here - Perishable Pundit

Embargoed (until July 15, 2010)Expert Panel ReportA Review of the Scienceon the PotentialHealth Effects ofPesticide Residueson Food and RelatedStatements Made byInterest GroupsAuthors:Penny Fenner-Crisp,EPA, RetiredCarl L. Keen,University of California, DavisJason Richardson,Robert Wood Johnson Medical SchoolRudy Richardson,University of MichiganKarl Rozman,University of Kansas2010

IntroductionAn expert panel was formed at the request ofthe Alliance for Food & Farming, a consortiumrepresenting growers in California. The panelwas formed to evaluate the scientific validity ofcertain materials prepared by the EnvironmentalWorking Group (EWG) and the Organic TradeAssociation (OTA) regarding the health effectsof pesticide residues on food and the nutritionalquality of organically grown food versusconventionally grown food.The panel included five respected scientistsfrom diverse backgrounds, including:• Dr. Penny Fenner-Crisp, U.S. EnvironmentalProtection Agency, RetiredThe panel was commissioned by the Alliancefor Food and Farming, but the sponsor did notparticipate in the production of this report. Thepanel met by conference call once to discuss abriefing prepared by the sponsor’s consultantand held a meeting in San Jose, California inAugust of 2009. At the San Jose meeting, threeof the panelists participated in person and twoparticipated by teleconference. Representativesof the sponsor observed the meeting, but werenot active participants.An outline of a consensus statement was draftedat the San Jose meeting. Subsequently drafts ofthis report were distributed to panelists until afinal version was agreed upon by all panelists.• Dr. Carl L. Keen, University of California,Davis, Department of Nutrition• Dr. Jason Richardson, Robert Wood JohnsonMedical School, Environmental and HealthSciences Occupational Institute• Dr. Rudy Richardson, University of Michigan,Environmental Health Sciences• Dr. Karl Rozman, Kansas University MedicalCenter, Pharmacology, Toxicology & TherapeuticsAttachment A provides biographical sketchesof the panelists. The panel included fourtoxicologists (Drs. Fenner-Crisp, J. Richardson,R. Richardson, and Rozman) and a nutritionist(Dr. Keen).3

BackgroundEWG recently distributed an updated “Shopper’sGuide to Pesticides” that lists 47 fruits andvegetables of which the top 12 commoditieswere shown to have the highest detection rates/numbers of pesticide residues (the “dirtydozen”). The Guide also includes the “Clean15,” a subset of the 47 commodities whichwere shown to have the lowest levels/numbersof pesticide residues. The Guide is available insupermarkets across the country and also canbe downloaded from an EWG-affiliated website(www.foodnews.org).The Guide includes a brief description of themethodology used to construct the list. A relatedEWG website contains slightly more informationon the basis for the list, including a list ofpublished references that were presumablyused in its development. The site contains tworelevant documents including a “Methodology”piece that presents a cursory description ofEWG’s methods for selecting the 47 commoditiesand a “How to Reduce Exposure” section thatincludes additional information about healthimpacts, including a list of citations that EWGalleges supports its claims.EWG’s “dirty dozen” list is as follows (startingwith the “worst”):1. Peach2. Apple3. Bell pepper4. Celery5. Nectarine6. Strawberries7. Cherries8. Kale9. Lettuce10. Grapes (imported)11. Carrot12. PearEWG’s “Clean 15” includes (starting withthe best):1. Onion2. Avocado3. Sweet corn4. Pineapple5. Mango6. Asparagus7. Sweet peas8. Kiwi9. Cabbage10. Eggplant11. Papaya12. Watermelon13. Broccoli14. Tomato15. Sweet potatoEWG assembled the list by analyzing databasesof pesticide residue measurements collected bythe U.S. Department of Agriculture (USDA) inits Pesticide Data Program (PDP) and theRegulatory Monitoring Program and Total DietStudy of FDA’s Center for Food Safety andApplied Nutrition.Within the EWG’s report, the discussion of theputative health effects of pesticide residues isvery limited, and thus difficult to criticallyevaluate. The only reference to this topic is theintroductory paragraph in the Shopper’s Guidewhere EWG states:“The growing consensus among scientistsis that small doses of pesticides and otherchemicals can cause lasting damage tohuman health, especially during fetaldevelopment and early childhood. Scientistsnow know enough about the long-termconsequences of ingesting these powerfulchemicals to advise that we minimize ourconsumption of pesticides.”4

