Occupational and Residential Exposure Assessment …...Occupational and Residential Exposure...

Occupational and ResidentialExposure Assessmentfor Pesticides

Edited by

CLAIRE A. FRANKLINPest Management Regulatory Agency, Health Canada and the R. Samuel McLaughlinCentre for Population Health Risk Assessment, Ottowa, Ontario, Canada

and

JOHN P. WORGANPest Management Regulatory Agency, Health Canada, Ottowa, Ontario, Canada

Innodata047001220X.jpg

Wiley Series in Agrochemicalsand Plant Protection

Series Editors:

Terry Roberts, Consultant, Anglesey, UK.Junshi Miyamoto (deceased), Formerly of Sumitomo Chemical Ltd, Japan

Previous Titles in the Wiley Series in Agrochemicals and Plant Protection:

The Methyl Bromide Issue (1996), ISBN 0 471 95521 3.Edited by C. H. Bell, N. Price and B. Chakrabarti

Pesticide Remediation in Soils and Water (1998), ISBN 0 471 96805 6.Edited by P. Kearney and T. R. Roberts

Chirality in Agrochemicals (1998), ISBN 0 471 98121 4.Edited by N. Kurihara and J. Miyamoto

Fungicidal Activity (1998), ISBN 0 471 96806 4.Edited by D. Hutson and J. Miyamoto

Metabolism of Agrochemicals in Plants (2000), ISBN 0 471 80150 X.Edited by Terry R. Roberts

Optimising Pesticide Use (2003), ISBN 0 471 49075 X.Edited by Michael F. Wilson

Pesticide Residues in Food and Drinking Water (2004), ISBN 0 471 48991 3.Edited by Denis Hamilton and Stephen Crossley


Edited by

CLAIRE A. FRANKLINPest Management Regulatory Agency, Health Canada and the R. Samuel McLaughlinCentre for Population Health Risk Assessment, Ottowa, Ontario, Canada

and

JOHN P. WORGANPest Management Regulatory Agency, Health Canada, Ottowa, Ontario, Canada

Copyright 2005 John Wiley & Sons Ltd, The Atrium, Southern Gate, Chichester,West Sussex PO19 8SQ, England

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Library of Congress Cataloging-in-Publication Data

Occupational and residential exposure assessment / edited by Claire A.Franklin, John P. Worgan.

p. cm. – (Wiley series in agrochemicals and plant protection)Includes bibliographical references and index.ISBN 0-471-48989-1 (cloth : alk. paper)

1. Pesticides – Toxicology. 2. Pesticides – Risk assessment. I. Franklin,Claire. II. Worgan, John P. III. Series.

RA1270.P4O223 2004615.9′02 – dc22

2004013109

British Library Cataloguing in Publication Data

A catalogue record for this book is available from the British Library

ISBN 0-471-48989-1

Typeset in 10/12pt Times by Laserwords Private Limited, Chennai, IndiaPrinted and bound in Great Britain by Antony Rowe Ltd, Chippenham, WiltshireThis book is printed on acid-free paper responsibly manufactured from sustainable forestryin which at least two trees are planted for each one used for paper production.

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Contents

Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vii

Series Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xi

Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xiii

Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xv

Introduction and Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1Claire A. Franklin and John P. Worgan

Section One: Exposure Assessment Methodologies

1 Assessment of Exposure for Pesticide Handlers in Agricultural,Residential and Institutional Environments . . . . . . . . . . . . . . . . 13Richard A. Fenske and Edgar W. Day, Jr

2 Development of Risk-Based Restricted Entry Intervals . . . . . . . . . 45Gary K. Whitmyre, John H. Ross, Michael E. Ginevan andDelmont Eberhart

3 Residential Post-Application Pesticide Exposure Monitoring . . . . . 71Robert G. Lewis

4 Residential (Non-Dietary) Post-Application Exposure Assessment . . 129Jeffrey Driver, John H. Ross, Muhilan Pandian, Jeff Evans andCurt Lunchick

Section Two: Databases and Models

5 Generic Operator Exposure Databases . . . . . . . . . . . . . . . . . . . . 173Joop J. van Hemmen and Katinka E. van der Jagt

6 Predictive Residential Models . . . . . . . . . . . . . . . . . . . . . . . . . . 209Yoshihide Matoba and Mark P. van Veen

vi CONTENTS

Section Three: Epidemiology

7 Exposure Assessment for Pesticides in EpidemiologicalStudies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 245Dick Heederik and Kay Teschke

