TECHNICAL REPORT Pesticide Exposure in …pediatrics.aappublications.org/content/pediatrics/130/6/e1765.full.pdfTECHNICAL REPORT Pesticide Exposure in Children abstract Pesticidesareacollectivetermforawidearrayofchemicalsintendedto

TECHNICAL REPORT

Pesticide Exposure in Children

abstractPesticides are a collective term for a wide array of chemicals intended tokill unwanted insects, plants, molds, and rodents. Food, water, and treat-ment in the home, yard, and school are all potential sources of children’sexposure. Exposures to pesticides may be overt or subacute, andeffects range from acute to chronic toxicity. In 2008, pesticides werethe ninth most common substance reported to poison control centers,and approximately 45% of all reports of pesticide poisoning were forchildren. Organophosphate and carbamate poisoning are perhaps themost widely known acute poisoning syndromes, can be diagnosed bydepressed red blood cell cholinesterase levels, and have availableantidotal therapy. However, numerous other pesticides that may causeacute toxicity, such as pyrethroid and neonicotinoid insecticides, herbi-cides, fungicides, and rodenticides, also have specific toxic effects;recognition of these effects may help identify acute exposures. Evidenceis increasingly emerging about chronic health implications from bothacute and chronic exposure. A growing body of epidemiological evi-dence demonstrates associations between parental use of pesticides,particularly insecticides, with acute lymphocytic leukemia and braintumors. Prenatal, household, and occupational exposures (maternaland paternal) appear to be the largest risks. Prospective cohort stud-ies link early-life exposure to organophosphates and organochlorinepesticides (primarily DDT) with adverse effects on neurodevelopmentand behavior. Among the findings associated with increased pesticidelevels are poorer mental development by using the Bayley index andincreased scores on measures assessing pervasive developmental dis-order, inattention, and attention-deficit/hyperactivity disorder. Relatedanimal toxicology studies provide supportive biological plausibility forthese findings. Additional data suggest that there may also be anassociation between parental pesticide use and adverse birth out-comes including physical birth defects, low birth weight, and fetaldeath, although the data are less robust than for cancer and neuro-developmental effects. Children’s exposures to pesticides should belimited as much as possible. Pediatrics 2012;130:e1765–e1788

INTRODUCTION

Pesticides represent a broad classification of chemicals that are appliedto kill or control insects, unwanted plants, molds, or unwanted animals(eg, rodents). “Pesticide” is a collective term for a wide array ofproducts but is often inappropriately used in reference to only insec-ticides. The universe of pesticide types and products is broad, and

James R. Roberts, MD, MPH, Catherine J. Karr, MD, PhD,and COUNCIL ON ENVIRONMENTAL HEALTH

KEY WORDSpesticides, toxicity, children, pest control, integrated pestmanagement

ABBREVIATIONSCDC—Centers for Disease Control and PreventionCI—confidence interval2,4-D—2,4-dichlorophenoxyacetic acidDDE—p,p′-dichlorodiphenyldichloroethyleneEPA—Environmental Protection AgencyES—Ewing sarcomaGI—gastrointestinalINR—international normalized ratioIPM—integrated pest managementNPDS—National Poison Data SystemOP—organophosphateOR—odds ratioPT—prothrombin timeRR—relative riskSGA—small for gestational ageTh2—T helper 2

This document is copyrighted and is property of the AmericanAcademy of Pediatrics and its Board of Directors. All authorshave filed conflict of interest statements with the AmericanAcademy of Pediatrics. Any conflicts have been resolved througha process approved by the Board of Directors. The AmericanAcademy of Pediatrics has neither solicited nor accepted anycommercial involvement in the development of the content ofthis publication.

The guidance in this report does not indicate an exclusivecourse of treatment or serve as a standard of medical care.Variations, taking into account individual circumstances, may beappropriate.

All technical reports from the American Academy of Pediatricsautomatically expire 5 years after publication unless reaffirmed,revised, or retired at or before that time.

www.pediatrics.org/cgi/doi/10.1542/peds.2012-2758

doi:10.1542/peds.2012-2758

PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).

Copyright © 2012 by the American Academy of Pediatrics

PEDIATRICS Volume 130, Number 6, December 2012 e1765

FROM THE AMERICAN ACADEMY OF PEDIATRICS

by guest on July 17, 2018www.aappublications.org/newsDownloaded from

a comprehensive review of all activeingredients is beyond the scope of thisreport. This review focuses on selectinsecticides, herbicides, and rodenticidesand specific chemical classes withinthese groups that have the greatestacute and chronic toxicity for children onthe basis of historical experience and/oremerging evidence (Table 1).

Several types of pesticides are notdiscussed in this report. Fumigants andfungicides, although potentially toxic,are less commonly involved in acutechildhood exposure and poisoning, ingeneral, so these are not included.Wood preservatives containing arsenicare also not included in this report. Thespecific compound containing arse-nic, copper chromium arsenate, hasbeen removed from the market sinceJanuary 2004. Older wood structurestreated with copper chromium arse-nate may still be found in homes, onplaygrounds, and in yards and shouldbe treated yearly with a waterproofsealant.1 Insect repellents, including N,N-diethyl-meta-toluamide and picaridin,are different from most pesticides inthat they are a product purposefullyapplied to human skin to prevent in-sect bites and are, in fact, not insecti-cides. These compounds are uniqueand have been reviewed recently.2

Although the severity of pesticideexposures and toxicity may be greaterin developing countries where regu-latory oversight and information islimited, the content of this technicalreport is oriented toward exposuresmost relevant to children residing inthe United States. Commonly usedinsecticides, including the organo-phosphates (OPs), carbamate, andpyrethroid classes, are discussed, asare the relatively new neonicotinoids.Other pesticides that will be discussedin some detail include the phosphonateherbicides (eg, glyphosate), chloro-phenoxy herbicides, and long-actinganticoagulants (rodenticides). For a

more comprehensive survey of theacute toxicity from the spectrum ofpesticide active ingredients and prod-ucts, see other sources.1,3

CHILDREN’S EXPOSURE:VULNERABILITY, MECHANISMS,AND SOURCES OF EXPOSURE

Children’s Unique Vulnerabilities

Children are uniquely vulnerable to up-take and adverse effects of pesticidesbecause of developmental, dietary, andphysiologic factors. Exposure occursthrough ingestion, inhalation, or dermalcontact. Unintentional ingestion by chil-dren may be at a considerably higherdose than an adult because of thegreater intake of food or fluids perpound of body weight. Children exhibitfrequent hand-to-mouth activity, and thisis an important source of increasedexposure in comparison with adults.4,5

Residential Factors

Fortunately, acute toxicity attributableto pesticide poisoning is relativelyuncommon in US children, and a pe-diatrician in general practice may notencounter such an event. However,subacute and chronic low-level expo-sure is common. Residential factorsthat influence chronic exposure in-clude the use of insecticides androdenticides in the home, and herbi-cide and fungicide use on lawns, aswell. Indoors, broadcast applicationsincluding sprays, “flea bombs,” andfoggers can leave lingering residuesin the air, carpet, toys, and housedust.6–9 Typical exploratory behavior,including playing on and crawlingacross the floor, increases the risk ofdermal, inhalation, and oral exposureto residues on surfaces or the airas it settles.10 Repeated and cumula-tive incidental exposure can also oc-cur. Pesticides can be measured inindoor air samples and persist in dustvacuumed from carpeted areas, up-holstered objects, and children’s toys,

such as stuffed animals, and can alsobe brought home from the work-place.11–14 Herbicides applied on thelawn or garden can be tracked intothe home, with residues building upover time.15 Applications of diazinon tolawns have been demonstrated to becarried indoors via the paws of petdogs.16 Residential pesticide residuelevels also vary geographically accord-ing to the specific pesticide needs inthe area. In Los Angeles, high levelsof chlorpyrifos and other insecticideswere found because of the large num-bers of crawling insects, fleas, and ter-mites. Conversely, in Iowa, there werehigh levels of the herbicides 2,4-dichlorophenoxyacetic acid (2,4-D)and dicamba because of weed-controlapplications.17

Residentially related sources may berelevant in other settings where chil-dren spend time, including school,child care, a relative’s home, etc,depending on indoor and outdoorpesticide use patterns and proximityto pesticide use. In a North Carolinastudy of 142 urban homes and pre-schools, chlorpyrifos was detected inall indoor air and dust samples.18

Biomonitoring Data for ExposureAssessment

The Centers for Disease Control andPrevention (CDC) conducts a population-based biomonitoring program asso-ciated with the NHANES.19 The mostrecent report includes biomarker datafor many organochlorine, OP, and car-bamate insecticides; herbicides; pyre-throid insecticides; and some otherpesticides. Testing of 44 pesticide metab-olites revealed that 29 were detectablein most people from whom sampleswere analyzed (ages 6–59 years), withOP and organochlorine insecticidesreported to be most prevalent in theUS population.19 Although the healthimplications of these “snapshot” sam-pling data are largely unknown, they do

e1766 FROM THE AMERICAN ACADEMY OF PEDIATRICS by guest on July 17, 2018www.aappublications.org/newsDownloaded from

provide a reference point on pesticidemetabolite distributions. Periodic reas-sessment also allows for evaluations ofpopulation-level exposure trends.

As noted previously, children’s uniquebehaviors and metabolic rate oftenplace them at risk for absorption ofhigher doses from contaminated envi-ronments in comparison with adults.One example evident from the bio-monitoring data is chlorpyrifos, a non-persistent OP insecticide. Althoughbanned in 2000 for use inside the home,it continues to be used in agriculture,including orchard fruits, such as applesand pears, and other dietary staples of

children. In the CDC biomonitoring data,chlorpyrifos-specific urinary metabo-lites were highest for the youngest agegroup assessed (6–11 years) comparedwith older children and adults.19

In contrast, biomonitoring of serummarkers of organochlorine insecti-cides and their metabolites, such asDDT, dieldrin, and chlordane, many ofwhich were banned from use in theUnited States in the 1970s and 1980s,revealed lower concentrations in theyoungest age group monitored (12–19years). Despite relatively lower con-centrations, the ongoing detection andthe higher levels with increasing age

likely reflect the influence of the ac-cumulation of these fat-soluble, per-sistent compounds over a lifetime.

Exposures From the Food Supply

In the general population, the foodsupply represents the most importantsource of exposure for organochlorinesand OPs. For pyrethroids, both foodresidues and household pest controlproducts are important sources.20 TheUS Environmental Protection Agency(EPA) regulates exposure to pesticidesin food by setting “tolerances,” whichare the maximum amount of pesticidesthat may legally remain in or on food

TABLE 1 Major Pesticide Classes and Selected Examples

Pesticide Class Examples Toxicity Comment, Uses

Organochlorines DDT, endrin, aldrin, chlordane,lindane

• High toxicity • Many organochlorines now banned in the UnitedStates

• Lindane has been banned in California, elsewhereused for control of lice and scabies

• DDT and other organochlorines have longmetabolic disposition and are stored in fattytissues and can persist in the environment

Organophosphates Parathion, chlorpyrifos,dichlorvos, acephate,methyl-parathion, malathion,phorate

• Most OPs are highly toxic • Parathion is banned for use in the United States• Malathion is considered relativelyless toxic than other OPs

• Chlorpyrifos is no longer approved for residentialuse

• Most others are used for insect control in bothagricultural and home settings

• Malathion is an approved treatment of head liceN-Methyl carbamates Aldicarb, carbaryl, carbofuran,

pirimicarb, propoxur• Aldicarb and carbaryl are both highly toxic • Insect control in agricultural and home settings• Other carbamates have a relatively moderate

toxicityPyrethrins and

pyrethroidsPermethrin, cyano-pyrethroids:

deltamethrin, cypermethrin,fenvalerate

• Permethrin has relatively low toxicity • Permethrin is a common pediculicide• Other pyrethroids have moderate toxicity • Most other pyrethroids are commonly used to

control insects, often used in home and gardenNeonicotinoids Imidacloprid • Relatively newer class of insecticides • Selective affinity toward insect nicotinic

acetylcholine receptors compared withmammalian nicotinic acetylcholine receptors

• Have relatively lower toxicity than OPs andcarbamates

• Often used as spot-on flea control for domesticanimals

N-Phenylpyrazoleinsecticides

Fipronil • Relatively newer class of insecticides • Often used as spot-on flea control for domesticanimals

• Yard treatments for insect controlPhosphonate herbicides Glyphosate • Because of primary mechanism of action, has

relatively low toxicity from active ingredient.• Acts on plant cell wall

• Toxicity often due to the accompanyingorganic solvent

• Commercially available in many products

Chlorophenoxyherbicides

2,4-D, 2,4,5-T • Moderate toxicity • Weed control

Dipyridyl herbicides Paraquat, diquat • Highly toxic • Infrequently used• Paraquat toxicity often requires lung transplant

Long-actinganticoagulants

Brodifacoum(superwarfarins)

• Rodenticides• Longer-acting than warfarin• Recently eliminated packaging as loose pellets

2,4,5-T, 2,4,5-trichlorophenoxy acetic acid.




and animal feed. The US Food and DrugAdministration is responsible for en-forcement of these tolerances, whichincludes a modest monitoring program,which analyzed 7234 total samples in2003. Among the domestically producedsamples, 49% of fruit, 29% of vegeta-bles, 26% of grain products, 24% offish/shellfish, and 0% of milk/dairytested had detectable but legally al-lowable pesticide residues. Only fruitand vegetables had residues above thelegal tolerance (approximately 2%each). Overall, the detection of residuesin the samples from imported fruitsand vegetables tested were less, butthe exceedances of legal toleranceswere greater (5%–7% of importedfruits/vegetables sampled).21 Consump-tion of organic food may lower pesti-cide exposure, as demonstrated bya study in which children were placedon an organic diet for a period of 5consecutive days. A rapid and dramaticdrop in their urinary excretion ofmetabolites of malathion and chlorpyrifosOP insecticides during the organic dietphase was observed.22

Agriculturally Related Exposures

Proximity to pesticide-treated agricul-tural areas or household membersthat work with pesticides presentsanother opportunity for contaminationof the residential environment forsome children. In a Washington Statestudy of children of agricultural work-ers and nonagricultural workers in anagricultural setting, pesticide levels incarpet dust and pesticide metabolitesin urine of residents increased withself-reported proximity of homes toorchard fields and during the pesticideapplication season.9,23 Similarly, in anagriculture center in California, pesti-cide residues of 3 chemicals used re-cently on crops were significantlycorrelated with house dust samples innearby homes and urine samplesamong their inhabitants. The findings

were noted in both farmworkers andnonfarmworkers.24 The presence of anagricultural worker in the home alsoincreases pesticide levels through“take-home” exposures.23 Children livingon a farm had higher urinary pesticidemetabolite levels than children not livingon a farm.25 Children themselves mayparticipate in agricultural work thatinvolves the use of pesticides or contactwith pesticide-treated foliage.26–28

Exposures From Drinking Water

Contamination of drinking water pres-ents another potential source of ex-posure, particularly for herbicides.A 10-year study (1992–2001) by theUS Geological Survey’s National Water-Quality Assessment program provideda national-scale view of pesticide oc-currence in streams and groundwa-ter. Overall, pesticides were detectedin more than 50% of sampled wellsfrom shallow groundwater tappedbeneath agricultural and urban areasas well as in 33% of the deeper wellsthat tap major aquifers used for wa-ter supply. The concentrations asso-ciated with these detections rarelyexceeded water quality health refer-ence levels (approximately 1% of the2356 domestic and 364 public-supplywells that were sampled). Herbicides,particularly the triazine class, werethe most frequently detected pesticidegroup in agricultural areas. (It shouldbe noted that atrazine and other tri-azine herbicides were monitored fromsurface water.) In urban areas, bothherbicides and insecticides (particu-larly diazinon and carbaryl) werefrequently detected. The greatestproportion of wells exceeding a healthreference level was for those tappingshallow groundwater beneath urbanareas. It is noteworthy that the de-tection of pesticides usually occurredas mixtures, and health referencelevels reflected exposure to a singleagent.29