The above statement does not include anycitations, thus complicating a direct evaluationof its relevance with respect to the amounts ofresidues that have been reported to be presenton the foods listed on the dirty dozen list.Another statement in the “How to reduceexposure” piece states that:“Even in the face of a growing body ofevidence, pesticide manufacturers continueto defend their products, claiming that theamounts of pesticides on produce are notsufficient to elicit safety concerns. Yet,such statements are often made in theabsence of actual data, since most safetytests done for regulatory agencies are notdesigned to discover whether low doseexposures to mixtures of pesticides andother toxic chemicals are safe, particularlyduring critical periods of development. Ingeneral, the government demands, andcompanies conduct, high dose studiesdesigned to find gross, obvious toxiceffects. In the absence of the appropriatetests at lower doses, pesticide and chemicalmanufacturers claim safety since the fulleffects of exposure to these mixtures ofchemicals have not been conclusivelydemonstrated (or even studied).”The most relevant points in this section are thecontentions that studies do not exist on lowdoses of pesticides and pesticide mixtures, bothof which are addressed later.The “How to Reduce Exposure” piece alsoraises issues associated with increasedvulnerability of children and criticism of theEnvironmental Protection Agency’s (EPA’s)regulation of pesticides.Similar to EWG, the Organic Trade Association(OTA) has made statements about the healtheffects of pesticide residues. The OTA focuseson the potential effects of these residues onchildren 1 :“In the past decade, research and analysishas shown that children may be muchmore at risk than adults for pesticideexposure, and may suffer greater harm tohealth and development from exposure.Yet standards for safety and tolerance limitsfor these chemicals rarely include adequateconsideration of risks to children.Recent laws now mandate factoring inthese risks and re-evaluating safety limits,but the wheels of re-evaluation have turnedvery slowly. [Note: OTA infers that this taskhas not been completed. However, it is inerror here. The re-evaluation of existingtolerances mandated by FQPA in 1996was completed in 2008]. Organic foods,therefore, may be especially important tomore fully protect children from the risksof exposure, even when pesticide levels infoods are within existing legal limits.Why are children at greater risk? First, theyingest more food and water per pound ofbody weight than adults, so any exposureis greater in proportion to their size.Second, these chemicals may be moreharmful to developing organs and bodilysystems, including neurological andreproductive systems, than they are tomature bodies.In a study published in May 2002 in FoodAdditives and Contaminants, organic foodswere shown to have significantly lowerpesticide residues than conventionally1See http://organicitsworthit.com/environment.html.5

grown foods (for a number of reasons, suchas persistent residues in soil that last formany years, some organic foods may stillshow residue).Other studies show the environmentalbenefits of organic agriculture to air, soiland water, lowering the total toxic burdento our ecosystems. As demand for organicfoods continues to grow, more farmers arelikely to view organic methods as a viableand marketable option, helping to stabilizesupply and price.2. The link between pesticide residues on fruitsand vegetables, and health effects, including:a. Scientific evidence linking pesticideresidues and health effectsb. The adequacy of the U.S. regulatory systemfor protecting against harmful levels ofpesticide residues, including effects toinfants and children.3. The evidence that organic foods have agreater nutritional quality than conventionallygrownfoods.It adds up to an evolving landscape thatincreasingly allows for--and makes acompelling and credible case for--includingorganic foods in children’s diets wheneverpossible. As concerned parents, teachers,administrators and foodservice professionalscreate and insist on innovation and reformin school lunch programs, organic foodsmake sense as part of the picture.”Regrettably, citations to scientific studies werenot provided in the above to support thesestatements, complicating their criticalevaluation.OTA has an additional document on pesticideexposures and children that focuses on studiesthat find lower pesticide exposures for thosethat have organic diets and cites several studiesthat conclude that there health effects associatedwith pesticide use for farm workers.Charge to the PanelThe panel was asked to address the followingissues:1. The basis for the EWG ranking of thecommodities by pesticide residue levels/numbers to come up with the list of 47 fruitsand vegetables, including the “dirty dozen.”Charge Question #1 – Is the basisfor selecting the “dirty dozen”scientifically sound?EWG briefly describes its methodology forselecting the list of 47 fruits and vegetables,including the “dirty dozen” on the“Methodology” portion of its Shopper’s Guideto Pesticides webpage. Data from the U.S.Department of Agriculture (USDA) PesticideData Program (PDP) and the Food and DrugAdministration’s (FDA) Pesticide RegulatoryMonitoring and Total Diet Study Programs wereused as the basis for characterizing the numbersand levels of residues of pesticides on thecommodities. EWG focused on the 47 fruitsand vegetables that were “reported eaten on atleast one tenth of one percent of all ‘eatingdays’ identified in the 1994-1996 USDA foodconsumption survey and with a minimum of100 pesticide test results from the years 2000 to2007.” EWG considered six measures ofcontamination on commodities:1. Percent of samples tested with detectablepesticides2. Percent of the samples with two or morepesticides3. Average number of pesticides found ona sample4. Average amount of all pesticides found6

5. Maximum number of pesticides foundon a single sample6. Number of pesticides found on thecommodity in totalEWG assigned each commodity a score of 1 to100, with 100 being the worst. However, thedetails on how the scoring for each of the sixmeasures was integrated into a composite scoreare not provided. Thus, the scores cannot bereadily reproduced.It is also unclear if EWG weighted the sixmeasures in any way. However, an idealweighting would place more emphasis on theconcentrations of the residues that weredetected, which appears to only be a part ofcriterion #4. Merely detecting a residue doesnot provide an adequate scientific basis forjudging whether or not there are potentialhealth effects.The Panel attempted to reproduce the EWGassessment, using the USDA PDP and FDAPesticide Residue Monitoring Program 2 datafrom 2000-2007. If one were to assemble a listof the commodities with the highest rankings,giving equal weight to each of the six measures,the ordering of the 47 commodities on the EWGlist appears reasonable, although a fewdifferences could occur with different (andequally arbitrary) assumptions.The Panel’s principal criticism of the list is thatthere was no attempt to consider the toxicityprofile of individual pesticides or to assess risk.Characterization of potential risk is the key tounderstanding if there should be any publichealth concern about health effects due to thepresence of pesticide residues in food. Inaddition to having information on the levels/numbers of pesticides on the commodities, it isnecessary to consider information on thetoxicity of the pesticides. A more scientificallysoundapproach would be to integrate the dataon the levels of residues (more than in just oneof six measures) with data on toxicity of thedetected pesticide(s). As it stands now, the EWG“dirty dozen” provides no basis to assess orunderstand the potential for risk.Furthermore, given the widespread mediaattention devoted to the list, it is disconcertingthat EWG has not to date shared its algorithmwith the scientific community or the public orsubjected it to an outside expert peer review, asit often demands of the regulatory agencieswhose activities it tracks.Charge Question #2 – Is there ascientific link between pesticideresidues on food and healtheffects, and is the U.S.regulatory system adequatefor limiting harmful levelsof pesticides on food?BackgroundThis section addresses the scientific evidenceon the question of whether pesticide residueson food are harmful to human health and therelated question of the adequacy of the U.S.regulatory system for limiting harmful levels ofpesticides on food.The Environmental Working Group (EWG) hasmade several claims about health effects as partof their “dirty dozen” campaign. One key quotefrom EWG’s materials is:2http://www.fda.gov/Food/FoodSafety/FoodContaminantsAdulteration/Pesticides/ResidueMonitoringReports/ucm125187.htm#fig1-06.7

