservatives and antifoulants. Wood preservatives, despite being exempt from the statutory definition of an

antimicrobial pesticide, are to be reviewed by EPA within the antimicrobial time frames if the data required to support the registration are the same as those required to support an antimicrobial pesticide. FIFRA § 3(h)(3)(E); 7 U.S.C. 136a(h)(3)(E) [18c].

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The 1996 Amendments directed EPA to promulgate regulations consistent with the statutory goals for completing antimicrobial actions within nine months of August 1996, the date of enactment of the new provision [20] Despite this statutory mandate, regulations have not yet been finalized as of the time of this writing. When issued, the regulations for antimicrobial registration actions will be codified at 40 C.F.R. Part 152 Subpart W[21]. In the meantime, the Antimicrobial Division has committed to process registrations subject to statutory deadlines within the prescribed time frames. It is important to note that EPA may conclude at the end of a specified review period that there are deficiencies in the application. In these instances, the applicant is required to address the deficiencies, usually by providing additional information or data, or revising administrative forms or labeling. In such instances the review time for the revised application is the same time period as that originally assigned.

4.3

Registration of a New Active Ingredient

EPA generally requires that a new active ingredient is registered before it can be used to formulate end-use products. As part of the application process, the following administrative forms must be submitted: Application for Registration (EPA Form 8570-1), Confidential Statement of Formula (EPA Form 8570-4), Certification with Respect to Citation of Data (EPA Form 8570-34), and public and EPA copies of the Data Matrix (EPA Form 8570-35). The proposed product label also must be submitted with the application package [22].

4.3.1

Active Ingredient Data Requirements

A complete set of data required to support the technical or pure grade of the active ingredient, otherwise known as “generic data,” must be submitted with the application package. A complete data package typically includes product chemistry data, acute, subchronic and chronic toxicity data, human exposure data, environmental fate data, ecotoxicity data, and residue data when the pesticide is to be registered for a food use. The toxicology database typically required for biocides, including antimicrobials (both food and nonfood-contact sites) that have a potential for high exposure, is referred to as a full “CORT” (Chronic, Oncogenicity, Reproductive and Teratogenicity) database. (Examples of high-exposure antimicrobial uses include swimming pool treatments, human and animal drinking water treatments, and aquatic outdoor uses such as ponds and irrigation ditches.) As a starting point, generally one should

4.3 Registration of a New Active Ingredient

refer to the data tables at 40 C.F.R. Part 158 for specific requirements. The data requirement regulations in the Code of Federal Regulations at the time this chapter was prepared (2001) were promulgated in 1984, and may not reflect current requirements. Any party considering preparing an application for registration of an active ingredient should consult with representatives of the respective EPA OPP Division (either the Registration Division or Antimicrobial Division, as appropriate) well in advance of finalizing a data package. EPA encourages these “pre-registration” meetings and typically requests that a prospective registrant prepare product labeling and other information that will enable its staff to determine appropriate data and other requirements for completing an application package. Testing submitted in support of registration must be performed to EPA Pesticide Assessment Guidelines (PAGs)[23] or equivalent standards and in compliance with EPA’s Good Laboratory Practice Standards (GLPs) [24]. EPA has been working on revising its data requirement regulations for almost a decade. The plan to publish a proposed regulation with updated data requirements has been delayed, but new regulations may be proposed in 2002. Antimicrobial Active Ingredient Data Requirements Data requirements for some antimicrobial pesticides differ from other biocides and agricultural pesticides. In 1987, EPA initiated a policy of “tiered” toxicology data requirements for antimicrobials, based on the potential exposure from their approved uses. The current (2001) interim OPP policy requires different “Tier I” or minimum databases for low-exposure antimicrobials, depending on whether registered for foodcontact or nonfood-contact use sites. (Antimicrobials with high-exposure uses are regulated in a manner consistent with other biocides with respect to data requirements, as discussed in Section 4.3.1.1, supra.)[25]. For low-exposure, food-contact uses, the “Tier I” toxicology data set includes an acute toxicity battery (acute oral, dermal and inhalation toxicity; eye and dermal irritation and dermal sensitization), two subchronic (90 day) oral toxicity studies, teratogenicity (onespecies), a mutagenicity battery and a two-generation reproductive toxicity study. Examples of indirect food-contact uses include hard surface sanitizers and slimicides used in manufacturing food-contact paper products. According to the current (2001) OPP interim policy, when the residue concentrations from indirect food contract use exceeds 200 parts per billion (ppb), the full CORT toxicity database described in Section 4.3.1, is required [26]. EPA currently requires more limited toxicity data for low exposure, nonfood-contact uses of antimicrobials. The “Tier I” database includes an acute toxicity battery, one 90 day study (usually by most common route of exposure), teratogenicity (one species) and a mutagenicity battery. Examples of low exposure uses include nonfood-contact material preservatives [27]. 4.3.1.1

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Follow-on Registration of an Active Ingredient In general, follow-on registrants of active ingredients are required to meet the same data requirements imposed on the original registrants of active ingredients. The requirements may be met by generating an additional, complete data package or by offering to compensate the original data submitter(s) for reliance on its (their) data [28]. Data protection and compensation are discussed in greater detail in Section 4.6. 4.3.1.2

4.3.2

Registration of End-use Product Formulations

FIFRA requires that each end-use pesticide formulation be registered prior to distribution or sale. Under most circumstances the formulated product is composed of one or more registered active ingredients and one or more “inert” (nonpesticidally active) ingredients. The application package consists of administrative forms, labeling, and product-specific data. The Application for Registration and Confidential Statement of Formula are the same forms used for an application for an active ingredient registration discussed earlier. Formulated Products Entitled to Formulator’s Exemption When a formulator of the end-use product purchases a registered active ingredient for use in the formulated product, it is entitled to a “formulator’s exemption.” Formulator’s exemption enables an applicant to obtain a registration without offering to compensate the original data submitter(s) for reliance on generic data [29]. The Formulator’s Exemption Statement (EPA Form 8570-27) must be submitted with the application package [30]. 4.3.2.1

4.3.2.2 Formulated Products Not Entitled to Formulator’s Exemption

In instances where the formulator of the end-use product is also the registrant of the active ingredient, EPA does not permit use of the formulator’s exemption. The applicant must complete a Certification with Respect to Citation of Data and Data Matrix. These forms must be consistent with the Certification and Data Matrix submitted in support of the active ingredient registration [31]. A registrant using an active ingredient from an unregistered source in its product formulation is responsible for satisfying all generic data requirements for the active ingredient. Consistent with the requirements for an applicant seeking a follow-on registration for an active ingredient (Section 4.3.1.3), either a complete data package must be submitted or applicable data must be cited and compensation offered. The Certification with Respect to Citation of Data and Data Matrix must be completed whether new data are submitted or existing data are cited. See the discussion at Section 4.6 for additional information.

4.3 Registration of a New Active Ingredient

4.3.2.3 Product-specific Data

Product-specific data necessary to support each new end-use formulation include product chemistry data and acute toxicity data, and efficacy data when the product’s label makes public health claims [32]. EPA requires the submission of efficacy data for all antimicrobial products that make public health claims, rodenticides, and some mammalian repellants. Insecticides and other biocides that make public health claims also may be required to submit efficacy data, although EPA has not consistently required efficacy data for these products. Even when EPA does not require submission of efficacy data, such data must be generated by the registrant, maintained in its files and submitted to EPA upon request [33]. 4.3.2.4 Applications for Formulated Product “Me-too” Registrations

The most common end-use registration is known as a “me-too” registration [34]. To qualify as a me-too, the formulation must be identical or substantially similar to another registered pesticide product in amount and identity of active ingredients, amount and identity of inert ingredients, use patterns, and use directions. FIFRA requires that EPA notify an applicant within 45 days as to the completeness of the me-too application. If the application is complete, EPA has 90 days in which to notify the applicant whether it has been approved [35]. EPA makes the ultimate determination whether the product is, in fact, identical or substantially similar by reviewing the Confidential Statement of Formula submitted for the me-too application and the Confidential Statement of Formula for the product referenced by the applicant. The requirements for me-too classification are strictly applied and many products do not qualify. Examples of products that do not qualify include products with: different active ingredient; registered active ingredient at a different percentage; significantly different inert ingredients; or similar inerts at a different percentage; new formulation type; label with different pests; different dose rates or different frequency of application or use. An application for a technical or manufacturing use product is not granted me-too status, because, at a minimum, the follow-on registrant of a technical or manufacturing use product must submit manufacturing process data, batch analyses, and physical and chemical characteristics. The submission of data requires EPA to conduct data reviews and eliminates the application from expedited processing.

