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    i

    PESTICIDES

    A Posi tion Paper of the

    AMERICAN COUNCIL

    ON SCIENCE AND HE ALTH

    Professor Allan S. Felsot

    Washington State University

    &HealthM y t h s v s . R e a l i t i e s

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    iii

    Pest ic ides & Heal th: Myths vs . Real i t ies

    John Berlau

    Compeiive Enerprise Insiue

    Christine Bruhn, Ph.D.Universiy o Caliornia, Davis

    Janice E. Chambers, Ph.D., D.A.B..,A..S.Mississippi Sae Universiy

    Jay Lehr, Ph.D.Te Hearland Insiue

    Bob Krieger, Ph.D.Universiy o Caliornia, iverside

    Manfred Kroger, Ph.D.Te Pennsylvania Sae Universiy

    Angela Logomasini, Ph.D.Compeiive Enerprise Insiue

    Alan McHughen, D.Phil.Universiy o Caliornia, iverside

    AcknowledgementsTe American Council on Science and Healh (ACSH) appreciaes

    he conribuions o he reviewers named below:

    ACSH acceps unresriced grans on he condiion ha i is solely responsible orhe conduc o is research and he disseminaion o is work o he public. Teorganizaion does no perorm proprieary research, nor does i accep supporrom individual corporaions or specific research projecs. All conribuions o

    ACSHa publicly unded organizaion under Secion 501(c)(3) o he Inernalevenue Codeare ax deducible.

    Individual copies o his repor are available a a cos o $5.00. educed prices or10 or more copies are available upon reques.

    Published by he American Council on Science and Healh, Inc.May 2011. Tisbook may no be reproduced in whole or in par, by mimeograph or any ohermeans, wihou permission o ACSH.

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    Table of ContentsAcknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .iii

    Table of Contents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . iv

    Executive Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

    A Rationale for Confronting Myths

    about Pesticide Technology . . . . . . . . . . . . . . . . . . . . . . . . . 3

    Pesticides with Benefits for All:

    An Agricultural Perspective . . . . . . . . . . . . . . . . . . . . . . . . . 5

    Agricultural Reality: The Economic Perspective . . . . . . . . . . . . . . . . . . . 5

    Agricultural Reality: Practical & Environmental Advantages

    of Crop Protection Chemicals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

    Pesticides with Benefits for All:

    A Public Health Perspective . . . . . . . . . . . . . . . . . . . . . . . . 11

    The Public Health Reality: Historical and Modern . . . . . . . . . . . . . . 11

    Synthetic Chemistry for Crop Protection: Humans Imitate

    Plants and Bacteria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14

    Technological Reality: Weve Always Copied

    the Good Ideas of Plants and Bacteria . . . . . . . . . . . . . . . . . . . . . . . 14

    Youve Come a Long Way, Baby . . . . . . . . . . . . . . . . . . . . . . 16

    The Reality of Modern Pesticide Technology:

    Dynamics & Evolution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16

    Its Still About the Dose(and Timing) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21

    The Reality of A Modern Biochemical Perspective

    on Toxicity, Hazard, and Risk . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21

    Thresholds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22

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    v

    Endocrine Disruption: Is It Just Hormonal? . . . . . . . . . . . . 25

    The Reality: Confusion Between a Changing Paradigm and a Shift

    in Focus, Away from Cancer, to a Different Physiological System . . 25

    Vetting and Regulating Pesticides . . . . . . . . . . . . . . . . . . . 28

    The Reality of Pesticide Regulation in the U.S.: An Example

    of Moving the Precautionary Principle from Idealistic Philosophyto Real World Implementation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28

    The Reality of Pesticide Regulation: Truckloads of Data on Every

    Conceivable Effect from Studies with Overlapping and Redundant

    Objectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31

    Whose Data Are They? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33

    How EPA Determines Safety Under the Mandates of the Law . . . . . 33

    Some Case Studies: Reports

    of Hazards Do Not Reflect Risks . . . . . . . . . . . . . . . . . . . . 35

    Atrazine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35Chlorpyrifos . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39

    Pyrethroid Insecticides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43

    Glyphosate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48

    Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52

    References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54

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    Executive Summary

    Will we aver a crisis o ood supply shorage? Tis quesion coninues oloom large alhough populaion growh rae has empered considerably,compared o projecions 30 years ago. Bu several years ago, as ood prices

    seemed o be on he verge o skyrockeing, owing o

    rapid increases in grain prices, we arguably go a aseo he uure. When you consider uncerainy abou cli-

    mae variabiliy and land use changes as well, we seem

    always on a precipice o doing wih less raher han

    more. Forunaely, agriculural echnology has hus ar

    kep pace wih a growing populaion. A crucial com-

    ponen o his oolbox has hisorically been a dynamic

    chemical echnology, led by he availabiliy o synheic

    erilizers and innovaions in chemical pes conrol.

    Tis repor analyzes he myhs surrounding pesicide

    science and correcs each wih a realisic perspecive o

    he echnology: how i is possible o kill pess wihou

    harming oher organisms, how he science is regulaed

    wih a precauionary perspecive, and, finally, wih an

    analysis o claims made abou hazards and he probabil-

    iy ha hese pose credible risks o healh. Tis repor

    makes he case or he benefis o pesicides, ranging

    rom he proecion o crop yields o he proecion o

    public healh. Indeed, he benefis are abundan enough

    ha one can simply sae ha he availabiliy o pesi-cides has significanly improved human healh.

    Conroversy surrounding pesicide use a firs

    glance would seem o dae back o he 1962 publicaion

    o achel Carsons Silen Spring. However, his superfi-

    cial analysis ignores he long hisory o pesicide conrol

    saues such as he Federal Food, Drug, and Cosmeic

    Ac (FFDCA 1938) and he Federal Insecicide, Fungi-

    cide, odenicide Ac (FIFR 1947). One migh argue

    abou he effeciveness o hese laws, bu hey have beenamended many imes, beore and afer Silen Spring,

    o address heir weaknesses. Indeed, perhaps he mos

    ar-reaching modificaion was he Food Qualiy Proec-

    ion Ac o 1996 which, or he firs ime, oriened he

    main law, FIFR, o consider risk o consumer healh

    as he only basis or re-regisering older chemicals and

    regisering new producs. Veneraion o Silen Springby

    advocacy groups has overlooked he reams o daa al-

    ready in he public secor ha Carson had been reading

    o inorm her lierary endeavor.

    And so, curren pesicide laws have evolved and

    are arguably he mos precauionary o all congressio-

    nal mandaes involving echnology. Indeed, we asser

    ha modern pesicide laws epiomize in acion an oh-

    erwise vacuous precauionary principle ha eschews

    risk assessmen as a basis or risk managemen. isk

    assessmen righully recognizes he oo ofen ignored

    principles ha all chemicals (wheher plan-derived

    or cooked up by humans) are subjec o he samephysical laws o hermodynamics and he principles

    o kineics. Such recogniion explains how we humans

    can ea a myriad mixure o plan chemicals, many

    o which are recognized as oxins hemselves, arising

    rom an evoluion o plan meabolism ha aids heir

    survival agains voracious predaors and he vagaries

    o weaher.

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    Execut ive Summary

    disposiion wihin he body, his repor specifically

    examines he claims abou our ypes o conempo-

    rary pesicidesarazine, chlorpyrios, pyrehroids,

    and glyphosae. In each case sudy, he published

    scholarly lieraure is used o show ha he percep-ion o adverse effecs has arisen as a resul o misak-

    ingeiher hrough ignorance or ideologylabora-

    ory sudies o oxicological mechanisms or analysis

    o risk based on consideraion o how he chemicals

    are acually used.

    One imporan poin o consider in any analysis

    o pesicide echnology is he evoluion o a dynamic

    sysem o managemen. Ta is, any repors o adverse

    effecs are deal wih by developmen and implemen-

    aion o new esing requiremens or by changes in

    permissible uses o a produc. Te sysem provides

    eedback o boh regulaory agencies and manuacur-

    ers hemselves. Te later have hisorically responded

    by a ocus on discovery o new producs ha mee he

    goals o a saer chemical echnology. Unorunaely,

    public atiudesed by atenion-seeking media

    scare sories seem ocused on he pas and ail o see

    a comparaively rapid change in chemical echnology

    and how i has been deployed. Similarly, public aten-ion is drawn o misinerpreaions and hal-analysis o

    sories o hazards. However, scruiny o he published

    lieraure has ailed o find evidence o a credible prob-

    abiliy o adverse human healh effecs derived rom

    he use o modern pesicides as occurs in he real world,

    no in he laboraory-generaed environmen. Despie

    he headlines o hazard, modern chemical echnology

    provides hope or coninued improvemen o human

    healh, wheher helping o make vegeables and ruis

    o high qualiy more abundan and cheaper, or o pre-

    serve (or indeed, enhance) he healh o individuals

    and sociey a large.

    In his background o survival, he principle o

    reasonable cerainy o no harm guides decisions

    abou releasing man-made pesicides o help in he

    batle o proec crop yields and ood qualiy. Eco-

    nomic analyses prove how ood supply would becomeprecarious wihou he use o chemical echnology.

    Epidemiological analyses prove how eliminaing an

    effecive surace-sprayed insecicide like DD has os-

    ered large oubreaks o malaria, he mosquio-borne

    scourge o 300 million humans a year. Ye despie

    he proven benefis o pesicides, years o research

    have shown ha hese valuable ools canno be used

    wihou proper managemen, and ha, moreover,

    hey should exhibi seleciviy o pess over nonarge

    organisms so ha hey become complemenary o

    naural biological conrol processes exising wihin all

    agriculural ecosysems.