NATIONAL DATA ON ACUTEEXPOSURE, MORBIDITY, ANDMORTALITY

Although some states (eg, Californiaand Washington) mandate the report-ing of pesticide-related illness, there isno national surveillance system forpesticide exposure and poisoning. TheAmerican Association of Poison ControlCenters’ National Poison Data System(NPDS [formerly known as the ToxicExposure Surveillance System]) com-piles annual data on pesticide expo-sures. Incidents reported by the NPDSare categorized by age (<6 years, 6–19years, and >19 years), reason (un-intentional, intentional, other, adversereaction), and outcome (none [nomorbidity], minor, moderate, major, ordeath). However, these data representself-reports from patients and/or fam-ily members and calls from medicaltreatment facilities. Although they areuseful to describe trends, they do notindicate true prevalence or incidence.Data are reported annually and, since2005, have been published in ClinicalToxicology.30

In 2009, pesticides were the tenth mostfrequently involved substance in hu-man exposure (3.9% of all NPDSreports) and the ninth most commonsubstance encountered in children(3.3% of pediatric NPDS reports).Nearly 55.8% of all single-substancepesticide exposures involved children≤19 years of age, and 94% of allpesticide ingestions were unintentional.Twenty-one of the reports from pesti-cide exposure resulted in death; how-ever, these were not categorized byage.30 Rates (calculated by using UScensus data for the catchment areaserved by the poison control center asthe denominator) of reported pesticidepoisonings described as moderate,major, and fatal declined from 1995 to2004 by approximately 42%. Thesharpest declines in poisonings werefrom OP and carbamate insecticides,


likely reflecting EPA regulatory action todiscontinue residential use of severalpreviously widely available OP andcarbamate insecticides on the basis ofchild health concerns.31

ACUTE TOXICITY MECHANISMSAND CLINICAL MANIFESTATIONS

OP and Carbamate Insecticides

OP and carbamates insecticides havebeen widely used for insect control inthe home and in agriculture since the1960s. During this period, OP andcarbamates usage largely replacedthe use of organochlorines becauseof environmental and human healthconcerns of the latter class. In the past10 years, chemical products in theOP and carbamate group have comeunder scrutiny, with subsequent reg-ulatory action based on humanhealth concerns. Examples include 2commonly used OPs with high acutetoxicity: parathion (banned) andchlorpyrifos (no longer allowed forresidential use). Other OPs that remainwidely used include dichlorvos, ace-phate, methyl-parathion, and mala-thion. Malathion has relatively loweracute toxicity among the OPs and isregistered for the treatment of headlice (Ovide). A well-known example ofa carbamate is aldicarb, although usehas largely been curtailed by regula-tory action because of its high toxicity.Commonly used carbamates includecarbaryl and pirimicarb.1,3

Toxicity, Clinical Signs, and Symptoms

OPs and carbamates exert a commonmechanism of action by inhibiting theacetylcholinesterase enzyme, therebyproducing accumulation of acetylcho-line at the synapses, neuromuscularjunction, and end organs, which resultsin excessive stimulation at those sites.The reaction is generally an irreversiblebinding by OPs and a reversible bind-ing by carbamates, and it influencestreatment approaches for each class of

insecticides. Consequently, acute poi-soning by OPs tends to be more severeand refractory than that of carbamates;however, variations are observed ineach class. There are some notablecarbamates (such as aldicarb) thathave equal if not greater toxicity thansome OPs.1,3

Acute clinical manifestations reflectthe development of cholinergic crisisand can arise from stimulation ofmuscarinic, nicotinic, and/or centralnervous system receptors (Table 2).Early findings can often mimic a flu-like illness and include hypersecre-tion. Miosis is a helpful diagnosticsign. The classic cardiovascular signis bradycardia, although early on,tachycardia may be present initiallybecause of nicotinic stimulation. Pro-gressive symptoms lead to muscleand respiratory problems. The centralnervous system may also be affected,signifying severe poisoning, particu-larly in children.1,3,32–34 Reviews ofcase series indicate that between20% and 30% will have seizures, andbetween 50% and 100% of childrenwill have lethargy, stupor, or coma.32–34

A high clinical suspicion plus di-rected and persistent environmentalhistory taking to identify potentialexposures are necessary to identifythese poisonings. Reviews of pedi-atric poisonings note that, histori-cally, most children were transferredto a referral center with the wrongpreliminary diagnosis and parentsinitially denied any exposure history.33,34

Laboratory Evaluation and Treatment

Poisoning with OPs and carbamatescan be detected on the basis of clini-cal findings and history of exposure.Laboratory confirmation can assist inthe diagnosis by using red blood celland plasma cholinesterase levels; bothare typically depressed with acutepoisoning, although there is somevariation among active ingredients as

well as variation in levels by severity ofpoisoning.35 Measurement techniquesand resultant levels vary among lab-oratories; therefore, clinicians willneed to check with their own labora-tory for reference values. Red bloodcell cholinesterase levels typically aremore specific for acute poisoning andwill be depressed longer than plasmacholinesterase levels (often 1–3months) until enzyme is replaced.3 In-terpretation of results can be dis-cussed with a pediatric environmentalhealth specialist or clinical toxicologist.

The parent active ingredient cannottypically be measured in biologicalspecimens. These compounds undergometabolic transformation in the liverand are excreted in the urine mostly intheir metabolized form, most of whichare nonspecific metabolites for allOPs.19 Exceptions include parathion,methyl-parathion, and chlorpyrifos, allof which have their own specific me-tabolite in addition to the nonspecificmetabolites. Urinary metabolites canbe measured, and human data areavailable from the CDC on a nationallyrepresentative sample.19 However, anevidence base to support clinical in-terpretation of urinary concentrationsis lacking.

Treatment of OP poisoning (and thisapplies to the acute treatment of anyother pesticide as well) begins with thebasics of advanced life support, withany necessary airway or breathingsupport as needed. Gastrointestinal(GI) decontamination is controversial.The American Academy of ClinicalToxicology and the European Associa-tion of Poisons Centres and ClinicalToxicologists issued a joint statementon the use of single-dose charcoal forpoisoned patients (inclusive of all typesof poisonings). They stated that activatedcharcoal is most effective when givenwithin 1 hour after the ingestion ofa poison, but routine administration inall poisonings is not recommended.




Activated charcoal is contraindicated ifthe patient does not have a protected orintact airway.36 A randomized controlledtrial evaluating the effect of multiple-dose charcoal for pesticide-poisonedpatients in Asia found no benefit, asmeasured by a reduction in mortality.37

Skin decontamination also is critically

important, and clothing should be re-moved. Medical personnel should takemeasures to protect themselves fromcontaminated skin and clothing, becausenumerous cases of hospital-acquired OPpoisoning have been documented.38

Parents or other family caregivers mayalso be at risk for skin contamination.

Seizures should be controlled with in-travenous lorazepam.3

Atropine can be given as a nonspecificantidote in both OP and carbamatepoisoning. It will reverse the musca-rinic effects of the poisoning; however,it is less effective on central nervoussystem effects. It is given as a dose of

TABLE 2 Clinical Signs and Symptoms

Class of Compounds Signs and Symptoms Special Notes, Laboratory Evaluations, Specific Treatments,or Antidote

Organophosphate and carbamateinsecticides

• Nonspecific early symptoms: headache, nausea,vomiting, abdominal pain, and dizziness

• Red blood cell and plasma cholinesterase levels

• Sometimes hypersecretion: sweating, salivation,lacrimation, rhinorrhea, diarrhea, and bronchorrhea

• Measure nonspecific metabolites for most OPs

• Progressive symptoms: muscle fasciculation, muscleweakness, and respiratory symptoms (bronchospasm,cough, wheezing, and respiratory depression)

• Specific metabolites can be measured for chlorpyrifosand parathion

• Bradycardia is typical, although early in acutepoisoning, tachycardia may be present

• Atropine is primary antidote

• Miosis • Pralidoxime is also an antidote for OP and acts asa cholinesterase reactivator

• Central nervous system: respiratory depression,lethargy, coma, and seizures

• Because carbamates generally produce a reversiblecholinesterase inhibition, pralidoxime is not indicatedin these poisonings

Pyrethroids • Dermal: skin irritation and paresthesia • At times have been mistaken for acute OP orcarbamate poisoning and treated with atropine withpotentially adverse or disastrous results

• Nonspecific symptoms including headache, fatigue,vomiting, diarrhea, and irritability

• Symptomatic treatment

• Similar findings found in OPs, including hypersecretion,muscle fasciculation, pulmonary symptoms andseizures

• Vitamin E oil for dermal symptoms

Neonicotinoids • Disorientation, agitation—severe enough to requiresedation, drowsiness, dizziness, weakness, and, insome situations, loss of consciousness

• Supportive care

• Vomiting, sore throat, abdominal pain • No available antidote• Ulcerations in upper GI tract • No available diagnostic test

Fipronil (N-phenylpyrazoleinsecticides)

• Nausea and vomiting • Supportive care• Aphthous ulcers • No available antidote• Altered mental status and coma • No available diagnostic test• Seizures

Organochlorines • Central nervous system: mental status changes andseizures

• Control acute seizures with lorazepam

• Paresthesia, tremor, ataxia, and hyperreflexiaGlyphosate (phosphonateherbicides)

• Nausea and vomiting • Supportive care• Aspiration pneumonia type syndrome• Hypotension, altered mental status, and oliguria insevere cases

• Aspiration pneumonia type syndrome• Pulmonary effects may in fact be secondary toorganic solvent

Chlorophenoxy herbicides • Skin and mucous membrane irritation • Consider forced alkaline diuresis with sodiumbicarbonate in IV fluids• Vomiting, diarrhea, headache, confusion

• Metabolic acidosis is the hallmark• Renal failure, hyperkalemia, and hypocalcemia

Long-acting anticoagulants (rodenticides) • Bleeding: gums, nose, and other mucous membranesites

• Consider PT (INR) or observation

• Bruising • Vitamin K indicated for bleeding (IV vitamin K) or forelevated PT (INR) (oral vitamin K)

IV, intravenous.


0.05 to 0.1 mg/kg per dose and may begiven as often as every 15 minutesuntil respiratory secretions are con-trolled.3 Notably, this dose is 10 timesthe usual dose given during a re-suscitation situation, because the pur-pose is to overcome complete blockadeof the muscarinic channel. Pralidoximeis also given as a specific antidote toreverse the acetylcholinesterase in-hibitor complex. The use of pralidoximecontinues to be of interest, particularlyin developing countries, although moststudies have been performed withadult patients.39,40 The World HealthOrganization recommends its use forall patients who require atropine.41 Itsuse is indicated for OP poisoning, be-cause cholinesterase inhibition usu-ally is permanent in OP poisoning. Useof pralidoxime usually is not neces-sary or recommended for carbamatepoisoning, because this inhibition isreversible.3

Pyrethrins and PyrethroidInsecticides

Pyrethrins and pyrethroids are a rela-tively more recent class of insecticidesthat have been largely replacing theuse of cholinesterase-inhibiting insec-ticides, especially in the consumermarket. These insecticides are used forstructural pest control in urban areas,in gardening or agriculture for rowcrops and orchards, and in the homefor pet sprays and shampoo.

The pyrethrins are botanically derivedfrom pyrethrum, an extract of thechrysanthemum plant. For these con-sumer products, pyrethrins are usuallycombined with another active in-gredient: either a longer-acting syn-thetically derived pyrethroid or oneof the cholinesterase inhibitors. Py-rethrins are not stable in heat orsunlight and, therefore, are usuallyused more for indoor application. Per-methrin is the most widely known ex-ample of a pyrethrin and is one of the

few products licensed for use to applyto human skin, because it is commonlyused as a pediculicide.3,42,43

Pyrethroids are synthetically derivedcompounds that have been modified tobe more stable in sunlight and heatand are, therefore, used more widelyfor insect control, especially outdoors.Toxicity varies widely among py-rethrins and pyrethroids, and, althoughthey are less acutely toxic as a classthan the cholinesterase insecticides,there is a subgroup of these com-pounds that has been modified witha cyano side chain. This modificationcreates a compound that is significantlymore resistant to degradation andpotentially more acutely toxic thanother pyrethroids. Commonly usedchemicals in this subgroup includedeltamethrin, cypermethrin, and fen-valerate—these are the insecticidesto which the majority of toxic signsand symptoms in the next sectionapply.43

Toxicology, Clinical Signs, andSymptoms

Pyrethroids exert their toxic effect byblocking the sodium channel at thelevel of the cell membrane. Mostclinical reports of poisoning occureither through excessive skin contactor through ingestion or inhalation. Theresult is continued hyperpolarization,effectively inhibiting cell function.Some types of pyrethroids also workat other sites, including voltage-dependent chloride channels andγ-aminobutyric acid–gated chloridechannels. This appears to be one ofthe reasons for a variety of toxicityfound among pyrethroid insecti-cides.42,43 Pyrethroids with a cyanogroup, also known as type II pyreth-roids, constitute most cases of humanpoisoning.42,43 Pyrethroids are wellabsorbed across the GI tract, butlimited penetration occurs across theskin barrier, which can limit acute

toxicity.42,44 Some pyrethroids havea high acute toxicity, usually after in-gestion.42,45 Pyrethroids are metabo-lized by the liver and excreted in theirmetabolic forms.

Pyrethroids have adverse effects onthe nervous system, GI tract, and skin.Specific signs and symptoms are foundin Table 2. Similar to OPs, musclefasciculation, weakness, an alteredlevel of consciousness, and seizurescan develop after exposures to somepyrethroids.42–45 Of note, paresthesias,including burning, tingling, stinging,and eventually numbness, are char-acteristic of pyrethroid exposure.46,47

The paresthesias appear to be dose-dependent and occur at pyrethroiddosages lower than what would causesystemic toxicity, thereby acting asa warning of exposure. The par-esthesias are self-limiting once expo-sure is eliminated.48

Laboratory Evaluation and Treatment

Pyrethroid toxicity is identified throughclinical history and knowledge of ex-posure to the agent. There are norapidly available diagnostic laboratorytests. Most pyrethroids are metabo-lized to 3-phenoxybenzoic acid, whichcan be recovered in the urine. CDCnational surveys provide biomonitor-ing information on pyrethroid urinarymetabolites and can act as compari-son for background measures of ex-posure in the general population.However, in the clinical setting, resultsof metabolite levels are usuallyobtained from specialty laboratoriesand are not immediately available;therefore, these results not useful inacute clinical management.

Paresthesias are generally self-limitingand resolve within 24 hours.46,48 Ifexposure is interrupted after the on-set of paresthesias and other dermalfindings, no additional treatment isnecessary. Vitamin E oil or creamhas been shown to improve the




symptoms associated with the par-esthesias.47 The mechanism is notcompletely clear; however, in experi-mental studies, vitamin E (α-tocopherol)blocked tetramethrin-modified sodiumchannels.49

Treatment of systemic pyrethroid poi-soning is supportive, in general, andthere are no specific antidotes. Be-cause of the similar features of cho-linesterase inhibitor poisoning, somepatients have been treated errone-ously with high atropine, sometimeswith disastrous results.45 Efforts havebeen aimed at antagonizing the so-dium current resulting from thepyrethroid blockade. Several medi-cations have been tested in the animalmodel, but, to date, none have beenconsidered effective antidotes for sys-temic pyrethroid poisoning in humans.For significant neurologic effects,patients should have standard de-contamination, including GI tract de-contamination, supportive respiratorycare, seizure control with diazepam orlorazepam, and careful dosing of atro-pine for excessive salivation.42 Properidentification of the offending agent isimperative to distinguish these poison-ings from OPs and often requires a highindex of suspicion and a thorough ex-posure history.