Section Four: Advances in Data Interpretation

8 Probabilistic Approaches to Aggregate and Cumulative RiskAssessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 275Robert L. Sielken, Jr

9 Dermal Absorption of Pesticides . . . . . . . . . . . . . . . . . . . . . . . . 317Betty C. Hakkert, J.J.M. (Han) van de Sandt, Jos G.M. Bessems andCees de Heer

10 Occupational and Residential Exposure Assessment forPesticides – Towards a Harmonized Regulatory Approach . . . . . . 341Christine A. Norman

Guidelines Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 381

Glossary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 389

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 409

Contributors

Jos G.M. BessemsTNO Chemistry, PO Box 360, NL-3700 AJ, Zeist, The Netherlands

Edgar W. Day, JrE. W. Day Consulting, 2536 Wayward Wind Drive, Indianapolis, IN46239-9443, USA

Cees de HeerTNO Chemistry, PO Box 360, NL-3700 AJ, Zeist, The Netherlands

Jeffrey Driverinfoscientific.com, Inc., 10009 Wisakon Trail, Manassas, VA 20111, USA

Delmont EberhartBayer CropScience, 2 T. W. Alexander Drive, Research Triangle Park, NC27709, USA

Jeff EvansUS Environmental Protection Agency, Office of Pesticide Programs, 1200Pennsylvania Avenue N. W., Washington, DC 20460, USA

Richard A. FenskePacific Northwest Agricultural Safety and Health Center, School of PublicHealth and Community Medicine, University of Washington, Seattle, WA98195, USA

Claire A. Franklin1

Pest Management Regulatory Agency, Health Canada, Sir Charles TupperBuilding, 2250 Riverside Drive, Postal Locator 6604D, Ottawa, ON K1A 0K9,Canada

Michael E. GinevanExponent, Inc., 1730 Rhode Island Avenue N. W. Suite 1100, Washington, DC22036, USA

Betty C. HakkertTNO Chemistry, PO Box 360, NL-3700 AJ, Zeist, The Netherlands

1Currently (2004) The R. Samuel McLaughlin Centre for Population Health Risk Assessment, Uni-versity of Ottawa, Ontario, Canada, and the Lifeline Group ([email protected])

viii CONTRIBUTORS

Dick HeederikInstitute for Risk Assessment Sciences for Research on the Environment, Healthand Food, Division of Environmental and Occupational Health, University ofUtrecht, PO Box 80176, 3508 TD Utrecht, The Netherlands

Robert G. LewisNational Exposure Research Laboratory, US Environmental Protection Agency,E205-01, Research Triangle Park, NC 27711-2055, USA

Curt LunchickBayer CropScience, 2 T. W. Alexander Drive, Research Triangle Park, NC27709, USA

Yoshihide MatobaEnvironmental Health Science Laboratory, Sumitomo Chemical Company, Ltd,4-2-1 Takatsukasa, Takarazuka, Hyogo 665–8555, Japan

Christine A. NormanPest Management Regulatory Agency, Health Canada, Sir Charles TupperBuilding, 2250 Riverside Drive, Postal Locator 6605E, Ottawa, ON K1A 0K9,Canada

Muhilan Pandianinfoscientific.com, Inc., 2275 Corporate Circle, Suite 200, Henderson, NV89014, USA

John H. Rossinfoscientific.com, Inc., 5233 Marimoore Way, Carmichael, CA 95608, USA

Robert L. Sielken, JrSielken & Associates Consulting, Inc., 3833 Texas Avenue, Suite 230, Bryan, TX77802, USA

Kay TeschkeDepartment of Health Care and Epidemiology, University of British Columbia,5804 Fairview Avenue, Vancouver, BC V6T 1Z3, Canada

Joop J. van HemmenTNO Chemistry, PO Box 360, 3700 AJ Zeist, The Netherlands

Mark P. van VeenTeam Nature, Landscape and Biodiversity RIVM, 9 Antonie vanLeeuwenhoeklaan, 3720 BA Bilthoven, The Netherlands

J.J.M. (Han) van de SandtTNO Chemistry, PO Box 360, NL-3700 AJ, Zeist, The Netherlands