    Indusry has responded o he goals and needs

    o a compaible pesicide echnology wih develop-

    men o ever more selecively oxic chemicals ha

    are used a comparaively low raes compared o he

    chemicals hey are replacing in he markeplace. Te

    recen generaions o EPA-designaed reduced-risk

    pesicides are in many cases ens o hundreds o imesless oxic o fish, birds, and nonarge predaors and

    parasioids han chemicals ha were inroduced o

    armers beween he 1950s and 1970s. However, he

    biochemical heory o ligand-recepor and enzyme-

    subsrae kineics, in combinaion wih consideraions

    o pharmacokineics, is applied herein o show ha

    some o he older chemicals acually presen litle risk

    o adverse effecs in associaion wih realisic environ-

    menal raes o use.

    Following explicaions o oxicological mecha-

    nisms o seleciviy and he imporance o consider-

    ing pharmacokineic acors influencing pesicide

    Despite the headlines of hazard, modern chemical technology

    provides hope for continued improvement of human health.

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    ing risk. While consumers are reacing by expressing

    heir eelings abou a generic echnology, he scienific

    exper is mos likely ocusing on he idiosyncrasies o

    an individual compound. Neverheless, general prin-

    ciples o biochemisry and physiology are imporan

    or assessing pesicide echnology. Applicaion o

    hese principles is crucial o properly regulaing as well

    as using he echnology. Furhermore, he benefis o

    he echnology mus be considered in ligh o he pos-sible and likely adverse consequences o notusing i.

    Te lieraure on he percepion and communica-

    ion o risk suggess ha perhaps consumers are no

    he real audience in need o inormaion abou he

    inricacies o pesicide echnology. For example, 84%

    o surveyed residens in Washingon Sae did no

    hink pesicide use and conrol was an environmenal

    problem (LaFlamme and VanDerslice 2004). I seems

    ha inormaion may be beter direced o legislaive

    members and heir saff (Cohen 1997). When hesecohors were surveyed, he mos desired inormaion

    was explanaions o how risk assessmens are con-

    duced, wih applicaion o paricular chemicals as an

    example. I legislaors and heir saffs are recepive o a

    beter undersanding o chemical echnology hrough

    risk assessmen, hen dispelling misconcepions abou

    pesicides as a precursor o raional risk manage-

    A Rationale for Confronting Mythsabout Pesticide Technology

    O

    ver he las decade, ood preerence surveys as well as sales saisics show anincreasing percenage o consumer preerence or buying organic, raw, and

    processed ood producs (Saba and Messina 2003; Hughner e al. 2007).Alhough he absolue numbers o individuals pur-

    chasing hese ood iems compared o convenional

    iems is sill quie small (Hughner e al. 2007), he daa

    seem o validae he percepion ha consumers gener-

    ally have a negaive opinion o pesicide use (Chipman

    e al. 1995; Makaouni 2002; Magnusson e al. 2003;

    Yiridoe e al. 2005). Tis negaive opinion is relaed o

    several concerns, ranging rom worry abou he healh

    effecs o pesicide residue exposure o a misrus oindusries synhesizing and markeing pesicides

    (Chipman e al. 1995; Slovic 1999). Various surveys

    also sugges ha consumers do no perceive any bene-

    fis rom he use o pesicide echnology (Hansen e al.

    2003). Consumers may undersand he need o man-

    age crop and livesock pess, bu hey may also hink

    ha pesicides are no necessary o achieve his goal,

    or, alernaively, ha hey are overused in agriculure

    (Chipman e al. 1995). isk percepion surveys gen-

    erally agree ha consumers view pesicides as a highhazard echnology ha is unconrollable, unknowable,

    and o litle benefi o hemselves (Chipman e al.

    1995; Slovic 1987).

    Given ha pesicide echnology encompasses

    a vas array o individual chemicals and ormulaed

    producs, changing consumer percepions seems o

    presen an insurmounable obsacle in communica-

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    A Rat iona le for Confro nt ing Myths about Pest ic ide Te chnology

    icide echnology, his repor will firs sae miscon-

    cepions or myhs abou pesicides ha can be gleaned

    rom a combinaion o risk percepion lieraure, as

    well as examining pesicide sories in he media (Fel-

    so 2010). Afer saing a myh, he realiy based onbiochemical principles will be explained. Similarly,

    misconcepions relaed o he real benefis o pesicide

    use will be answered wih examples o how pesicides

    acually conribue o proecion o human healh and

    a general improvemen in wellbeing. Finally, o illus-

    rae how misundersandings o he naure o oxicol-

    ogy and epidemiology sudies conribue o a skewed

    conflaion o hazard and risk, he repor will review

    some commonly used biodegradable pesicides and

    atemp o alleviae issues o specific concern. By dis-

    cussing misconcepions and realiies abou pesicide

    echnology, and highlighing paricular pesicides,

    his repor can provide risk communicaors wihin he

    business communiy and governmen wih a sronger

    echnical basis or discussing pesicide issues.

    One cavea needs emphasis up ron. Argumens

    promoing global benefis rom pesicide echnologies

    as heyve evolved over he pas 40 years are no argu-

    mens agains ensuring ha hese compounds havelitle risk as hey are used. aher, our regulaory sys-

    em or pesicides has acually been quie precauion-

    ary. Ironically, as calls or adopion o a precauionary

    principle in place o a risk assessmen process have

    begun o permeae governmenal regulaory aciviy,

    pesicides are arguably he one echnology where so-

    called enes o his principle are acively praciced.

    Tus, anoher objecive o his repor is o clariy

    muliple aspecs o pesicide echnology ha mus

    be known i we wish o move pas he myh ha we

    have no properly considered hazards in he mids o

    overwhelming benefis.

    men may no be an insurmounable ask. Afer all,

    legislaures mandae regulaion o he echnology.

    egulaors hemselves, hereore, mus undersand

    undamenal biochemical principles, as hey regulae

    many kinds o chemicals.Ye simply educaing regulaors may no be an e-

    ecive way o dispel misconcepions. Comparisons o

    lay and exper opinion abou chemical hazards in gen-

    eral revealed unpredicable disagreemens abou he

    hazard and risk o chemical echnology among expers

    (or example, regulaors and academic or indusry re-

    searchers engaged in some aspec o oxicology) ha

    were no oo differen rom hose expeced beween

    consumers and expers (raus e al. 1992; Merz e

    al. 1998). I here is as wide a divergence o opinion

    among expers hemselves as ha which occurs be-

    ween expers and consumers, one canno expec o

    be very successul a risk communicaion unless some

    o hese percepions are addressed direcly. Perhaps

    wihin he echnical communiy isel insufficien a-

    enion has been paid o common wisdom in order

    o deermine operaional misconcepions abou pesi-

    cide echnology in general.

    Tis repor is a response o a need expressed oracual inormaion among legislaive auhoriies, bu

    i also addresses expers hemselves by considering

    enuous he assumpion o agreemen abou he risks

    o chemical echnologies. Our analysis subsiues ac-

    ual inormaion (some undamenal principles o ox-

    icology based on biochemical conceps, an overview

    o properies o modern reduced risk pesicides, and

    a delineaion o pesicide benefis o human wellbe-

    ing) or misconcepions specifically abou pesicide

    echnology.

    o communicae he undamenal principles o

    oxicology necessary or appropriaely regulaing pes-

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    Pesicide and erilizer use has been recorded since

    ancien imes, suggesing ha ecosysem managemen

    is no a recen culural atribue. In he conex o mod-

    ern agriculure, he objecives o pesicide use are o

    increase producion efficiency and yields; reduce he

    cos o ood and, especially, o increase he availabiliy

    o grains, ruis, and vegeables; improve ood qualiyand losses during ranspor and sorage; improve soil

    conservaion; and ensure a sable and predicable ood

    supply (NRC 2000).

    Pesicide use is widespread on arms, bu more

    imporanly, differen classes o pesicides are differen-

    ially used (NRC 2000; Padgit e al. 2000), suggesing

    ha growers make decisions based on need raher

    han solely on prophylaxis. For example, in he U.S.

    during 2002 approximaely 303 million acres o crops

    were harvesed, and 95% were reaed wih some ype

    o pesicide. However, 64% o he acreage was reaed

    o conrol weeds (i.e., herbicide use), 22% o conrol

    insecs (insecicide use), 6% o conrol diseases and

    nemaodes (ungicide and nemaicide use). Anoher

    4% o he crop acreage was reaed wih a plan growh

    regulaor or rui hinning, growh conrol, or deolia-

    ion (Felso and acke 2007).

    Pesticides with Benets for All:An Agricultural Perspective

    Myth: Farmers use pesicides or heir own economic gain wihou regard or needor a social responsibiliy o proec he environmen. Pesicides are no needed or

    arming, as has been proven by he increasing adopion o organic arming.

    Agricultural Reality: The Economic Perspective

    Te proporional use o differen kinds o pesicides

    (i.e., herbicides, insecicides, ungicides, ec.) shows ha

    armers do no monolihically use he chemicals on ev-

    ery acre. aher, he daa show ha use is ied o specific

    need. Furhermore, he inensiy o specific pesicide

    classes also varies significanly by crop. Grains end o

    be disproporionaely reaed wih herbicides, bu ruiand vegeables mosly receive insecicide and ungicide

    applicaions (able I). Farmers use he echnology

    ha conrols he pes a hand bu, imporanly, use

    is driven by need as influenced by weaher condiions,

    anicipaed and acual pes inesaions, and he balanc-

    ing o coss and reurns.