4.3.3

Amendments to Change Existing Registrations

Once a pesticide product has been registered, the registrant may have to submit an application for amendment in order to make changes to the product’s formulation or the product’s labeling. The contents of an application for amendment depend on the

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type of change proposed. An application form must be submitted, identifying the nature of the change sought by the amendment. A Confidential Statement of Formula must be submitted if a change is proposed to the formula. Draft revised labeling must be submitted if a labeling change is sought. Data may be required, depending on the nature of the amendment [36].

4.3.4

Changes Not Requiring Amendments

EPA permits some limited types of labeling, formulation, or other changes by use of notification, rather than amendment [37]. The advantage to availing oneself of the ability to notify is that the change being notified may be implemented by the registrant coincidentally with submission of the notification to EPA. The one exception to this rule is that FIFRA requires that any change in the labeling of an antimicrobial pesticide is subject to a 60 day waiting period or approval of the notification by EPA, whichever occurs first [38]. A registrant must certify that the notification complies with all EPA requirements and that no other changes have been made to labeling or the formula [39]. Some other minor changes may be made to the pesticide label without notifying EPA [40]. They include correction of typographical or printing errors, and change in name or address of the registrant, except those that involve change in ownership, and redesign of the label format. These are examples only; other minor changes may be permitted, but EPA’s regulations and guidance should be consulted for further information.

4.4

Regulation of Biocides Used in, on, or in Contact with Food 4.4.1

EPA Regulation of Pesticide Chemicals in or on Food

FFDCA provides the authority for regulating residues of substances in food. Section 408, administered by EPA, regulates “pesticide chemical residues” in food. When seeking registration of a pesticide chemical that will result in residues in or on food, a party must apply for both a registration pursuant to FIFRA Section 3 and submit a petition for a tolerance or exemption from tolerance pursuant to FFDCA Section 408. A tolerance is the legal limit of a residue that may be present in a specified food or food group, promulgated as a regulation and published in the Code of Federal Regulations [41]. An exemption from tolerance is a determination by EPA that the total

4.4 Regulation of Biocides Used in, on, or in Contact with Food

amount of the pesticide chemical in food, under prevailing conditions of use, involves no hazard to public health. Exemptions from tolerance are published as regulations by EPA [42].

4.4.2

FDA Regulation of Food Additives

Section 409, administered by FDA, regulates “food additives,” substances resulting or reasonably expected to result in being a component of food as a result of their intended use [43]. A food additive petition may be required for a biocide proposed for a foodcontact use [44]. FDA reviews the petition and makes a determination whether the showing of safety by the petitioner is adequate. If approved, a regulation is published providing for the general use of the substance for the specified food-contact use [45].

4.4.3

FDA Regulation of Food-contact Substances

Alternatively, a party may determine it is appropriate to prepare a Premarket Notification (PMN) for a food-contact substance [45a]. This regulatory category, defined as “any substance intended for use as a component of materials used in manufacturing, packing, packaging, transporting, or holding food if such use is not intended to have a technical effect on food,” was created by amendments to FFDCA in 1997. FDA has 120 days from date of receipt to object to the notification, thereby preventing marketing of the FCS. If FDA determines the safety assessment prepared by the notifier is adequate and no objection is filed within 120 days, the substance may be marketed. In contrast to the general applicability of a food additive regulation, the notification is proprietary to the manufacturer listed in the notification [46].

4.4.4

Overlapping EPA and FDA Jurisdiction for Antimicrobial Food-Contact Uses

FQPA, because of an inadvertent drafting error, transferred jurisdiction for antimicrobials, which historically had been regulated as food additives by FDA under FFDCA Section 409, to EPA as “pesticide chemical residues” subject to regulation under FFDCA Section 408 [47]. In 1998 ARTCA was enacted and partially restored jurisdiction for food-contact antimicrobial pesticides to FDA, while also continuing EPA’s regulatory authority for these compounds [48]. The result is a complex scheme of both separate and shared responsibility for antimicrobial food-contact uses between EPA and FDA.

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A brief summary (Tables 4.2 and 4.3) of the FFDCA jurisdictional provisions, as amended by ARTCA, is provided below [49]. However, the jurisdictional distinctions are complex and an interested party should consult with legal advisors and/or the two agencies to determine the appropriate regulatory programs applicable to a particular food-contact use of an antimicrobial pesticide. Table 4.2

Examples of antimicrobials regulated by EPA and FDA.

*

Antimicrobial applied to water that contacts food in facilities where food processing occurs [50]

*

*

Antimicrobial preservative that is a component of an article with food contact, but in which the antimicrobial has no intended ongoing effect on the article or on the article’s food-contact surface (for example, a preservative of the plastic or latex incorporated into a piece of equipment used in a food processing facility.) [54] Antimicrobial used in food packaging material (for example, slimicides used in pulp and paper mills in the wet-end of paper and paperboard production and preservatives in food-contact paper coatings.) [52]

*

*

Tab. 4.3.

*

Dually regulated by FDA as a food additive (either indirect or secondary direct) under FFDCA Section 409 and by EPA as a pesticide under FIFRA Dually regulated by FDA as a food additive (either indirect or secondary direct) under FFDCA Section 409 and by EPA as a pesticide under FIFRA.

Dually regulated by FDA as a food additive (either indirect or secondary direct) under FFDCA Section 409 and by EPA as a pesticide under FIFRA

Examples of Antimicrobials Regulated Solely by EPA.

*

Antimicrobials used on permanent and semipermanent surfaces (for example, a hard-surface sanitizer) [53]

*

*

Antimicrobials in treated articles marketed with claims that the antimicrobial is intended to have a pesticidal effect on the food-contact surfaces [54]

*

*

Antimicrobials and other pesticide products applied on raw agricultural commodities (RACs) and for which there is no processing in the field or in facilities receiving the RACs [55]

*

EPA, as a result of ARCTA’s enactment, now has sole jurisdiction for the regulation of antimicrobials used on permanent and semipermanent surfaces (e.g., surfaces of equipment that contact food). These uses are subject to registration under FIFRA and to the tolerance or tolerance exemption requirements of FFDCA Section 408 EPA has sole jurisdiction for regulating antimicrobials used in treated articles making pesticidal claims. The treated articles could be subject to the tolerance and tolerance exemption requirements of FFDCA Section 408. EPA retains its historic sole jurisdiction. These pesticides are subject to the tolerance and tolerance exemption requirements of FFDCA Section 408

A party wanting to market an antimicrobial pesticide also subject to regulation by FDA as a food additive or a food-contact substance, must comply with FDA’s requirement separately from the EPA registration action. Either a petition for a food additive regulation or a premarket notification (PMN) for a food-contact substance must be

4.4 Regulation of Biocides Used in, on, or in Contact with Food

prepared and submitted to the FDA Center for Food Safety and Applied Nutrition, (CFSAN), Office of Food Additive Safety. (The specific FDA requirements and procedures for obtaining a regulation permitting use of the substance as a food additive or preparing and submitting a PMN are not discussed in this article.) Additional information is available through the FDA CFSAN Internet Home Page, www.cfsan.fda.gov. Compliance with FDA requirements pursuant to FFDCA Section 409 does not enable a party to market the subject biocide product. It also must be registered by EPA before it can be sold or distributed as a pesticide and the FDA-regulated use must be explicitly referenced on the product’s label. EPA at the present (2001) has interpreted its statutory responsibility as requiring it to assess food-contact antimicrobial pesticides consistent with FQPA risk assessment provisions and independent of any FDA action, prior to issuing a FIFRA registration [56]. These EPA assessments are in addition to FDA’s reviews and decisions and may result in different regulatory standards (that is, permissible residue levels) for the same uses or even conflicting regulatory conclusions. FQPA requires EPA to aggregate all anticipated risks from dietary exposure, exposure resulting from occurrence of the pesticide in drinking water, and exposure from residential and other nonoccupational uses. FQPA also requires EPA to consider whether an additional ten-fold safety factor, intended to protect infants and children, should be imposed, reduced, eliminated, or even increased in completing the risk assessment for the final regulatory decision on the pesticide. See Section 4.5.2 for additional discussion of FQPA risk assessments.