Organochlorine Insecticide(Lindane)

The discussion of acute toxicity fororganochlorines is focused on lindane,because most other organochlorinecompounds have been banned for use inthe United States. Other organochlorines,including DDT and some of the cyclo-dienes, including chlordane and dieldrin,are important compounds, because theycan still persist in human and environ-mental samples. These chronic expo-sures are of continuing concern fordevelopmental health effects, includingimmunotoxicity, endocrine disruption,and neurodevelopmental insults (see

Chronic Health Effects of Pesticide Ex-posure).

Lindane, also known technically as theγ-isomer of hexachlorocyclohexane, isstill approved in some states forcontrol of lice and scabies. However,in a comparison of in vitro activityagainst lice with other pediculicides, itwas the least effective.50 It is effi-ciently absorbed across the skin (ap-proximately 9%) and even more soacross abraded skin, such as withsevere excoriations from scabies.51,52

Signs and symptoms are noted inTable 2. Treatment is supportive andincludes decontamination and thecontrol of seizures with lorazepam.There is no specific antidote. Lindanehas been banned in California be-cause of high levels found in the wa-ter supply.53

Neonicotinoids

Neonicotinoids are a new class ofinsecticides based on metabolic alter-ations of nicotine. They are used pri-marily in agriculture and are gainingwidespread use for flea control ondomestic animals. They act on thenicotinic N-acetylcholine receptors andselectively displace acetylcholine. Theydo have a relatively selective affinityfor insects as opposed to mammals,although there have been a fewreports of human poisoning.54–56 Themost commonly used neonicotinoid inthe United States is imidacloprid. In-formation about toxicity and signs andsymptoms can be found in Tables 1and 2.

N-Phenylpyrazoles

Fipronil is the primary representativeof this class and was developed in themid-1990s. It is widely used in fleacontrol on domestic pets. It is alsoused in ant and roach bait stations, ag-riculture crops, and lawn treatments.It acts by inhibiting γ-aminobutyricacid–gated chlorine channels. The

inhibition will block chloride passageand result in hyperexcitability of thecell.57–59 Signs and symptoms arereported in Table 2.

HERBICIDES

Chlorophenoxy Herbicides

Chlorophenoxy herbicide compoundsare often mixed with fertilizers and areused both in agriculture and on resi-dential lawns. These compounds arewell absorbed from the GI tract but arenot well absorbed after inhalational ordermal exposure.60 Examples of com-monly used chlorophenoxy herbicidesare 2,4-D and 2,4,5-trichlorophenoxyacetic acid. The half-lives of thesecompounds range between 13 and 39hours. They are mostly excreted un-changed in the urine; excretion can begreatly enhanced in an alkaline envi-ronment.3,61,62 More toxic substancesthat can be produced during themanufacture of these herbicides in-clude dioxins, which were contam-inants of the herbicide Agent Orangeand were found in the Love Canalchemical dump site.63

Primary initial effects are on the skinand mucous membranes. Severe poi-soning will result in metabolic acidosisand possibly renal failure.3,61,64 Specificsymptoms are discussed in Tables 1and 2. The compounds can be mea-sured in the urine, although similar topyrethroid insecticides, analyses aregenerally performed at specialty labo-ratories, so results are usually notimmediately available to clinicians.Treatment is primarily supportive andmay also include forced alkaline di-uresis by adding sodium bicarbonateto the fluids and establishing a highurine pH and high urine flow.3,61,65

Phosphonate Herbicides(Glyphosate)

Glyphosate is a commonly used her-bicide and is commercially available in


many products. Glyphosate acts on thecell wall of plants, so, theoretically, itshould have no effect on human cells,at least by way of its primary mech-anism of action. Despite this, there arenumerous reports in the medical lit-erature of adverse events after humanexposure, particularly unintentionalingestions. Patients have presented withsigns and symptoms consistent with anaspiration pneumonia–like syndrome,and the offending agent may be thehydrocarbon solvent with which theglyphosate is mixed. Treatment is pri-marily supportive, and providers shouldbe vigilant for aspiration pneumonia.

RODENTICIDES (LONG-ACTINGANTICOAGULANTS)

Most currently used rodenticides be-long to the class of warfarin-typeanticoagulants. Unlike warfarin, thesuperwarfarin agents, such as brodi-facoum, have a much longer half-life.Although they have traditionally beenavailable as pellets that can be spreadaround or in a box that the rat canconsume, the EPA has recently changedthe type of products that are available toconsumers. Since 2008, superwarfarinscan only be sold as a child-resistant baitstation instead of loose pellets.66

The mechanism of action is inhi-bition of the synthesis of vitaminK–dependent clotting factors. As such,the primary manifestations of toxicityare bleeding and easy bruisability. Insevere cases, bleeding may be life-threatening. Clinicians who suspectthat their patients may have ingesteda superwarfarin should consider ob-taining a prothrombin time (PT; alsoknown as the international normal-ized ratio [INR]).3 However, severalstudies that have analyzed cohorts ofexposed children have found very fewsubjects with an elevated PT (INR) oractive bleeding. Therefore, in sit-uations in which it is unclear whethera child ingested more than a few

pellets, it is reasonable to simply ob-serve the child.67–70 Most patients canbe managed in the outpatient settingas long as the ingestion has beenrecognized early.71

Treatment is vitamin K and should bereserved for patients with elevated PT(INR) levels or active bleeding. Withsevere bleeding or shock, a trans-fusion of blood or plasma is indicatedas well.3

CHRONIC HEALTH EFFECTS OFPESTICIDE EXPOSURE

The health implications of the nonacute,relatively low, but often repetitive andcombined exposures encounteredroutinely by children are an ongoingfocus of concern and inquiry for sci-entists, regulators, and parents.72,73

Pediatricians are well placed to pro-vide guidance to parents about poten-tial long-term or subtle health effectsfrom pesticide residues on food, inwater, or used in homes or schoolsand on exposure-reduction strategies.However, surveys suggest pediatriciansoften feel ill-prepared with training inthis topic, underscoring the impor-tance of improving educational oppor-tunities for clinical providers.74–76

The associated health effects ofchronic pesticide exposure in childrenvary, reflecting the diversity of toxi-cological properties of this broadgroup of differing chemicals. Some ofthe important end points of concerninclude an increased risk of cancer,abnormal neurodevelopment, asthma,perturbation of gestational growth, andendocrine-mimicking effects. Healtheffects of pesticides and the currentrelative strength of the evidence baseare reviewed in subsequent sectionsfor each of these health outcomes.

Childhood Cancer

All pesticides undergo in vitro andanimal testing to determine their

likelihood of causing cancer. The EPAmaintains a list and classification of allactive ingredients in pesticides andtheir potential for carcinogenicity. Themethod of identifying potential carci-nogenicity has changed. Before 1996,pesticides were assigned a letterclassification (eg, pesticides with the“C” classification were considered“possibly carcinogenic”). Subsequently,pesticides have been assigned a cate-gory such as “likely to be carcinogenicto humans,” “suggestive evidence ofcarcinogenic potential,” “inadequate ev-idence,” and “not likely.” These catego-ries are not directly comparable, soboth classifications (before 1996) andcategories (after 1996) continue to exist.

The pesticides that are categorized as“possibly carcinogenic” or “likely tobe carcinogenic to humans” areavailable from the EPA via an e-mailedreport.77 Included in this report aresome well-known and widely usedOPs, carbamates, pyrethroids, andfungicides. Within classes of pesti-cides, variation in carcinogenicity po-tential exists. Note that a pesticide,such as cypermethrin, that has“replaced” use of cancer-causing OPshas cancer-causing potential.

A substantial amount of observationalepidemiological data demonstrate alink between pesticide exposure andchildhood cancers.78–87 However, theevidence base includes studies thatfound no association between child-hood cancers and pesticides or fewassociations that cannot be ruled outas a chance finding.88,89 Overall, themost comprehensive reviews of theexisting literature implicate an asso-ciation of pesticides with leukemiaand brain tumors.78,79

Leukemia

In 1998, Zahm and Ward79 reviewed 18studies assessing the relationship be-tween pesticide exposure and leukemia;13 studies found an elevated risk, and,




for 6 of those studies, the associationwas statistically significant. The mostfrequently occurring associationsamong the studies were betweenpesticide exposure and acute lym-phocytic leukemia.

A 2007 review by Infante-Rivard andWeichenthal78 summarized the 1998review of Zahm and Ward and updatedfindings from recent studies. Althoughit was previously postulated thatchildhood exposure to agriculturalproducts or proximity to an agricul-tural setting would present the highestrisks, the most commonly associatedpesticide exposure in childhood acutelymphocytic leukemia studies washousehold insecticide use. Cases weremore likely to have had preconceptionexposure and/or exposures in utero inmost studies. The main limitations withthe studies in the 1998 review includedcrude exposure assessment, concernfor recall bias, small numbers of ex-posed cases, and mixing of differentleukemia types.78

In the updated review, 5 of 6 recentcase-control studies found a statisti-cally significant relationship betweenpesticide exposure and leukemia.84,85,90–92

In particular, 2 studies included themost detailed exposure assessment todate and reported findings related toa dose/exposure–response gradient.84,85

The primary risk factors were mater-nal exposure to pesticide between theperiods of preconception throughpregnancy. The largest of the 2 stud-ies had 491 cases and an equalnumber of controls, focused only onacute lymphocytic leukemia, includeda measure of frequency of use, andconsidered genetic susceptibility. Formaternal use of herbicides, plantinsecticides, and pesticides for treesduring pregnancy, the odds ratio (OR)was 1.84 (95% confidence interval [CI],1.32–2.57), 1.97 (95% CI, 1.32–2.94),and 1.70 (95% CI, 1.12–3.59), re-spectively. For parental use during the

child’s postnatal life, OR was 1.41 (95%CI, 1.06–1.86), 1.82 (95% CI, 1.31–2.52),and 1.41 (95% CI, 1.01–1.97) after ex-posure to herbicides, plant insecticides,and pesticides for trees, respectively.84

To further explore associations betweenpesticides and leukemia, a group ofauthors conducted 2 meta-analyses.They provided similar and additionalsupport to the associations describedpreviously. One examined studies thatincluded parental occupational expo-sure (prenatally and in early childhood)and leukemia in their offspring. Mater-nal occupational exposure, but not pa-ternal occupational exposure, was foundto be associated with leukemia. Thereported OR was 2.09 (95% CI, 1.51–2.88)for overall pesticide exposure, 2.38(95% CI, 1.56–3.62) for insecticide ex-posure, and 3.62 (95% CI, 1.28–10.3) forherbicide exposure.93 The second meta-analysis assessed pesticide exposure inthe home and garden setting. In thismeta-analysis, 15 studies were included,and exposures during pregnancy tounspecified pesticides, insecticides, andherbicides were all associated withleukemia (OR, 1.54 [95% CI, 1.13–2.11],2.05 [95% CI, 1.80–2.32], and 1.61 [95%CI, 1.2–2.16], respectively).94

Brain Tumors

Zahm and Ward’s 1998 review included16 case-control studies examiningassociations between brain tumorsand pesticide exposures. Of these, 12found an increased risk estimate ofbrain tumors after pesticide exposure;7 of these findings reached statisticalsignificance. Associated exposureswere most often from parental useof pesticides in the home, in the gar-den, and on pets. Interpretation ofthese studies is difficult given theinadequate exposure assessments,small numbers because of a relativelyrare childhood outcome, and a mix-ture of brain tumor types amongcases.79

Since 1998, 10 additional studies havebeen published, all but one of whichdemonstrated an increased risk esti-mate of cancer with maternal and/orpaternal exposure, although not allstudies demonstrated statistical sig-nificance. Some of the more robustfindings come from a case-controlstudy with 321 cases of astrocyto-mas. The risk estimate from maternaloccupational exposure to insecticidesbefore or during pregnancy was 1.9(95% CI, 1.1–3.3). The risk estimatesfor paternal exposure for insecticides,herbicides, and fungicides were 1.5,1.6, and 1.6, respectively. These riskestimates were just short of reachingstatistical significance.87 In a cohortstudy of more than 200 000 patients,paternal exposure in any occupationand in agricultural/forestry precedingconception was associated with anincreased risk of central nervoussystem tumors (relative risk [RR], 2.36[95% CI, 1.27–4.39] and RR, 2.12 [95%CI, 1.08–4.39], respectively).83 For allstudies, it appears that prenatal ex-posure to insecticides, particularly inthe household, as well as both ma-ternal and paternal occupational ex-posure before conception throughbirth represent the most consistentrisk factors.83,86,87,95–100

Ewing Sarcoma

Two case-control studies were per-formed to evaluate potential parentaloccupational exposures and the de-velopment of Ewing sarcoma (ES). Onestudy of 196 cases and matched con-trols found an association between ESin boys age 15 years or younger andhousehold pesticide extermination (OR,3.0; 95% CI, 1.1–9.2). There was no as-sociation between parental occupa-tional exposure to pesticides and ES.101

A study in Australia compared 106cases of either ES or peripheral prim-itive neuroectodermal tumor with 344population-based controls. Exposures


included prenatal exposure from con-ception through pregnancy and alsoincluded parental exposures throughthe time of the child’s diagnosis. Nota-ble elevated risks were observed formothers who worked on farms (OR,2.3; 95% CI, 0.5–12.0), mothers whohandled pesticides (OR, 2.3; 95% CI,0.6–8.5), patients who ever lived ona farm (OR, 2.0; 95% CI, 1.0–3.9), andfarming fathers at the time of con-ception and/or pregnancy (OR, 3.5; 95%CI, 1.0–11.9).102 Of note in this study, all95% CIs include 1.0, so they did notreach statistical significance, althoughsome ORs approached it.

In summary, there is some evidence ofincreased risk of developing severalchildhood cancers after preconceptionand/or prenatal exposure to pesti-cides. The strongest evidence appearsto be for leukemia, which is a relativelymore common type of childhood can-cer than brain tumors. Maternal ex-posure to insecticides and paternaloccupational exposure appear to carrythe greatest risk.