    Te benefis o crop proecion chemicals or im-

    proving and proecing crop produciviy is difficul

    o separae rom he effecs o hybrid seed echnol-

    ogy and oher plan breeding advances. Neverheless,

    an examinaion o crop yields relaive o land under

    producion shows ha boh ypes o echnologies

    have had major conribuions. For example, he grea-

    es proporion o U.S. armland is devoed o corn

    producion. A hisorical examinaion o area o land,

    yields, and he inroducion o differen echnologies

    over ime suggess ha insec conrol (mainly o he

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    Pest ic ides wi th Benef i ts for Al l : An Agricul tural Perspect ive

    and umigans, in crop producion efficiency is sug-

    gesed by poao producion saisics. In 1900, nearly

    3 million acres o poaoes were harvesed, yielding an

    average o 52 cw/acre (USDA2005). In 1950, aver-

    age yields were 153 cw/acre. In crop year 2004, 1.2million acres o harvesed poaoes yielded an average

    752 cw/acre. Surely, advances in plan breeding play

    an imporan role in producion increases, bu by he

    1950s, umigans or conrol o nemaodes became

    widely available nearly coincidenally wih he

    corn rooworm complex) has grealy enhanced he

    effeciveness o hybrid seed echnology (Figure 1).

    Furhermore, he inroducion o modern synheic

    herbicides aciliaed widespread adopion o conser-

    vaion illage in he Corn Bel, which in urn grealy re-duced he major cause o environmenal degradaion

    in Norh Americasoil erosion and sedimenaion in

    rivers (Pimenel e al. 1995).

    Perhaps an even more compelling case or he role

    o crop proecion chemicals, especially ungicides

    Crop Herbicide Insecticide Fungicide

    Corn 95 29

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    7

    Pest ic ides & Heal th: Myths vs . Real i t ies

    o decreased pesicide use or no use seem large, he

    acual decrease in yields (and consequen effecs on

    consumer prices) would depend on he availabiliy o

    oher alernaive crop proecion echnologies or prac-

    ices (NC 2000). For example, field crops like corncan be grown wih minimal herbicide use i illage is

    used more requenly. Addiionally, hand weeding, as

    is ofen praciced in cerified organic crop producion,

    along wih illage, can subsiue or herbicide use.

    However, aggregae analysis o grain, vegeable, and

    rui crop managemen, assuming only hand weeding

    and illage wihou herbicide use, showed an average

    yield reducion o 20 percen (Gianessi and eigner

    2007). Furhermore, subsiuion o increased illage

    or weed conrol would couner he benefis o re-

    duced illage or soil conservaion.

    Vegeable and rui producion would likely be

    he mos adversely affeced by wholesale loss o use o

    insecicides and ungicides, owing o heir dispropor-

    ional problems wih insec pess and plan pahogens.

    Loss o pesicide availabiliy would also adversely a-

    ec consumer prices, and poenially mean a loss o

    domesic sources o supply as producion is relocaed

    o oher regions (Zilberman e al. 1991).Is imporan o realize ha he economic reurn-

    cos raio or pesicide use is generally avorable. Te

    raio depends on he specific crop because he annual

    commodiy price mus be acored in, as well as he

    sie-specific yield and expenses due o chemical pur-

    chases. Neverheless, older esimaes or reurn ranged

    rom $4-$29 or every $1 spen (Mecal and Luckman

    1975), and more recen esimaes sugges a $3-$6 rae

    o reurn per $1 spen (Zilberman e al. 1991; Pimenel

    e al. 1992). Significan or he grower is he compara-

    ively low incremenal cos o pesicide use relaive o

    all producion expenses. Te mos recen esimae

    (crop year 2002) is ha purchase o pesicides repre-

    sens 4.4% o oal expenses, compared o he 12.7%

    o expenses or hired and conrac arm labor (USDA

    2004). Pesicides hemselves help lower coss by sub-

    siuing or labor. For example, rui hinning required

    widespread adopion o mineralized erilizers. Bu he

    producion rends srongly sugges an environmenal

    benefi because presenly seven imes more poaoes

    are produced per acre han were produced in 1900. I

    one hus exrapolaes or oher crops ha yields haveincreased owing o adopion o modern echnolo-

    gies like improved breeding using bioechnology and

    chemical pesicides, hen a large benefi is a reurn o

    arm land o oher uses, such as oress and/or prairies

    and conservaion o naural areas, as well as residences

    or a burgeoning populaion.

    Wha is more, he aggregae economic benefis

    associaed wih pesicide use have been subjeced o

    various empirical modeling exercises and expressed

    as he loss o producion i pesicides were no used

    (NC 2000). Producion losses during he mid-1980s

    were esimaed o be as high as 37% o oal oupu

    (Pimenel e al. 1992). Tis esimaed loss occurred

    despie pesicide use, bu he esimae seems raher

    high when assessed agains specific crop analyses. For

    example, one o he mos desrucive pess o poaoes,

    lae bligh disease, broke ou in he Columbia Basin o

    Washingon Sae and Oregon during 1995. Fungicide

    use rose rom ypically wo applicaions per season oas many as 12 (Johnsoneal. 1997). However, yield

    differences beween he pre- and pos-bligh oubreak

    were only 4-6 percen. On he oher hand, wihou any

    managemen, he bligh epidemic could have reduced

    yields 30-100 percen.

    Oher economic analyses have projeced he e-

    ec on resh and processed vegeable and rui yields

    i pesicide use were reduced 50 percen or simply

    no used a all (nuson e al. 1993). educions

    in resh rui yields were 40 percen and 75 percen,

    respecively. Subsanial reducions were projeced in

    grain producion under condiions o no herbicide

    use (Fernandez-Cornejo e al. 1998). Anoher sudy

    esimaed ha a oal pesicide use ban would require

    an addiional 2.5 million acres o vegeable and rui

    producion o make up or he yield loss (aylor

    1995). Alhough modeling esimaes o he impacs

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    Pest ic ides wi th Benef i ts for Al l : An Agricul tural Perspect ive

    by cerified organic growers. For example, spinosad

    insecicide, a complex macrocyclic lacone saccharide

    derived rom a bacerial ermenaion culure, is used

    by odays cherry growers regardless o heir produc-

    ion philosophy. Even hough NOSB policy ends oavoid subsances ha are oxic, spinosad has a bio-

    chemical mode o acion ha would classiy i as a ype

    o neurooxin (Sparks e al. 2001; Orr e al. 2009).

    Te puriy o organic ood is urher dispelled

    by analyical surveys o organic commodiies o reveal

    ha some conain synheic pesicide residues boh

    banned and currenly regisered, albei much less re-

    quenly han so-called convenional oods (Baker e

    al. 2002). esidues in organic commodiies are likely

    inadveren, due o airborne ranspor and deposiion,

    as well as soil residues rom pas use. ecognizing

    he ubiquiy and mobiliy o environmenal residues,

    NOP rules allow inadveren pesicide residues up

    o 5 percen o he esablished ederal olerance level

    wihou a loss o organic cerificaion. Wheher one

    likes or dislikes pesicide use, pas pracices influence

    residues in ood. However, curren residue sudies

    indicae ha he vas majoriy o convenional oods

    have no detectable pesticide residues (FDA 2009;USDA AMS 2009).

    In summary, various economic analyses are in

    agreemen ha pesicide use has been definiely as-

    sociaed wih profiable reurns o armers (and hus

    o sociey), and i is no rue ha pesicides are used

    on every crop indiscriminaely. Te realiy is ha

    some crops require disproporionaely more herbicide

    use and some crops require more insecicide and/or

    ungicide use. Tus, effors o globally limi pesicide

    use ail o ake ino accoun specific and local needs

    or crop proecion. Furhermore, cerified organic

    producers have an array o pesicides hey can use un-

    der he rules o he NOSB. Pas land pracices have led

    o deecions o pesicide residues in organic ood, bu

    curren analyical surveys show ha so-called conven-

    ionally produced ood mos ofen has no deecable

    pesicide residues.

    in he pome rui indusry is mosly done by chemical

    hinners bu sill requires some hand hinning i loads

    are deemed excessive.

    Perhaps he mos popular misconcepion among

    consumers o organic oods is ha such producs lackpesicide residues and oher addiives. Te basis or

    his belie is he ofen-repeaed argumen ha organic

    agriculure disinguishes isel rom convenional

    producion mehods because no synheic pesicides

    are used. Prolonged pronouncemens o no synheic

    pesicide use easily evolve ino a consumer percepion

    o no pesicide use. Conracion o no synheic use

    o he equivalency o no use a all may be aciliaed

    by he myh ha somehow synheic subsances are

    generically differen in heir adherence o hermody-

    namic laws and reaciviy han naural subsances.

    Te realiy is ha U.S. rules or cerificaion o

    organic producion allow or he willul use o ap-

    proved crop proecion producs. Under he Federal

    Insecicide, Fungicide, and odenicide Ac (FIFR)

    many o heses producs are legally pesicides and

    mus be regisered wih EPA (Felso and acke

    2007). However, organic growers by rule canno use

    synheic maerials unless approved by he NaionalOrganic Sandards Board (NOSB). Bu no pesicide

    (NOSB-approved or oherwise) can be used in any

    ype o arming pracice unless veted by EPA firs.

    EPA does a comprehensive risk assessmen on all

    chemicals submited or regisraion, using he raw

    daa submited by a prospecive pesicide regisran.

    Similarly, NOSB conracs wih he Organic Maerials

    esearch Insiue (OMI) o do a comprehensive

    hazard assessmen o maerials proposed or cerified

    organic producion. In ha case, similar quesions

    are asked, excep ha he OMI speculaes wheher

    a candidae produc is really needed and hereore a

    credible subsiue. One crierion would be ha i is

    less hazardous. Alhough a perspecive o hazard di-

    ers rom one ha uses hazard along wih exposure o

    characerize risk, some o he acive ingrediens used

    by nonorganic growers are he same as hose used

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    Pest ic ides & Heal th: Myths vs . Real i t ies

    Te inorganic pesicides used during he firs hal o

    he 20h

    cenury and he firs wave o synhesized pesi-cides afer 1950 were generally broad specrum bu no

    necessarily adequae or all cropping sysems (Sern e

    al. 1959). Over he las hiry years new chemisries

    have been inroduced o narrow he specrum o ac-

    iviy. Along wih new ormulaions and applicaion

    mehods, modern pesicides can be beter ailored o

    specific crops pes problems. Similarly, insecicides

    inroduced over he las 15 years are also much less

    oxic o he naural bioconrol organisms han he

    broad-specrum synheics inroduced during he1950s. Furhermore, modern pesicides rapidly de-

    grade in he environmen and do no bioaccumulae

    in lipid issues as did he chlorinaed hydrocarbon and

    cyclodiene pesicides ha were heavily used prior o

    heir ban in he early 1970s.