4.4.5

EPA Identification of Biocides as Food Contact

Historically, the determination of whether a pesticide’s uses were considered food or nonfood contact depended on its use consistent with the requirements of FFDCA Section 408 or 409. There are indications that EPA in the future may regard certain biocide uses, which are not considered by FDA to be food-contact uses and are not regulated pursuant to FFDCA, as subject to regulation consistent with the FQPA safety standards for pesticides used on food. Examples of such uses could include disinfectants used on hard surfaces and followed by potable water rinses, sanitizers used on food surfaces in residences, and insecticides used in food processing facilities for crack and crevice treatment. These uses have not previously been considered food uses. A prospective registrant should seek clear guidance from EPA during a pre-registration meeting, not only on the data that will be required for registration, but also on the risk assessment criteria that will be used for the registration review.

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4.5

Pesticide Re-registration 4.5.1

Expedited Re-registration

In 1988 Congress amended FIFRA to require EPA to re-register (re-evaluate) all pesticide products containing any active ingredient registered prior to 1984. The re-registration process was to be “expedited” and completed by fiscal year 1997 [57]. That completion date was extended on several occasions to 2002 and now has been extended to 2006. EPA was directed to bring all databases supporting pesticide registrations to current standards. When the amendments were enacted, the standards were considered to be consistent with the data requirements at 40 C.F.R. Part 158, which were finalized in 1984. Data call-ins (see Section 4.8.1) were issued for these active ingredients with existing databases that did not meet 1984 requirements. To re-register pesticides, EPA evaluates the risks posed by each active ingredient and each use of the active ingredient to make a re-registration decision. Active ingredients may not qualify for re-registration; in other instances, some uses of a particular active ingredient may not be re-registered. Frequently, risk mitigation measures are imposed in order for the active ingredient to be re-registered. Examples of risk mitigation have included reduction in use rates, increased requirements for personal protective equipment to be worn by applicators, and extended periods before re-entry to a treated area is permitted. EPA’s extensive review of the use, chemistry, toxicology, environmental, and ecological impacts, and the resultant risk assessments are published in a Re-registration Eligibility Decision (RED) document [58]. Following EPA’s comprehensive review of each active ingredient and publication of the RED document, each end-use formulation containing the active ingredient also must be re-registered. End-use product re-registration involves updating product-specific chemistry, toxicity, and where required, efficacy data, and revising the label to be consistent with the decisions and limitations in the RED.

4.5.2

Tolerance Reassessment

The re-registration process was changed by the passage of FQPA and its requirement that EPA reassess all existing tolerances and exemptions from tolerance by 2006 [58a]. Re-registration is being conducted in conjunction with the tolerance reassessment activities. As a result, all re-registration decisions involving pesticides regulated under both FIFRA and FFDCA Section 408 now must take into consideration the new risk assessment criteria established by FQPA. The risk assessment factors introduced by

4.6 Data Protection and Data Compensation Procedures

FQPA are: application of an uncertainty factor of ten (which may be eliminated, maintained, reduced, or increased); aggregation for a single active ingredient of all exposures from dietary, drinking water, and residential and other nonoccupational sources; and cumulative risk assessments when EPA determines that a group of active ingredients has a common mechanism of toxicity. FQPA also requires the evaluation of the endocrine disrupter effects of pesticides and other chemical compounds. EPA is currently developing its program, which will apply to all chemical compounds, and it is not discussed further in this chapter.

4.5.3

Fifteen Year Registration Review

FQPA added a provision to FIFRA requiring EPA to publish regulations for procedures to accomplish the periodic (every 15 years) review of existing registrations [59]. An Advanced Notice of Proposed Rulemaking (ANPR) was published on April 26, 2000 for public comment [60]. The ANPR was very preliminary and sought recommendations from the public. Numerous issues are raised by this statutory requirement and are unresolved at this time, including how to determine the date on which to base the 15-year review period for any active ingredient, priorities that should be established for the order in which active ingredients are reviewed, and how to handle nonconventional chemicals, including antimicrobials and possibly other biocide categories. EPA has provided no indication about when proposed regulations to implement periodic reregistration will be published for public review and comment.

4.6

Data Protection and Data Compensation Procedures

Pesticides regulated pursuant to FIFRA are subject to “exclusive use,” mandatory data citation and compensation, and binding arbitration requirements. Exclusive use protection is provided for new active ingredients for a period of ten years following the date of the first registration of a new active ingredient. During the period of exclusive use, data may not be cited by another registrant without the written consent of the original data submitter [61]. Outside this period of exclusive use, FIFRA provides that data may be cited without the permission of the original data submitter to support various types of pesticide applications. Data citation is not a free ride, but a form of mandatory licensing. Under FIFRA, data are compensable for a period of 15 years following the date of their first submission to EPA and may be cited in support of an application for initial registration by a follow-on registrant, an experimental use permit (EUP), an amendment to an

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existing registration or application for a new registration adding a new use to an existing active ingredient registration, and for re-registration [62]. The mandatory data citation rights granted by FIFRA are limited to federal registrations. Individual states may require the submission of data before a registration or license is granted by the state. Such state requirements are outside the scope of FIFRA’s mandatory data citation provisions. For example, the California EPA Department of Pesticide Regulation (CDPR) requires applicants to provide copies of all data submitted to US EPA OPP, which it independently reviews to make its own registration decisions [63]. CDPR does not recognize offers of compensation made under FIFRA and an applicant must obtain the right to rely on another party’s data, to the extent required by CDPR, separate from the offer of compensation pursuant to FIFRA [64]. See Section 4.12 for additional information on state pesticide registration requirements and procedures. The mandatory data citation provisions similarly do not provide any party citing the data with copies of the cited data. EPA is required to make health and safety data generated by a registrant in support of a pesticide available to the public [64]. However, EPA is prohibited from disclosing information submitted by a registrant or applicant in support of a registration, to the employee or agent of a foreign or multinational pesticide producer [64b]. This provision is intended to prevent use of studies obtained from EPA in support of registration in another jurisdiction, in circumvention of FIFRA data protection and compensation provisions. It is possible for individual parties to negotiate an agreement whereby the original data submitter provides a hard copy of the data to the party offering compensation, along with the right to use the data for purposes of obtaining registrations in other nations or jurisdictions. However, such actions are outside the scope of and not required by FIFRA’s data citation provisions.