“The growing consensus among scientistsis that small doses of pesticides and otherchemicals can cause lasting damage tohuman health, especially during fetaldevelopment and early childhood.Scientists now know enough about thelong-term consequences of ingesting thesepowerful chemicals to advise that weminimize our consumption of pesticides.”(EWG, undated)In addition, EWG argues that toxicity testingrequired by EPA for pesticides is “not designedto discover whether low dose exposures tomixtures of pesticides and other toxic chemicalsare safe, particularly during critical periods ofdevelopment.” (EWG, undated)The Organic Trade Association (OTA) focuseson potential effects for children and argues thatEPA’s toxicity testing requirements areinadequate: “Yet standards for safety andtolerance limits for these chemicals rarelyinclude adequate consideration of risks tochildren. 3 ”General Science of Pesticide ResidueHealth StudiesLittle published research directly addresses thepotential health effects of exposures to pesticideresidues in the diet. For example, epidemiologicstudies that compare populations with differentlevels of pesticide dietary exposures are lacking.The vast majority of studies to date that haveexamined the potential for health effectsresulting from pesticide exposure in childrenare in populations with higher (and, primarily,non-dietary) exposures than the generalpopulation, including children of farm workersand pesticide applicators (Arcrury et al., 2007;Eskenazi et al., 2004), as well as childrenexposed through repeated indoor pesticideapplication (Berkowitz et al., 2004). Of thesestudies, most have focused on theorganophosphate pesticides (e.g. chlorpyrifosand diazinon) and found that the levels thatthese populations were exposed to were muchhigher than the general population. Based ondata from NHANES, the median level of theprimary metabolite of the pesticide chlorpyrifos,TCP, in the urine is 1.7 μg/L, whereas medianlevels of TCP in the more highly-exposedpopulations are 45%, 94%, and 341% greaterthan the NHANES values (Arcrury et al., 2007;Eskenazi et al., 2004; Berkowitz et al., 2004).This comparison suggests that the predominantsources of exposure in these studies are fromnon-dietary sources.The lack of published literature on health effectsarising directly from pesticide residues in foodwould seem to be evidenced in the fact thatneither EWG nor OTA cite a single study thatspecifically examines exposure via this pathway.Most of the studies that EWG and OTA citeaddress exposures as a consequence ofoccupational activities or in environments at/near application sites (e.g., Andersen et al.,2008; Garry et al., 2002; Hoppin et al., 2006).These scenarios generally result in exposuressubstantially greater than dietary exposures. Forexample, in EPA’s chlorpyrifos risk assessment,the Agency estimates that the short-term dermalexposure for an aerial applicator to be 50 µg/kg/day with an absorbed dose of 1.5 µg/kg/day,assuming a 3% dermal absorption (EPA, 2006).The estimated inhalation exposure is 0.7 µg/kg/day for a total dose estimate of 2.2 µg/kg/day.By comparison, the estimated chronic dietaryexposure is 0.0008 µg/kg/day and the estimatedacute dietary exposure is 0.02 µg/kg/day. Thus,the estimated occupational exposure estimateis between 100-3000 times higher than theestimated dietary exposure. Given that EPAuses the 99.9th percentile for acute dietaryexposure estimates and the 50th percentile forchronic dietary and occupational exposureestimates, the higher end of the range (3000) islikely the more accurate.3See http://organicitsworthit.com/environment.html.8