    A ourh benefi sems rom herbicide use in grain

    producion hroughou he Corn Bel. Beore he ad-

    ven o synheic chemical herbicides like arazine, ero-

    sion was severe on even genly sloping lands becausearmers relied on he moldboard plow and urher

    culivaion o he soil during crop growh o conrol

    weeds. Many environmenal scieniss agree ha eu-

    rophicaion and sedimenaion o aquaic resources

    due o runoff and erosion rom agriculural land is he

    mos imporan cause o waer qualiy impairmen,

    no o menion being reponsible or ransporaion

    problems as rivers backfill wih sedimen. By he

    1960s, a ew herbicides were commercially available

    In addiion o heir economic benefis accruing

    rom he objecives or which hey are used, pesicideshave cerain advanages over oher pracices or crop

    proecion (as well as producion) ha make hem very

    convenien, efficien, and cos-effecive (Mecal and

    Luckman 1975). Firs, or mos cropping sysems, pes-

    icides are he only pracical available echnology be-

    cause oher echnologies are no available, unproved,

    or do no work efficienly. For insance, hybrids o cer-

    ain crops may lack a pes-resisan culivar. In oher

    cases, a nonchemical pes conrol pracice ails o work

    over ime. An example o he later siuaion is he ap-paren adapaion o wesern corn rooworms o he

    pracice o annual corn-soybean roaions ha were

    very successul in reducing he need or soil inseci-

    cides (Sammons e al. 1997; ondon and Gray 2004).

    Second, pesicides have rapid curaive acion in

    prevening loss o crop yield or proecing human and

    animal healh. Tus, hey can be used when a pes

    populaion becomes inolerable. One o he enes

    o inegraed pes managemen (IPM) is eschewingprophylacic sprays in avor o as needed reamens.

    Tus, here may be a very shor window o ime during

    which he pes needs o be conrolled, and nonchemi-

    cal mehods may lack a rapid enough acion.

    Tird, he diversiy o locaions where crops are

    grown means differen pes complexes hrive under

    a wide range o climaic condiions. Pesicides have

    a wide range o properies, uses, and mehods o ap-

    plicaion ha can cover many problems as hey arise.

    Agricultural Reality: Practical & EnvironmentalAdvantages of Crop Protect ion Chemicals

    The diversity of locations where crops are grown means different

    pest complexes thrive under a wide range of climatic conditions.

    Pesticides have a wide range of properties, uses, and methods

    of application that can cover many problems as they arise.

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    Pest ic ides wi th Benef i ts for Al l : An Agricul tural Perspect ive

    lands available or wildlie conservaion (Cooper and

    Dobson 2007). Direc conrol o human and livesock

    pess (as discussed in he ollowing secions) creae

    similar secondary benefis or economic produciviy,

    public healh, and longeviy.An analysis o hisorical and conemporary man-

    agemen o coton pess provides anoher affirmaion

    o he benefi o pesicide echnology and also sug-

    gess indirec benefis beyond a specific crop (Naranjo

    and Ellsworh 2009). Coton has hisorically been a

    crop requiring arguably he highes per acre inensiy

    o pesicide use. Coton pes managemen in Arizona

    has evolved ino a highly sraegic sysem ha employs

    boh naural biological conrol organisms (i.e., preda-

    ors and parasioids) bu also relies on highly selecive

    insecicides or conrolling he mos imporan pess,

    which include he pink bollworm and whieflies.

    Pink bollworms have been managed by use o coton

    culivars bred o conain he highly selecive bace-

    rial oxin proein derived rom he naurally occurring

    insec pahogen Bacillus huringiensis. Deploymen

    o such culivars can conserve predaor populaions.

    Te whiefly, on he oher hand has, been successully

    managed by judicious inegraion o highly seleciveinsecicides ha affec insec developmen. Te avail-

    abiliy o such insecicides has no only increased pro-

    is by reducing he overall need or pesicides, i has

    also indirecly benefied oher regional crops atacked

    by whieflies: Tese now show an overall reducion in

    heir populaions. Tus, innovaive pesicide echnol-

    ogy has resuled in an unprecedened sabiliy o eco-

    sysem services and major economic and environmen-

    al gains in Arizona coton ha has exended o benefi

    he enire agroecosysem o he region (Naranjo and

    Ellsworh 2009).

    and allowed armers o consider subsiuing chemical

    conrol o weeds or urning he soil over and hereby

    making i highly suscepible o he erosion caused by

    wind and spring rains on bare soil. No-ill agriculure

    bloomed, especially in corn producion, because arm-ers were able o rely on herbicides. Aggregae soil ero-

    sion rom illed soil in our Corn Bel saes (Illinois,

    Indiana, Iowa, Nebraska) was esimaed a 14.9 ons/

    acre/year bu only 2.8 ons/acre/year rom unilled

    grain fields (Gianessi and eigner 2006).

    Furhermore, by eliminaing he need o ill soil,

    herbicides also allow or he conservaion o uel. Over

    111 million gallons o uel may be saved by using her-

    bicides insead o illage in he aoremenioned our

    Corn Bel Saes (Gianessi and eigner 2006). Low-

    ered emissions o greenhouse gases are also associaed

    wih a reducion in uel use (oberson e al. 2000).

    In addiion o uel reducions, an increased yield

    or every dollar invesed in agriculural producion

    significanly reduces per acre increases in carbon emis-

    sions; his is by virue o avoiding he land clearing

    oherwise necessary o mainain sufficien producion

    or an increasing populaion (Burney e al. 2010).

    Tus, curren analyses suppor he idea ha pesicideechnology also conribues o environmenal qualiy

    by virue o enhancing yield.

    wo oher recen analyses also suppor he con-

    clusion ha here are boh direc and indirec benefis

    o pesicide echnology. Alhough he direc benefis

    o suppression o pes densiy, and hus suppression

    o damage, are obvious, indirec benefis can also be

    considerable. Some examples o he later include

    increased financial resources or a communiy, due

    o greaer producer profis; increased consumer ac-

    cess o resh ruis and vegeables; and an increase in

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    on a coninen like Arica, where publicly financed

    programs are inrequen, and poor when hey exis.

    Anophelesmosquioes oday sill ransmi per annum

    over 500 million cases o malaria (WHO 2010), a

    disease caused byPlasmodium falciparum, a prois re-

    quiring boh he mosquio and human body in which

    o complee is lie cycle. Malaria causes paroxysms

    o ever, ofen several imes each day. Wih so many

    ineced, economies become inefficien as workers are

    sruck ill. And because inan and child nuriion is

    so deficien in hese counries, a nearly unimaginable

    800,000 children die rom mosquio-ransmited ma-

    laria each year.

    Bu many counries have malaria under conrol.

    Tey adoped he use o DD, he chemical echnol-

    ogy used by he miliary during WWII and by he

    European Command afer he war o conrol mos-

    quio populaions. Daa on malaria incidence beore

    and afer he adven o DD proved ha he pesicidecould be effecive wihou causing acue harm (Hayes

    1991). Te evidence or lack o acue harm became

    apparen when millions o Europeans were direcly

    dused o conrol lice ha ransmited a orm o yphus

    caused by he bacerium Ricketsia.

    However, DD was essenially banned in he U.S.

    in 1972 when he recenly-creaed EPA decided o

    Daily lie in he developed counries o he Wes

    is no likely plagued by insec-ransmited inecious

    diseases. While i is rue ha he yellow ever vecor

    mosquio Aedes aegypi once hauned he srees o

    New Orleans, a program o publicly financed mosqui-

    o conrol arose in he 1960s and spread hroughou

    he U.S. o dampen he disease-ransmission poenial

    o insecs. Even so, over he las decade, Wes Nile

    virus, ransmited by he bie o he Culex mosquio,

    has spread rom New York o Caliornia, becoming

    endemic in every sae (Arsob e al. 2009). Lyme dis-

    ease, a spriochee bacerium ransmited by he bie o

    he iny deer ick, disables nearly 20,000 people each

    year (Bacon e al. 2008); i is in many places now in

    he U.S., alhough he epicener is in New England.

    Insec bies are mosly a nuisance o ciizens in highly

    developed counries, bu he las decade o Wes Nile

    virus epidemiology shows he need or vigilance abou

    inecious disease conrol even as megaciies and ex-urbs pave over widening expanses o naural lands.

    Furhermore, he widespread oubreak and spread o

    Wes Nile virus has had observably negaive impacs

    on bird populaions (LaDeau e al. 2007).

    ecen experience indicaes he need or vigilance

    agains arhropod-vecored diseases even in devel-

    oped counriesbu he siuaion is surely more dire

    Pesticides with Benets for All:A Public Health Perspective

    Myth: Pesicides offer no benefi o public healh and, arguably, derac rom i.

    The Public Health Reality: Historical and Modern

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    Pest ic ides wi th Benef i ts for Al l : A Publ ic Heal th Perspect ive

    Mosquio larval, egg-laying, and breeding habia

    mus be moniored and managed. Wesern counries

    now use insecicides based on microbial oxins, name-

    ly Bacillus huringiensis israeliensis (Bi) and Bacillus

    sphaericus.BiandB. sphaericusare incredibly specific,naurally occurring baceria ha are oxic only when

    ingesed by mosquio larvae. Tese organisms are sill

    deemed pesicides, specially regulaed under EPAs

    biopesicides program (EPA 2010).