4.6.1

Procedures for Compliance with Data Protection and Compensation Requirements

An applicant may cite data other than exclusive-use data, without the permission of the original data submitter, as long as the applicant has made an offer of compensation to the original submitter(s). FIFRA requires that the applicant submit a copy of the offer to EPA along with proof of delivery. EPA has implemented this provision by requiring that an applicant submit with its application a Certification With Respect To Citation Of Data, certifying that an offer of compensation has been made or that permission has been granted [65]. In general, there are two types of compensation offers. The first is the “cite-all” method, by which the follow-on registrant cites all data on file with EPA for a particular active ingredient [66]. The advantage to using the cite-all method is that it is the

4.6 Data Protection and Data Compensation Procedures

most expeditious to obtaining a registration. EPA does not conduct a review of the data or perform a risk assessment in order to reach a registration decision, instead relying on its previous registration decisions. The principal disadvantage to the data cite-all method is that the data citer may well have to pay more in compensation than if using the selective method. For example, the data citer may have to agree to provide compensation to multiple parties or for multiple studies satisfying a particular guideline requirement. Use of the cite-all method also may result in the data citer being required to pay compensation for studies that are not needed for the uses it seeks to register. The other general type of compensation offer is the “selective” method of citation. One uses the selective method when only specific studies are cited. For example, where multiple studies have been submitted for a single guideline, the selective citer may cite only one. A selective citer also can limit its compensation offer to those studies that are required to support a particular use, not all the uses that have been registered by the original data submitter and for which data are on file with EPA [67]. The major drawback to the selective method of citation is that EPA must determine whether all the data cited would be sufficient to conduct a risk assessment that supports the uses of the follow-on registrant. Because EPA must make an independent risk assessment decision, the selective method of citation often leads to significant delays. Follow-on registrants also may follow a hybrid data strategy–submitting some studies and using the “selective cite-all” method for particular guideline requirements [67a]. When using selective cite-all, a follow-on registrant may submit its own data and/or selectively cite studies to fulfill certain guideline requirements, but, for other guideline requirements, cite all data on file satisfying those particular guidelines.

4.6.2

Compensation Offers and Arbitration

A valid offer of compensation must include an offer to submit to binding arbitration in the event that agreement on the amount of compensation or other terms cannot be reached. EPA’s regulations on the cite-all, selective, and selective cite-all methods of offering compensation provide detailed guidance on the contents of a valid offer letter for each method. Any party to a data compensation proceeding may initiate binding arbitration if agreement has not been reached within 90 days following receipt of the original compensation offer. Arbitration is conducted under the American Arbitration Association rules for commercial arbitrations. Parties may elect to have either one or three arbitrators. The parties to the arbitration must share the costs of the arbitration, including

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fees charged by the arbitrator(s). An arbitration decision is final and cannot be appealed to a court unless fraud has been perpetrated in the course of the arbitration [68]. Arbitration decisions are not made public on a routine basis. Parties to an arbitration may elect to make portions of a decision public. However, arbitration decisions provide no legal precedents. Each arbitration decision stands on its own merits. Because there is a lack of precedent, there are no general standards that apply to arbitrations.

4.6.3

EPA’s Role in Data Compensation

EPA acts to ensure that it has received appropriate certification of the manner in which a follow-on registrant has satisfied applicable data citation and compensation requirements. If EPA believes that it has received all necessary certifications, it does not independently determine that all appropriate offers have been made. Moreover, EPA does not participate in negotiations or arbitration proceedings and takes no position on the appropriate amount of compensation. If a registrant believes that another party has cited its data without making a proper offer to pay, the registrant has one year in which to petition EPA to cancel the registration [69]. If EPA determines that a data citer failed to make a valid offer, to negotiate in good faith, to participate in binding arbitration or to pay an award, EPA may cancel the registration [70].

4.6.4

Data Call-ins and Offers to Jointly Develop Data

EPA is authorized to require additional data to be submitted in support of an existing registration. When EPA issues such a requirement, known as a “data call-in,” and there are two or more registrants of the existing active ingredient, the statute provides for the joint development of the data. Joint data development is not mandatory, but is encouraged. When data are jointly developed, registrants offer to jointly support development of such data. Offers to jointly develop data are similar to those made by follow-on registrants; however, such offers are irrevocable. If the registrants fail to agree on the terms of a joint data development arrangement, any party subject to the data call-in may initiate binding arbitration [71].

4.7 EPA Regulation of Pesticide Inert Ingredients

4.6.5

Data Protection and Compensability under FFDCA for Active and Inert Ingredients

As discussed in Section 4.4.1, EPA requires information on the residues of pesticides in food pursuant to FFDCA Section 408. FQPA granted EPA the authority to provide exclusive use and data compensation protection for data required under FFDCA to the same extent provided by FIFRA [72]. EPA is currently working to implement this provision to FFDCA. To the extent that the same data are required for the registration of an active ingredient and to support tolerance petitions, data protection and compensability already are assured under FIFRA. Implementing a new system primarily impacts inert ingredients that are subject to the tolerance requirements of FFDCA.

4.7

EPA Regulation of Pesticide Inert Ingredients

Following the publication of a 1987 policy statement, EPA divided inert ingredients into categories or “lists” in an effort to prioritize them for testing or other regulatory action. The lists are publicly available at http://www.epa.gov/opprd001/inerts/, but have not been updated in several years and may not be complete. The categories are: *

* * * *

List 1 “Inert Ingredients of Toxicological Concern” (registrants with formulations containing at least one inert ingredient from this list have been required to substitute with another inert ingredient or to amend the label to name the “toxic” inert ingredient and satisfy the requirements EPA has required through the issuance of a data call-in); List 2 “Potentially toxic inert ingredients with high priority for testing.”; List 3 Inerts of “unknown toxicity”; List 4A Inerts of “minimal concern”; List 4B Inerts for which EPA has determined it has sufficient information to conclude that the current use does not adversely impact human health or the environment [73].

EPA ultimately intends to move all inert ingredients onto either List 1, List 4A, or List 4B. Many of the inert ingredients that are currently on List 3 have been “grandfathered”, that is, accepted for use at the present time based on use prior to 1987. As discussed in Section 4.5.2, supra, because EPA is now required to assess all tolerances and tolerance exemptions that have been previously issued for inert ingredients with food uses, the requirements articulated in its 1987 policy are being reassessed. EPA intends to publish a comprehensive policy statement on its risk assess-

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ment methodology for inert ingredients in 2002. In the meantime, it has begun to use the methodology for clearances [73a]. The total percentage of all inert ingredients in a pesticide formulation is contained in the ingredient statement on a pesticide label, along with the percentage of each individual active ingredient. However, FIFRA does not require individual inert ingredients to be named on the label. In fact, information on the identity or the percentage quantity of any deliberately added inert ingredient in a pesticide is exempt from disclosure “unless [EPA] has first determined that disclosure is necessary to protect against an unreasonable risk of injury to health or the environment” [74].

4.8

Registrants’ Continuing Obligations

4.8.1

Data Call-ins

EPA is authorized to require additional data to maintain a pesticide’s existing registration. To do so, EPA notifies all registrants of a product that contains a particular active (or inert) ingredient, using a “data call-in” (DCI). A DCI provides a list of all data that are to be generated and, in the case of an active ingredient, a list of all parties receiving the data call-in. Each registrant has 90 days in which to respond. Two or more registrants may agree to share in the cost of developing the necessary data, as discussed in Section 4.4.4. If the registrants fail to agree on terms for sharing the costs of data development within 60 days of receipt of the DCI, any of the registrants may initiate binding arbitration [75]. If a registrant does not wish to generate data, in its response to the DCI it will be required to voluntarily cancel its registration(s) containing the affected ingredient. Such registrant is usually granted a specified period of time during which it may sell its existing stocks of the product(s). If a registrant does not respond to the data call-in within the requisite time, EPA is authorized to issue a Notice of Intent to Suspend (NOIS). A registrant may request a hearing to contest the NOIS. If it has not done so within 30 days, the suspension is final and effective. EPA may establish an existing stocks period that it deems appropriate in such cases [76].