Only one study cited by EWG is centered ondietary exposure (Petersen et al., 2008), but itfocuses on polychlorinated biphenyls (PCBs)and methyl mercury (neither of which arepesticides) and only secondarily addressesoccupational exposure to pesticides. Otherstudies cited by EWG focus on non-pesticidessuch as PCBs, phthalates and dioxins (Lundqvistet al., 2006; Stewart et al., 2008; Swan et al.,2005).There is a substantial literature on the healthbenefits of consuming fruits and vegetables.Numerous published studies show that theconsumption of fruit and vegetable-rich diets isassociated with a reduced risk for high bloodpressure; reduced risk of heart disease, stroke,and probably some cancers; and a lower risk ofocular and digestive problems 4 (e.g., Law et al.,1998; Liu and Russell, 2008; Joshipura et al.,1999; Appel et al., 1997).Individuals who consume large amounts offruits and vegetables likely have higher dietaryconsumption of pesticides, compared toindividuals with lower fruit and vegetableconsumption 5 . Of course, the research showingthe positive effects of fruit and vegetableconsumption does not shed much light on thequestion of whether or not the presence of lowlevels of pesticide residues may detract from, orhave no impact on, the beneficial effects ofconsuming these foods. However, it stronglysupports the hypothesis that some of the allegedadverse effects of dietary consumption of lowlevel pesticide residues are not of the samescale as the beneficial effects of consumingfruits and vegetables; otherwise, the adverseeffects from dietary pesticide consumptionwould be evident in these studies.EPA’s Regulatory ProcessWhile there is little scientific literature thatdirectly addresses potential adverse effects frompesticide exposures in the diet, the safety of theU.S. food supply with respect to pesticideresidues can be evaluated by examining EPA’sregulatory process.Some of the most important points about EPA’sregulatory process include:• EPA requires more toxicity testing forpesticides used on food than any use categoryof chemicals.• The development of toxicity reference levelsfor pesticides representing a “reasonablecertainty of no harm” includes theincorporation of uncertainty factors that serveto achieve this regulatory standard. Typically,assessments include at least a 10-folduncertainty factor for extrapolating fromanimals to humans, and a 10-fold factor forintraspecies variability, unless empirical dataare available to show a different factor betterreflects the data at hand. Furthermore, EPA,when establishing tolerances (the legal limitson foods) must include an additional 10-foldsafety factor for infants, children or fetusesunless there is convincing evidence that adifferent factor is appropriate.• As a default, cancer risk is evaluated using alinear, no-threshold model and a 1 in amillion acceptable risk level, unless theavailable data support the use of a margin-ofexposureapproach.• For acute exposures, EPA bases the assessmenton the 99.9th percentile of exposure fordifferent subpopulations, which is greaterthan the percentiles typically used in riskassessments in other EPA programs.4http://www.hsph.harvard.edu/nutritionsource/what-should-you-eat/vegetables-and-fruits/.5It is true that an organic diet will lead to lower pesticide residue consumption. However, only a relatively small fraction of the populationconsumes only organic food and many of the studies showing the benefits of fruits and vegetables contain subjects for which organic dietswere not available for most of their lives.9

• EPA is obligated to assess the aggregate risk toa single pesticide from all dietary and nonoccupationalexposures when decidingwhether or not to approve a new or continueduse on a single commodity.• EPA also must evaluate the combined riskassociated with pesticides and othersubstances to which the general populationmay be exposed that have a commonmechanism of toxicity using cumulative riskassessment methods. To date, the members ofgroups of organophosphate, N-methylcarbamates, chlorotriazine, and chloracetanilidepesticides have been assessed. A large groupof synthetic pyrethroid insecticides arecurrently undergoing evaluation.In accordance with the mandates of the FoodQuality Protection Act of 1996, EPA’s updatedrisk assessments have resulted in the reductionof use rates, numbers of allowable uses, andthe cancellation of all registrations of manychemicals and product formulations.The U.S. Department of Agriculture (USDA)manages a monitoring program which measureslevels of pesticide residues on a wide variety offoods. The Pesticide Data Program (PDP) dataindicate that pesticide residues measured ondomestic and/or imported commodities rarelyexceed EPA tolerances, and, generally, are oneor more orders of magnitude below the legallimit. In 2007, residues exceeding the EPAtolerance were detected in only 0.4% of 11,683samples (USDA, 2008). While it would bedesirable to further limit the already smallnumber of samples that have residues exceedingtolerances, it is important to note that thetoxicity of a pesticide does not factor intoestablishing a tolerance, and the tolerance levelrepresents an exposure that is often substantiallyless than levels shown to cause effects in animaltesting.Summary Conclusions forCharge Question #2The Panel’s summary conclusions include:1. Pesticide residues on food represent a smallexposure compared to occupationalexposure. There are no studies that specificallylink pesticide residues in the diet with healtheffects. Those epidemiologic studies thatposit a link to health effects evaluatepopulations living in primarily agriculturalenvironments and who are also exposed viaother pathways. However, even these studiesare insufficient to establish causalrelationships. The exposures of these subjectsare primarily from pathways in addition tofood, with these pathways accounting formuch higher levels of exposure. These studiesare not capable of assessing any contributionthat pesticide residues in the diet may maketo the risk of exposure to these substances.2. EPA has adopted a public health protectiveapproach to ensure “a reasonable certaintyof no harm” (the legal standard mandated inFQPA) from consuming pesticide residueson food. It incorporates the most sophisticated,data-rich set of risk assessment methods thatEPA conducts. Contrary to OTA’s assertion,the process explicitly considers infants,children and pregnant women and has anadded layer of protection for thesesubpopulations. While there will always besome uncertainty associated with evaluatingthe possibility of small health risks, theavailable scientific evidence shows that EPA’sprocess is appropriately and adequatelyhealth-protective.3. EWG states that there is a “growing consensusamong scientists” “that small doses ofpesticides and other chemicals can causelasting damage to human health, especiallyduring fetal development and earlychildhood.” If “small doses” is understood tomean the doses one receives from pesticideresidues in food, this statement is not supportedby the existing scientific evidence.10