    In addiion o habia managemen or mosquio

    conrol, individuals are encouraged o proec hem-

    selves wih mosquio neting around heir beds a

    nigh. Emphasis has been placed on using insecicide-

    impregnaed bed neting, which can be effecive when

    whole communiies are included in conrol programs.

    However, even such relaively passive conrol mea-

    sures are very much influenced by he ype o insec-

    icide deployed (e.g., irrian vs. non-irrian effecs)

    (Curis and Mnzava 2000), urher illusraing ha he

    benefis o pesicides depend on he appropriae use o

    specific chemicals.

    One aspec o proecing public healh ha is

    no ofen menioned is he poenial o pesicides o

    reduce microbial conaminaion and he associaedproducion o ungal oxins. Overlooked is he use o

    chlorine and oher disinecans, all o which are reg-

    isered pesicides, in waer reamen. U.S. consumers

    appreciae waer devoid o bacerial conaminans and

    know implicily ha bacerial inecion rom drinking

    waer is very rare here. However, inadequaely reaed

    public supplies do occur, as evidenced by he oubreak

    o cryposporidium in a Wisconsin waer supply dur-

    ing 1993 (Macenzie e al. 1994). A waer-borne ou-

    break o pahogenicE. coli in Walkeron, ON during

    2000 was also definiively conneced o inadequae

    chlorinaion (Hrudey e al. 2003).

    Ani-pesicide aciviss may ry o asser ha pes-

    icide use is all abou blemish-ree rui and vegeables.

    rue, use o crop proecion echnologies reduces

    marking and scarring, hereby filling o overflowing

    produce couners wih picure-book ood. Bu insec

    suspend is regisraion or any agriculural use. (In

    ac, he decision was enirely he work o EPAs firs

    adminisraor, William uckelshaus.) Unorunaely,

    he hisory o agriculural use o DD and is demise

    as an effecive pes conrol echnology on crops hasbeen conflaed wih is coninued success wih mos-

    quio conrol in lesser developed counries o Arica,

    pars o Lain America, and pars o Asia. Alhough

    DD was memorialized ino inamy by achel Car-

    sons Silen Spring, i was he agriculural use o he

    chemical ha go i ino rouble, no he public healh

    use. Even so, since Carsons ime, how DD is used in

    public healh has been he key o is successul conrol

    o mosquioes where hey mater, in he house. During

    and shorly afer WWII, spraying o DD was wide-

    spread in he environmen. However, by he 1950s i

    was well known ha mosquioes resed on walls and

    ceilings o buildings. Tus, by he lae 1950s research-

    ers had already esablished he efficacy o a space

    spray, wherein only resing areas on walls would be

    reaed (Barlow and Hadaway 1956).

    o his day, he public likely does no undersand

    how DD is acually used, and hus visions o Silen

    Springdominae he conversaion. So prevalen is hemisundersanding ha a number o counries decided

    o eschew is use wih devasaing consequences

    or malarial incidence. e-adopion o he limied

    spraying o house walls was associaed wih a rapid

    decline in malarial incidence (obers e al. 1997).

    However, aerial spraying or mosquioes is sill viewed

    as effecive under cerain circumsances or some

    insec vecored diseases. Te benefis o using aduli-

    cides o conrol Wes Nile virus mosquio vecors have

    been shown o subsanially exceed coss as well as e-

    ecively proec human healh wihou adverse healh

    effecs or ecological problems rom pesicide exposure

    (Peerson e al. 2006; Davis e al. 2007; Carney e al.

    2008; Barber e al. 2010).

    Perinenly, public healh proecion specialiss

    have long known ha DD alone is no enough o

    conrol he scourge o malaria-inesed mosquioes.

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    Pest ic ides & Heal th: Myths vs . Real i t ies

    are sarling or jus our major Bel Saes alone (i.e.,

    Illinois, Indiana, Iowa, Nebraska). Economic analysis

    o labor requiremens in he absence o herbicide use

    has esimaed he need or a oal o 338 million hours

    o work by over wo million workers (Gianessi andeigner 2006). Considering ha less han 2% o he

    enire US populaion (approximaely 6 million peo-

    ple) works on arms, replacing chemicals wih people

    is no pracical.

    Perhaps jus as imporan is o quesion how peo-

    ple would are doing srenuous physical labor in he

    sun or a ypical 8-hour work day. Sun exposure may

    explain elevaed lip cancer risks, as well as he slighly

    elevaed skin cancer risk, among armers (Aquavella

    e al. 1998). Musculoskeleal healh would likely be

    seriously impaired, given he physical naure o hand-

    pulling and hoeing weeds. As evidence o such physi-

    cally adverse impacs, Caliornia insiued an admin-

    israive policy prohibiing he use o shor-handled

    hoes. Organic letuce growers rely on hand weeding

    o atain profiable producion and have peiioned

    he Sae o Caliornia agains sricer labor rules,

    osensibly because sufficienly effecive approved her-

    bicides are unavailable ( James 2005). Tus he lacko appropriae available pesicides adds o labor coss

    as i simulaneously raises he issue o hand-weeding

    labors impac on worker healh.

    Te oregoing sory o public healh benefis now

    comes ull circle, back o he hisorical roos o using

    pesicides direcly o affec insecs afflicing our bodies.

    Te flowers o chrysanhemums (specifically Chysan-

    hemum cinerariaefolium) were used in he early 1800s

    by Souheasern Europeans and Persians o produce an

    exrac called pyrehrum ha alleviaed a lice sufferers

    scourge. Tus, over a span o less han 200 years, we

    have aken and improved upon Moher Naures chem-

    isry o improve our own public healh. W hich leads o

    he nex myh abou chemical pesicides.

    eeding causes harm ha makes a ood more suscep-

    ible o ungal invasion. Cerain ungi commonly

    associaed wih crops produce mycooxins ha have

    well-documened physiological effecs in mammals,

    including humans and livesock (Marasas 2001). Al-lowing insec or plan disease injury o progress wih-

    ou proecing a crop only increases he likelihood o

    mycooxin residues. Indeed, he problems graviy is

    evidenced by an inernaional sandard or maximum

    allowable residues o mycooxins. Furhermore, he

    value o proecing crops agains direc insec eeding

    has been proven wih he adopion o corn geneically

    bred wih a gene romBacillus huringiensis(called B

    corn) o produce a very insec-specific proein ha

    kills he European corn borer. Tis insec damages

    corn and is arguably he major cause o ungal myco-

    oxin conaminaion, as damaged seed is pushed ino

    sorage. Mycooxins are considered boh human and

    livesock hazards wih carcinogenic, neurooxic, and

    eraogenic effecs. However, B corn has subsanially

    lower levels o mycooxin conaminaion han corn no

    proeced agains corn borers (Bakan e al. 2002; Wu

    2006). Tus B corn, which is regulaed as a pesicide,

    helps keep grain qualiy wihin esablished regulaorysandards ha proec agains mycooxin exposure.

    One pracical benefi o pesicide use ha is ofen

    overlooked is ied boh o public healh proecion o

    workers as well as economics o producion. Herbi-

    cides, which are used more requenly and in greaer

    quaniies han any oher pesicide class, are quickly

    applied o all kinds o crops and hus eliminae he

    need or hand labor o hoe ou weeds (Gianessi and

    eigner 2007). Hand labor is expensive, and is avail-

    abiliy is diminished by a shorage o people willing o

    become par o a migran worker culure ha moves

    rom arm o arm. One applicaion o herbicides or

    weed conrol in a single field is worh he hand labor o

    ens o hundreds o workers. Te aggregae numbers

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    ecion agains predaceous proiss or oher baceria.

    A perinen example o humans using such hazardous

    bacerial meabolies is he subcuaneous injecion or

    opical epidermal applicaion o he highly oxic bou-

    linim neurooxin, which is derived rom he anaerobic

    ood spoilage organism Colsridium boulinin; i is

    commonly used or cosmeic or correcive purposes

    (Collins and Nasir 2010).

    Te examples o aceic acid and boulinin, as well

    as oher insances o naural oxins in ood, are bu

    some examples o he many incidenal chemicals pro-

    duced by plans and/or baceria ha are quie oxic in

    high doses. Cerain ungi o he genusAspergillusgrowon cereals and produce chemicals called aflaoxins ha

    are hundreds o imes more poen han any synheic

    pesicide synhesized by humans. Ye our perspecive

    abou he risks o pesicides does no apply oAspergil-

    lus, as our concerns are ocused on he imely applica-

    ion o a ungicide on sored grainshe righ hing o

    do in order o proec ood and aver healh problems.

    Many organisms, especially plans, produce chem-

    icals incidenal o heir normal energy-producing bio-

    chemisry ha uncion o ward off predaors, proec

    seeds, or atrac insecs or pollinaion (Ames e al.

    1990a, 1990b; Ames and Gold 1997). Someimes,

    hese chemicals are jus by-producs o meabolism

    ha may serve oher purposes, or hey are perhaps

    excreory producs ha would be oxic i allowed o

    accumulae in he cells. Someimes we can only specu-

    lae abou he evoluionary role o hese chemicals.

    For example, apples conain aceic acid. Alhough is

    a naural componen o apples, he acid is neverheless

    lised as a hazardous subsance, and he MSDS sheeliss horrific adverse effecs rom exposure, including

    vomiing, diarrhea, ulceraion, bleeding rom ines-

    ines and circulaory collapse. Perhaps he evoluion-

    ary benefi o such a meabolic pahway and sorage

    in rui accrued rom he known anisepic qualiies o

    aceic acid (Levine 1940). Similarly, baceria produce

    well-known oxins ha osensibly provide some pro-

    Synthetic Chemistry for CropProtection: Humans Imitate

    Plants and Bacteria

    Myth: Synheic chemical pesicides are unnaural and canno be degraded. Tus,hey are paricularly dangerous in comparison wih naural producs derived romplans.