4.8 Registrants’ Continuing Obligations

4.8.2

Reporting Adverse Effects Information

FIFRA requires that “[i]f at anytime after registration of a pesticide the registrant has additional factual information regarding unreasonable adverse affects on the environment of the pesticide, the registrant shall submit such information to [EPA]” [77]. EPA has promulgated complex comprehensive regulations to implement this provision [78]. The agency also has issued a number of PR Notices to further clarify its interpretation of this provision and its regulations [79]. The regulations cast a very broad net in terms of the information that must be reported. First, it broadly defines a “registrant” and, in some cases, requires a former registrant to report adverse effects for a period of five years following cancellation or transfer of a pesticide. There is an indefinite reporting obligation for any product involved in product liability litigation [80]. Information potentially reportable includes laboratory studies, information about pesticide residues on food or feed or in water, information on metabolites, degradates, contaminants and impurities, toxic or adverse effects incident reports, and some failure of performance information. There is also an extremely broad “catch-all” provision requiring that a “registrant ... submit ... [any] information ... that EPA might regard ... as raising concerns about the continued registration of a product” [81]. The requirement for toxic or adverse effect incident reporting is extremely broad. As long as three conditions are met, the incident is considered to be reportable by EPA: * *

*

the registrant is aware or has been informed that exposure may have occurred; the registrant is aware or has been informed that a toxic or adverse effect has been alleged; the registrant has, or can obtain, information concerning where the incident occurred, the pesticide or product involved, and the name of a contact to whom to direct questions regarding the alleged incident.

Perhaps the most important aspect of EPA’s incident reporting standard is that any opportunity for a registrant to determine causation, that is, make a reasoned judgment that a causal relationship exists between an alleged exposure and an alleged effect, has been eliminated [82]. There is a complex process for categorizing exposure types and severity of effects, which impact how and when to report. The regulations also provide specific instructions on when toxicology, ecological, exposure, epidemiology and other studies trigger the reporting threshold. Adverse effects information acquired by foreign parents or subsidiaries, if directly relevant to a pesticide registered in the United States, is subject to EPA’s reporting requirements. Reporting deadlines run from 15 days for a repor-

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table fatality to 90 days for minor severity categories. EPA’s regulations and other guidance documents should be consulted when attempting to determine reporting obligations [83].

4.8.3

Other Reporting and Recordkeeping Requirements

Each domestic and foreign facility where a pesticide that enters US commerce is manufactured, formulated, packaged, repackaged, labeled, or relabeled must obtain an EPA establishment registration [84]. Registered establishments are provided unique establishment numbers. Registered establishments are required to annually report the volume of each pesticide produced in or exported to the US [85]. Registrants and all other producers of pesticides are required to maintain records of all pesticide production for two years. EPA’s regulations specify the information that must be maintained in the production records [86].

4.9

Pesticide Import and Export Requirements

EPA regulates the import and export of pesticides. Any importer of registered or unregistered pesticide to the United States must submit to the applicable EPA Regional Office, prior to arrival of the pesticide shipment, a “Notice of Arrival of Pesticide and Devices” (NOA). The EPA Regional Office completes the NOA and returns it to the importer. The importer then must present the NOA to the Customs Office at the port of entry. The explicit notification to EPA of each and every pesticide shipment affords the agency the opportunity to review shipments prior to their arrival. It also requires explicit EPA approval of entry for any unregistered pesticide. The imported registered pesticides must conform with EPA’s regulations, including all EPA-required pesticide labeling. EPA may refuse to admit a shipment that upon analysis does not conform to its declared contents and the registrant may be subject to enforcement action [87]. FIFRA permits EPA to regulate exports including labeling and pre-shipment requirements for unregistered pesticides. All exported pesticides must bear appropriate FIFRA labeling. The registrant or the distributor of the product is required to translate into the language of each country to which the distributor is aware the product will be sent. The elements of the pesticide label subject to the multilingual translation requirements are (i) the EPA pesticide producing establishment number, (ii) all warning or caution statements, (iii) a statement “Not registered for use in the United States,” if such statement is applicable, (iv) the ingredient statement, (v) the name of the producer, the registrant or other person for whom the pesticide was produced, and

4.10 Cancellation and Suspension

(vi) the product’s weight or measure. Translation of additional warning statements for certain highly toxic pesticides also may be required [88]. In addition, the distributor or shipper of an unregistered pesticide must obtain foreign purchaser acknowledgement prior to shipment. The statement from the foreign purchaser must explicitly acknowledge its understanding that the pesticide is not registered for sale or use in the United States. Information on shipments of unregistered pesticides must be reported to EPA by the exporter, on either a per shipment or annual basis. EPA transmits copies of all foreign purchaser acknowledgments to the applicable national authorities [89].

4.10

Cancellation and Suspension

EPA is authorized to cancel a registration only following issuance of formal notice to a registrant of its intent. The registrant must be afforded the opportunity to a hearing. At the hearing evidence is presented as to whether the standard for cancellation has been met, that is, either the pesticide or its labeling does not comply with FIFRA, or, “when used in accordance with widespread and commonly recognized practice, [the pesticide] generally causes unreasonable adverse effects on the environment”. EPA must consult with the Secretary of Agriculture, or in the case of a public health pesticide, the Secretary of Health and Human Services, 60 days prior to sending the notice to the registrant. The cancellation is final 30 days after receipt by the registration or publication, whichever occurs later, unless the registrant corrects the identified problems or requests a hearing [90]. EPA regulations govern the conduct of cancellation hearings [91]. Any party to the hearing, including the presiding EPA Administrative Law Judge (ALJ), may request review of relevant scientific facts by a committee of the National Academy of Sciences (NAS). EPA then is required to make a final decision based on evidence from the hearing and NAS report, if one has been requested [92]. A final EPA decision is subject to review by either a federal district court or federal court of appeals, depending on the nature of the order being appealed [92a]. EPA also is authorized to order the emergency suspension of a pesticide, if “necessary to prevent imminent hazard” during the cancellation proceedings. A registrant may request an expedited hearing within five days of the notice. Under certain circumstances, EPA may issue an emergency order prior to its issuance of the notice of cancellation [93]. EPA regulations provide rules of practice for conducting expedited hearings [94]. Suspension orders are reviewable by US courts, consistent with judicial review granted by FIFRA, even when the final cancellation proceeding applicable to the suspension has not been completed [95].

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4.11

EPA Enforcement Authority

EPA has a number of enforcement tools available to deal with violations of FIFRA [96]. EPA may issue an order to “stop sale, use, or removal” [97]. EPA also is authorized under the law to obtain a US district court order to seize the product, if unregistered, misbranded, adulterated, or otherwise in violation [98]. FIFRA also authorizes EPA to assess civil penalties for each separate offense [99]. A party has the right to contest the penalty in a hearing before an ALJ. Registrants and applicants “knowingly” violating any provision of FIFRA are subject to criminal prosecution under FIFRA. Penalties may include a fine or imprisonment for not more than one year, or both [100].

4.12

Pesticide Licensing in Individual States

Each state requires that a registrant obtain a state registration or license prior to the sale or distribution of a pesticide product within its borders. A license or registration is granted for a period of either one or two years. Fees ranging from US$ 20 to more than US$ 2000 are required with each initial registration and each subsequent renewal. The documentation required by each state varies. Most states issue registrations, but do not require submission or review of data. However, several states, including California, Florida, and Massachusetts, require submissions similar to those required by EPA and make registration decisions independent of EPA’s. A state is not authorized to register a pesticide not registered by EPA. However, a state may decline to register for sale within its borders a pesticide that has obtained EPA registration.