4. The EWG has provided a list of scientificpublications to justify their claims abouthealth effects of pesticide residues. None ofthe papers cited differentiated dietaryexposures from other pathways. Therefore,none of the studies is sufficient to draw aconclusion that there are adverse healtheffects associated with pesticide residues onfood.5. EWG states “Scientists now know enoughabout the long-term consequences ofingesting these powerful chemicals to advisethat we minimize our consumption ofpesticides.” The Panel agrees that pesticideintake should be limited; it is the opinion ofthe Panel that EPA does a sound job inlimiting it to levels meeting the “reasonablecertainty of no harm” FQPA standard.6. EWG implies that toxicity tests are inadequate.In contrast to this idea, the Panel notes thatEPA requires more data for pesticides residueson food than for chemical in other usecategories. Contrary to EWG’s assertion,these studies must include at least one dosethat shows no effects. If the study results donot reveal a no-effect level, then either thestudy must be repeated until a no-effect levelis identified or have an additional uncertaintyfactor applied to the lowest dose showingminimal effects, yielding a surrogate noeffectlevel. There is also a requirement fordevelopmental neurotoxicity testing, designedto assess the potential for neurological effectson developing fetuses and children, for thosepesticides known or suspected of possessingneurotoxic potential.Charge Question #3 – Is therea difference in the nutritionalquality of organically-grownfood compared to food grownusing conventionalagriculture?There is a perception among many consumersthat organically-grown food is nutritionallysuperior in some respects to food grown withconventional agriculture. Two hypotheses havebeen put forward to explain the potentialdifferences. One hypothesis is thatconventionally-grown plants have morenitrogen available to them through the use ofsynthetic fertilizers. As a consequence, theresources of the plants are diverted towardssupporting growth resulting in a decrease in theproduction of plant secondary metabolites suchas organic acids, polyphenolics, chlorophyll,and amino acids, all of which may have somenutritional benefit (Winters and Davis, 2006).Another hypothesis is that organic productionmethods lead to greater stresses on plants. Astressed plant then may expend more resourcesin the synthesis of its own chemical defensemechanisms, which, in turn, may yieldsubstances which would not have positivenutritional effects (Winters and Davis, 2006).Generally, controlled studies have shown mixedresults. Some support the conclusion thatorganic production methods lead to increasesin nutrients. Other studies show no demonstrabledifferences. A recent analysis conducted by theLondon School of Hygiene & Tropical Medicineprovides a comprehensive review of theavailable literature (Dangour et al., 2009). Theauthors identified 46 studies with sufficientdocumentation and quality upon which theyperformed a systematic review. Elevennutritional categories were evaluated. Thenitrogen content of conventionally-grownplants was higher, and the phosphorus andtitratable acidity levels were higher fororganically-grown plants. These differenceswere considered biologically plausible due to11

differences in fertilizer use (nitrogen andphosphorus) and ripeness at harvest (titratableacidity). There was no difference for theremaining eight categories, including some keyones, including Vitamin C, phenolic compounds,magnesium, calcium, potassium, zinc, totalsoluble solids, and copper. The authorsconcluded that:“The current analysis suggests that a smallnumber of differences in nutrient contentexist between organically and conventionallyproduced foodstuffs and that, whereasthese differences in content are biologicallyplausible, they are unlikely to be of publichealth relevance.”The authors encourage more research in this area.The Scientific Status Summary on OrganicFoods from the Institute for Food Technologists(IFT) echoes the conclusions of the Londonreview (Winters and Davis, 2006). The IFTSummary discusses a variety of issuessurrounding organic foods, including: (1) levelsof pesticides, (2) nutritional value, (3) naturallyoccurring toxins, and (4) microbiological safety,and includes a summary of a number of keystudies comparing organic and conventionalfoods with respect to nutrient levels.The IFT Summary states:In some cases, organic foods may havehigher levels of plant secondarymetabolites; this may be beneficial withrespect to suspected antioxidants such aspolyphenolic compounds, but also maybe of potential health concern whenconsidering naturally occurring toxins.Some studies have suggested potentialincreased microbiological hazards fromorganic produce or animal products dueto prohibition of antimicrobial use, yetother studies have not reached the sameconclusion. Bacterial isolates from foodanimals raised organically appear to showless resistance to antimicrobial agents thanthose food animals raised conventionally.While many studies demonstrate thesequalitative differences between organicand conventional foods, it is premature toconclude that either food system is superiorto the other with respect to safety ornutritional composition. Pesticide residues,naturally occurring toxins, nitrates, andpolyphenolic compounds exert theirhealth risks or benefits on a dose-relatedbasis, and data do not yet exist to ascertainwhether the difference in the levels of suchchemicals between organic foods andconventional foods are of biologicalsignificance.”It is important to state that the nutrient levels innatural plants can vary for a wide variety ofreasons. It is plausible for plants grown underdifferent conditions, such as conventionalversus organic agriculture, to have differentnutritional qualities. However, there is noconvincing reason to believe that any oneproduction method is consistently superior inregard to nutrition. This is borne out by theavailable data which shows mixed resultsregarding systematic difference betweenfoodstuffs grown with conventional versusorganic agriculture.It is also notable, as the IFT review details, thatthere is no convincing evidence of greatermicrobiological risk associated with organicfood, as some have suggested. Themicrobiological risk may be more related to thequality of the production method and theprevention of contamination than from theparticular production method used.12