Neurodevelopment/Neurobehavioral Effects

Many pesticides have well-describedacute neurotoxicant properties thathave been described previously in thisreport in relation to human poisoningepisodes and acute toxic mechanisms.However, information on the potentialneurodevelopmental toxicity arisingfrom chronic, low-level exposure ingestational or postnatal life is in-adequate or lacking for most pesti-cides in use. There is a growingavailable evidence base supporting anadverse effect on neurodevelopmentfrom 2 classes of insecticides, theorganochlorines (specifically DDT andits metabolite p,p′-dichlorodiphenyldi-chloroethylene [DDE]) and, most re-cently, OPs. Several recent reviews ofthe evidence base are now avail-able.103–105

Although chronic neurologic sequelaeafter acute OP poisoning have beenobserved in multiple adult studies,the epidemiological data on childrenare limited.106,107 A recent neuro-psychological evaluation of healthyschool-aged children who had experi-enced hospitalization for acute OPpoisoning before the age of 3 yearsfound subtle but significant deficitsin their ability to restrain and controltheir motor behaviors comparedwith both children who had no historyof poisoning and children who hada history of early life poisoning withkerosene.108

Of greater public health concern isthe potential neurotoxicity from rou-tinely encountered chronic exposures.This is the subject of study in ongoing,large National Institutes of Health/EPA-sponsored prospective birth cohorts.Studies in 2 urban settings and a ruralfarmworker community have enrolledwomen during pregnancy with anobjective assessment of exposure bythe use of environmental measure-ments and biological monitoring.104,109,110

Follow-up assessment of neurodevel-opment and neurobehavior in theirchildren with the use of validated toolssuch as the Brazelton Neonatal As-sessment Scales, the Bayley Scales ofInfant Development, the Child BehaviorChecklist, and IQ testing at comparableintervals is being conducted. To date,remarkably similar findings relatingadverse neurodevelopmental and neu-robehavioral outcomes associated withprenatal OP exposure have been madein these distinct cohort studies. Forexample, in 2 cohorts, the BrazeltonNeonatal Behavioral Assessment Scalewas administered in the first weeksof life. In both, deficits in the primi-tive reflex domain were noted withthe other 6 of 7 Brazelton NeonatalBehavioral Assessment Scale do-mains not associated with prenatalOP exposure.111,112 Two of the cohorts

have published their Bayley Mentaland Psychomotor Developmental In-dex results conducted during thetoddler years (ages 2–3).113,114 Sig-nificantly poorer mental developmentwas associated with higher OP expo-sure in both, whereas one of thecohorts also observed OP-associateddeficits in the motor scale at 3 yearsof age. Results of Child BehaviorChecklist assessments are alsoavailable for 2 cohorts, conducted at2 years of age in one and 3 to 4 yearsof age in the other. Significantly in-creased scores representative of per-vasive developmental disorder wereassociated with higher OP exposure inboth.113,114 One cohort also had in-creased scores for inattention andattention-deficit/hyperactivity disordersubscales.114 All 3 cohorts have founddecrements in IQ testing associatedwith higher prenatal exposures at thetime of follow-up at 7 years of age.115–117

In one of the cohorts, postnatal ex-posure effects in the child have beeninvestigated and reported. Interestingly,improved mental development based onBayley’s Index at 12 and 24 months ofage is associated with higher contem-porary child excretion of OP urinarymetabolites. Explanations for this aredebated but include theories that chil-dren with higher cognitive abilities mayexplore their environments more thor-oughly and, as such, experience higherexposure.

Recently, a US-based cross-sectionalanalysis demonstrated that childrenwith high urinary concentrations ofOP metabolites were more likely tohave a diagnosis of attention-deficit/hyperactivity disorder. This study useddata from a representative sample of 8-to 15-year-old children collected as partof the NHANES conducted by the CDC.118

One study based in Ecuador has ex-amined the relationship of OP exposureon neurodevelopment in school-agedchildren.119 Prenatal exposure (based




on mother occupational history ques-tionnaire) was associated with a de-crease on the Stanford-Binet copyingtest among the study subjects at 7years of age. Their concurrent exposure(on the basis of OP urinary metabolites)was associated with an increase insimple reaction time.

The toxicological mechanisms that un-derlie the adverse neurodevelopmentalobservations are also under inves-tigation. Interestingly, noncholinergicmechanisms are being deciphered inanimal models and in vitro studies,distinct from the well-described mech-anism of acute OP toxicity (cholines-terase inhibition) and occurring atdoses much lower than required toinhibit cholinesterase.120

Well-designed recent cohort studies andprevious work including animal modelssuggest that OP exposures that arebeing experienced by US children mayhave adverse neurodevelopmental con-sequences. The plasticity of these effectsand clinical implications are as yet un-clear, although continued assessmentsas these cohorts age and enter schoolage are planned and may add clarity.The potential modification of these ef-fects on the basis of genetic factors,specifically metabolic enzymes involvedin pesticide detoxification pathways, arealso being explored in these cohorts. Forexample, preliminary analyses indicatethat children with a particular variantof the paraoxonase I gene, which isassociated with lower levels of this OP-metabolizing enzyme, may be at higherrisk of health consequences from OPexposure.121,122

Although DDT has not been used sincethe early 1970s, its persistence in theenvironment and fat solubility results inongoing detection of the parent com-pound and breakdown product (DDE) incontemporary US populations.19 Thepotential adverse neurodevelopmentalconsequences of prenatal DDT (2studies) and DDE (several studies) was

studied in one of the recent cohortsdescribed previously in this report,which was a predominately MexicanAmerican farmworker population. Inthis cohort, maternal serum DDT levelswere negatively associated with mentaldevelopment and psychomotor de-velopment at 12 and 24 months.123

Maternal serum DDE was associatedwith reduced psychomotor developmentat 6 months and mental development at24 months. A review of the overall evi-dence base reveals that studies ofin utero DDE exposure and neuro-development are mixed, with at least 2studies showing decrements in psy-chomotor function. Both of the 2 studiesthat have evaluated effects of DDT ex-posure observed cognitive deficits.103

In summary, the existing and recentlyemerging evidence base suggests thatorganochlorine and OP exposure inearly life, particularly prenatally, mayhave adverse consequences on childneurodevelopment.

Physical Developmental Effects

In addition to neurodevelopmentaltoxicity, there is also considerableconcern of physical developmentaltoxicity to the embryo and fetus frompesticide exposure. These concernsarise from multiple epidemiologicalstudies that have investigated their re-lationship to adverse pregnancy out-comes including intrauterine growthretardation, preterm birth, fetal death,and congenital anomalies. The availablestudies are heterogeneous in design,are conflicting in results, and often havean insufficient exposure assessment.Nonetheless, pesticides remain one ofthe most common environmental ex-posures of concern cited in relation toadverse pregnancy outcomes and havebeen the focus of recent reviews on thetopic, which include weight of the evi-dence evaluations.124–126

Among studies that are able to addressspecific types of pesticide exposures,

there are more data focused on theorganochlorine and OP insecticides orphenoxy or triazine herbicides. Theserepresent the currently or historically(eg, organochlorine) most heavily usedpesticides. This review summarizes thehighlights of the existing evidence basewith a focus on studies that incorporatedirect measures of exposure for in-dividual study subjects.

Fetal Death and Birth Defects

A California-based case-control studyfound an increased risk of fetal deathattributable to congenital anomalieswhen OP application occurred in theresidential area of the mother duringweeks 3 through 8 of pregnancy—consistent with organogenesis.127 Oneother study found an elevated risk ofspontaneous abortion associated withchlorophenoxy herbicides. However,as with some studies of birth defectsdiscussed previously, this study alsorelied on self-report and less reliablemeans of exposure assessment.128

Results are not consistent, becauseother studies have not found associ-ation of parental exposure to OPswith spontaneous abortion or still-birth.129–131

Birth defects will be discussed first,followed by other adverse birth out-comes. The more common birthdefects include orofacial clefts, limbdefects, and neural tube defects, whichare generally the defects studied inrelationship to pesticide exposures.Although several studies have foundassociations of maternal or paternalexposures with a wide variety of birthdefect categories, all of the studiesused indirect measures of exposureand most were ecological study de-signs, making interpretation of theadverse birth outcome evidence baseinadequate and unreliable.125

A 1995 review article discussed theavailable evidence for associationsbetween birth defects and potential


pesticide exposure.132 Five studies wereincluded that assessed various birthdefects (central nervous system, oralcleft, limb defects) compared with ma-ternal agricultural occupation. Four ofthose 5 reported an elevated RR or anOR ranging from 1.6 to 5.0; however, only2 were statistically significant.133–137

Of note, in these studies, there was notan assessment to any single pesticide;rather, the “exposure” was maternaloccupation.

Six additional studies from this periodevaluated maternal pesticide exposureat work and the development of birthdefects. Of the 5 studies with an ele-vated OR or RR, ranging from 1.3 to7.5,138–142 3 were statistically signifi-cant. Unfortunately, some of thesestudies included small numbers ofcases, and others were likely to havesignificant exposure misclassification.The conclusion of this review was thatthere are some indications of elevatedrisk but no clearly convincing evi-dence.143

Two studies from Minnesota havereported a relationship between phys-ical defects in children and paternaloccupation of pesticide applicator. Thefirst study compared data from a birthregistry between 1989 and 1992. Ageographic section of Minnesota thathad the highest agriculture activity andhighest frequency of use of chloro-phenoxy herbicides and fungicides wasalso found to have the highest rate ofbirth defects (30.0/1000). By compari-son, the general population in this sameregion had a birth defect rate of 26.9/1000. Interestingly, there was a seasonaleffect, with the highest frequency oc-curring in infants who were conceivedin the spring, the same time as mostherbicide and some fungicide applica-tion (OR, 1.36; CI, 1.10–1.69).144 Thesecond study is a cross-sectional studythat used a survey of licensed appli-cators and subsequently more in-depthinterviews of either/both the applicator

and female partners of licensed appli-cators when possible. The study even-tually included live births fathered by536 applicators. The birth defect ratein this study was 31.3/1000, which isstatistically significantly higher thanwhat the previous study found for thegeneral population. Again, there wasa significant difference in season ofconception (7.6% in spring versus 3.7%in other seasons).145

Studies of birth defects often includeall types within the analysis because ofinsufficient numbers of individualdefects to allow adequate power ofstatistical analyses. A meta-analysisused 19 studies that had sufficientdata to be included to estimate theeffects of pesticides on orofacialclefting. Maternal occupational expo-sure to pesticides was associated withorofacial clefts (OR, 1.37; 95% CI, 1.04–1.81). There was a weaker associationfor paternal occupation (OR, 1.16; 95%CI, 0.94–1.44).146 Studies on 3 otherbirth defects—cryptorchidism, hypo-spadias, and polythelia—will be dis-cussed in the section on endocrineeffects.

In summary, a small risk elevation isnoted for birth defects and pesticideexposure, but the findings are notrobust, and the data specific to pes-ticide subtypes are not adequate.

Adverse Birth Outcomes (Low BirthWeight, Decreased Gestational Age)

DDT (and its major metabolite DDE) isthe organochlorine that has been mostextensively examined in relation tobirth defects, fetal death, and fetalgrowth, with mixed findings. Fetalexposures, as determined by maternalserum or umbilical cord blood levels,have been associated with pretermbirth, decreased birth weight, andintrauterine growth retardation.147–151

However, not all studies reportedsignificant associations between ex-posure with infant birth weight or

preterm birth, including a relativelyrecent study of Mexican Americanfarmworking women in the UnitedStates with higher exposures in com-parison with a similar group of a na-tional sample of nonfarmworkingMexican American women.142,152 In thelargest cohort study to date (a UScohort of births between 1959 and1966), DDE concentrations in maternalserum during pregnancy demon-strated a dose–response relationshipto risk of preterm delivery and de-livering small for gestational age(SGA) infants.147

Exposure to pesticides is associatedwith risk of decreased birth weight. Ina study conducted before recent reg-ulatory actions that reduced theirresidential use, exposure to the OPschlorpyrifos and diazinon were asso-ciated with decreased birth weight ina New York City cohort.110 In anotherNew York City cohort, birth weightwas reduced among mothers withhigher OP exposure levels in preg-nancy, but only among those witha genetic polymorphism of an OP de-toxification enzyme (paraoxonase 1 orPON1).150 In a similar longitudinalpregnancy cohort conducted amongLatina farmworkers in agriculturalCalifornia, no association of maternalpregnancy exposure to OPs and birthweight was determined, but a re-duction in gestational age was asso-ciated.153

An ecological study determined thatwomen in a rural region of Iowa withincreased levels of triazine, metola-chlor, and cyanazine herbicides in thedrinking water had an elevated risk ofdelivering an infant with intrauterinegrowth retardation compared withwomen in other parts of the state.154

A study based in France reported thatatrazine levels in municipal drinkingwater throughout pregnancy werenot associated with increased risk ofdelivering an SGA infant but that the




risk of delivering an SGA infant in-creased when the third trimester oc-curred in whole or in part during theperiod of May through September,when atrazine levels typically peak.155

Summary: Physical DevelopmentalDefects

In summary, the true extent and natureof pesticide exposure on adverse fetalgrowth and birth outcomes is un-known despite suggestive epidemio-logical studies that link some of themost widely used pesticides to re-duced intrauterine growth, fetal death,preterm birth, and congenital anom-alies. Very little is known about manypesticide types in current use, in-cluding synthetic pyrethroids andcarbamate insecticides, rodenticides,and fungicides. Studies that examinethe timing and extent of exposure topesticides and exposure to pesticidemixtures with validated exposure as-sessment techniques including bi-ological markers are needed. Thepotential for differential vulnerabilitiesbecause of genetic polymorphismsthat influence the toxicological prop-erties of these exposures must also beexplored.

ENDOCRINE EFFECTS

An emerging concern, although lesswell studied in humans, is the potentialeffects that some chemicals includingpesticides may have on the endocrinesystem. Some of the most notablepesticides thought to have such effectsare the organochlorine pesticides,such as DDT, endosulfan, methoxychlor,chlordecone, chlordane, and dieldrin.Other herbicides (atrazine, 2,4-D, andglyphosate) and fungicides (vinclozo-lin) also have some endocrine activ-ity.156–159 The associations are verycomplex and are primarily based onin vitro and animal studies. Estrogen-mimicking properties tend to be themost commonly reported, although

effects on androgen and thyroid hor-mones, among others, are alsoreported. Feminization has been notedin alligators found in lakes highlycontaminated by organochlorine pes-ticides.160 Hayes et al161 have studiedthe effects of atrazine on amphibiansand have noted a 10-fold decrease intestosterone from exposure to 25 ppbof atrazine in mature male frogs. Themechanism of the latter appears to beactivation of the enzyme aromatase,which promotes conversion of tes-tosterone to estrogen.162

The human epidemiology literature islimited on endocrine effects frompesticides. One report from Macedonianoted some degree of early pubertalfindings, primarily premature the-larche, which was hypothesized to berelated to organochlorine pesticideexposure.163 A study in 2000 with 48patients, 18 of which had cryptorchi-dism, first raised the hypothesis aboutan association with organochlorinepesticides. An association betweencryptorchidism and organochlorinepesticide levels has been hypothe-sized.164 Since then, additional case-control studies have been conductedto examine the effects of organo-chlorines on endocrine-related birthoutcomes, cryptorchidism, hypospa-dias, and/or polythelia. Two focusedon fetal exposures from maternal levelsof DDE alone and development ofcryptorchidism and hypospadias.165,166

Bhatia et al165 calculated an OR of 1.34(95% CI, 0.51–3.48) for the associationof cryptorchidism and DDE and 1.18(95% CI, 0.46–3.02) for the associationof hypospadias and DDE. Longneckeret al166 estimated an OR of 1.3 (95% CI,0.6–2.4) for the association betweenDDE and cryptorchidism and an OR of1.2 (95% CI, 0.6–2.4) the associationbetween DDE and hypospadias. Themodest association is felt to be in-conclusive with the imprecision in riskestimates and suggests that a larger

sample size may be needed. A thirdcase-control study found inconclusiveresults on the effect of heptachlor andβ-hexachlorocyclohexane levels in preg-nant women on cryptorchidism. Forheptachlor, the OR was 1.2 (95% CI, 0.6–2.6), and for β-hexachlorocyclohexane,the OR was 1.6 (95% CI, 0.7–3.6). Thesample size in this study was 219 cases,compared with 564 controls.167

Two nested case-control studies haveexamined the possibility that multipleorganochlorine compounds will havea cumulative effect on the develop-ment of urogenital abnormalities inboys.168,169 Fernandez et al168 reportedthat total xenoestrogens as well asdetectable pesticide levels were as-sociated with cryptorchidism and/orhypospadias. They found elevatedORs in the range of 2.19 for endosul-fan to 3.38 for lindane. All 95% CIswere noted to be statistically signifi-cant. The study in Finland and Denmarkreported a significant relationship be-tween chlordane and cryptorchidismbut no other relationships between 7other individual organochlorines. How-ever, combined analysis of the 8 per-sistent pesticides did demonstratea statistically significant increase incryptorchidism in exposed boys.169

Testing chemicals is an important andnecessary step for the EPA to determinepotential long-term risks from pesticideduring the registration or re-registrationprocess. There has been progress in thedevelopment of appropriate biomarkersto evaluate chemicals for the presenceof endocrine-disruption qualities. Theability to measure DDE and dioxinsfrom human milk has been developed.170

More recently, a biomarker for xenoes-trogen mixtures was developed inSpain.171

In summary, there is compellingbasic science evidence for endocrine-mimicking effects of several pesti-cide chemicals that is sound andscientifically plausible. Human data


are slowly emerging but not yet con-clusive.172

Asthma

Given the widespread use of pesticidesand the high morbidity of asthma inchildren, questions have been raisedregarding pesticides as triggers as wellas risk factors for incident disease.Concern is raised by a mounting adultoccupational literature associating pes-ticides with asthma or other measuresof respiratory health. In addition, pre-liminary toxicological data providemechanisms that link pesticides andasthma. An important limitation of mostepidemiological studies to date is thelack of exposure specificity regardingpesticide chemicals or chemical classes.In addition, studies regarding childrenare few.