CONTRIBUTORS ix

Katinka E. van der Jagt2

TNO Chemistry, PO Box 360, 3700 AJ Zeist, The Netherlands

Gary K. Whitmyrerisksciences, 2111 Wilson Boulevard, Suite 600, Arlington, VA 22201, USA

John P. WorganPest Management Regulatory Agency, Health Canada, Sir Charles TupperBuilding, 2250 Riverside Drive, Postal Locator 6604D, Ottawa, ON K1A0K9, Canada

2Currently (2004) European Commission JRC, European Chemicals Bureau, Ispra, Italy

Series Preface

There have been tremendous advances in many areas of research directed towardsimproving the quantity and quality of food and fibre by chemical and othermeans. This has been at a time of increasing concern for the protection of theenvironment, and our understanding of the environmental impact of agrochem-icals has also increased and become more sophisticated, thanks to multidisci-plinary approaches.

Wiley recognized the opportunity for the introduction of a series of bookswithin the theme ‘Agrochemicals and Plant Protection’ with a wide scope thatincludes chemistry, biology and biotechnology in the broadest sense. This seriesis effectively a replacement for the successful ‘Progress in Pesticide Biochemistryand Toxicology’, edited by Hutson and Roberts, which has run to nine volumes. Inaddition, it complements the international journals Pesticide Science and Journalof the Science of Food and Agriculture, published by Wiley on behalf of theSociety of Chemical Industry.

Volumes already published in this series cover a wide range of topics, includingenvironmental behaviour, plant metabolism and chirality, and a volume devotedto fungicidal activity. These together cover a wide scope and form a highly col-lectable series of books within the constantly evolving science of plant protection.

As I write this preface, I remain deeply saddened by the death in 2003of Dr Junshi Miyamoto, who contributed so much to this series as my Co-Editor-in-Chief. More significantly, Junshi will be remembered for his lifetimeachievements in agrochemical biochemistry, toxicology and metabolism – andnot least for the energy he displayed in international activities aimed at harmo-nizing knowledge within the field of agrochemicals. He leaves us with a wealthof scientific publications.

Terry RobertsAnglesey, UKJuly 2004

THE SERIES EDITORS

Dr Terry R Roberts is an independent consultant, based in Anglesey, NorthWales, UK. He was Director of Scientific Affairs at JSC International, based inHarrogate, UK, from 1996 to 2002, where he provided scientific and regulatory

xii SERIES PREFACE

consulting services to the agrochemical, biocides and related industries, with anemphasis on EU registrations.

From 1990 to 1996, Dr Roberts was Director of Agrochemical and Envi-ronmental Services with Corning Hazleton (now Covance) and was with ShellResearch Ltd for the previous 20 years.

He has been active in international scientific organizations, notably the OECD,IUPAC and ECPA, over the past 30 years. He has published extensively and isnow Editor-in-Chief of the Wiley Series in Agrochemicals and Plant Protection.

Dr Junshi Miyamoto (deceased) was Corporate Advisor to the SumitomoChemical Company for 45 years, since graduating from the Department of Chem-istry, Faculty of Science, Kyoto University. After a lifetime of working in thechemical industry, Dr Miyamoto acquired a wealth of knowledge in all aspectsof mode of action, metabolism and toxicology of agrochemicals and industrialchemicals. He was a Director General of the Takarazuka Research Centre of theSumitomo Chemical Company, covering the areas of agrochemicals and biotech-nology, as well as environmental health sciences. He was latterly President of theDivision of Chemistry and the Environment, IUPAC, and in 1985 received theBurdick Jackson International Award in Pesticide Chemistry from the AmericanChemical Society, and in 1995, the Award of the Distinguished Contribution toScience from the Japanese Government. Dr Miyamoto published over 190 orig-inal papers and 50 books in pesticide science, and was on the editorial board ofseveral international journals, including Pesticide Science.

Preface

Pesticides are a class of products essential for sustainable agriculture and goodpublic health. Lack of clarity in some of the published literature and a generalmisunderstanding of the difference between the hazard of a pesticide and theactual risk have heightened public anxiety over the use of such materials. Ofparticular concern is the potential for pesticide residues to harm the health ofadults and especially that of their children. To fully understand the potentialrisk that might occur when a pesticide is used, it is imperative that accurateand reliable estimates of exposure be available. This information, along with thetoxicological profiles, enable risk assessors to determine whether the pesticidecan be used without harming health and the environment.