Abbreviations

ALJ: Administrative Law Judge ANPR: Advanced Notice of Proposed Rulemaking ARTCA: Antimicrobial Reform Technical Corrections Act BPD: European Union’s Biocides Product Directive CDPR: CalEPA (California Environmental Protection Agency) Department of Pesticide Regulation. More information is available at http://www.cdpr.ca.gov. CFR: Code of Federal Regulations CFSAN: FDA’s Center for Food Safety and Applied Nutrition. More information is available at www.cfsan.fda.gov. CORT: Chronic, Oncogenicity, Reproductive, and Teratogenicity data CSF: Confidential Statement of Formula DCI: Data Call-in

References

EPA: US Environmental Protection Agency. More information is available www.epa.gov. FCS: Food-contact Substance FDA: US Food and Drug Administration. More information is available www.fda.gov. FFDCA: Federal Food, Drug, and Cosmetic Act. More information is available www4.law.cornell.edu/uscode/21/ch9.html. FIFRA: Federal Insecticide, Fungicide, and Rodenticide Act. More information available at www.epa.gov/pesticides/fifra.htm. FQPA: Food Quality Protection Act of 1996. More information is available www.epa.gov/oppfead1/fqpa. FR: Federal Register GLPs: Good Laboratory Practice Standards NAS: National Academy of Science NOA: Notice of Arrival NOIS: Notice of Intent to Suspend OPP: EPA’s Office of Pesticide Programs. More information is available at www.epa.gov/pesticides. PAG: Pesticide Assessment Guidelines PMN: Premarket notification PR Notice: Pesticide Regulation Notice. More information is available at http://www.epa.gov/PR_Notices. RACs: Raw agricultural commodities RED: Re-registration Eligibility Decision. More information is available at www.epa.gov/pesticides/reregistration/status.htm. SRRD: EPA’s Special Review and Re-registration Division

at

at at is at

References

References

[1] Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), 7 U.S.C. § 136 et. seq. [2] Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. § 321 et seq. [3] FIFRA § 3; 7 U.S.C. 136a. [4] FIFRA § 3(c)(1)(C); 7 U.S.C. 136a(c)(1)(C). [5] FIFRA § 4; 7 U.S.C. 136a-1. [6] FIFRA § 3(g); 7 U.S.C. 136a(g). [7] FIFRA § 12(a); 7 U.S.C. 136j(a). [8] FIFRA § 6(a)(2); FIFRA §§ 7, 8, and 9; 7. U.S.C. 136d(a)(2), 136e, 136f, and 136 g. [9] FIFRA § 3(c)(2)(B); 7 U.S.C. 136a(c)(2)(B). [10] FIFRA § 17; 7 U.S.C. 136o. [11] FFDCA § 408; 21 U.S.C. 346a.

[12] FFDCA § 409; 21 U.S.C. 348. [13] Food Quality Protection Act of 1996 (FQPA), Pub. L. 104-170, 1996. [14] Antimicrobial Regulation Technical Corrections Act of 1998 (ARTCA), Pub. L. 105-324, 1998. [15] FIFRA § 3(h); 7 U.S.C. 136a(h). [16] FIFRA § 3(h)(2); 7 U.S.C. 36a(h)(2). [16a] FIFRA § 3(h)(3)(A); 7 U.S.C. 36a(h)(3)(A). [16b] FIFRA § 3(h)(3)(A)(ii)(III); 7 U.S.C. 36a(h)(3)(A)(ii)(III). [17] FIFRA § 3(c)(3)(B); 7 U.S.C. 136a(c)(3)(B). [18] FIFRA § 2(mm)(1)(A); 7 U.S.C. 136(mm)(1)(A). [19] FIFRA § 3(h)(2); 7 U.S.C. 36a(h)(2).

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4 Regulation of Biocides in the United States [20] FIFRA § 3(h)(3); 7 U.S.C. 136a(h)(3). [21] Proposed regulations were published by EPA September 17, 1999 at 64 Federal Register (FR) 50671. Final regulations have not yet been promulgated. [22] EPA’s pesticide registration forms are available to be downloaded from EPA’s website, www.epa.gov/opprd001/forms/. A registration kit also is available at this site. EPA’s regulations on registration procedures are at 40 C.F.R. Part 152. [23] 40 C.F.R. § 158.108. [24] 40 C.F.R. Part 160. [25] EPA presented draft data requirements in 1997 to the FIFRA Science Advisory Panel for its review and recommendations. This draft is available on the Antimicrobial Division website (www.epa.gov/oppad001/ regpolicy.htm). The data requirements in this draft document reportedly have been revised and are not consistent with EPA’s current interim policy. However, the draft provides insight into EPA’s approach to requiring data for antimicrobial registrations. [26] EPA has not published any formal document describing its interim policy for antimicrobial data requirements. However, one articulation of the requirement for antimicrobial products intended for food-contact uses can be found in the Preliminary Risk Assessment for the active ingredient, 1,4-bis(bromoacetoxy)2-butene. The availability of this preliminary risk assessment was announced in the June 6, 2001 Federal Register. 66 FR 30460. [27] (www.epa.gov/oppad001/regpolicy.htm) The 1997 draft (see note[25]) for nonfoodcontact, low-exposure antimicrobials included in its Tier I database both acute neurotoxicity and immunotoxicity testing requirements. Reportedly, these data currently are not routinely required. [28] FIFRA § 3(c)(1)(F); 7 U.S.C. 136a(c)(1)(F). [29] FIFRA § 3(c)(2)(D); 7 U.S.C. 136a(c)(2)(D). [30] 40 C.F.R. § 152.85. [31] See generally 40 C.F.R. Part 152 Subpart E, Procedures to Ensure Protection of Data Submitters Rights. See also PR Notice 98-5, available at www.epa.gov/ opppmsd1/PR_Notices/.

[32] The applicant should consult the EPA pesticide data tables at 40 C.F.R. Part 158. The provision at 40 C.F.R. § 158.102 provides information on determining data requirements for manufacturing or technical products and end-use products. [33] 40 C.F.R. § 158.690. In particular, refer to footnote 1 following the data table. [34] Me-too registration procedures are not addressed in EPA’s regulations at this time. Information on preparation of me-too applications and criteria for qualifying me-too status can be found in EPA’s Pesticide Registration Manual, available as part of the pesticide registration application kit. [35] FIFRA § 3(c)(3)(B); 7 U.S.C. 136a(3)(c)(B). [36] 40 C.F.R. § 152.44. [37] 40 C.F.R. § 152.46. PR Notice 98-10 provides specific examples of labeling changes and product chemistry changes that may be accomplished by notification. [38] FIFRA § 3(c)(9)(C); 7 U.S.C. 136a(c)(9)(C). [39] PR Notice 98-10 provides the text of an acceptable certification statement. [40] Label changes that may be made without notifying EPA are enumerated in PR Notice 98-10. [41] 40 C.F.R. Part 180. Subpart B provides information on procedures for filing petitions. Subpart C provides specific tolerances. [42] 40 C.F.R. Part 180, Subpart D. [43] General information on food additives is at 21 C.F.R. Part 170. [44] FDA’s procedural regulations on food additive petitions are at 21 C.F.R. Part 171. [45] FDA regulations on indirect and secondary direct food additives are found at 21 C.F.R. Parts 173, 174, 175, 176, 177, and 178. [45a] Food and Drug Administration Modernization Act of 1997 (FDAMA). Pub. L. 105-115. [46] FFDCA § 409(h)(6); 21 U.S.C. 348(h)(6). [47] Food Quality Protection Act of 1996 (FQPA), Pub. L. 104-170 , 1996. [48] Antimicrobial Regulation Technical Corrections Act of 1998 (ARTCA), Pub. L. 105-324 , 1998. [49] FFDCA § 201(q)(1); 21 U.S.C. 321(q)(1). [50] FFDCA § 201(q)(1)(B)(i); 21 U.S.C. 321(q)(1)(B)(i).