    Technological Reality: Weve A lways C opie dthe Good Ideas of Pl ants and Bacter ia

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    15

    Pest ic ides & Heal th: Myths vs . Real i t ies

    Humans have always used chemical echnology.

    Wheher he chemicals are made by plans, baceria,

    or by our own hands is irrelevan. Some have main-

    ained here is a difference beween chemicals rom

    he ropical rain oress and chemicals rom he gianchemical indusries. Bu principles o environmenal

    chemisry would dicae ha behavior o a chemical

    is governed primarily by hermodynamics, no how

    i was made.

    Some would say ha our coevoluion wih plans

    over many generaions has allowed us o deoxiy many

    o he naural dieary chemicals. Consider, however,

    ha many o our oods are recen invenions o selec-

    ive breeding ha sill possess he same poenially

    oxic chemicals as heir wild ancesors.

    In considering synheic pesicides, a credible

    argumen can be made or he human use o ools o

    synhesize oher useul ools, e.g., pesicides, as an

    evoluionary adapaion. Tis adapaion is analo-

    gous o he evoluion o secondary meabolic pah-

    ways in plans ha resul in biochemicals proecive

    o heir survival.

    Because chemicals produced by plans are unc-

    ional, evoluion has arguably resuled in a orm o

    chemical echnology. Trough our own chemical

    echnology, aren we jus imiaing our boanical

    and bacerial counerpars? For example, Swiss cheeseresuls rom bacerial species ha produce subsanial

    amouns o propionic acid when growing on milk

    producs. Te propionic acid is a by-produc, along

    wih he carbon dioxide ormaion ha creaes he a-

    miliar holes, bu i also suppresses prolific ungal (i.e.,

    mold) growh (Suomalainen and Mayra-Makinen

    1999). oday, humans add synhesized propionaes o

    baked goods o obain he same proecion.

    Members o indigenous culures have long used

    plans as heir medicines. Te knowledge o which

    plans o use, how o prepare hem, and he amouns

    o adminiser has been passed rom generaion o

    generaion. Isn he use o flora or our benefi, our

    survival, a orm o chemical echnology? Perhaps we

    should consider generaions o rial and error in dis-

    covering beneficial and harmul plans as analogous o

    a risk assessmen process.

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    16

    and is one environmenal oxidaion produc, DDE,

    drove i o move readily ino he amosphere. Such a

    mechanism, commonly called phase pariioning in

    he field o environmenal chemisry, was arguably he

    mos influenial process in widespread environmenal

    disribuion o DD. Unorunaely, is properies o

    persisence, along wih broad-specrum biological ac-

    iviy agains pess and beneficial insecs (e.g., preda-

    ors and parasioids eeding on he pess) alike made

    i a poor choice or use in agriculure afer WWII. Add

    he rapid developmen o insecs resisan o is effecs,

    and he sage was se or enomologisslong beore

    he publicaion o Silen Springo recommend ha i

    no be used on field and orchard crops.

    Evidence o he dynamic naure o indusrys re-

    sponse o changing pes-conrol needs, and hus is

    abiliy o synhesize and es new chemical designs, is

    a new group o chemicals called organophosphorus(OP) insecicides ha were inroduced ino commer-

    cial agriculure in he lae 1960s. Soon hereafer, a sec-

    ond group, called mehyl carbamae (CB) insecicides,

    was inroduced. OP and CB insecicides had shor

    persisence in he environmen, and a leas some

    were no quie as oxic o predaors and parasioids.

    A he very leas, hey gave growers more opions or

    Te argumens se orh in his repor by no means

    deend he properies o DD as ideal. aher, he

    aoremenioned discussion ocused on DDs effecive-

    ness in conrolling resing adul mosquioes when he

    compound is used in a very specific and locally confined

    manner inside o a dwelling. Furhermore, i is used

    no solely bu as an adjunc o pyrehroid insecicide-

    impregnaed mosquio neting. Ideally, governmen-

    unded programs o habia managemen would accom-

    pany individuals atemps a mosquio conrol.

    All chemicals have disinc physicochemical prop-

    eries ha make hem behave differenly rom each

    oher. Chemicals wih similar srucural elemens, i.e.,

    arrangemen o he same aoms, will behave similarly

    ye sill possess idiosyncraic properies. Chemicals

    having divergen srucural elemens will be even more

    unlike one anoher. Tus, o conclude ha all pesicides,

    because hey can kill pess, are jus like DD is o seri-ously lack an undersanding o basic chemisry, no o

    menion he complexiy o biochemical ineracions.

    Te specific physicochemical properies o DD

    ha made i unique were very low waer solubiliy (i is

    pracically insoluble in waer) and resisance o exen-

    sive degradaion in organisms or on plan suraces. On

    he oher hand, he very low waer solubiliy o DD

    Youve Come a Long Way, Baby

    Myth: Pesicides used oday are all jus like DD, and hus jus as dangerous. Allpesicides are alike and have no changed since DD. All synheic chemicals areequally hazardous.

    The Reality of Modern Pesticide Technology:Dynamics & Evolution

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    17

    Pest ic ides & Heal th: Myths vs . Real i t ies

    o he naural pyrehrins. By he lae 1970s, new insec

    growh regulaors were synhesized based on naural

    hormones or plan meabolies ha exhibied eiher

    juvenile hormone agonisic or anagonisic aciviy

    (Menn and Henrick 1981). Te later endeavors wereenhanced by basic research on specific biochemical

    and physiological sysems o pess. Te second orm

    o bioraional design was he combinaion o more

    radiional synhesis mehods wih he opimizaion

    o srucure-aciviy relaionships, which occasionally

    resuled in compounds ha could affec specific physi-

    ological mechanisms o insec pess. For example, an

    array o compounds have been synhesized based on

    he model compound diflubenzuron, serendipiously

    ound o inhibi he synhesis o chiin in he insec

    exoskeleon (Menn 1980). Tese ypes o compounds

    are sill being used oday, and more recen discover-

    ies o heir effecive use as ermiicides have won EPA

    Presidenial Green Chemisry Awards. Many o hese

    compounds wih effecs on specific insec physiologi-

    cal sysems could be used a low raes per acre, owing

    o heir poen effecs on he pess even beter, heir

    impacs on predaors were low, because hey have o

    be direcly eaen or maximal biological effec.Te idea o a silver bulle, as exemplified by

    DDs deploymen and overuse in agriculure, had

    disappeared rom he mindse o indusrial research

    by he mid 1980s; his was because new discoveries o

    chemicals wih compleely differen modes o acion

    coninued unabaed. Te new bevy o chemicals since

    he lae 1980s evenually were recognized by EPA as

    meeing heir crieria or reduced risk (EPA 1993).

    Tese chemicals were ulimaely used a lower use

    raes han many oher chemicals previously markeed,

    and hey were even less oxic o mammals, birds, fish,

    inegraing chemical use wih biological conrol (Sern

    e al. 1959).

    As DD and relaed compounds ell ino disavor

    in agriculure, and pressure rom regulaory decisions

    mouned, growers became heavily relian on OP andCB insecicides. Overreliance on one echnology ofen

    leads o pes resisance, bu again he dynamic naure

    o he echnology shone: Te Briish had sared work-

    ing on modiying he naural insecicidal componens

    o pyrehrum exracs, i.e., he pyrehrins, o produce

    ligh-sable compounds, and hus longeviy in he field

    beyond a ew hours. Forunaely, such compounds

    were ar less oxic han he OPs o mammals, which

    is always o concern or worker healh, as well as or

    birds. Unorunaely, fish were quie suscepible o he

    new synheic derivaive o he naural pyrehrins

    jus as hey were o he naural producs. However, he

    amouns used dropped rom wo or more pounds ap-

    plied per acre o ranges o 0.1-0.2 pounds per acre. Ap-

    propriae iming o applicaion, combined wih good

    soil managemen pracices o proec agains erosion,

    could resolve he likelihood o runoff ino aquaic hab-

    ias in sufficien quaniies or fish kills. Tus anoher

    chemical wih a differen mode o biochemical acionwas added o he growers oolbox. Unorunaely,

    overreliance on a paricular chemical again resuled in

    developmen o resisan insecs.

    By he ime o pyrehroid developmen, inseci-

    cide manuacurers had begun o ocus on he concep

    o bioraional design o chemicals wih insecicidal

    aciviy (Menn and Henrick 1981). Tis concep ook

    wo orms. Firs, naural producs wih biological ac-

    iviy could be inkered wih, alering heir srucure

    o more precisely arge heir aciviy. Developmen o

    synheic pyrehroids were iniially based on srucures

    The idea of a silver bullet, as exemplied by DDTs deployment

    and overuse in agriculture, had disappeared from the mindset of

    industrial research by the mid 1980s.

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    Youve Come a Long Way, Baby

    could be applied o a bluegrass lawn or a field o whea

    wihou damaging i. Ineresingly, dichlorophenol, a

    puaive meabolie o 2,4-D, is synhesized naurally

    by a soil ungus and is isomeric analog is used by some

    icks as a sex pheromone, as well as an an repellen bya grasshopper species (Gribble 1998). Te discovery

    o he specific biological aciviy o 2,4-D reieraes an

    imporan concep in biochemisry alluded o beore

    seleciviy. Tus, as maniesed by he aoremenioned

    evoluion o insecicide chemisry, synheic organic

    chemical herbicides invened circa WWII allowed or

    biological seleciviy beween animals and plans bu

    also wihin he Plan ingdom isel.