This book documents the current state of knowledge in occupational (applica-tors and field workers) and residential exposure assessment and outlines the waysin which exposure data are used in assessing the risks of pesticides to humans.The importance of developing standardized methods for measuring exposure,building mathematical models and interpreting data to foster internationally har-monized, scientifically sound decisions is discussed. Because pesticides are usedglobally, the opportunities for international collaboration in generating the dataand in assessing the risks are identified in each chapter and then discussed in thefinal chapter.

Many of the principles used in pesticide exposure assessment are applicable toother classes of chemicals, and it is hoped that this book will encourage cross-fertilization among disciplines. In particular, continued international co-operationand harmonization will be essential to ensure the protection of workers and thegeneral public from the adverse effects of pesticides.

This book would not have been possible without the knowledge and dedicationof all of the authors who generously contributed chapters to this text. We thankthem for this and for their patience in seeing this project through to completion.

CLAIRE FRANKLIN AND JOHN WORGANJuly 2004

Acknowledgements

The Editors wish to acknowledge assistance in the review of manuscripts byTye Arbuckle, Health Canada, David E. Camann, Southwest Research Institute,Sueli de Freitas and Helen H. McDuffie, University of Saskatchewan, MichaelE. Ginevan, Exponent, Inc., Paul Hamey, UK Pesticide Safety Directorate,Curt Lunchick, Bayer CropScience, Mary Mitchell and Christine Norman, PestManagement Regulatory Agency, John H. Ross, infoscientific.com and ThomasThongsinthusak, California Department of Pesticide Regulation. We thank oureditors at John Wiley & Sons, Ltd, Chichester, UK, Lynette James, David Andoand Martin Rothlisberger, for bringing our book to fruition.

Introduction and Overview

CLAIRE A. FRANKLIN1 and JOHN P. WORGANPest Management Regulatory Agency, Health Canada, Ottawa, Ontario, Canada

ASSESSMENT OF RISKS TO HUMANS EXPOSEDTO PESTICIDES 2The Four Steps in Risk Assessment 2

Hazard Identification 2Dose–Response Assessment 3

Margin of Safety Approach 3Quantitative Risk Assessment 3

Exposure Assessment 4Risk Characterization 4

RISK MANAGEMENT 5ADVANCES IN DATA INTERPRETATION 5

Probabilistic Approaches 5Recognition of the Tier Approach 5Aggregate Exposure 6Cumulative Exposure 6Impact of New Scientific Advances 7Post-Registration Monitoring 7

HARMONIZATION OF REGULATORY APPROACHES 8SUMMARY 9

The purpose of this book is to document the current state of knowledge inthe field of occupational and residential exposure assessment and to outline theways that exposure data are used in assessing the risks of pesticides to humansin occupational and residential settings. Recommendations for improvements toexposure assessment are also proposed.

Over the past 30 years, there has been increasing awareness of the need tohave estimates of exposure for workers applying pesticides, for field workersinvolved in handling pesticide-treated crops and for the general public who comeinto contact with pesticides in their homes, their gardens, their schools and other

1Currently (2004) The R. Samuel McLaughlin Centre for Population Risk Assessment, Universityof Ottawa, Ontario, Canada

Occupational and Residential Exposure Assessment for Pesticides. Edited by C. A. Franklin and J. P. Worgan 2005 John Wiley & Sons, Ltd ISBN: 0-471-48989-1

2 OCCUPATIONAL AND RESIDENTAL EXPOSURE ASSESSMENT

public places. In the early days, exposure estimates were carried out to understandwhy workers were getting sick after applying certain products or after workingin the fields picking crops. Now, quantitative estimates of exposure have becomean integral component of the regulatory decision-making process on whether apesticide should be registered for use or remain on the market post-registration.Many jurisdictions also have regulations requiring companies to submit reportsconcerning adverse effects attributable to the use of their products, and epidemi-ology studies are carried out to study the health effects of pesticides on largerpopulations. Furthermore, data from all pathways of exposure are required, andthe emphasis is now being placed on distributional data rather than point esti-mates. These developments have highlighted the need for accurate estimates ofexposure over a wide range of circumstances or scenarios, hence leading toimproved methods for analyzing pesticides and more precise ways of extrapolat-ing the data.