References [51] FFDCA § 201(q)(1)(B)(ii); 21 U.S.C. 321(q)(1)(B)(ii). [52] FFDCA § 201(q)(1)(B)(ii); 21 U.S.C. 321(q)(1)(B)(ii). [53] FFDCA § 201(q)(1)(B)(ii); 21 U.S.C. 321(q)(1)(B)(ii). [54] FFDCA § 201(q)(1)(B)(ii); 21 U.S.C. 321(q)(1)(B)(ii). Currently there are no treated articles legally available in US markets that make claims of pesticidal activity. All such articles would be considered to make public health claims, which must be registered as pesticide products and substantiated by product performance data. See, generally, 40 C.F.R. § 152.25(a) and PR Notice 2000-1. No protocols have been developed that would enable a registrant to demonstrate the requisite product performance in support of a registration. [55] FFDCA § 201(q)(1)(B)(i); 21 U.S.C. 321(q)(1)(B)(i). [56] See, for example, the Preliminary Risk Assessment for the active ingredient, 1,4-bis(bromoacetoxy)-2-butene, note [26]. [57] FIFRA § 4; 7 U.S.C. 136a-1. [58] RED documents other than those published in the early 1990s are available on EPA’s website at www.epa.gov/pesticides/ reregistration/status.htm. [58a] FFDCA § 408(q); 21 U.S.C. 346a(q). [59] FIFRA § 3(g); 7 U.S.C. FIFRA 136a(g). [60] 65 FR 24585, April 26, 2000. [61] FIFRA § 3(c)(1)(F)(i); 7 U.S.C. 136a(c)(1)(F)(i). [62] FIFRA § 3(c)(1)(F)(iii); 7 U.S.C. 136(a)(c)(1)(F)(iii). [63] Title 3, Cal. Code of Reg. §§ 6159 and 6172. [64] Title 3, Cal. Code of Reg. § 6170(c). [64a] FIFRA § 10(d)(1); 7 U.S.C. 136h(d)(1). [64b] FIFRA § 10(g)(1); 7 U.S.C. 136h(g)(i). [65] 40 C.F.R. Part 152 Subpart E provides information on the procedures required by EPA in order to ensure that data protection and compensation requirements are met. [66] 40 C.F.R. § 152.86. [67] 40 C.F.R. § 152.90. [67a] 40 C.F.R. § 152.95. [68] FIFRA § 3(c)(1)(F)(iii); 7 U.S.C. 3(c)(1)(F)(iii).

[69] 40 C.F.R. § 152.99(b). [70] 40 C.F.R. § 152.99(a)(1). [71] FIFRA § 3(c)(2)(B)(ii); 7 U.S.C. 136a(c)(2)(B)(ii). [72] FFDCA § 408(i); 21 U.S.C. 346a(i). [73] Inert Ingredients in Pesticide Products; Policy Statement, 52 FR 13305, April 22, 1987. 66 FR 57671, November 16, 2001. [74] FIFRA § 10(d)(1); 7 U.S.C. 136h(d)(1). [75] FIFRA § 3(c)(2)(B)(i); 7 U.S.C. 136a(c)(2)(B)(i). [76] FIFRA § 3(c)(2)(B)(i); 7 U.S.C. 136a(c)(2)(B)(i). [77] FIFRA § 6(a)(2); 7 U.S.C d(a)(2). [78] 40 C.F.R. Part 159 Subpart D, Reporting Requirements for Risk/Benefit Information. [79] PR Notices 98-3, 98-4, and 2000-8. [80] 40 C.F.R. § 159.160. [81] 40 C.F.R. § 159.195. [82] 40 C.F.R. § 159.184 and PR Notices 98-3 and 98-4. [83] 40 C.F.R. Part 159 and PR Notices 98-3 and 98-4. [84] 40 C.F.R. §§ 167.3, 167.85. [85] 40 C.F.R. § 167.85. [86] 40 C.F.R. § 169.2. [87] FIFRA § 17(c); 7 U.S.C. 136o(c). [88] 40 C.F.R. § 168.65. [89] 40 C.F.R. § 168.75. [90] FIFRA § 6(b); 7 U.S.C. 136d(b). [91] 40 C.F.R. Part 164 Subparts A and B. [92] FIFRA § 6(d); 7 U.S.C. 136d(d). [92a] FIFRA § 16; 7 U.S.C. 136n. [93] FIFRA § 6(c); 7 U.S.C. 136d(c). [94] 40 C.F.R. Part 164 Subpart C. [95] FIFRA § 6(c)(4); 7 U.S.C. 136d(c)(4). [96] FIFRA § 12; 7 U.S.C. 136j. This section sets forth unlawful acts, including, in part, sales of unregistered, adulterated, or misbranded pesticides; use in a manner inconsistent with the pesticide’s labeling; falsification of an application for registration or other records; and failure to file required reports. [97] FIFRA § 13(a); 7 U.S.C. 136k(a). [98] FIFRA § 13(b); 7 U.S.C. 136k(b). [99] FIFRA § 14(a); 7 U.S.C. 136l(a). [100] FIFRA § 14(b); 7 U.S.C. 136l(b).

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5

Regulatory Control of Biocides in Other Countries Sara Kirkham and Mel Cooke

5.1

Introduction

The regulation of biocides is very varied in those countries with developed chemical control schemes. Some major markets such as Japan have no specific scheme for biocide regulation, and they are treated as ordinary industrial chemicals. Others countries have rigorous schemes, but applied only to certain biocide use categories such as wood preservatives or public-use disinfectants. In this respect, the world situation mirrors that prevalent in Europe before the European Biocidal Products Directive (BPD) (see Chapter 3). The BPD has been very influential, and several non-European countries are moving towards harmonization with the BPD. The BPD is seen as the most rigorous of the regulatory regimes, so that a supplier of biocides in compliance with the BPD will have few extra data requirements in other jurisdictions. In analogy with the European situation, the Organization for Economic Co-operation and Development strives to harmonize requirements for biocide notification amongst its membership of 30 industrialized nations and beyond. However, such world-wide harmonization is many years away. It is an impossible task to give in detail the requirements for all biocides in all countries. Many countries do not recognize biocides as a separately identifiable group of chemicals, and often there is no legal definition. Biocides, as recognized in the EU, therefore often fall under a mix of legislative schemes intended for industrial chemicals, cosmetics, agricultural pesticides, veterinary products, and pharmaceuticals. Each scheme has its own detailed requirements and is administered by different authorities. Often, there are difficult issues of scope between these different schemes, so that an insect repellent used on skin may be viewed as a cosmetic, a biocide, an industrial chemical, or as a medicine. These details, while important, are too complex for thorough investigation in one chapter. More significantly, the information is difficult to ascertain for most countries, unless one is prepared to apThe Biocides Business: Regulation, Safety and Applications. Edited by Derek J. Knight and Mel Cooke Copyright ª 2002 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN: 3-527-30366-9

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proach directly the appropriate authorities, and that they are prepared to engage in dialogue. We have tried to present detail as we think it is most useful, concentrating on the major economic areas (except the EU and USA, covered in other chapters) with the most developed regulatory schemes. For brevity, we have mainly assumed the biocide to be a standard chemical, i.e. not polymeric, or an article, or itself a microorganism, or formed in situ.

5.2

Japan

There is no specific registration system for most biocidal products in Japan. Biocides, such as wood preservatives, and swimming pool disinfectants, are covered by the same legislation as ordinary chemicals, but note that some biocides are subject to control at the local (prefecture) level. In Japan, as with the European scheme, some specific applications, for examples fly sprays, biocides with food-contact applications, or uses with humans or livestock, may be covered by other specific legislative schemes. These borderline issues are beyond the scope of this overview. Japan is an important economic area for export of biocides, and because the chemical legislation is significantly different from notification schemes in Europe and the USA, we will describe the most important regulations in some detail. Chemical control of new chemicals in Japan is complicated because different authorities administer the applicable laws. An experienced local agent may be better able to achieve a supply of chemicals in Japan owing to a greater understanding of the philosophy and practice of the various schemes and authorities, and a greater knowledge of the available exemptions and derogations from notification. The manner and courtesy with which they are approached may also influence the outcome of any interaction within Japanese authorities. Having a pre-consultation with each Japanese regulatory authority can facilitate the notification process, especially if foreign study reports are to be submitted. There are some differences in testing methods and interpretation of the test results, especially in biodegradability and bioaccumulation, although the Japanese test methods are, in principle, based on OECD guidelines.