There is indirect evidence that pesti-cides skew the immune response to-ward the T helper 2 (Th2) phenotypeassociated with atopic disease. TheNational Institutes of Health/EPA-sponsored rural birth cohort de-scribed above regarding evaluation ofneurodevelopmental effects has alsoobserved that maternal agriculturalwork was associated with a 26% in-crease in proportion of Th2 cells in their24-month-old infants’ blood samples.173

The percentage of Th2 cells was asso-ciated with both physician-diagnosedasthma and maternal report of wheezein these infants. This population oflargely Mexican American farmwork-ers was selected for study on thebasis of the relatively high use of OPpesticides in this agricultural area.

Animal-based toxicological mechanis-tic models include OP-induced airwayhyperreactivity via alteration in mus-carinic receptor function in airwaysmooth muscle and oxidative stressinduced by OP-related lipid perox-idation.174–177

The few epidemiological data on pesti-cides and respiratory health in children

have mixed results. In a cohort of ruralIowan children, any pesticide use in-doors or any outdoor use in the pre-vious year was not significantlyassociated with asthma symptoms andprevalence.178 Contrarily, a cross-sectional analysis of Lebanese chil-dren identified increased risk ofchronic respiratory symptoms, in-cluding wheeze, among those with anypesticide exposure in the home, expo-sure related to parent’s occupation,and use outside the home. The highestrisk was observed for children whoseparents had occupational exposure topesticides (OR, 4.61; 95% CI, 2.06–10.29).179 However, given this study’scross-sectional design, it is not possibleto discern whether the pesticide expo-sure preceded the diagnosis of asthma.

Among exposures in the first year oflife explored in a nested case-controlstudy of the Southern CaliforniaChildren’s Health Study, both herbi-cides and pesticides/insecticides hada strong association with asthma di-agnosis before 5 years of age (OR,4.58 [95% CI, 1.36–15.43] and OR, 2.39[95% CI, 1.17–4.89], respectively).180

More published data are availableregarding adult farmers and adultrural residents. These studies moreconsistently support a link betweenpesticides and respiratory symptomsor chronic respiratory disease, suchas asthma.181,182 For example, use ofmultiple individual pesticides wasevaluated in relation to self-reportedepisodes of wheeze in the previousyear in a large cohort of commercialpesticide applicators (adults) andfarmers enrolled in the AgriculturalHealth Study.182 Among the pesticidesclasses, several OPs showed associa-tions with wheeze, including severalthat demonstrated a dose–responsetrend. Chlorpyrifos, malathion, andparathion were positively associatedwith wheeze among the farmers; forthe commercial applicators, the OPs

chlorpyrifos, dichlorvos, and phoratewere positively associated with wheeze.Among commercial applicators, thestrongest OR was for applying chlorpyr-ifos on more than 40 days per year (OR,2.40; 95% CI, 1.24–4.65). Elevated risk forwheeze related to herbicide use wasalmost exclusively associated withchlorimuron-ethyl (urea-derivative class).

Similar studies addressing the re-spiratory health implications for chil-dren for specific pesticide chemicaltypes or groups are rare. However, forDDT, there is some emerging evidencefor a link between metabolites of DDTand asthma risk.183,184 In a prospectivecohort study of children in Spain,wheezing at 4 years of age increasedwith increasing levels of DDE at birth.The adjusted RR for the children withexposure in the highest quartile was2.63 (95% CI, 1.19–4.69). The use ofphysician-diagnosed asthma (occurringin 1.9% of children) instead of wheezingas the outcome variable also resultedin a positive association, although itwas not statistically significant.184

In summary, the available data re-garding chronic exposure to pesticidesand children’s respiratory health re-main limited. Studies that incorporatepesticide-specific exposure assess-ment and markers of biological mech-anisms and consider the influence oftiming of exposure across the lifespan are needed.

THE PESTICIDE LABEL

Pesticides for sale or use in the UnitedStates must be registered with the EPA,and this includes approval of theproduct label, which contains the EPAregistration number. The pesticide labelcontains several types of informationthat may be important in understandingand preventing acute health con-sequences associated with their use.185

The product label identifies the active in-gredient and provides the manufacturer’s




contact information. The label does notspecify the particular class of pesti-cide for the active ingredient, whichmay make it difficult for a physician toidentify potential toxic effects. In-formation about “other” or “inert”ingredients, which may account for upto 99% of the product, is not requiredto be disclosed on the label. Theseconstituents include chemicals withknown toxicity. The physician treatinga patient may request this from themanufacturer; however, delay in in-formation may compromise optimalclinical care. The local or regionalpoison control center plays an im-portant role as a resource for anysuspected pesticide poisoning. TheEPA is currently considering rule-making changes that would expandthe disclosure of information on inertingredients. One of the options underconsideration includes labeling 100%of the ingredients.186

The “directions for use” section on thelabel explains when, how, and wherethe pesticide may be applied. The la-bel is considered the law; therefore,any use of the product in a mannerinconsistent with the label is a viola-tion of the Federal Insecticide, Fungi-cide, and Rodenticide Act (Pub L No.80-104).187 Information on recom-mended storage of the product anddisposal of the container is alsoprinted on the label.

The label will contain a signal wordand symbol to identify acute toxicitypotential: “danger” along with theword poison and the skull and cross-bones symbol signifies high acutetoxicity; “warning” signifies moderateacute toxicity; and “caution” representsslight acute toxicity. There is a sectionfor precautionary statements regard-ing the potential hazards to peopleor pets and the actions that can betaken to reduce these hazards, suchas wearing gloves or other protectiveequipment. Basic first aid advice for

responding to dermal, inhalational,and/or oral exposure is provided. Somelabels contain a “note for physicians”that includes specific medical in-formation. The label does not provideany information or warnings aboutthe potential for chronic toxicity aris-ing from normal use or misuse of thepesticide. An example of an interactivepesticide label can be found at the EPAWeb site.188 It includes “pop-up” fea-tures that define each of the compo-nents on the pesticide label.

STATE OF PESTICIDE KNOWLEDGEAMONG PEDIATRICIANS

Self-reported medical education andself-efficacy suggests pediatriciansare not well prepared to identifypesticide exposure and illness, in-cluding taking a relevant environ-mental history or discussing pesticiderisks with their patients.189–191 Even inagricultural areas of the Pacific North-west, where pesticide use is heavy,a survey of health care providers whoserve high volumes of agriculturalfarmworkers and their families foundthat 61% did not feel comfortableresponding to patient/client questionsregarding pesticides on the basis oftheir training, background, and experi-ence.75 Among academic pediatricianswith an interest in pediatric environ-mental health, pesticides were amongthe topics they felt least prepared toteach to their trainees.192 Given thewidespread use of pesticides and con-cerns for child health, opportunities toincrease pesticide competency in pe-diatric medical education are likely toprevent missed diagnoses and reduceexposure because of improved antici-patory guidance.

Clinicians must have a high index ofsuspicion to identify pesticide poi-soning. Identification and treatment ofacute pesticide poisoning requiresfamiliarity with the toxic mechanismsand related signs and symptoms of the

pesticide classes. For example, whenevaluating a patient with status epi-lepticus or mental status changes,certain insecticides belong in the dif-ferential among the numerous andmore common etiologies. Eliciting anenvironmental history will help de-cipher the relative importance ofpesticides in further clinical decision-making. The environmental history isa general tool for addressing poten-tially hazardous environmental expo-sures and is discussed in detail in thePediatric Environmental Health man-ual from the AAP.193

EFFORTS TO REDUCE PESTICIDEEXPOSURE

Dietary Considerations

Dietary modifications can help reducepesticide exposure. As mentioned pre-viously, consuming organic produce hasshown a reduced amount of urinarypesticide levels in comparison witha conventional diet.22 Because manyfood-based pesticide residues occur onthe surface of food crops, other prac-tical approaches may be used to reduceexposures by washing produce, peelingoff outer layers of leafy vegetables, andremoving peels from fruits and vegeta-bles. Trimming fat from meat and fatand skin from poultry and fish mayreduce residues of persistent pesti-cides, such as the organochlorines, thatconcentrate in animal fat.

Efforts to address and reduce chronicpesticide exposure via the food supplyin children have included regulatoryapproaches that consider the uniquevulnerability of the developing child inpolicy decision-making. For example,the 1996 Food Quality Protection Act(Pub L No. 104-170, Section 405) re-quired that the EPA use an additional10-fold margin of safety regardinglimits of pesticide residues on food(unless there are data that showa less stringent residue level is safe for


prenatal and postnatal development;for description, see http://www.epa.gov/opp00001/factsheets/riskassess.htm).

Integrated Pest Management

In addition to food residues, use ofpesticides in and around the home andother settings where children spendtime (child care, school, and play-grounds and sports fields) is an im-portant influence on the chronic andcumulative exposure to pesticidesamong US children. Most of the pestproblems that occur indoors as well ascontrol of lawn and garden pestscan be addressed with least toxicapproaches, including integrated pestmanagement (IPM) techniques. IPMfocuses on nontoxic and least toxiccontrol methods to address pestproblems have been promoted andadopted for residential, school, andagricultural settings (fact sheetsavailable at http://www.epa.gov/opp00001/factsheets/ipm.htm).

“Integrated” refers to employment ofcomplementary strategies of pestcontrol, which may include mechani-cal devices; physical devices; genetic,biological, and cultural management;and chemical management. For ex-ample, to control cockroaches, a fam-ily could be counseled to keepgarbage and trash in containers withwell-fitted lids, eliminate plumbingleaks or other sources of moisture,store food in insect-proof containers,vacuum cracks and crevices, clean upspills immediately, and use the least-toxic insecticides, such as boric acid,in cracks and crevices or bait sta-tions. The goal is to target the pestand limit the effect on other organ-isms and the environment. Althoughdeveloped with a focus on agriculturalinsect pests, IPM programs andknowledge have extended to addressweeds and pest control in residentialsettings and schools, commercial

structures, lawn and turf, and com-munity gardens.

Within agriculture, IPM has been rec-ognized and promoted for decades;however, inadequate leadership, co-ordination, and management of USDepartment of Agriculture IPM pro-grams were identified as impedimentsto adequate progress in a 2001 re-port.194 The report provided the basisfor an ongoing national roadmap ef-fort to improve ongoing developmentof increased IPM in agriculture.

To protect children, IPM in schools hasbeen recommended by the US De-partment of Agriculture, EPA, AmericanPublic Health Association, and NationalParent Teacher Association. Many statesand local municipalities have adoptedprograms and resources to encourageIPM in public places, in addition to homesand schools (see Table 3). IPM strategiesseek to minimize insecticide use by ap-plying strategies such as cleaning upfood and water, sealing cracks andcrevices, and using pesticides that arecontained in baits or traps, which arefar less likely to pose a health concerncompared with any type of broadcastspray application. Avoiding combinationproducts with pesticides and fertilizers(ie, “weed and feed” preparations) isadvised for lawn maintenance, becausethese tend to result in overapplication ofpesticides. Hand weeding is alwaysa reasonable alternative to herbicides.However, if an herbicide is to be used,some (such as glyphosate) have betteracute human toxicity profiles than oth-ers (such as 2,4-D). Even so, glyphosateis not without its risks. Most cases ofmoderate to severe toxicity have oc-curred after intentional (suicidal) in-gestion.195 Using safe storage practices(in a locked cabinet or building) andnot reusing pesticide containers areimportant components toward theprevention of acute poisonings af-ter unintentional ingestion by smallchildren. Reliable resources for use-

ful information on pest-control alter-natives and safe use of pesticides areavailable from the EPA and Universityof California-Davis (Table 3).

Spraying in the Community: Rightto Know

Although there is no federal mandatefor notification of pesticide use incommunities, many states, locales, orschools have implemented require-ments for posting warning signs ordeveloping registries to alert individ-uals of planned pesticide application(see Table 3). These are designed toallow the public to make decisions toavoid exposures during application orsoon after from residues. Other localpolicies that have been developed in-clude restricting spray zones that cre-ate buffers from schools or other areasor restrict specific types of pesticideproducts in schools. Pediatricians canplay a role in the promotion of de-velopment of model programs andpractices in the communities andschools of their patients. For example,in some communities, pediatricianshave participated in local organizationsthat have successfully advocated for nopesticide application in schools.

SUMMARY

Pesticides are a complex group ofchemicals with a wide range of acuteand chronic toxicity. Poison controlcenters report lower rates of moresevere poisonings but continue to re-port similar total numbers of acuteexposures among children. There isa growing body of literature thatsuggests that pesticides may inducechronic health complications in chil-dren, including neurodevelopmental orbehavioral problems, birth defects,asthma, and cancer. Pediatricians area trusted source of information forfamilies and communities, althoughcurrent training focused on pesticidetoxicity and environmental health, in




http://www.epa.gov/opp00001/factsheets/riskassess.htm



http://www.epa.gov/opp00001/factsheets/ipm.htm

http://www.epa.gov/opp00001/factsheets/ipm.htm

general, is limited. Pediatricians shouldbe familiar with the common pesticidetypes, signs and symptoms of acutetoxicity, and chronic health implications.Efforts should bemade to limit children’sexposure as much as possible and toensure that products released to themarketplace have been appropriatelytested for safety to protect fetuses,infants, and children from adverseeffects.