ASSESSMENT OF RISKS TO HUMANS EXPOSEDTO PESTICIDES

It is generally considered that the acceptability of a pesticide should be basedon the nature and degree of risk it poses. This necessitates a knowledge ofboth the toxicity of the pesticide, as determined through extensive testing inanimals, and the level of exposure to people under defined conditions to beable to fully characterize the risk. The defined conditions include such factorsas the type of equipment (open or closed systems), application rate, the use ofpersonal protective equipment, such as gloves and coveralls, and the type of jobthe worker performs. These conditions are then grouped into ‘use scenarios’.Initially, the focus was on agricultural workers. More recently, there has beenincreased emphasis on non-occupational or residential risk assessment, especiallydetermining the potential risks of pesticides to children.

THE FOUR STEPS IN RISK ASSESSMENT

Hazard Identification

This is carried out by testing the pesticide in a variety of animal species overa range of doses administered by the oral, dermal and inhalation routes at vari-ous life stages and for increasing durations of time ranging from a single acuteexposure, a short-term exposure and a chronic (lifetime) exposure. Only toxicendpoints that are relevant to humans are used in the risk assessment. Althoughsome of the acute and short-term studies are carried out by using the dermal andthe inhalation routes of exposure, the bulk of the studies, including the long-term,reproduction and teratology studies, are carried out by using only the oral route.These data are appropriate for estimating risks due to exposure to pesticides viafood residues. They are less useful for estimating worker and residential risk

INTRODUCTION AND OVERVIEW 3

because exposure is primarily via the dermal, and to a lesser extent, the inhala-tion route. To overcome this problem, the amount of pesticide that is absorbedthrough the skin (either the % absorbed or the rate of absorption) is estimated inanimals. The absorption factor can then be used to calculate the absorbed dose,thus enabling comparison with the oral toxicity data.

There are scientific uncertainties involved in the conduct of a risk assessment.For example, toxicology data generated in animals are extrapolated to humansand there are different sensitivities within a human population. To deal withthese uncertainties, regulatory agencies worldwide apply safety or uncertaintyfactors. A 100-fold safety factor (10 for species differences × 10 for sensitivity)is generally used, but this can range upwards or downwards depending on thenature of the data and the completeness of the database. In North America, anadditional 10-fold factor is required unless there is evidence to show that childrenare not more sensitive to the effects of the pesticide. Following review of thetoxicology data, consideration is given to which safety or uncertainty factorsshould be used in the next step.

Dose–Response Assessment

Margin of Safety Approach

Most chemicals do not cause toxic or adverse effects until a certain dose has beengiven. These are called threshold chemicals. The lowest dose level at which thereare no adverse effects observed in the test animals is called the No ObservedAdverse Effect Level (NOAEL) and is the starting point for the calculation ofthe reference dose. While the terminology used may differ among regulatoryagencies, the concepts are similar. In North America, the term margin of safetyor exposure is used, whereas in Europe an Acceptable Operator Exposure Level(AOEL) is used. Care is taken to choose the NOAEL for an effect which isrelevant to humans and that the duration, frequency and route of exposure in thetest animals are relevant to the human exposure.

The next step is to calculate a reference dose (RfD) by dividing the NOAELby the safety or uncertainty factors appropriate for the pesticide under review.Additional safety factors can be used for severity of the toxicological effect,if sensitive sub-populations such as children are likely to be exposed to thepesticide and if there are scientific uncertainties in the data. This approach isused for establishing the risk from exposure to threshold chemicals.

Quantitative Risk Assessment

A different approach, called a quantitative risk assessment, is used for non-threshold effects, such as cancer. Sophisticated statistical models are used toextrapolate the experimental animal data obtained at high doses to the low expo-sures predicted in humans. The linearized multistage (LMS) model is frequently


used for regulatory purposes. From it, the lifetime cancer risk for an averagedaily lifetime exposure can be calculated.

Exposure Assessment

This is a critical component of risk assessment and is the focus of this book.If the exposure estimate is inaccurate, it can have serious ramifications on thedecision. Too low and there might be unacceptable risks to people exposed to thepesticide. Too high and the pesticide might not be registered or the uses couldbe severely limited. Recently, there have been significant changes in the waythat exposure assessments are carried out. Exposure assessment methodologiesfor agricultural and residential settings, including re-entry into treated areas, arediscussed in the four chapters in Section One of this book.