    By he lae 1950s, he mos inensely used pes-

    icide o all ime, arazine, was synhesized and dis-

    covered o have only one biochemical effec a field

    applicaion raesnamely, inhibiion o a paricular

    elecron accepor in Phoosysem II o plans. Ara-

    zines poency is selecively limied o broadlea weeds

    bu has no aciviy agains grasses like corn. o curail

    a long sory, herbicide synhesis coninued o produce

    compounds wih oher modes o acion specific o

    and aquaic inverebraes (able 2, Figures 2-5). Wih

    some excepions, hese chemicals ended o be more

    selecive or killing pess raher han predaors. Tus,

    even more opporuniy arose or compaibly inegra-

    ing hese new chemisries ino programs ha wouldry o deploy ecologically-based, inegraed pes man-

    agemen sraegies.

    Te hisorical use o herbicides and he evoluion

    o chemical classes parallel ha o he insecicides

    wih a major excepion. Prior o WWII, abou he only

    herbicides available ha could be pracically used on

    fields were dinirophenolic compounds like dinoseb

    and DNOC. Tese uncouplers o oxidaive phosphory-

    laion had a general mechanism o oxiciy ha made

    hem nonselecive or weeds, insecs, and ungi. How-

    ever, by he 1940s 2,4-D was discovered and ound o

    mimic he naural plan hormone auxin (indole-3-aceic

    acid), ushering in he discovery o a very specific plan

    mechanism o oxic acion. Tus, biological aciviy

    a field applicaion raes was only applicable o plans

    and no animals. Surprisingly, 2,4-D was only oxic o

    cerain dicoyledon (broadlea) plans. Tus, 2,4-D

    Table 2. Comparative mammalian toxicity of insecticides registered over the last

    decade and designated as reduced risk by EPA.

    Active

    Ingredient

    Commercial

    Formulation

    Oral LD50

    (mg/kg)

    Dermal LD50

    (mg/kg)

    NOAEL

    (mg/kg/d)

    Azinphos-methyl Guthion 4.4 155 0.149

    Chlorpyrifos Lorsban 223 222 0.03

    Acetamiprid Assail 1064 >2000 7.1

    Indoxacarb Advion 1277 >5000 2

    Pyriproxyfen Esteem 4253 >2000 35Methoxyfenozide Intrepid >5000 >2000 10.2

    Novaluron Rimon >5000 >2000 1.1

    Pymetrozine Fulfil >5000 >2000 0.377

    Spinosad Success >5000 >2000 2.7

    Rynaxypyr Altacor >5000 >5000 158

    o place he concep o reduced risk in perspecive, parameers or azinphos-mehyl and chlorpyrios are shown because hese were

    developed prior o EPAs iniiaive, saed in P Noice 93-2 (EPA 1993).

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    recepor or any ineracion o occur. In addiion o

    srucure, molecular ineracions are also influenced

    by physicochemical properies relaed o molecular

    charges and hydrophobiciy. Such ineracions oc-

    cur very readily i he srucures o a oxican and is

    recepor are highly complemenary. In such cases, he

    subsance is considered highly poen. Ineracionswould occur wih srucures no as complemenary

    only under condiions o inordinaely high oxican

    concenraions, ypically hose no likely o be ound

    in he environmen bu cerainly possible o creae

    in he lab when animals are esed. A oxican requir-

    ing exremely high concenraions in order o have

    an ineracion wih an enzyme or recepor, and hus

    cause an adverse physiological reacion, would be

    considered o have low poency. In summary, hen,

    oxiciy is a propery inheren o any molecule, allow-ing i o elici an adverse physiological response when

    an organism has specific enzymes, recepors, or oher

    macromolecules whose hree-dimensional srucures

    are complemenary.

    Te naure o undamenal hermodynamic and ki-

    neic laws governing chemical ineracions prescribes

    ha any molecule could, hypoheically, inerac wih

    Ulimaely, consumers wan o know wheher any

    echnology is sae. Te concep o chemical saey

    among regulaory oxicologiss is undersood no as a

    quaniaive uniary concep bu raher as a descripion

    o a probabiliy o a reasonable cerainy o no harm.

    Te validiy o he concep o reasonable cerainy o

    no harm, which is acually more science policy hanscience, depends on a disincion among he erms

    oxiciy, hazard, and risk. Disinguishing hese

    erms and, moreover, defining hem rom a biochemi-

    cal perspecive, is crucial or a raional argumen abou

    he naure o pesicide use in modern sociey.

    oxiciy is an inheren propery o boh a paricu-

    lar molecule (called he subsrae or ligand) and any

    organismal enzymes or recepors (issue cell macro-

    molecules) ha i can reac or inerac wih. Such in-

    eracion resuls in a physiological reacion ha couldbe inimical o he survival o an organism, and hus

    he subsrae or ligand would be called a oxican. By

    definiion, pesicides are inimical o he lives o pess,

    hus pesicides are oxicans. Te concep o inheren

    propery reers o he ac ha he hree-dimensional

    srucure o any oxican mus be complemenary

    o he hree dimensional srucure o an enzyme or

    Its Still About the Dose(and Timing)

    Myths: Exposure o pesicides resuls in adverse healh effecs. Hazards o pesicidesare equivalen o he risk o adverse effecs.

    The Reality of A Modern Biochemical Perspectiveon Toxic ity, Hazard, and Ri sk

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    I t s St i l l About the Dose (and Timin g)

    reacion o do somehing abou i? We are cauious by

    naure and hus wan o be careul when we have knowl-

    edge o poenial harm. Te problem is knowing he

    appropriae amoun o resources (financial, inellecual,

    ec.) o expend on managing wha may be only poen-ial harm, sincebecause hazard is conexuali may

    never be maniesed, or i may be maniesed only under

    he mos exreme condiions o chemical use.

    o judge jus how worried we should be abou a

    oxican in he environmen, and hereore allocae

    he appropriae atenion o is hazardousness, we

    have o undersand he risk o adverse effec. isk is

    also conexual, bu a simple definiion is he prob-

    abiliy (likelihood) ha adverse effecs would occur

    under a specific siuaion or se o condiions. Ofen,

    regulaory oxicologiss will express risk as a uncion

    o oxiciy and exposure. Tus, risk is he probabil-

    iy or likelihood ha he array o known hazards o a

    subsance will acually occur i or when an organism

    is exposed. I exposure is nonexisen, hen he likeli-

    hood o an effec is nil. I exposure does occur, hen

    he likelihood o he subsance being a hazard is con-

    diioned no only on he dose bu also on he age, gen-

    der, and healh o ha organism as well as he specificroue o exposure. Te imporan poin is ha he risk

    o adverse effecs afer exposure o a subsance may be

    low or high, depending on all he acors affecing he

    hazards o ha subsance.

    Thresholds

    Low levels o exposure, even o a highly poen

    oxican, may have a low probabiliy o causing an ad-verse effec. In any case o exposure, wheher hrough

    skin conac, inhalaion, or oral ingesion, a number o

    physiological processes occur o modulae he dose or

    concenraion o oxican arriving a he cellular level,

    and hus he probabiliy o ineracion wih enzymes

    or recepors. All o hese physiological processes ha

    deermine wha amoun o oxican arrives a he sie

    o he cell enzymes or recepors is described by phar-

    any oher molecule. However, he concenraion o he

    wo molecules mus be sufficienly high or he iner-

    acion o have any reasonable probabiliy o occurring.

    Tis later concep leads o he definiion o hazard.

    Hazard describes he poenial o a chemical o causeharm under a paricular se o condiions. In oher

    words, oxicans are no inherenly hazardous unless

    he conex is conducive o he sufficien ineracion o

    he oxican wih he paricular enzymes or recepors

    o which i is complemenary. o sudy how chemicals

    inerac wih organisms, scieniss in he laboraory

    always creae condiions in which he subjec chemical

    will be hazardous. Ofen he condiions are concen-

    raions (or doses) o chemical sufficien o cause an

    observable response in a es populaion o organisms.

    I he condiions o he exposure change (or example,

    using a very low dose) hen he hazard may change or

    simply disappear alogeher.

    Experimens repeaedly show ha naural and

    synheic subsances a one dose may have no adverse

    effecs on an organism, bu a anoher higher dose can

    cause harm. Tis concep, requenly called he dose

    makes he poison, is he undamenal principle guid-

    ing oxicological sudies, and i is discussed in all basicoxicology exbooks. O course, ha popular oxico-

    logical aphorism belies more complex ineracions

    beween a subsance and is effecs on an organism.

    Te dose required o cause deleerious effecs wihin

    a populaion o organisms can vary depending on he

    roue o exposure (oral, dermal, or inhalaional), he

    lengh o ime over which i is adminisered (acue

    versus chronic), and he age, sex, and healh o an or-

    ganism. Neverheless, he appearance or magniude o

    an effec o any subsance is ied o is dose. Hazard,

    hereore, can be hough o as a subsances dose-rela-

    ed array o possible deleerious effecs on an organism

    o a specific age, gender, and healh saus exposed via

    oral, dermal, and/or inhalaional pahways.

    Should he knowledge ha a subsance is hazard-

    ous, i.e., poenially harmul under a specific se o cir-

    cumsances, precipiae a corresponding (and urgen)

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    Pest ic ides & Heal th: Myths vs . Real i t ies

    esearchers sudying he ineracion o oxicans

    wih whole animals (in vivosudies) or wih animal

    issues, cells, and macromolecules (in viro sudies)

    atemp o esablish a hreshold or a physiological or

    biochemical reacion. Tey use a wide range o doses(exposures) and concenraions. Te hreshold is

    ofen repored as an empirical dose level in which no

    observable adverse effec (i.e., he NOAEL) occurs.

    o deermine he NOAEL, however, he researcher

    mus expose an animal o sufficienly high concenra-

    ions o see wha a ypical response looks like. Te

    dose jus causing a reacion is called he LOAEL

    (lowes observable adverse effecs level). For any

    one specific response, he proporion o animals re-

    sponding orms a monoonic uncional relaionship

    wih he dose ha is mahemaically depiced as an

    S-shaped curve (Figure 6). For any effec, hereore,

    he researcher can esimae he proporion o he

    populaion responding o a paricular dose. Similarly,

    he researcher can esimae when no responses in a

    populaion will occur.

    macokineics. Pharmacokineic sudies examine rae

    and exen o chemical upake processes ollowing

    dermal, oral, and inhalaional exposures. Te amoun

    o oxican enering ino he sysemic circulaion

    (bloodsream) is sudied and hen ollowed o issubsequen disribuion among all body regions down

    o he cellular level. Te oxican amoun changes as i

    is degraded by enzyme sysems and excreed (some-

    imes unalered) rom he body. Whaever oxican

    is lef over rom all hese pharmacokineic processes

    arrives a he sie o he poenial enzymes or recep-

    ors complemenary enough in srucure o have any

    probabiliy o ineracion. Te specific ineracions are

    called pharmacodynamics.