LEAD AUTHORSJames R. Roberts, MD, MPHCatherine J. Karr, MD, PhD

COUNCIL ON ENVIRONMENTALHEALTH EXECUTIVE COMMITTEE,2012–2013Jerome A. Paulson, MD, ChairpersonAlice C. Brock-Utne, MDHeather L. Brumberg, MD, MPHCarla C. Campbell, MDBruce P. Lanphear, MD, MPHKevin C. Osterhoudt, MD, MSCEMegan T. Sandel, MDLeonardo Trasande, MD, MPPRobert O. Wright, MD, MPH

FORMER EXECUTIVE COMMITTEEMEMBERSHelen J. Binns, MD, MPHJames R. Roberts, MD, MPH

Catherine J. Karr, MD, PhDJoel A. Forman, MDJames M. Seltzer, MD

LIAISONSMary Mortensen, MD – Centers for DiseaseControl and Prevention/National Center forEnvironmental HealthWalter J. Rogan, MD – National Institute ofEnvironmental Health SciencesSharon Savage, MD – National CancerInstitute

STAFFPaul Spire

TABLE 3 Pesticide and Child Health Resources for the Pediatrician

Management of Acute Pesticide Poisoning

Recognition and Management ofPesticide Poisonings

Print: fifth (1999) is available in Spanish, English(6th edition available 2013)http://www.epa.gov/pesticides/safety/healthcare/handbook/handbook.htm

Regional Poison Control Centers 1-800-222-1222

Chronic Exposure Information/Specialty Consultation

The National Pesticide MedicalMonitoring Program (NPMMP)

Cooperative agreement between Oregon StateUniversity and the EPA

[email protected]

NPMMP provides informational assistance by e-mailin the assessment of human exposure topesticides

or by fax at 541-737-9047

Pediatric Environmental HealthSpecialty Units (PEHSUs)

Coordinated by the Association of Occupational andEnvironmental Clinics to provide regionalacademically based free consultation for healthcare providers

http://www.aoec.org/PEHSU.htmToll-free telephone number 888-347-AOEC (2632)

Resources for Safer Approaches to Pest Control

EPA Consumer information documents http://www.epa.gov/oppfead1/Publications/Cit_Guide/citguide.pdf

Citizens Guide to Pest Controland Pesticide Safety

• Household pest control• Alternatives to chemical pesticides• How to choose pesticides• How to use, store, and dispose of them safely• How to prevent pesticide poisoning• How to choose a pest-control company

Controlling pests Recommended safest approaches and examples ofprograms

http://www.epa.gov/pesticides/controlling/index.htm

The University of California IntegrativePest Management Program

Information on IPM approaches for common homeand garden pests

http://www.ipm.ucdavis.edu

Other Resources

National research programs addressingchildren’s health and pesticides

NIEHS/EPA Centers for Children’s EnvironmentalHealth & Disease Prevention Research

www.niehs.nih.gov/research/supported/centers/prevention

The National Children’s Study www.nationalchildrensstudy.gov/Pages/default.aspxEPA Pesticide product labels www.epa.gov/pesticides/regulating/labels/product-labels.

htm#projectsThe National Library of Medicine “Tox Town” Section on pesticides that includes a comprehensive

and well-organized list of Web link resources onpesticides

http://toxtown.nlm.nih.gov/text_version/chemicals.php?id=23

NIEHS, National Institute of Environmental Health Sciences.


http://www.epa.gov/pesticides/safety/healthcare/handbook/handbook.htm

http://www.aoec.org/PEHSU.htm

http://www.epa.gov/oppfead1/Publications/Cit_Guide/citguide.&emsp;pdf

http://www.epa.gov/oppfead1/Publications/Cit_Guide/citguide.&emsp;pdf

http://www.epa.gov/pesticides/controlling/index.htm

http://www.ipm.ucdavis.edu

www.niehs.nih.gov/research/supported/centers/prevention

www.nationalchildrensstudy.gov/Pages/default.aspx

www.epa.gov/pesticides/regulating/labels/product-labels.&emsp;htm#projects

www.epa.gov/pesticides/regulating/labels/product-labels.&emsp;htm#projects

http://toxtown.nlm.nih.gov/text_version/chemicals.php?id=23

REFERENCES

1. American Academy of Pediatrics, Com-mittee on Environmental Health. Pesti-cides. In: Etzel RA, Balk SJ, eds. PediatricEnvironmental Health. 2nd ed. Elk GroveVillage, IL: American Academy of Pediat-rics; 2003

2. Katz TM, Miller JH, Hebert AA. Insectrepellents: historical perspectives andnew developments. J Am Acad Dermatol.2008;58(5):865–871

3. Reigart JR, Roberts JR. Recognition andManagement of Pesticide Poisoning. 5thed. Washington, DC: US EnvironmentalProtection Agency; 1999

4. Freeman NC, Hore P, Black K, et al. Con-tributions of children’s activities to pesti-cide hand loadings following residentialpesticide application. J Expo Anal EnvironEpidemiol. 2005;15(1):81–88

5. Freeman NC, Jimenez M, Reed KJ, et al.Quantitative analysis of children’s micro-activity patterns: The Minnesota Chil-dren’s Pesticide Exposure Study. J ExpoAnal Environ Epidemiol. 2001;11(6):501–509

6. Lewis RG, Fortune CR, Blanchard FT,Camann DE. Movement and deposition oftwo organophosphorus pesticides withina residence after interior and exteriorapplications. J Air Waste Manag Assoc.2001;51(3):339–351

7. Hore P, Robson M, Freeman N, et al.Chlorpyrifos accumulation patterns forchild-accessible surfaces and objects andurinary metabolite excretion by childrenfor 2 weeks after crack-and-crevice ap-plication. Environ Health Perspect. 2005;113(2):211–219

8. Curwin BD, Hein MJ, Sanderson WT, et al.Pesticide contamination inside farm andnonfarm homes. J Occup Environ Hyg.2005;2(7):357–367

9. Lu C, Fenske RA, Simcox NJ, Kalman D.Pesticide exposure of children in an ag-ricultural community: evidence of house-hold proximity to farmland and takehome exposure pathways. Environ Res.2000;84(3):290–302

10. Fenske RA, Black KG, Elkner KP, Lee CL,Methner MM, Soto R. Potential exposureand health risks of infants following in-door residential pesticide applications.Am J Public Health. 1990;80(6):689–693

11. Whyatt RM, Garfinkel R, Hoepner LA, et al.Within- and between-home variability inindoor air insecticide levels during preg-nancy among an inner-city cohort fromNew York City. Environ Health Perspect.2007;15(3):383–389

12. Gurunathan S, Robson M, Freeman N,et al. Accumulation of chlorpyrifos onresidential surfaces and toys accessibleto children. Environ Health Perspect. 1998;106(1):9–16

13. Coronado GD, Vigoren EM, Thompson B,Griffith WC, Faustman EM. Organophos-phate pesticide exposure and work inpome fruit: evidence for the take-homepesticide pathway. Environ Health Per-spect. 2006;114(7):999–1006

14. Julien R, Adamkiewicz G, Levy JI, BennettD, Nishioka M, Spengler JD. Pesticideloadings of select organophosphate andpyrethroid pesticides in urban publichousing. J Expo Sci Environ Epidemiol.2008;18(2):167–174

15. Nishioka MG, Lewis RG, Brinkman MC,Burkholder HM, Hines CE, Menkedick JR.Distribution of 2,4-D in air and on surfa-ces inside residences after lawn applica-tions: comparing exposure estimatesfrom various media for young children.Environ Health Perspect. 2001;109(11):1185–1191

16. Morgan MK, Stout DM, Jones PA, Barr DB.An observational study of the potential forhuman exposures to pet-borne diazinonresidues following lawn applications. En-viron Res. 2008;107(3):336–342

17. Colt JS, Lubin J, Camann D, et al. Com-parison of pesticide levels in carpet dustand self-reported pest treatment practi-ces in four US sites. J Expo Anal EnvironEpidemiol. 2004;14(1):74–83

18. Morgan MK, Sheldon LS, Croghan CW,et al. Exposures of preschool children tochlorpyrifos and its degradation product3,5,6-trichloro-2-pyridinol in their every-day environments. J Expo Anal EnvironEpidemiol. 2005;15(4):297–309

19. Centers for Disease Control and Pre-vention, National Center for Environmen-tal Health Division of Laboratory Sciences.National Report on Human Exposure toEnvironmental Chemicals. Atlanta, GA:Centers for Disease Control and Pre-vention; 2005. NCEH Pub. No. 05-0570.Available at: www.cdc.gov/exposurereport/.Accessed June 8, 2011

20. Riederer AM, Bartell SM, Barr DB, RyanPB. Diet and nondiet predictors of urinary3-phenoxybenzoic acid in NHANES 1999-2002. Environ Health Perspect. 2008;116(8):1015–1022

21. US Food and Drug Administration. Centerfor Food Safety and Applied Nutrition.Pesticide Residue Monitoring Program2003. Available at: www.cfsan.fda.gov/

∼dms/pes03rep.html. Accessed June 8,2011

22. Lu C, Toepel K, Irish R, Fenske RA, Barr DB,Bravo R. Organic diets significantly lowerchildren’s dietary exposure to organo-phosphorus pesticides. Environ HealthPerspect. 2006;114(2):260–263

23. Curl CL, Fenske RA, Kissel JC, et al. Eval-uation of take-home organophosphoruspesticide exposure among agriculturalworkers and their children. EnvironHealth Perspect. 2002;110(12):A787–A792

24. Harnly ME, Bradman A, Nishioka M, et al.Pesticides in dust from homes in an ag-ricultural area. Environ Sci Technol. 2009;43(23):8767–8774

25. Curwin BD, Hein MJ, Sanderson WT, et al.Pesticide dose estimates for children ofIowa farmers and non-farmers. EnvironRes. 2007;105(3):307–315

26. Shipp EM, Cooper SP, del Junco DJ, BolinJN, Whitworth RE, Cooper CJ. Pesticidesafety training among farmworker ado-lescents from Starr County, Texas. J AgricSaf Health. 2007;13(3):311–321

27. Gamlin J, Diaz Romo P, Hesketh T. Ex-posure of young children working onMexican tobacco plantations to organo-phosphorous and carbamic pesticides,indicated by cholinesterase depression.Child Care Health Dev. 2007;33(3):246–248

28. Eckerman DA, Gimenes LS, de Souza RC,Galvão PR, Sarcinelli PN, Chrisman JR. Agerelated effects of pesticide exposure onneurobehavioral performance of adoles-cent farm workers in Brazil. NeurotoxicolTeratol. 2007;29(1):164–175

29. Gilliom RJ. Pesticides in U.S. streams andgroundwater. Environ Sci Technol. 2007;41(10):3408–3414

30. Bronstein AC, Spyker DA, Cantilena LR, Jr;Green JL, Rumack BH, Giffin SL. 2009 An-nual Report of the American Associationof Poison Control Centers’ National PoisonData System (NPDS): 27th Annual Report.Clin Toxicol (Phila). 2010;48(10):979–1178

31. Blondell JM. Decline in pesticide poison-ings in the United States from 1995 to2004. Clin Toxicol. 2007;45(5):589–592

32. Lifshitz M, Shahak E, Sofer S. Carbamateand organophosphate poisoning in youngchildren. Pediatr Emerg Care. 1999;15(2):102–103

33. Zwiener RJ, Ginsburg CM. Organophosphateand carbamate poisoning in infants andchildren. Pediatrics. 1988;81(1):121–126

34. Sofer S, Tal A, Shahak E. Carbamate andorganophosphate poisoning in early




www.cdc.gov/exposurereport/

www.cfsan.fda.gov/&tnqh_x223C;dms/pes03rep.html

www.cfsan.fda.gov/&tnqh_x223C;dms/pes03rep.html

childhood. Pediatr Emerg Care. 1989;5(4):222–225

35. Roberts DM, Aaron CK. Management ofacute organophosphorus pesticide poi-soning. BMJ. 2007;334(7594):629–634

36. Chyka PA, Seger D, Krenzelok EP, Vale JA;American Academy of Clinical Toxicology;European Association of Poisons Centresand Clinical Toxicologists. Position state-ment: single-dose activated charcoal. ClinToxicol (Phila). 2005;43(2):61–87

37. Eddleston M, Juszczak E, Buckley NA, et al;Ox-Col Poisoning Study collaborators.Multiple-dose activated charcoal in acuteself-poisoning: a randomised controlledtrial. Lancet. 2008;371(9612):579–587

38. Geller RJ, Singleton KL, Tarantino ML, et al;Centers for Disease Control and Pre-vention (CDC). Nosocomial poisoning as-sociated with emergency departmenttreatment of organophosphate toxicity—Georgia, 2000. MMWR Morb Mortal WklyRep. 2001;49(51-52):1156–1158

39. Pawar KS, Bhoite RR, Pillay CP, Chavan SC,Malshikare DS, Garad SG. Continuouspralidoxime infusion versus repeated bo-lus injection to treat organophosphoruspesticide poisoning: a randomised con-trolled trial. Lancet. 2006;368(9553):2136–2141

40. Eddleston M, Eyer P, Worek F, et al. Pralidox-ime in acute organophosphorus insecticidepoisoning—a randomised controlled trial.PLoS Med. 2009;6(6):e1000104

41. World Health Organization, InternationalProgramme on Chemical Safety. PoisonsInformation Monograph G001. Organophos-phorus Pesticides. Geneva, Switzerland:World Health Organization; 1999

42. Ray DE, Forshaw PJ. Pyrethroid insecti-cides: poisoning syndromes, synergies,and therapy. J Toxicol Clin Toxicol. 2000;38(2):95–101

43. Ray DE, Fry JR. A reassessment of theneurotoxicity of pyrethroid insecticides.Pharmacol Ther. 2006;111(1):174–193

44. Dorman DC, Beasley VR. Neurotoxicologyof pyrethrin and the pyrethroid insecti-cides. Vet Hum Toxicol. 1991;33(3):238–243

45. He F, Wang S, Liu L, Chen S, Zhang Z, Sun J.Clinical manifestations and diagnosis ofacute pyrethroid poisoning. Arch Toxicol.1989;63(1):54–58

46. Tucker SB, Flannigan SA. Cutaneous effectsfrom occupational exposure to fenvalerate.Arch Toxicol. 1983;54(3):195–202

47. Tucker SB, Flannigan SA, Ross CE. In-hibition of cutaneous paresthesia result-ing from synthetic pyrethroid exposure.Int J Dermatol. 1984;23(10):686–689

48. Wilks MF. Pyrethroid-induced paresthesia—a central or local toxic effect? Clin Toxicol(Phila). 2000;38(2):103–105

49. Song JH, Narahashi T. Selective block oftetramethrin-modified sodium channels by(+/-)-alpha-tocopherol (vitamin E). J Phar-macol Exp Ther. 1995;275(3):1402–1411

50. Meinking TL, Serrano L, Hard B, et al.Comparative in vitro pediculicidal efficacyof treatments in a resistant head licepopulation in the United States. ArchDermatol. 2002;138(2):220–224

51. Feldmann RJ, Maibach HI. Percutaneouspenetration of some pesticides and her-bicides in man. Toxicol Appl Pharmacol.1974;28(1):126–132

52. Ginsburg CM, Lowry W, Reisch JS. Ab-sorption of lindane (gamma benzenehexachloride) in infants and children.J Pediatr. 1997;91(6):998–1000

53. US Environmental Protection Agency. Lin-dane; Cancellation order. Fed Regist. 2006;71(239):74905–74907. Available at: www.epa.gov/fedrgstr/EPA-PEST/2006/December/Day-13/p21101.htm. Accessed June 28,2011

54. Tomizawa M, Casida JE. Neonicotinoid in-secticide toxicology: mechanisms of se-lective action. Annu Rev PharmacolToxicol. 2005;45(7):247–268

55. Matsuda K, Buckingham SD, Kleier D, RauhJJ, Grauso M, Sattelle DB. Neonicotinoids:insecticides acting on insect nicotinicacetylcholine receptors. Trends Pharma-col Sci. 2001;22(11):573–580

56. David D, George IA, Peter JV. Toxicology ofthe newer neonicotinoid insecticides:imidacloprid poisoning in a human. ClinToxicol (Phila). 2007;45(5):485–486

57. Bloomquist JR. Ion channels as targetsfor insecticides. Annu Rev Entomol. 1996;41:163–190

58. Ratra GS, Casida JE. GABA receptor sub-unit composition relative to insecticidepotency and selectivity. Toxicol Lett. 2001;122(3):215–222

59. Hainzl D, Cole LM, Casida JE. Mechanismsfor selective toxicity of fipronil insecticideand its sulfone metabolite and desulfinylphotoproduct. Chem Res Toxicol. 1998;11(12):1529–1535

60. Arnold EK, Beasley VR. The pharmacoki-netics of chlorinated phenoxy acid herbi-cides: a literature review. Vet Hum Toxicol.1989;31(2):121–125

61. Friesen EG, Jones GR, Vaughan D. Clinicalpresentation and management of acute2,4-D oral ingestion. Drug Saf. 1990;5(2):155–159