It is important that the exposure estimate be realistic yet protective of humanhealth and that it takes into account the frequency and duration of exposure.Uncertainties in the exposure assessment, including the fact that exposure stud-ies are carried out under controlled circumstances, may be compensated for byusing conservative assumptions such as maximum application rate, upper boundvalues and 100 % dermal penetration. These conservatisms can have a negativeimpact on the regulatory decision and could be avoided with access to morecomplete data.

Generic databases, such as PHED, EUROPOEM, ARTF and others, have beendeveloped to increase the confidence in the exposure estimates since many moredata points from a wide range of different studies are included. Details on howthese databases are constructed, the different ways in which the data are normal-ized and recommendations on how databases can be improved and harmonizedare discussed in Chapters 5 and 6.

Risk Characterization

Once the estimated human exposure level has been quantified, its acceptabilityis determined by comparing it to the reference dose. If lower than the referencedose, it is considered to provide a sufficient margin of safety and is therefore notassociated with unacceptable health risks. During the risk characterization phase,consideration must be given to the strengths, limitations and uncertainties in theexposure and hazard assessments to accurately characterize risk and the potentialfor adverse effects.

One of the challenges is the necessity to convert the human exposure levelinto an absorbed dose to enable a comparison with the RfD to be made. This isdiscussed in detail in Chapter 9.

The importance of accurate and relevant exposure data to the reliability ofthe risk assessment derived from both the margin of safety approach and thequantitative cancer risk assessment cannot be over-emphasized.


RISK MANAGEMENT

Once the risks have been characterized, it may be necessary to reduce exposurelevels if the pesticide is to be eligible for registration. This step is called riskmanagement and entails exploring options for reducing exposure and recalculat-ing the risks to see if they are within an acceptable range. The options range fromlimiting the amount of pesticide that can be sold, limiting the uses for the product,requiring different formulation types and packaging, restricting the type of equip-ment that could be used to load and deliver the pesticide, requiring applicators towear gloves, coveralls, respirators or use ‘closed-cab’ systems, and establishingre-entry intervals to protect field workers. Regulatory agencies may also restrictuse of a pesticide to trained certified applicators or require that registrants imple-ment a product stewardship programme. North American regulatory agenciesare increasingly favouring engineering controls, such as closed mixing/loadingsystems, closed cabs for application equipment and improved lower exposureformulations and packaging, as the most effective ways to reduce exposure andwork to further improve engineering controls should continue. The protectivevalues of some of these mitigation measures are discussed in Chapters 1 and 2.More complete and realistic data on the protective values of these mitigationmeasures could assist in the refinement of exposure assessments.

It must be determined whether the risk mitigation options selected are feasibleand provide a realistic use pattern, and whether compliance can be enforced.Another significant consideration is that options are cost-sensitive and are unlikelyto be accepted if their cost exceeds the economic value of the commodity onwhich the pesticide is to be used.

ADVANCES IN DATA INTERPRETATION

PROBABILISTIC APPROACHES

There is a transition away from using a deterministic approach in which highend or upper bound point estimates and default values are used towards using aprobabilistic approach in distributional models which incorporate complex datasets to build realistic estimates of exposure. While probabilistic dietary expo-sure assessments can now be carried out routinely for many pesticides, availableoccupational and residential exposure data sets are typically insufficiently robust.Work on developing newer exposure databases (e.g. ARTF, ORETF, AHETF andEUROPOEM II) and distributional use pattern data would facilitate this transition.The topic of probabilistic exposure assessment is covered in Chapter 8.

RECOGNITION OF THE TIER APPROACH

Regulatory agencies have adopted an internationally accepted tiered approachto occupational exposure assessment. Similar tiered approaches are also used


for residential and dietary exposure assessments. The tiered approach was firstpresented by Henderson and colleagues at a workshop on ‘Risk Assessment forWorker Exposure to Agricultural Pesticides’ in the Hague in 1993. Each tierrequires more refined and complex data and hence provides a more accuratemeasure of exposure. Assessments are typically started at lower, less complextiers and proceed to higher tiers as required. This approach economizes resourcesand focuses efforts on chemicals of greatest concern. Tier 1 involves estimatingexposure using generic data and conservative default assumptions such as 100 %dermal absorption, maximum application rate and upper bound hectares treatedper day. If the exposure exceeds the RfD, a further refinement (Tier 2) may bemade with validated supporting data on variables such as dermal absorption, usepattern (e.g. typical application rates and areas treated per day) or effectivenessof protective clothing and engineering controls. If the Tier 2 exposure estimateexceeds the reference dose, a field study (Tier 3) may be conducted. In mostcases, a biomonitoring study, supported by complete knowledge of human phar-macokinetic data, would be required to provide a more accurate and realisticestimate of exposure. At the highest tier, a probabilistic assessment could be car-ried out by using distributional data from a modern generic exposure database orfrom an individual biomonitoring study, combined with distributional data on usepattern (e.g. rates of application and areas treated per day). This tiered approachis discussed in Chapter 5.