    Te combinaion o pharmacokineic processes

    and he kineics o pharmacodynamic ineracions

    may resul in adverse physiological effecs. Generally

    speaking, he physiological sysems mos ofen sud-

    ied are he nervous and endocrine sysem, alhough

    he immune sysem is necessarily included because

    hese hree sysems communicae wih one anoher.

    Te relaionship can be expressed as he numbers responding o any given dose meric. I he numbers are ransormed o he cumulaive

    proporion (i.e., percen) o he populaion responding, hen an S-shaped curve resuls, which can be described by a logisic mahemaical

    uncion. A some dose, no measurable response is observed, and his dose is designaed he no observable adverse effec level (NOAEL)

    or concenraion (NOAEC). Te LOAEL represens he dose a which an adverse effec is saisically significanly differen rom he

    response in he conrol. Te LD50 and ED50 represen he median response in he populaion (i.e., 50% response) or eiher lehaliy

    (L) or any oher measured response (E).

    Dose (mg/kg)or Concentration (mg/L)

    NumbersResponding

    50% Response (median)

    PopulationResponse

    (Cumulative%)

    Dose (mg/kg)or Concentration (mg/L)

    100%

    50%

    0%

    Slope

    LOAEL

    NOAEL

    LD50

    ; LC50

    ED50

    ; EC50

    Figure 6. Typical monotonic relationship between increasing dose

    (or concentration) and population response.

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    I t s St i l l About the Dose (and Timin g)

    cal exposure in he environmen (i.e., ouside o he

    laboraory).

    In summary, hen, he oxiciy o a chemical is an

    inheren propery relaed o is srucural abiliy o in-

    erac wih some complemenary enzyme or receporin a cell. I he srucures are highly complemenary,

    such ha he probabiliy o ineracion is high, hen he

    oxican is considered highly poen; bu i srucural

    complemenariy is low, he oxican has low poency.

    egardless o poency, pharmacokineic processes

    modiy he probabiliy o pharmacodynamic inerac-

    ions, and hus all oxicans have hresholds or an

    effec. Perinenly, hese ineracions and hresholds

    apply o all chemicals, naural and synheic, because

    all are under conrol o he undamenal laws o her-

    modynamics and kineics.

    Te ype o experimen ha allows consrucion

    o he aoremenioned dose-response curves and de-

    erminaion o a no-effecs hreshold alls under he

    rubric o regulaory oxicology. Tese experimens

    are mos useul or assessing risk o an adverse effecollowing exposure under environmenal condiions.

    Furhermore, experimens ha atemp o define a

    hreshold or an effec are quie differen in objecive

    han experimens ha are designed o undersand

    he mechanism o an effec. Tese later experimens

    dominae he published oxicology lieraure oday.

    However, hose experimens necessarily use high

    enough doses so ha an effec is always maniesed

    and can hereore be sudied. Alhough inormaive

    rom he perspecive o a basic biochemical under-

    sanding, mechanisic experimens are no very useul

    or characerizing he risk o effecs ollowing chemi-

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    consrained by undamenal laws o hermodynamics

    and kineics. More specifically, over he las several

    decades, oxicological ocus has shifed rom carci-

    nogenic responses o endocrine sysem responses.

    Whereas he 1950s hrough he 1980s ocused on car-cinogenic mechanisms largely ied o ineracions wih

    he genome, during he ime beween he lae1980s

    and now, ocus has shifed o chemicals (synheic and

    naural) and heir ineracions wih recepors o he

    endocrine sysem. A firs, he esrogen recepor, ow-

    ing o inense ineres in reproducive biology, was he

    objec o mos scruiny, bu now he esoserone (i.e.,

    androgen) and hyroid recepors have been hrown

    ino he mix.A handul o sudies puaively indicaing ha

    chemicals a very low levels o exposure could resul in

    endocrine-mediaed aleraions in issues o neonaal

    rodens, especially male prosae gland srucure, sug-

    gesed ha a new perspecive on oxicans was needed

    (vom Saal e al. 1997). O course, ones percepion

    o wha consiues a low dose requires empering

    by how he dose is adminisered and a query as o

    In he hisory o biology, hose remembered by

    poseriy are individuals who have creaed a paradigm

    shif in hinking abou undamenal lie processes.

    Perhaps a he pinnacle o paradigm shifers is Charles

    Darwin. Indeed, an ofen-quoed paraphrase is noh-ing in biology makes sense excep in he ligh o evolu-

    ion (Dobzhansky 1964), and o course we have Dar-

    win o hank or generaing a line o inquiry leading o

    he modern heory o biological evoluion. Cracking

    he geneic code, ollowing he discovery o he sruc-

    ure o DNA, resuled in a plehora o new mehods o

    sudy how lie works a he molecular level. O course,

    as we sudy differen levels o organizaion, rom cells

    o issues o organs o whole organisms, new proper-ies emerge ha are increasingly difficul o describe in

    simple molecular erms.

    In he conex o biological hisory, perhaps we

    shouldn be surprised ha some researchers would

    enjoy being called paradigm shifers. However, chang-

    ing he ocus o sudy rom one physiological sysem

    o anoher is no a paradigm shif, because all possible

    ineracions o oxicans in he new sysem are sill

    Endocrine Disruption:Is It Just Hormonal?

    Myth: Consideraion o endocrine disrupion changes he paradigm o wha weknow abou pesicide effecs. Dose makes he poison is no longer relevan because

    pesicides affec he endocrine sysem a levels equivalen o environmenal exposures.

    The Reality:Confusion Between a Changing Paradigmand a Shift in Focus, Away from Cancer, to a DifferentPhysiological System

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    Endocrine Disrupt ion: Is I t Jus t Hormonal?

    are incredibly low i he ligand concenraion is low.

    Similarly, ligand-recepor ineracions are reduced

    and slowed down as a chemicals poency decreases

    (Figure 9). Tereore, no paradigm has really shifed.

    ecall he premise ha mechanisic sudies are no de-

    signed o show he hreshold level o plausible effecs.

    Ye reexaminaion o Figure 7 does show a definiive

    hreshold (i.e., a 0.002 g/kg), even or he drug DES,

    arguably o similar or greaer poency o esrogen in

    binding o he esrogen recepor (Okluicz and Leavit

    1988; Hendry e al. 1999, 2004).

    wheher he specified dose was chosen, because any

    dose lower would no resul in he measured effec a

    all. In addiion o observaions o a sligh difference in

    male prosae gland weigh beween dosed and conrol

    animals (vom Saal e al. 1997), as one example o anendocrine sysem paradigm-changing effec, he dose-

    response relaionship accompanying he observaion

    was nonmonoonic. In oher words, he observed e-

    ecs on gland weigh did no vary in a locksep linear

    ashion wih increasing doses (Figure 7). Te high-

    es dose caused loss o gland weigh and mid-doses

    caused increase in gland weigh. Te validiy o he

    conclusions o hese early repors has been quesioned

    on grounds o saisical inadequacies (Haseman e al.

    2001) or have been judged inconclusive, imprecise,

    and o uncerain biological relevance (Melnick e

    al. 2002). Neverheless, he problem in inerpreing

    nonmonoonic responses arises when wo differen

    physiological phenomena are acually being measured

    by he same endpoin, such as gland weigh changes.

    For example, no pahology oher han gland weigh

    changes may occur a low doses, bu a high doses

    oxiciy may se in and gland weigh changes are ac-

    ually due o a differen phenomenon, such as grealyincreased cell deah.

    egardless o he cause o a nonmonoonic re-

    sponse (assuming he same physiological response is

    acually being measured on each side o he dosage

    range), recepor (e.g., esrogen recepor) ineracions

    wih ligands (e.g., esrogen or a oxican) are governed

    by he principles o biochemical kineics. Tus, he

    paradigm has no shifed; concenraion o he ligand

    sill influences recepor-ligand complexaion. ineic

    analyses o molecule-molecule ineracions can show

    he probabiliy o hose ineracions as a uncion o

    dose (or concenraion). An illusraion o his con-

    cep can help dispel he myh ha low doses rom

    environmenal exposures o hormonally acive agens

    are inordinaely hazardous. Tus, Figure 8 shows ha

    ligand-recepor complexes, he kineic mechanism ini-

    iaing a hormonally induced physiological response,

    140

    120

    100

    80

    60

    40

    20

    00 0.002 0.02 0.2 2 20 200

    ProstateGlandChange

    RelativetoControl(%)

    Diethylstilbestrol Dose (g/kg body weight)

    A A

    B

    B

    B AB

    C

    DES, a drug given o reduce miscarriages during he 1960s, and

    also used as a simulaory hormone in catle eed, has a poency

    similar in magniude o ha o esradiol. Tis graph is based

    on he one presened in vom Saal e al. (1997) ha arguably

    iniiaed concerns abou nonmonoonic effecs o hormonally

    acive agens. Te daa are shown as percenage change in gland

    weigh relaive o he conrol (100%), and he graph has been

    rescaled o sar rom zero change. Bars wih he same leters

    are no significanly differen rom one anoher (probably