62. Prescott LF, Park J, Darrien I. Treatment ofsevere 2,4-D and mecoprop intoxication

with alkaline diuresis. Br J Clin Pharma-col. 1979;7(1):111–116

63. Schecter A, Birnbaum L, Ryan JJ, ConstableJD. Dioxins: an overview. Environ Res.2006;101(3):419–428

64. Keller T, Skopp G, Wu M, Aderjan R. Fataloverdose of 2,4-dichlorophenoxyaceticacid (2,4-D). Forensic Sci Int. 1994;65(1):13–18

65. Proudfoot AT, Krenzelok EP, Vale JA. Posi-tion Paper on urine alkalinization. J Tox-icol Clin Toxicol. 2004;42(1):1–26

66. US Environmental Protection Agency. Finalrisk mitigation decision for ten rodenti-cides. Available at: www.epa.gov/fedrgstr/EPA-PEST/2006/December/Day-13/p21101.htm. Accessed June 28, 2011

67. Ingels M, Lai C, Tai W, et al. A prospectivestudy of acute, unintentional, pediatricsuperwarfarin ingestions managed with-out decontamination. Ann Emerg Med.2002;40(1):73–78

68. Smolinske SC, Scherger DL, Kearns PS,Wruk KM, Kulig KW, Rumack BH. Super-warfarin poisoning in children: a pro-spective study. Pediatrics. 1989;84(3):490–494

69. Shepherd G, Klein-Schwartz W, AndersonBD. Acute, unintentional pediatric brodi-facoum ingestions. Pediatr Emerg Care.2002;18(3):174–178

70. Mullins ME, Brands CL, Daya MR. Un-intentional pediatric superwarfarin expo-sures: do we really need a prothrombintime? Pediatrics. 2000;105(2):402–404

71. Caravati EM, Erdman AR, Scharman EJ,et al. Long-acting anticoagulant rodenti-cide poisoning: an evidence-based con-sensus guideline for out-of-hospitalmanagement. Clin Toxicol (Phila). 2007;45(1):1–22

72. US Environmental Protection Agency. FoodQuality Protection Act of 1996. Pub L No.104-170 (1996)

73. Karr CJ, Solomon GM, Brock-Utne AC.Health effects of common home, lawn,and garden pesticides. Pediatr Clin NorthAm. 2007;54(1):63–80, viii

74. Roberts JR, Balk SJ, Forman J, ShannonM. Teaching about pediatric environmen-tal health [letter]. Ambul Pediatr. 2009;9(2):129–130

75. Karr C, Murphy H, Glew G, Keifer MC,Fenske RA. Pacific Northwest health pro-fessionals survey on pesticides and chil-dren. J Agromed. 2006;11(3-4):113–120

76. McCurdy LE, Roberts JR, Rogers B, et al.Incorporating environmental health intopediatric medical and nursing education.Environ Health Perspect. 2004;112(17):1755–1760


www.epa.gov/fedrgstr/EPA-PEST/2006/December/Day-13/p21101.htm






77. US Environmental Protection Agency, Officeof Pesticide Programs. Chemicals evaluatedfor carcinogenic potential. Available at:www.epa.gov/pesticides/carlist. AccessedJune 8, 2011

78. Infante-Rivard C, Weichenthal S. Pesticidesand childhood cancer: an update of Zahmand Ward’s 1998 review. J Toxicol EnvironHealth B Crit Rev. 2007;10(1-2):81–99

79. Zahm SH, Ward MH. Pesticides and child-hood cancer. Environ Health Perspect.1998;106(suppl 3):893–908

80. Buckley JD, Robison LL, Swotinsky R, et al.Occupational exposures of parents ofchildren with acute nonlymphocytic leu-kemia: a report from the Childrens Can-cer Study Group. Cancer Res. 1989;49(14):4030–4037

81. Cordier S, Iglesias MJ, Le Goaster C, GuyotMM, Mandereau L, Hemon D. Incidenceand risk factors for childhood braintumors in the Ile de France. Int J Cancer.1994;59(6):776–782

82. Davis JR, Brownson RC, Garcia R, Bentz BJ,Turner A. Family pesticide use and child-hood brain cancer. Arch Environ ContamToxicol. 1993;24(1):87–92

83. Feychting M, Plato N, Nise G, Ahlbom A.Paternal occupational exposures andchildhood cancer. Environ Health Per-spect. 2001;109(2):193–196

84. Infante-Rivard C, Labuda D, Krajinovic M,Sinnett D. Risk of childhood leukemia as-sociated with exposure to pesticides andwith gene polymorphisms. Epidemiology.1999;10(5):481–487

85. Ma X, Buffler PA, Gunier RB, et al. Criticalwindows of exposure to household pesti-cides and risk of childhood leukemia.Environ Health Perspect. 2002;110(9):955–960

86. Schüz J, Kaletsch U, Kaatsch P, Meinert R,Michaelis J. Risk factors for pediatrictumors of the central nervous system:results from a German population-basedcase-control study. Med Pediatr Oncol.2001;36(2):274–282

87. van Wijngaarden E, Stewart PA, Olshan AF,Savitz DA, Bunin GR. Parental occupationalexposure to pesticides and childhoodbrain cancer. Am J Epidemiol. 2003;157(11):989–997

88. Reynolds P, Von Behren J, Gunier RB,Goldberg DE, Hertz A, Harnly ME. Child-hood cancer and agricultural pesticideuse: an ecologic study in California. Envi-ron Health Perspect. 2002;110(3):319–324

89. Reynolds P, Von Behren J, Gunier RB,Goldberg DE, Harnly M, Hertz A. Agriculturalpesticide use and childhood cancer inCalifornia. Epidemiology. 2005;16(1):93–100

90. Infante-Rivard C, Sinnett D. Preconcep-tional paternal exposure to pesticides andincreased risk of childhood leukaemia.Lancet. 1999;354(9192):1819–1820

91. Meinert R, Schüz J, Kaletsch U, Kaatsch P,Michaelis J. Leukemia and non-Hodgkin’slymphoma in childhood and exposure topesticides: results of a register-basedcase-control study in Germany. Am J Epi-demiol. 2000;151(7):639–646, discussion647–650

92. Alexander FE, Patheal SL, Biondi A, et al.Transplacental chemical exposure andrisk of infant leukemia with MLL genefusion. Cancer Res. 2001;61(6):2542–2546

93. Wigle DT, Turner MC, Krewski D. A sys-tematic review and meta-analysis ofchildhood leukemia and parental occu-pational pesticide exposure. EnvironHealth Perspect. 2009;117(10):1505–1513

94. Turner MC, Wigle DT, Krewski D. Residen-tial pesticides and childhood leukemia:a systematic review and meta-analysis.Environ Health Perspect. 2010;118(1):33–41

95. Flower KB, Hoppin JA, Lynch CF, et al.Cancer risk and parental pesticide appli-cation in children of Agricultural HealthStudy participants. Environ Health Per-spect. 2004;112(5):631–635

96. Cordier S, Mandereau L, Preston-Martin S,et al. Parental occupations and childhoodbrain tumors: results of an internationalcase-control study. Cancer Causes Con-trol. 2001;12(9):865–874

97. McKinney PA, Fear NT, Stockton D; UKChildhood Cancer Study Investigators.Parental occupation at periconception:findings from the United Kingdom Child-hood Cancer Study. Occup Environ Med.2003;60(12):901–909

98. Heacock H, Hertzman C, Demers PA, et al.Childhood cancer in the offspring of malesawmill workers occupationally exposedto chlorophenate fungicides. EnvironHealth Perspect. 2000;108(6):499–503

99. Rodvall Y, Dich J, Wiklund K. Cancer risk inoffspring of male pesticide applicators inagriculture in Sweden. Occup EnvironMed. 2003;60(10):798–801

100. Schreinemachers DM. Cancer mortality infour northern wheat-producing states.Environ Health Perspect. 2000;108(9):873–881

101. Moore LE, Gold L, Stewart PA, Gridley G,Prince JR, Zahm SH. Parental occupationalexposures and Ewing’s sarcoma. Int JCancer. 2005;114(3):472–478

102. Valery PC, McWhirter W, Sleigh A, WilliamsG, Bain C. Farm exposures, parental oc-cupation, and risk of Ewing’s sarcoma in

Australia: a national case-control study.Cancer Causes Control. 2002;13(3):263–270

103. Rosas LG, Eskenazi B. Pesticides and childneurodevelopment. Curr Opin Pediatr.2008;20(2):191–197

104. Eskenazi B, Rosas LG, Marks AR, et al.Pesticide toxicity and the developingbrain. Basic Clin Pharmacol Toxicol. 2008;102(2):228–236

105. Jurewicz J, Hanke W. Prenatal andchildhood exposure to pesticides andneurobehavioral development: review ofepidemiological studies. Int J Occup MedEnviron Health. 2008;21(2):121–132

106. Keifer MC, Mahurin RK. Chronic neurologiceffects of pesticide overexposure. OccupMed. 1997;12(2):291–304

107. Eskenazi B, Bradman A, Castorina R.Exposures of children to organophos-phate pesticides and their potential ad-verse health effects. Environ HealthPerspect. 1999;107(suppl 3):409–419

108. Kofman O, Berger A, Massarwa A, FriedmanA, Jaffar AA. Motor inhibition and learningimpairments in school-aged children fol-lowing exposure to organophosphatepesticides in infancy. Pediatr Res. 2006;60(1):88–92

109. Berkowitz GS, Obel J, Deych E, et al. Expo-sure to indoor pesticides during pregnancyin a multiethnic, urban cohort. EnvironHealth Perspect. 2003;111(1):79–84

110. Perera FP, Rauh VA, Tsai WY, et al. Effectsof transplacental exposure to environ-mental pollutants on birth outcomes ina multiethnic population. Environ HealthPerspect. 2003;111(2):201–205

111. Young JG, Eskenazi B, Gladstone EA, et al.Association between in utero organophos-phate pesticide exposure and abnormalreflexes in neonates. Neurotoxicology. 2005;26(2):199–209

112. Engel SM, Berkowitz GS, Barr DB, et al.Prenatal organophosphate metabolite andorganochlorine levels and performanceon the Brazelton Neonatal Behavioral As-sessment Scale in a multiethnic preg-nancy cohort. Am J Epidemiol. 2007;165(12):1397–1404

113. Eskenazi B, Marks AR, Bradman A, et al.Organophosphate pesticide exposure andneurodevelopment in young Mexican-American children. Environ Health Per-spect. 2007;115(5):792–798

114. Rauh VA, Garfinkel R, Perera FP, et al. Im-pact of prenatal chlorpyrifos exposure onneurodevelopment in the first 3 years oflife among inner-city children. Pediatrics.2006;118(6). Available at: www.pediatrics.org/cgi/content/full/118/6/e1845




www.epa.gov/pesticides/carlist

115. Rauh V, Arunajadai S, Horton M, et al.Seven-year neurodevelopmental scoresand prenatal exposure to chlorpyrifos,a common agricultural pesticide. EnvironHealth Perspect. 2011;119(8):1196–1201

116. Bouchard MF, Chevrier J, Harley KG, et al.Prenatal exposure to organophosphatepesticides and IQ in 7-year-old children.Environ Health Perspect. 2011;119(8):1189–1195

117. Engel SM, Wetmur J, Chen J, et al. Prenatalexposure to organophosphates, para-oxonase 1, and cognitive development inchildhood. Environ Health Perspect. 2011;119(8):1182–1188

118. Bouchard MF, Bellinger DC, Wright RO,Weisskopf MG. Attention-deficit/hyper-activity disorder and urinary metabo-lites of organophosphate pesticides.Pediatrics. 2010;125(6). Available at:www.pediatrics.org/cgi/content/full/125/6/e1270

119. Grandjean P, Harari R, Barr DB, Debes F.Pesticide exposure and stunting as in-dependent predictors of neurobehavioraldeficits in Ecuadorian school children.Pediatrics. 2006;117(3). Available at: www.pediatrics.org/cgi/content/full/117/3/e546

120. Slotkin TA, Levin ED, Seidler FJ. Compara-tive developmental neurotoxicity of or-ganophosphate insecticides: effects onbrain development are separable fromsystemic toxicity. Environ Health Perspect.2006;114(5):746–751

121. Holland N, Furlong C, Bastaki M, et al.Paraoxonase polymorphisms, haplotypes,and enzyme activity in Latino mothers andnewborns. Environ Health Perspect. 2006;114(7):985–991

122. Furlong CE, Holland N, Richter RJ, BradmanA, Ho A, Eskenazi B. PON1 status of farm-worker mothers and children as a pre-dictor of organophosphate sensitivity.Pharmacogenet Genomics. 2006;16(3):183–190

123. Eskenazi B, Marks AR, Bradman A, et al. Inutero exposure to dichlorodiphenyltri-chloroethane (DDT) and dichlor-odiphenyldichloroethylene (DDE) andneurodevelopment among young MexicanAmerican children. Pediatrics. 2006;118(1):233–241

124. Windham G, Fenster L. Environmentalcontaminants and pregnancy outcomes.Fertil Steril. 2008;89(suppl 2):e111–e116,discussion e117

125. Weselak M, Arbuckle TE, Foster W. Pesti-cide exposures and developmental out-comes: the epidemiological evidence. JToxicol Environ Health B Crit Rev. 2007;10(1-2):41–80

126. Stillerman KP, Mattison DR, Giudice LC,Woodruff TJ. Environmental exposuresand adverse pregnancy outcomes: a re-view of the science. Reprod Sci. 2008;15(7):631–650

127. Bell EM, Hertz-Picciotto I, Beaumont JJ. Acase-control study of pesticides and fetaldeath due to congenital anomalies. Epi-demiology. 2001;12(2):148–156

128. Arbuckle TE, Savitz DA, Mery LS, Curtis KM.Exposure to phenoxy herbicides and therisk of spontaneous abortion. Epidemiol-ogy. 1999;10(6):752–760

129. Salazar-García F, Gallardo-Díaz E, Cerón-Mireles P, Loomis D, Borja-Aburto VH. Re-productive effects of occupational DDTexposure among male malaria controlworkers. Environ Health Perspect. 2004;112(5):542–547

130. Arbuckle TE, Lin Z, Mery LS. An exploratoryanalysis of the effect of pesticide expo-sure on the risk of spontaneous abortionin an Ontario farm population. EnvironHealth Perspect. 2001;109(8):851–857

131. Savitz DA, Arbuckle T, Kaczor D, Curtis KM.Male pesticide exposure and pregnancyoutcome. Am J Epidemiol. 1997;146(12):1025–1036

132. Nurminen T. Maternal pesticide exposureand pregnancy outcome. J Occup EnvironMed. 1995;37(8):935–940

133. Schwartz DA, LoGerfo JP. Congenital limbreduction defects in the agricultural set-ting. Am J Public Health. 1988;78(6):654–658

134. Bjerkedal T. Use of medical registration ofbirth in the study of occupational hazardsto human reproduction. In: Hemminki K,Sorsa M, Vainio H, eds. OccupationalHazards and Reproduction. Washington,DC: Hemisphere Publishing Corporation;1985:313–321

135. Hemminki K, Mutanen P, Luoma K, SaloniemiI. Congenital malformations by the pa-rental occupation in Finland. Int ArchOccup Environ Health. 1980;46(2):93–98

136. McDonald AD, McDonald JC, Armstrong B,et al. Congenital defects and work in preg-nancy. Br J Ind Med. 1988;45(9):581–588

137. Schwartz DA, Newsum LA, Heifetz RM. Pa-rental occupation and birth outcome in anagricultural community. Scand J WorkEnviron Health. 1986;12(1):51–54

138. Restrepo M, Muñoz N, Day NE, Parra JE, deRomero L, Nguyen-Dinh X. Prevalence ofadverse reproductive outcomes in a pop-ulation occupationally exposed to pesti-cides in Colombia. Scand J Work EnvironHealth. 1990;16(4):232–238