ReferencesAndersen, H.R.; Schmidt, I.M.; Grandjean, P.;Jensen, T.K.; Budtz-Jorgensen, E.; Kjærstad,M.B.; Bælum, J.; Nielsen, J.B.; Skakkebæk,N.E.; Main, K.M. 2008. Impaired reproductivedevelopment in sons of women occupationallyexposed to pesticides during pregnancy,Environmental Health Perspectives, 116, 566-572.Appel, L.J.; Moore, T.J.; Obarzanek, E., et al.1997. A clinical trial of the effects of dietarypatterns on blood pressure. DASH CollaborativeResearch Group. New England Journal ofMedicine. 336, 1117-1124.Berkowitz, G.S.; Wetmur, J.G.; Birman-Deych,E.; Obel, J.; Lapinksi, R.H.; Godbold, J.H.;Holzman, I.R.; Wolff, M.S. 2004. In uteropesticide exposure, maternal paraoxonaseactivity, and head circumference. EnvironmentalHealth Perspectives, 112, 388-391.Dangour, A.D., Dodhia, S.K., Hayter, A., Allen,E., Lock, K. and Uauy, R. 2009. Nutritionalquality of organic foods: a systematic review.American Journal of Clinical Nutrition. 90, 680-685.Environmental Working Group (undated)Materials on the “Dirty Dozen” available atwww.foodnews.org.EPA. 2006. Reregistration eligibility decisionfor chlorpyrifos. Available at http://www.epa.gov/pesticides/reregistration/status.htm.Eskanazi, B.; Harley, K.; Bradman, A.; Weltzien,E.; Jewell, N.P.; Barr, D.B.; Furlong, C.E.;Holland, N.T. 2004. Association of in uteroorganophosphate pesticide exposure and fetalgrowth and length of gestation in an agriculturalpopulation. Environmental Health Perspectives,112, 1116-1124.Garry, V.F.; Harkins, M.E.; Erickson, L.L.; Long-Simpson, L.K.; Holland, S.E.; Burroughs, B.L.2002. Birth defects, season of conception, andsex of children born to pesticide applicatorsliving in the Red River Valley on Minnesota,USA. Environmental Health Perspectives, 110Supplement 3, 441-449.Hoppin, J.A.; Umbach, D.M.; London, S.J.;Lynch, C.F.; Alavanja, M.C.; Sandler, D.P. 2006.Pesticides and adult respiratory outcomes inthe Agricultural Health Study, Annals of theNew York Academy of Science, 1076, 343-354.Joshipura, K.J.; Ascherio, A.; Manson, J.E., et al.1999. Fruit and vegetable intake in relation torisk of ischemic stroke. Journal of the AmericanMedical Association. 282, 1233-1239.Klaassen, C. 2007. Casarett & Doull’s toxicology:the basic science of poisons. McGraw-HillProfessional.Law M.R.; Morris J.K. 1998. By how much doesfruit and vegetable consumption reduce therisk of ischaemic heart disease? EuropeanJournal of Clinical Nutrition. 52, 549-556.Liu C.; Russell R.M. 2008. Nutrition and gastriccancer risk: an update. Nutrition Review. 66,237-249.Lundqvist, C.; Zuurbier, M.; Leijs, M.; Johansson,C.; Ceccatelli, S.; Saunders, M.; Schoeters, G.;ten Tusscher, G.; Koppe, J.G. 2006. ActaPaediatr. Supplement. 95, 55-64.Petersen, M.S.; Halling, J.; Bech, S.; Wermuth,L.; Weihe, P.; Nielsen, F.; Jørgensen, P.J.; Budtz-Jørgensen, E.; Grandjean, P. 2008. Impact ofdietary exposure to food contaminants on therisk of Parkinson’s disease. Neurotoxicology,29, 584-590.13

Stewart, P.W.; Lonky, E.; Reihman, J.; Pagano, J.;Gump, B.B.; Darvill, T. 2008. The relationshipsbetween prenatal PCB exposure and intelligence(IQ) in 9-year old children. EnvironmentalHealth Perspectives, 116, 1416-1422.Swan, S.H.; Main, K.M.; Liu, F.; Stewart, S.L.;Kruse, R.L.; Calafat, A.M.; Mao, C.S.; Redmon,J.B.; Ternand, C.L.; Sullivan, S.; Teague, J.L. etal. 2005. Decrease in anogenital distanceamong male infants with prenatal phthalateexposure. Environmental Health Perspectives,113, 1056-1061.USDA. 2008. Pesticide data program – progressreport. Available at http://www.usda.gov/.Winter, C.K. and Davis, S.F. 2006. ScientificStatus Summary for Organic Foods, Institute ofFood Technologists, Journal of Food Science.71, R117-R124.14

