Pesticide IllnessPesticide IllnessPart 4Part 4

Chronic Health EffectsChronic Health EffectsLaws and RegulationsLaws and Regulations

Prepared by:Rupali Das, MD, MPH, California Department of Health Services, Michael O’Malley, MD, MPH, University of California, Davis, Laura Styles, MPH, Public Health Institute

22

PesticidesPesticidesChronic Health EffectsChronic Health Effects

Respiratory (asthma)Respiratory (asthma)Neurological Neurological Reproductive and DevelopmentalReproductive and DevelopmentalCarcinogenicCarcinogenic

33

Chronic Toxicity of PesticidesChronic Toxicity of Pesticides

Types of chronic effectsTypes of chronic effects– Cumulative effects of low level exposuresCumulative effects of low level exposures– Persistent effects of acute exposurePersistent effects of acute exposure

Individual evaluationsIndividual evaluations– Epidemiologic studies Epidemiologic studies – Specific associationsSpecific associations– Classification of reproductive, cancer Classification of reproductive, cancer

toxicitytoxicity

44

Chronic Effect Studies: Chronic Effect Studies: Design & InterpretationDesign & Interpretation

Pre-exposure information absentPre-exposure information absent Exposure difficult to measureExposure difficult to measure Selection of control groups importantSelection of control groups important Multiple, variable compoundsMultiple, variable compounds Confounders, unknown exposuresConfounders, unknown exposures

55

Pesticides and Asthma, Children Pesticides and Asthma, Children

Increase in pediatric asthmaIncrease in pediatric asthma Suspected factorsSuspected factors

– Air pollutionAir pollution– GeneticsGenetics– Hygiene hypothesisHygiene hypothesis– Chemicals, including pesticidesChemicals, including pesticides

66

Pesticides and Asthma, AdultsPesticides and Asthma, Adults

Farmer occupationFarmer occupation– Canada (Hoppin et al. 2002)Canada (Hoppin et al. 2002)– US (Senthilselvan et al. 1992)US (Senthilselvan et al. 1992)

Case reportsCase reports– Pyrethrin, tetramethrin, Pyrethrin, tetramethrin,

allethrin, chlorothalonil, allethrin, chlorothalonil, fluazinamfluazinam

77

Chronic Neurologic Effects of Chronic Neurologic Effects of PesticidesPesticides

OrganophosphateOrganophosphatess

Increased vibration Increased vibration sense; Motor, sensor sense; Motor, sensor neuropathy; Cognitive, neuropathy; Cognitive, affective deficitsaffective deficits

Methyl bromide, Methyl bromide, sulfuryl fluoridesulfuryl fluoride

Olfactory, cognitive, Olfactory, cognitive, behavioral deficitsbehavioral deficits

Paraquat, othersParaquat, others Parkinson’s Disease?Parkinson’s Disease?

88

Case Case

Subway Rider Exposed to SarinSubway Rider Exposed to Sarin 35 year-old man 35 year-old man

exposed to sarin with exposed to sarin with severe dyspnea, severe dyspnea, convulsionsconvulsions

Comatose, slightly Comatose, slightly cyanotic; miosis; cyanotic; miosis; profuse muscarinic profuse muscarinic symptomssymptoms

Source: EHP/NIEHS

99

Subway Rider Exposed to SarinSubway Rider Exposed to Sarin

Neurobehavioral Status at 6 monthsNeurobehavioral Status at 6 months

Test resultsTest results– No global intellectual impairment No global intellectual impairment – Performance impairmentsPerformance impairments– Retrograde amnesia Retrograde amnesia – Passivity and shallow affectPassivity and shallow affect

Mild neurobehavioral dysfunctionMild neurobehavioral dysfunction

1010

MPTP

MPP+

Paraquat

Parkinson’s DiseaseParkinson’s Disease Association with Paraquat Association with Paraquat

1111

Parkinson’s DiseaseParkinson’s Disease Pesticide Theory Pesticide Theory

Direct toxinsDirect toxins– NeurotoxinsNeurotoxins

Dieldrin, rotenoneDieldrin, rotenone– Mitochondrial toxinsMitochondrial toxins

Chlordane, paraquat, permethrinChlordane, paraquat, permethrin Modulators of metabolismModulators of metabolism

– DDT, organophosphates, pyrethrinsDDT, organophosphates, pyrethrins

1212

Parkinson’s Disease Parkinson’s Disease Postulated CausesPostulated Causes

20% family history 20% family history Environmental associationsEnvironmental associations

– Farmer occupation Farmer occupation – Any occupational pesticide exposureAny occupational pesticide exposure– Living on a farmLiving on a farm

Pesticides Pesticides – Initiator, promoter, or effect modifier?Initiator, promoter, or effect modifier?