139. Restrepo M, Muñoz N, Day N, et al. Birthdefects among children born to a pop-

ulation occupationally exposed to pesti-cides in Colombia. Scand J Work EnvironHealth. 1990;16(4):239–246

140. McDonald JC, Lavoie J, Côté R, McDonaldAD. Chemical exposures at work in earlypregnancy and congenital defect: a case-referent study. Br J Ind Med. 1987;44(8):527–533

141. Lin S, Marshall EG, Davidson GK. Potentialparental exposure to pesticides and limbreduction defects. Scand J Work EnvironHealth. 1994;20(3):166–179

142. Zhang J, Cai WW, Lee DJ. Occupationalhazards and pregnancy outcomes. Am JInd Med. 1992;21(3):397–408

143. Nurminen T, Rantala K, Kurppa K, HolmbergPC. Agricultural work during pregnancyand selected structural malformationsin Finland. Epidemiology. 1995;6(1):23–30

144. Garry VF, Schreinemachers D, Harkins ME,Griffith J. Pesticide appliers, biocides, andbirth defects in rural Minnesota. EnvironHealth Perspect. 1996;104(4):394–399

145. Garry VF, Harkins ME, Erickson LL, Long-Simpson LK, Holland SE, Burroughs BL.Birth defects, season of conception, andsex of children born to pesticide applica-tors living in the Red River Valley of Min-nesota, USA. Environ Health Perspect.2002;110(suppl 3):441–449

146. Romitti PA, Herring AM, Dennis LK, Wong-Gibbons DL. Meta-analysis: pesticides andorofacial clefts. Cleft Palate Craniofac J.2007;44(4):358–365

147. Longnecker MP, Klebanoff MA, Zhou H,Brock JW. Association between maternalserum concentration of the DDT metabo-lite DDE and preterm and small-for-gestational-age babies at birth. Lancet.2001;358(9276):110–114

148. Ribas-Fitó N, Sala M, Cardo E, et al. Asso-ciation of hexachlorobenzene and otherorganochlorine compounds with anthro-pometric measures at birth. Pediatr Res.2002;52(2):163–167

149. Weisskopf MG, Anderson HA, Hanrahan LP,et al; Great Lakes Consortium. Maternalexposure to Great Lakes sport-caught fishand dichlorodiphenyl dichloroethylene,but not polychlorinated biphenyls, is as-sociated with reduced birth weight. Envi-ron Res. 2005;97(2):149–162

150. Wolff MS, Engel S, Berkowitz G, et al.Prenatal pesticide and PCB exposures andbirth outcomes. Pediatr Res. 2007;61(2):243–250

151. Siddiqui MK, Srivastava S, Srivastava SP,Mehrotra PK, Mathur N, Tandon I. Persis-tent chlorinated pesticides and intra-uterine foetal growth retardation:


a possible association. Int Arch OccupEnviron Health. 2003;76(1):75–80

152. Fenster L, Eskenazi B, Anderson M, et al.Association of in utero organochlorinepesticide exposure and fetal growth andlength of gestation in an agriculturalpopulation. Environ Health Perspect. 2006;114(4):597–602

153. Eskenazi B, Harley K, Bradman A, et al.Association of in utero organophosphatepesticide exposure and fetal growth andlength of gestation in an agriculturalpopulation. Environ Health Perspect. 2004;112(10):1116–1124

154. Munger R, Isacson P, Hu S, et al. In-trauterine growth retardation in Iowacommunities with herbicide-contaminateddrinking water supplies. Environ HealthPerspect. 1997;105(3):308–314

155. Villanueva CM, Durand G, Coutté MB,Chevrier C, Cordier S. Atrazine in munici-pal drinking water and risk of low birthweight, preterm delivery, and small-for-gestational-age status. Occup EnvironMed. 2005;62(6):400–405

156. Reigart JR, Roberts JR. Pesticides inchildren. Pediatr Clin North Am. 2001;48(5):1185–1198, ix

157. Gasnier C, Dumont C, Benachour N, Clair E,Chagnon MC, Séralini GE. Glyphosate-based herbicides are toxic and endo-crine disruptors in human cell lines.Toxicology. 2009;262(3):184–191

158. Silva MH, Gammon D. An assessment ofthe developmental, reproductive, andneurotoxicity of endosulfan. BirthDefects Res B Dev Reprod Toxicol. 2009;86(1):1–28

159. Molina-Molina JM, Hillenweck A, Jouanin I,et al. Steroid receptor profiling of vinclo-zolin and its primary metabolites. ToxicolAppl Pharmacol. 2006;216(1):44–54

160. Guilette LJ JrCrain DA, Gunderson MP,et al. Alligators and endocrine disruptingcontaminants: a current perspective. AmZool. 2000;40:438–452

161. Hayes TB, Collins A, Lee M, et al. Her-maphroditic, demasculinized frogs afterexposure to the herbicide atrazine at lowecologically relevant doses. Proc NatlAcad Sci USA. 2002;99(8):5476–5480

162. Fan W, Yanase T, Morinaga H, et al.Atrazine-induced aromatase expression isSF-1 dependent: implications for endo-crine disruption in wildlife and re-productive cancers in humans. EnvironHealth Perspect. 2007;115(5):720–727

163. Krstevska-Konstantinova M, Charlier C,Craen M, et al. Sexual precocity after im-migration from developing countries toBelgium: evidence of previous exposure to

organochlorine pesticides. Hum Reprod.2001;16(5):1020–1026

164. Hosie S, Loff S, Witt K, Niessen K, Waag KL.Is there a correlation between organo-chlorine compounds and undescendedtestes? Eur J Pediatr Surg. 2000;10(5):304–309

165. Bhatia R, Shiau R, Petreas M, WeintraubJM, Farhang L, Eskenazi B. Organochlorinepesticides and male genital anomalies inthe child health and development studies.Environ Health Perspect. 2005;113(2):220–224

166. Longnecker MP, Klebanoff MA, Brock JW,et al. Maternal serum level of 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene and riskof cryptorchidism, hypospadias, and pol-ythelia among male offspring. Am J Epi-demiol. 2002;155(4):313–322

167. Pierik FH, Klebanoff MA, Brock JW,Longnecker MP. Maternal pregnancyserum level of heptachlor epoxide,hexachlorobenzene, and beta-hexa-chlorocyclohexane and risk of cryptor-chidism in offspring. Environ Res. 2007;105(3):364–369

168. Fernandez MF, Olmos B, Granada A, et al.Human exposure to endocrine-disruptingchemicals and prenatal risk factors forcryptorchidism and hypospadias: a nestedcase-control study. Environ Health Perspect.2007;115(suppl 1):8–14

169. Damgaard IN, Skakkebaek NE, Toppari J,et al; Nordic Cryptorchidism Study Group.Persistent pesticides in human breastmilk and cryptorchidism. Environ HealthPerspect. 2006;114(7):1133–1138

170. LaKind JS, Berlin CM, Park CN, Naiman DQ,Gudka NJ. Methodology for characterizingdistributions of incremental body burdensof 2,3,7,8-TCDD and DDE from breast milkin North American nursing infants. JToxicol Environ Health A. 2000;59(8):605–639

171. Fernandez MF, Aguilar-Garduño C, Molina-Molina JM, Arrebola JP, Olea N. The totaleffective xenoestrogen burden, a bio-marker of exposure to xenoestrogenmixtures, is predicted by the (anti)estro-genicity of its components. Reprod Toxicol.2008;26(1):8–12

172. Rogan WJ, Ragan NB. Some evidence ofeffects of environmental chemicals on theendocrine system in children. Int J HygEnviron Health. 2007;210(5):659–667

173. Duramad P, Harley K, Lipsett M, et al.Early environmental exposures and in-tracellular Th1/Th2 cytokine profiles in24-month-old children living in an agri-cultural area. Environ Health Perspect.2006;114(12):1916–1922

174. Fryer AD, Lein PJ, Howard AS, Yost BL,Beckles RA, Jett DA. Mechanisms of or-ganophosphate insecticide-induced air-way hyperreactivity. Am J Physiol LungCell Mol Physiol. 2004;286(5):L963–L969

175. Lein PJ, Fryer AD. Organophosphorusinsecticides induce airway hyperreactivityby decreasing neuronal M2 muscarinicreceptor function independent of acetyl-cholinesterase inhibition. Toxicol Sci. 2005;83(1):166–176

176. Gultekin F, Ozturk M, Akdogan M. Theeffect of organophosphate insecticidechlorpyrifos-ethyl on lipid peroxidationand antioxidant enzymes (in vitro). ArchToxicol. 2000;74(9):533–538

177. Ranjbar A, Pasalar P, Abdollahi M. Inductionof oxidative stress and acetylcholinester-ase inhibition in organophosphorous pes-ticide manufacturing workers. Hum ExpToxicol. 2002;21(4):179–182

178. Merchant JA, Naleway AL, Svendsen ER,et al. Asthma and farm exposures ina cohort of rural Iowa children. EnvironHealth Perspect. 2005;113(3):350–356

179. Salameh PR, Baldi I, Brochard P,Raherison C, Abi Saleh B, Salamon R. Re-spiratory symptoms in children and ex-posure to pesticides. Eur Respir J. 2003;22(3):507–512

180. Salam MT, Li YF, Langholz B, Gilliland FD;Children’s Health Study. Early-life environ-mental risk factors for asthma: findingsfrom the Children’s Health Study. EnvironHealth Perspect. 2004;112(6):760–765

181. Hoppin JA, Umbach DM, London SJ, LynchCF, Alavanja MC, Sandler DP. Pesticidesand adult respiratory outcomes in theagricultural health study. Ann N Y AcadSci. 2006;1076:343–354

182. Hoppin JA, Umbach DM, London SJ, LynchCF, Alavanja MC, Sandler DP. Pesticidesassociated with wheeze among commer-cial pesticide applicators in the Agricul-tural Health Study. Am J Epidemiol. 2006;163(12):1129–1137

183. Karmaus W, Kuehr J, Kruse H. Infectionsand atopic disorders in childhood andorganochlorine exposure. Arch EnvironHealth. 2001;56(6):485–492

184. Sunyer J, Torrent M, Muñoz-Ortiz L, et al.Prenatal dichlorodiphenyldichloroethylene(DDE) and asthma in children. EnvironHealth Perspect. 2005;113(12):1787–1790

185. US Environmental Protection Agency. Pes-ticide product labels. Available at: www.epa.gov/pesticides/regulating/labels/product-labels.htm#projects. Accessed June 6,2011




www.epa.gov/pesticides/regulating/labels/product-labels.htm#projects



186. Weinhold B. Mystery in a bottle: will theEPA require public disclosure of inertpesticide ingredients? Environ HealthPerspect. 2010;118(4):A168–A171

187. US Environmental Protection Agency. Fed-eral Insecticide, Fungicide, and Rodenti-cide Act (FIFRA). Available at: www.epa.gov/oecaagct/lfra.html. Accessed May 4,2011

188. US Environmental Protection Agency.“Read the Label First” interactive pesti-cide label. Available at: www.epa.gov/pesticides/kids/hometour/label/read.htm.Accessed June 6, 2011

189. Balbus JM, Harvey CE, McCurdy LE. Edu-cational needs assessment for pediatric

health care providers on pesticide toxicity.J Agromed. 2006;11(1):27–38

190. Kilpatrick N, Frumkin H, Trowbridge J,et al. The environmental history in pedi-atric practice: a study of pediatricians’attitudes, beliefs, and practices. EnvironHealth Perspect. 2002;110(8):823–827

191. Trasande L, Schapiro ML, Falk R, et al.Pediatrician attitudes, clinical activities,and knowledge of environmental health inWisconsin. WMJ. 2006;105(2):45–49

192. Roberts JR, Balk SJ, Forman J, ShannonM. Teaching about pediatric environmen-tal health. Acad Pediatr. 2009;9(2):129–130

193. American Academy of Pediatrics, Com-mittee on Environmental Health. Taking an

environmental history and giving antici-patory guidance. In: Etzel RA, Balk SJ, eds.Pediatric Environmental Health. 2nd ed.Elk Grove Village, IL: American Academy ofPediatrics; 2003:39–56

194. US General Accounting Office. Agriculturalpesticides: management improvementsneeded to further promote integrated pestmanagement. Available at: www.gao.gov/new.items/d01815.pdf. Accessed June 12, 2012

195. Roberts DM, Buckley NA, Mohamed F,et al. A prospective observational studyof the clinical toxicology of glyphosate-containing herbicides in adults withacute self-poisoning. Clin Toxicol (Phila).2010;48(2):129–136


www.epa.gov/oecaagct/lfra.html

www.epa.gov/oecaagct/lfra.html

www.epa.gov/pesticides/kids/hometour/label/read.htm

www.epa.gov/pesticides/kids/hometour/label/read.htm

www.gao.gov/new.items/d01815.pdf

www.gao.gov/new.items/d01815.pdf

DOI: 10.1542/peds.2012-2758 originally published online November 26, 2012; 2012;130;e1765Pediatrics

HEALTHJames R. Roberts, Catherine J. Karr and COUNCIL ON ENVIRONMENTAL


ServicesUpdated Information &

http://pediatrics.aappublications.org/content/130/6/e1765including high resolution figures, can be found at:

Referenceshttp://pediatrics.aappublications.org/content/130/6/e1765#BIBLThis article cites 181 articles, 16 of which you can access for free at:

Subspecialty Collections

son_prevention_subhttp://www.aappublications.org/cgi/collection/injury_violence_-_poiInjury, Violence & Poison Preventionental_healthhttp://www.aappublications.org/cgi/collection/council_on_environmCouncil on Environmental Healthhttp://www.aappublications.org/cgi/collection/current_policyCurrent Policyfollowing collection(s): This article, along with others on similar topics, appears in the

Permissions & Licensing

http://www.aappublications.org/site/misc/Permissions.xhtmlin its entirety can be found online at: Information about reproducing this article in parts (figures, tables) or

Reprintshttp://www.aappublications.org/site/misc/reprints.xhtmlInformation about ordering reprints can be found online:


http://http://pediatrics.aappublications.org/content/130/6/e1765

http://pediatrics.aappublications.org/content/130/6/e1765#BIBL

http://www.aappublications.org/cgi/collection/current_policy

http://www.aappublications.org/cgi/collection/council_on_environmental_health

http://www.aappublications.org/cgi/collection/council_on_environmental_health

http://www.aappublications.org/cgi/collection/injury_violence_-_poison_prevention_sub

http://www.aappublications.org/cgi/collection/injury_violence_-_poison_prevention_sub

http://www.aappublications.org/site/misc/Permissions.xhtml

http://www.aappublications.org/site/misc/reprints.xhtml

DOI: 10.1542/peds.2012-2758 originally published online November 26, 2012; 2012;130;e1765Pediatrics

HEALTHJames R. Roberts, Catherine J. Karr and COUNCIL ON ENVIRONMENTAL


http://pediatrics.aappublications.org/content/130/6/e1765located on the World Wide Web at:

The online version of this article, along with updated information and services, is

ISSN: 1073-0397. 60007. Copyright © 2012 by the American Academy of Pediatrics. All rights reserved. Print the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois,has been published continuously since 1948. Pediatrics is owned, published, and trademarked by Pediatrics is the official journal of the American Academy of Pediatrics. A monthly publication, it


http://pediatrics.aappublications.org/content/130/6/e1765

Documents

TECHNICAL REPORT Pesticide Exposure in …pediatrics.aappublications.org/content/pediatrics/130/6/e1765.full.pdfTECHNICAL REPORT Pesticide Exposure in Children abstract Pesticidesareacollectivetermforawidearrayofchemicalsintendedto