Attachment A –Biographical Sketches of the PanelistsDr. Penny Fenner-CrispDr. Fenner-Crisp served as the ExecutiveDirector of the ILSI Risk Science Institute (RSI)from December 2000 until August 2004,following a 22-year career at US EPA. Herduties at EPA included nearly 12 years servingin several capacities as the Senior ScienceAdvisor, Deputy Director and Director of theHealth Effects Division of the Office of PesticidePrograms. Earlier assignments included servingas the Director of the Health and EnvironmentalReview Division (HERD) of the Office ofPollution Prevention and Toxics (OPPT) andSenior Toxicologist in the Health Effects Branchof the Office of Drinking Water (ODW). Sheplayed key roles in the development of manyEPA risk assessment policies and practicesprimarily related to human health and wasinvolved in the activities of several internationalorganizations as an expert on several WHOIPCS working groups, as a member of the WHOExpert Panel of the Joint Meeting on PesticideResidues for nine years and as the lead U.S.Delegate to several workgroups of the OECDtest guidelines program. In April, 2000, shereceived the Agency’s highest award, theFitzhugh Green Award, for her contributions onbehalf of EPA to its international activities.Dr. Fenner-Crisp received her Ph.D. inPharmacology from the University of TexasMedical Branch in Galveston and is a memberand former officer of several professionalscientific societies including of the Society ofToxicology and the Society for Risk Analysis.She has been a Diplomate of the AmericanBoard of Toxicology since 1984 and served onits Board of Directors from 2001-2005. Sheserved on EPA’s Endocrine Disruptor MethodsValidation Subcommittee from 2001-2004 andthe Strategic Science Team of the AmericanChemistry Council’s Long-range ResearchInitiative from 2002-2005. Currently, she is amember of the Board of Directors of theMidwest Center for Environmental Science andPublic Policy, the Drinking Water Committee ofEPA’s Science Advisory Board and EPA’s NationalPollution Prevention and Toxics AdvisoryCommittee. She also is a member of theNational Academies of Sciences expert groupcharged with conducting a review of the Workerand Public Health Activities Programadministered by the Department of Energy andthe Department of Health and HumanServices.Dr. Carl L. KeenDr. Carl L. Keen is the Mars Chair inDevelopmental Nutrition, Professor of Nutrition& Internal Medicine, and a Nutritionist in theAgricultural Experiment Station at the Universityof California at Davis. Dr. Keen received hisB.S. and Ph.D. degrees in Nutrition from theUniversity of California, Davis. Dr. Keen´sresearch group has four main areas of focus.The first concerns the influence of diet onembryonic and fetal development. A significantproportion of birth defects are the consequenceof embryonic and fetal malnutrition. A thesis inthe laboratory is that the correction of suboptimalnutritional deficiencies during earlydevelopment should result in a markedreduction in pregnancy complications. Thesecond research theme in the group is the studyof gene-nutrient interactions, with an emphasison how subtle changes in cell nutrientconcentrations can influence the expression ofselect genes. The third major research theme inthe group is the study of how diet influencesoxidant defense systems and cellular oxidativedamage. The fourth area of research in thelaboratory is on the effects of diet on thedevelopment and progression of vasculardisease. A current hypothesis in the laboratoryis that the putative cardiovascular healthbenefits associated with plant food-rich dietscan be attributed in part to their flavanolcontent. Dr. Keen’s group has over 600 peerreviewedscientific papers in the above areas.15

Dr. Jason RichardsonJason Richardson, M.S., Ph.D. is an AssistantProfessor in the Department of Environmentaland Occupational Medicine at Robert WoodJohnson Medical School and Resident Memberof the Environmental and Occupational HealthSciences Institute. He received his M.S. andPh.D. degrees from Mississippi State Universitywhere he conducted research on mixturesof organophosphate pesticides and thedevelopmental neurotoxicity of organophosphatesduring critical periods of development. He thencompleted postdoctoral training in MolecularNeuroscience and Neurotoxicology at EmoryUniversity. His research at EOHSI focuses onthe role of environmental exposures duringdevelopment and how such exposures interactwith genetic susceptibility to produceneurological disease.Dr. Rudy RichardsonDr. Richardson is the Dow Professor ofToxicology and Associate Professor of Neurologyat the University of Michigan School of PublicHealth. He received his B.S. (magna cumlaude) in Chemistry from Wichita StateUniversity. Upon achieving Ph.D. candidacy inChemistry at SUNY Stony Brook, he transferredto Harvard, where he earned the Sc.M. andSc.D. degrees in Physiology/Toxicology. Afterpostdoctoral work in Neurochemistry at theMedical Research Council Toxicology Unit inCarshalton, England, he joined the Universityof Michigan as Assistant Professor of Toxicology.Apart from sabbatical leaves at Warner-Lambert/Parke-Davis (now Pfizer) in Ann Arbor and theUniversity of Padua in Italy, Dr. Richardson hasbeen based at Michigan, where he has risenthrough the ranks to full professor. During1993-1999 he served as director of theToxicology Program and in 1998 he wasappointed as the Dow Professor of Toxicology.He is board-certified by the American Board ofToxicology (DABT). His research has focusedon mechanisms of acute and delayedneurotoxicity of organophosphorus compounds.Currently he uses kinetics, molecular modelingand mass spectrometry to understand interactionsof toxicants with target macromolecules and todevelop biomarkers of exposure, toxicity anddisease.Dr. Karl RozmanDr. Rozman is a Professor of Pharmacology,Toxicology & Therapeutics at the KansasUniversity Medical Center. He holds a Ph.D.from the University of Innsbruck in Organicand Pharmaceutical Chemistry. He is aDiplomate of the American Board of Toxicologyand a member of many journal editorialboards. Dr. Rozman’s research is aimed atelucidating the mechanism of toxicity ofchlorinated aromatic hydrocarbons (CAH) andrelated compounds. The cause of2,3,7,8-tetrachlorodibenzo-p-dioxin-induceddeath (and related compounds) in rats is acombination of appetite suppression andinhibition of gluconeogenesis, whereas in miceit appears to be inhibition of gluconeogenesisalone, leading to a lethal hypoglycemia.Currently three lines of research are beingpursued: 1) elucidation of the molecularmechanism(s) of action leading to CAH-inducedenzyme inhibition; 2) investigation of thesubchronic and chronic toxicities of TCDD andits higher chlorinated homologues as well asother heterocyclic analogues such as chlorinatedphenothiazines (CPT), and 3) studying femalereproductive toxicity of both CAH and CPT. Dr.Rozman has studied chlorinated pesticidesextensively such as DDT, hexachlorbenzene,pentachlorophenol, dieldrin, heptachlor,chlordane and more. He has published morethan 30 original manuscripts on these topicsand has written many book chapters and reviewarticles on chlorinated pesticides as well as onorganophosphates.16