5.2.1

Chemical Substances Control Law

The Japanese Law Concerning the Examination and Regulation of Manufacture etc., of Chemical Substances came into force on 16 April 1974, and was the first new chemicals notification scheme in the world. The legislation is commonly referred to as the Chemical Substances Control Law (CSCL). Until 2000, the CSCL was jointly adminis-

5.2 Japan

tered by the Ministry of International Trade and Industry (MITI), who dealt with the environmental aspects, and the Ministry of Health and Welfare (MHW). The various Japanese ministries have since had changed responsibilities and names. From 8 January 2001, the new Ministry of the Environment (MoE) has also been involved in assessing notifications. Also MITI has been re-named the Ministry of Economy, Trade and Industry (METI). The MHW has amalgamated with the Ministry of Labor (MoL) to form the Ministry of Health, Labor, and Welfare. To keep the distinction between the CSCL and the parallel workplace scheme (see later), the abbreviation MHW will be applied to the section of this Ministry dealing with the CSCL. The main objective of the CSCL is to protect humans from exposure to hazardous substances, including biocides, via the environment, and in particular via the food chain. The CSCL therefore emphasizes assessment of detrimental health effects caused by persistent, accumulating, and chronically toxic substances. Such chemicals are subject to very stringent regulatory actions. The law also identifies substances that are nonbiodegradable but nonbioaccumulative, which were previously evaluated as safe without a full evaluation of their chronic toxic effects. The CSCL notification scheme is, in principle, a stepwise process (see Figure 5.1), beginning with a biodegradation study, and there is a possibility of having to consult with METI part way through. Also, with CSCL notifications, regulatory decisions regarding the test material description are often relevant. Thus, it can take over two years for notification to be able to import or manufacture a new substance in Japan. In order to save time, the notifier may risk testing the parent substance (and not the environmental degradants) and conduct the biodegradation, bioaccumulation, and screening toxicity studies concurrently.

The Inventory of Existing Substances Notifiable new substances are those chemicals not included in MITI/MHW’s List of Existing Chemical Substances, MITI/MHW’s list of notified new safe chemical substances or MITI/MHW’s list of designated chemical substances. These various inventories are commonly referred to as the MITI List (presumably the term METI List will soon catch on). Although there is a separate inventory for the workplace notification scheme (see Section 5.3), the MITI List is normally searched first because an almost up-to-date English version is available as the Handbook of Existing and New Chemical Substances (the Handbook) [1]. Any substance included in the inventory is not notifiable, and is loosely referred to as an existing substance. Nevertheless, there is an administrative distinction between truly existing substances in commerce in Japan when the scheme came into force (as listed in the white pages of the Handbook) and the notified substances (as listed in the green pages). 5.2.1.1

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5 Regulatory Control of Biocides in Other Countries

Fig. 5.1. Flow scheme for Japanese Chemical Substance Control Law Notification.

Each part of the Handbook is split into sections, based on type of chemical, and there is an index by Chemical Abstract Services (CAS) number. However, there is a practical difficulty in determining that a substance not present by CAS number is genuinely not listed in the inventory. This is because there are many entries, especially for existing substances, which have a very broad descriptions. This means that computer searches

5.2 Japan

using various systems (e.g. CAS and Ariel) can result in false negative results. A chemist can search the handbook by structural class, but for many complex substances it is difficult to give definitive advice whether or not a substance is present on the inventory. Japanese industry take a pragmatic and flexible interpretation of the generic inventory entries. Notified biocidal substances are listed on the inventory after a variable period, which may be several years, during which any competitors have to re-notify. A potential new notifier has no means to establish whether their substance has already been notified but not yet listed, or to find out the identity of a first notifier in order to attempt to share the original data, so that sometimes the same new substance is tested twice. The Handbook is always out of date, but notified substances are gazetted periodically. Hence the only way to be sure a substance has not been notified and placed on the “MITI List” is to check the Japanese-language CD-ROM version of the inventory or the official gazette. Exemptions from Notification The notification requirements of the CSCL do not apply to the following biocide applications, because they are subject to separate Japanese control procedures: direct food additives, food packaging (i.e. indirect food additives), detergents for cleaning food-contact materials, agricultural pesticides, and cosmetics (but see below). Note that other provisions of the CSCL still apply to these products exempt from notification. An example of the Japanese approach to dealing with situations of ambiguous legal basis is with ingredients of cosmetic products. It is clear from the CSCL that a new substance (e.g. a cosmetic preservative) is not notifiable when supplied in Japan only in the final cosmetic product. According to the strict interpretation of the Law, however, a new substance for exclusive use to formulate cosmetic products is notifiable if imported or supplied neat. Nevertheless, until about 1998, it was virtually unknown for import of such cosmetic ingredients to be rejected by Japanese customs on the grounds that a MITI number is needed. This may be because an influential Japanese publication [2] clearly states that cosmetic ingredients are exempt from notification. Note that, independent of any requirements under the CSCL, notification under the Industrial Safety and Health Law (see later) is required if the biocide is used in the workplace in formulating cosmetic products. Furthermore, there is a parallel cosmetic approval scheme to ensure safety of cosmetic ingredients. There is a low-volume exemption (LVE) scheme for new substances manufactured or imported at below one tonne per annum. This upper limit applies to all suppliers combined, and hence, if there is more than one exemption in operation for the same substance, the permitted quantities would have to be shared out. Applications must be made annually. Technical and administrative information and certain non-GLP phy5.2.1.2

107

108

5 Regulatory Control of Biocides in Other Countries

sico-chemical data have to be provided. Note that the Japanese manufacturer or importer must make the LVE application, whereas a non-Japanese exporter can make a standard notification. Standard Notification As mentioned, the CSCL notification scheme is designed to evaluate the potential human hazard from exposure to new chemicals through the environment, and the effects of degradants may need to be considered. Impurities contained at above 1 % in a new chemical substance are regarded as components of a mixture. In principle, each such impurity should be tested separately for notification. One benefit of this approach is that the technical-grade substance is considered to be a mixture of notified/existing substances, and consequently its composition can be varied freely if needed. One option is to use purified substances as the test material. Alternatively, the doses used for the three toxicity screening tests can be corrected to 100 %, for a purity below 99 %. Poorly defined reaction mixtures consisting of isomers and congeners can be tested and notified as the mixture. New substances must be notified three months before manufacture or import. For CSCL notification, the Japanese test methods are based on those of the OECD, although some are more stringent, and the standard EU studies have to be enlarged. Many of the studies have to be reported in a prescribed format with the data interpreted in a specific way. There is mutual acceptance of GLP between the EU Member States and Japan. Consequently, the Japanese regulatory authorities will accept foreign studies. In principle, existing GLP-compliant studies conducted to OECD/EU methods for non-Japanese notifiers are acceptable, but the results have to be suitable for interpretation by the Japanese authorities, which in practice may mean only a positive test result is accepted. The first stage in the testing program is to evaluate the biodegradation potential of the substance. To pass the MITI ready biodegradability test, and hence be classified as a safe chemical substance under the CSCL scheme, virtually complete mineralization is necessary (i.e. the only degradants are carbon dioxide and water). The ready biodegradation test is technically demanding, as a mass balance and characterization of degradants is required, and is often best conducted at an experienced Japanese laboratory. If the substance undergoes partial mineralization in the MITI (I) ready biodegradation test, METI/MoE may require a MITI (II) inherent biodegradation study to be conducted on the parent substance, before deciding what to test further. The authorities require that only safe degradation products be produced, so stable degradants may have to be further tested for bioaccumulation and toxicity. Unless complete mineralization is achieved in the ready biodegradation test, the next stage will be to evaluate the bioaccumulation potential of either the parent substance or its environmental degradants. Before conducting Pow (n-octanol-water parti5.2.1.3

5.2 Japan

tion coefficient) or fish bioaccumulation studies, it is worthwhile considering the alternative of assessing the bioaccumulation potential by analogy to chemically similar compounds which have already been tested, either notified new substances or selected existing substances, evaluated and published by METI. If the tested analogue has log Pow