1313

EndpointsEndpoints– ReproductiveReproductive– DevelopmentalDevelopmental

ExposureExposure– Maternal Maternal – PaternalPaternal

Reproductive & Developmental Reproductive & Developmental Effects of Pesticide ExposureEffects of Pesticide Exposure

1414

Reproductive & Developmental Effects Reproductive & Developmental Effects

Maternal ExposureMaternal Exposure Agricultural exposureAgricultural exposure

– Spontaneous abortions & fetal deathSpontaneous abortions & fetal death– Congenital malformationsCongenital malformations

Greenhouse workersGreenhouse workers– Reduced fecundabilityReduced fecundability– Excess stillbirthsExcess stillbirths

1515

Reproductive & Developmental EffectsReproductive & Developmental Effects Paternal ExposurePaternal Exposure

DocumentedDocumented– Azospermia, OligospermiaAzospermia, Oligospermia

Dibromochloropropane (DBCP)Dibromochloropropane (DBCP)SuggestedSuggested

– Reduced sex ratio (M/F)Reduced sex ratio (M/F)– Spontaneous abortion, preterm Spontaneous abortion, preterm

deliverydelivery

1616

Occupation surrogate for exposureOccupation surrogate for exposure Poor exposure assessmentPoor exposure assessment Exposure usually to multiple Exposure usually to multiple

pesticidespesticides Timing of exposure uncertainTiming of exposure uncertain Control for other toxins may be poorControl for other toxins may be poor

Reproductive & Developmental EffectsReproductive & Developmental Effects Methodological ProblemsMethodological Problems

1717

•34 year-old woman with spontaneous abortion at 17 weeks gestation

•Smokes ½ pack/day; occasional home pesticide use; 2 healthy children

•Fetal pathology: one stub for leg, shortened umbilical cord, no genitals.

CaseCase

WWoman with Spontaneousoman with Spontaneous AbortionAbortion

1818

Woman with SpontaneousWoman with Spontaneous AbortionAbortion Occupational HistoryOccupational History

Seasonal worker in Seasonal worker in seed-retailing seed-retailing

Became pregnant Became pregnant one month after one month after starting work. starting work.

Husband is a postal Husband is a postal workerworker

1919

Woman with SpontaneousWoman with Spontaneous AbortionAbortion Maternal Exposure HistoryMaternal Exposure History

OccupationalOccupational– Captan: animal teratogenCaptan: animal teratogen– Carboxin: growth suppression, high dosesCarboxin: growth suppression, high doses– Chlorpyrifos: no evidenceChlorpyrifos: no evidence– Methoxychlor: teratogen; estrogenicMethoxychlor: teratogen; estrogenic– Thiram: reduced growth at high dosesThiram: reduced growth at high doses

Home Home – Permethrin: reduced fertility, high dosesPermethrin: reduced fertility, high doses

2020

Pesticides and CancerPesticides and Cancer

Animal dataAnimal data– High dose laboratory studiesHigh dose laboratory studies

Human dataHuman data– Epidemiological studiesEpidemiological studies

2121

Postulated Mechanisms ofPostulated Mechanisms of Pesticide CarcinogenicityPesticide Carcinogenicity

MechanismMechanism Pesticide ExamplesPesticide Examples

GenotoxicityGenotoxicity Captan, DBCPCaptan, DBCP

Tumor promotionTumor promotion OrganochlorinesOrganochlorines

Hormonal actionHormonal action Atrazine, ziramAtrazine, ziram

ImmunotoxicityImmunotoxicity Aldicarb, 2,4-DAldicarb, 2,4-D

Peroxisome Peroxisome proliferationproliferation

2,4-D, 2,4,5-T2,4-D, 2,4,5-T

2222

InsecticidesInsecticides:: dichlorvos, organochlorines dichlorvos, organochlorines HerbicidesHerbicides:: amitrole, cyanazineamitrole, cyanazine FumigantsFumigants:: ethylene oxide, formaldehydeethylene oxide, formaldehyde FungicidesFungicides:: captan, maneb, zinebcaptan, maneb, zineb Growth regulatorsGrowth regulators:: daminozidedaminozide

Pesticide Animal CarcinogensPesticide Animal Carcinogens

2323

Pesticides & Cancer inPesticides & Cancer in FarmersFarmers

Low mortality due to other causesLow mortality due to other causes Elevated risks for cancer Elevated risks for cancer Most studies on male farmersMost studies on male farmers Limited data on specific exposuresLimited data on specific exposures Other hazards Other hazards

2424

Pesticides and Cancer Associations:Pesticides and Cancer Associations:

Human Epidemiologic StudiesHuman Epidemiologic Studies

LindaneLindane: Lymphoma: Lymphoma Dichlorvos, methoxyclorDichlorvos, methoxyclor: Leukemia: Leukemia 2,4-D, diazinon2,4-D, diazinon: Non-Hodgkin’s : Non-Hodgkin’s

lymphomalymphoma AtrazineAtrazine: Ovarian: Ovarian ArsenicalsArsenicals: Lung, skin: Lung, skin