Attachment B –EPA’s Regulatory Process for Pesticide Residues on FoodBackground on Pesticide RegulationEPA regulates pesticides under the FederalInsecticide, Fungicide, and Rodenticide Act(FIFRA) and the Federal Food, Drug, andCosmetic Act (FFDCA). These acts weresignificantly amended in 1996 by the FoodQuality Protection Act (FQPA). FQPA was, atleast partly, motivated by the National ResearchCouncil’s (NRC’s) 1993 report “Pesticides in theDiet of Infants and Children,” whichrecommended changes to EPA’s risk assessmentmethods for pesticide residues on food,particularly to provide better protection forinfants and children. FQPA called for enhancedstringency in the system of regulation forpesticides and adopted “a reasonable certaintyof no harm” standard.The EPA regulates the residues of pesticides onfood commodities using an extensive riskassessment process, with two key elements: (1)characterization of toxicity through an extensivebody of required tests, and (2) estimation ofdietary exposure through the use of modelscoupling data on food consumption with dataon pesticide residues from field trials, monitoringdata, etc.Toxicity TestingThe EPA requires more toxicity data foragricultural pesticides of conventional chemistrythan any for other type of chemical. The datarequirements for pesticides are detailed in 40CFR Part 158. The required toxicity tests forthese pesticides used on food include:• Acute oral toxicity – rat• Acute dermal toxicity• Acute inhalation toxicity – rat• Primary eye irritation – rabbit• Primary dermal irritation• Dermal sensitization• Acute neurotoxicity – rat• 90-day oral – rodent• 90-day oral – non-rodent• 21/28 day dermal• 90-day neurotoxicity• Chronic oral – rodent• Carcinogenicity – two rodent species• Prenatal developmental toxicity• Reproduction and fertility effects• Bacterial reverse mutation assay• In vitro mammalian cell assay• In vivo cytogenetics• Metabolism and pharmacokinetics• ImmunotoxicityAll of these studies are conducted under GoodLaboratory Practices (GLP) and the data arereviewed by EPA before they are judgedacceptable for risk assessment.As listed in 40 CFR 158.500, there several othertoxicity tests that EPA can conditionally requireif needed to refine the risk assessment (e.g.,developmental neurotoxicity). Also, manyregistrants voluntarily conduct additionaltoxicity studies to refine the risk assessment oftheir chemicals or to fulfill requirements inother countries. Also, at its discretion, EPA canuse open literature data to refine theassessment.17

Development of ToxicityReference ValuesFollowing the receipt, review and acceptanceof the toxicity data by EPA, toxicity referencevalues are derived for acute and chronicexposure durations, and for lifetime cancer risk,if the pesticide is found to be a carcinogen. EPAuses standard methods to calculate the toxicityreference values, except that they must add anadditional 10-fold safety factor to protectchildren, unless the available data show thatsome other factor is more appropriate (seebelow).One of the most significant changes mandatedin FQPA was the obligation of the agency toapply an additional default safety factor of 10for the added protection of infants and children.The “FQPA 10X factor” can be adjusted if “onthe basis of reliable data, such margin will besafe for infants and children.” As an example, ifit can be shown that there is no difference intoxicity for infants and fetuses, compared toadults and there are no databases deficiencies,then the FQPA factor may be reduced to as littleas 1X.The first step in the process is the determinationof the point-of-departure for risk assessment.Historically, the point-of-departure was a noobserved adverse effect level (NOAEL) from atoxicity study of appropriate duration. However,EPA is moving away from the use of NOAELswhen possible, and, instead, derivingbenchmark doses (BMDs). As an example, EPAhas derived BMDs for cholinesterase-inhibitors,including organophosphates and N-methylcarbamates. To estimate the BMD for this class,EPA first finds whether the brain or red bloodcell (RBC) compartments are more sensitive.The BMD for the point-of-departure is usuallychosen as the estimated dose that causes a 10%inhibition of either brain or RBC cholinesterase,whichever gives a lower result. This approach ismore conservative than other agencies such asthe World Health Organization (WHO) whichrecommends a 20% inhibition for the point-ofdeparture.EPA applies various uncertainty factors to thepoint-of-departure, generally including adefault 10-fold factor for animal-to-humanextrapolation (interspecies variation) and adefault 10-fold factor for intraspecies variation.Chemical-specific data, when available, wouldprompt the application of chemical-specificuncertainty factors. EPA may also applyadditional factors for database deficiencies orfor extrapolation from subchronic to chronicexposures.For cancer risk assessment, as a default, EPAtypically uses a linear, no-threshold doseresponsemodel to estimate a unit risk (orpotency) factor, based on tumor rates in theanimal studies. The unit risk factor can bemultiplied by a lifetime average exposure toestimate a lifetime risk. In many cases,depending upon the number and nature of theobserved tumor types and number of speciesshowing a positive carcinogenic response, amargin-of-exposure approach to the quantitativerisk assessment may be preferred.Exposure AssessmentEPA estimates dietary exposure to pesticidefood residues using residue data collected infield trials, post-harvest, or in market basketsurveys, in combination with data on foodconsumption.Pesticide registrants obtain registrations for apesticide on a crop-specific basis. Therefore,for each crop that a pesticide is used on, theregistrant must submit field trial data thatinclude measurements of pesticide residues onthe commodity following an application at themaximum application rate and minimum18