AGGREGATE EXPOSURE

Until recently, it has been generally accepted practice to assess pesticide exposureseparately for each source (dietary, drinking water and residential). As a resultof legislative changes, there has been a shift away from single-source, single-pathway and single-route assessments in North America for non-occupationalexposure. Aggregate exposure assessment for a single active ingredient is car-ried out by combining exposures from all sources, including residential expo-sure, food residues and drinking water. The development of novel approachesand associated scientific challenges to aggregating exposure are discussed inChapter 8.

CUMULATIVE EXPOSURE

For classes of pesticides that cause their toxic effects through a common mecha-nism of toxicity, the non-occupational exposures to all members of the class haveto be aggregated and used in a cumulative risk assessment. In 2003, the UnitedStates Environmental Protection Agency (USEPA) published a framework outlin-ing how cumulative risk assessments should be conducted. There is no questionthat this approach has provided significant challenges to toxicologists, exposureassessors and risk assessors. Much of the developmental work on how to conduct


cumulative risk assessments has been carried out on the organophosphorous (OP)pesticides since they act through a common mechanism of toxicity. The USEPApublished a revised OP cumulative risk assessment in 2001 and will finalize reg-istration decisions based on this assessment. In the USA, thirty two (32) differentOP active ingredients registered for a wide range of agricultural and residentialuses were included in the cumulative assessment. This complex assessment isvery ‘data-rich’ and is based on probabilistic approaches as much as possible. Aspointed out in this document, cumulative risk assessment cannot be achieved byadding up the aggregate risk assessment for each OP because many of these prod-ucts are alternatives for each other and may not be used at the same time or forthe same uses. Realistic exposure scenarios must be developed in order to definethe times and routes of exposure to the critical pesticides linked to the commontoxic effect. The task is complex, because the possibility exists that there may beconcurrent exposures through multiple pathways to a number of pesticides fromthe same cumulative group. How aggregate and cumulative exposure assessmentscan be carried out is discussed in Chapter 8.

IMPACT OF NEW SCIENTIFIC ADVANCES

If the estimated level of exposure is less than the reference dose (RfD), thepesticide is considered to be safe to use. The aggregation (addition) of the amountof exposure received from each source will increase the total exposure to a levelwhich may then exceed the RfD. In addition to aggregation increasing the levelof exposure, the reference dose is becoming smaller because of the use of extrasafety factors to protect children. The trend towards lower reference doses impactsboth residential and worker risk assessments.

The need for aggregate and cumulative non-occupational exposure assessments,and lower reference doses for all assessments, means that some pesticides will faillower-tier risk assessments and without more refined exposure data they mighteven fail higher-tiered assessments. For example, in North America many of theresidential uses of the OPs have been discontinued as a result of the aggregate riskassessments. As a result, there has been increased emphasis on gathering bettertoxicology and exposure data to reduce the conservatisms that are contained inthe current system.

POST-REGISTRATION MONITORING

Once a pesticide is in use, post-registration monitoring could be conducted tofurther characterize the potential exposure under conditions of typical use. Occu-pational exposure studies carried out for registration purposes are conductedin compliance with the label requirements. While regulatory agencies compen-sate for such controlled conditions through the application of safety factors andother conservative assumptions, post-registration monitoring of workers usingtypical Personal Protective Equipment (PPE), rates of application and treating


a typical number of hectares per day would provide additional insight intopotential risk under conditions of actual use. Such data could also be usefulin determining a distribution of exposures for probabilistic assessments. Thesepost-registration monitoring studies could be conducted by using the passivedosimetry or biomonitoring techniques described in Chapter 1 and provide vali-dation of pre-registration studies.