2525

Pesticides Associated with Cancer: Pesticides Associated with Cancer: Organophospates, CarbamatesOrganophospates, Carbamates

Non-Hodgkin’s lymphomaNon-Hodgkin’s lymphoma – OrganophosphatesOrganophosphates– CarbamatesCarbamates

Lung cancerLung cancer LeukemiaLeukemia

2626

Pesticides Associated with Cancer: Pesticides Associated with Cancer: Chlorophenoxy Herbicides Chlorophenoxy Herbicides

Non-Hodgkin’s Non-Hodgkin’s lymphoma lymphoma – Farmers, gardenersFarmers, gardeners

Soft tissue sarcomaSoft tissue sarcoma

2727

Pesticides and Childhood CancerPesticides and Childhood Cancer Malignancies linked to pesticidesMalignancies linked to pesticides

– LeukemiaLeukemia– Brain cancerBrain cancer– Non-Hodgkin’s lymphomaNon-Hodgkin’s lymphoma– Wilm’s tumorWilm’s tumor– Ewing’s sarcomaEwing’s sarcoma

2828

Pesticides and Childhood CancerPesticides and Childhood Cancer Childhood Pesticide ExposureChildhood Pesticide Exposure Widespread home pesticide use Widespread home pesticide use Pet products, insecticidal Pet products, insecticidal

shampoosshampoos Vertical concentration gradient Vertical concentration gradient Deposit on toys, furnitureDeposit on toys, furniture

2929

Pesticides and Childhood CancerPesticides and Childhood Cancer Risk FactorsRisk Factors

Parental home/garden pesticide useParental home/garden pesticide use Parental occupational exposure Parental occupational exposure Prenatal exposurePrenatal exposure

Sou

rce:

US

DA

3030

Human Pesticide Cancer Studies: Human Pesticide Cancer Studies: Methodological IssuesMethodological Issues

Case definition may not be preciseCase definition may not be precise Recall biasRecall bias Small samplesSmall samples Crude exposure assessmentCrude exposure assessment Timing of exposure cannot be Timing of exposure cannot be

confirmedconfirmed Genetic-environmental interactionsGenetic-environmental interactions

3131

SummarySummaryChronic Pesticide IllnessChronic Pesticide Illness

Risks depend on pesticideRisks depend on pesticide– Neurological disease: Organophosphates Neurological disease: Organophosphates – Cancer: Chlorophenoxy herbicides Cancer: Chlorophenoxy herbicides – Reproductive toxicity: Methyl bromideReproductive toxicity: Methyl bromide

Preventing illnessPreventing illness– Targeted use reductionTargeted use reduction– Worker protectionWorker protection– Reduced home useReduced home use

3232

Pesticide Laws and RegulationsPesticide Laws and Regulations

FederalFederal– Federal Insecticide, Fungicide, and Federal Insecticide, Fungicide, and

Rodenticide Act (1972)Rodenticide Act (1972)– Federal Food, Drug, and Cosmetic Act Federal Food, Drug, and Cosmetic Act

(1939)(1939)– Worker Protection Standard (1992) Worker Protection Standard (1992) – Food Quality Protection Act (1996)Food Quality Protection Act (1996)

State laws varyState laws vary

3333

Federal Insecticide, Fungicide, and Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA)Rodenticide Act (FIFRA)

Control of distribution, sale, use Control of distribution, sale, use Gives US EPA authority to Gives US EPA authority to

– Study pesticide consequencesStudy pesticide consequences– Require pesticide purchase Require pesticide purchase

registrationregistration Requires Requires

– Pesticide applicator certification Pesticide applicator certification – Registration, proper labelingRegistration, proper labeling

3434

Federal Food, Drug, and Federal Food, Drug, and Cosmetic Act (FFDCA)Cosmetic Act (FFDCA)

Allows US EPA to Allows US EPA to establish establish tolerances for tolerances for pesticides in foodpesticides in food

Small fraction of Small fraction of marketed food marketed food tested for pesticide tested for pesticide residueresidue

3535

Worker Protection StandardWorker Protection Standard

Reduce farmworker pesticide illnessReduce farmworker pesticide illness

Hazard training and communication, Hazard training and communication, decontamination facilities, decontamination facilities, notification, emergency medical notification, emergency medical carecare

3636

Food Quality Protection Act (FQPA)Food Quality Protection Act (FQPA)

Health-based standard for Health-based standard for pesticides in foodspesticides in foods

Requires US EPA to review Requires US EPA to review tolerances for pesticide tolerances for pesticide tolerances in foodtolerances in food

Focus on childrenFocus on children

3737