Post-registration monitoring could also be useful for aggregate exposure assess-ments for residential use pesticides. There is the potential for a pesticide tocontaminate surface and ground water, dust, soil and surfaces in the home throughdirect application or ‘track-in’, as well as air. Given the requirement to conductaggregate exposure assessment, it is important that there be post-registration mon-itoring data to provide realistic estimates of the pesticide levels in some of thesemedia. Such data may also provide an indication of the relative significance ofvarious exposure pathways. While not the subject of this present book, such anapproach is used by regulatory agencies in higher-tier dietary risk assessmentswhereby refined monitoring data for foods (e.g total diet studies and market basketsurveys) are used to provide realistic estimates of potential food exposure. Mon-itoring of pesticides in drinking water may also be required for some pesticides.

Many epidemiology studies have to rely on recall responses to questionnairesto estimate exposure for workers and the general population. The need for real-istic and accurate measures of exposure for epidemiology studies is the topicof Chapter 7. Post-registration monitoring of residues in various media, and ofworkers or the general public using passive dosimetry and biomonitoring, wouldalso provide better surrogates of exposure for epidemiology studies. Limitedpopulation-based biomonitoring studies have been carried out and provide anindication of potential exposure to pesticides in the general population. Thesestudies are described in Chapter 4.

Some regulatory agencies also require the reporting of adverse effects. Suchpost-registration monitoring data can supplement and validate risk assessmentsfor pesticides under re-evaluation and provide useful information for further riskmitigation and management.

HARMONIZATION OF REGULATORY APPROACHES

In the past few years, there have been increasing efforts towards internationalharmonization of approaches to pesticide exposure assessment. Harmonizationallows exposure assessors to share expertise and resources and develop bettermethods. Ongoing efforts towards international harmonization are discussed inChapter 10. The development of generic databases has provided an impetus forharmonization of methodologies for generating the data. Further harmonizationwould increase the number of studies that could be included in databases, thusimproving the exposure estimates derived from them. The use of harmonizedfactors for dermal absorption and clothing penetration, plus protective factors


for clothing and equipment, as well as the use of consistent triggers for expo-sure assessments, harmonized route-specific considerations and generic transfercoefficients, would improve enormously the quality of the data and enable muchlarger databases to be built. New requirements for assessing residential expo-sure in the context of aggregate exposure have also spurred exposure assessorsto develop common approaches and methodologies. Further development ofcommon approaches and databases would significantly increase accuracy andconfidence in residential assessments. To promote harmonization, it is essentialthat researchers and regulators have a common vocabulary and methods. One ofthe outcomes of this book is a glossary of terms, and its writing has benefittedenormously from the work of the Exposure Terminology Subcommittee of theInternational Program on Chemical Safety (IPCS) Exposure Assessment PlanningWorkgroup of the World Health Organization (WHO).

SUMMARY

Pesticides are a class of products that are essential for sustainable agriculture andfor good public health, especially in light of the increase in vector-borne diseasessuch as ‘West Nile Virus’ and the ongoing challenge of malaria control. Publicanxiety regarding the impact of exposure to pesticides on their health and thatof their children underscores the importance of generating accurate and reliableexposure data so that appropriate decisions may be taken on the registration anduse of these products. The need for monitoring data to identify where there mightbe problems resulting from the use of pesticides is also critical.

The field of exposure assessment is currently going through a rapid phaseof development and in order to assist the reader in keeping up with this, aReference List of Guidelines (Bibliography) is provided at the end of this book.It is recognized that this listing is not complete, but hopefully it will provide thereader with the basic sources from which more detailed and up-to-date searchesmay be conducted.

The ten chapters in this book cover various aspects of exposure assessment inagricultural and residential settings, ranging from generation of the data, buildingof databases to synthesize the empirical data, use of the data in epidemiologystudies, new approaches to aggregate exposure assessment for a single pesticide,and cumulative exposure assessment for pesticides that have the same mode oftoxicity, to a discussion of the importance of international harmonization on thegeneration and use of exposure data.

The goal of this text is to provide a critical assessment of the current state ofknowledge of exposure assessment of pesticides and to provide recommendationsto advance our ability to fully characterize and accurately assess their potentialexposure and risks. While the focus is on pesticides, many of the principles arealso applicable to other classes of chemicals and it is hoped that this book willhelp encourage cross-fertilization among various disciplines. Significant progress


has been made in the last decade, but further work is required in several key areasto meet the challenges posed by the newer developments described above. In par-ticular, continued international co-operation and harmonization will be essentialto ensure the protection of workers and the general public from the adverse effectsof pesticides.

Section OneExposure Assessment Methodologies

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