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Oct 25Oct 25PesticidesPesticides

Classification based on type of pest they controlClassification based on type of pest they control InsecticidesInsecticides FungicidesFungicides HerbicidesHerbicides RodenticidesRodenticides--more in your EPA reading--more in your EPA reading

PesticidesPesticides

OrganophosphatesOrganophosphates CarbamatesCarbamates OrganochlorinesOrganochlorines Pyrethrins & PyrethroidsPyrethrins & Pyrethroids

Toxicology in environmental healthToxicology in environmental health

Molecular toxicologyMolecular toxicology EpidemiologyEpidemiology Clinical diagnosisClinical diagnosis

Toxico-epidemiologyToxico-epidemiology

Exposure-outcome relationshipsExposure-outcome relationships Dose-effect relationshipsDose-effect relationships

Exposure assessmentExposure assessment

Environmental samplingEnvironmental sampling– AirAir– WaterWater– Soil/dustSoil/dust

Biomarker samplingBiomarker sampling

BloodBlood UrineUrine FecesFeces FatFat

HairHair NailNail MeconiumMeconium

Pilot study on the developmental Pilot study on the developmental effects of pesticide exposure in effects of pesticide exposure in

rural South Africarural South Africa

Makhatini flats in the KwaZulu Makhatini flats in the KwaZulu Natal ProvinceNatal Province

From left to right: Dr. Mariam Murtharda, Patricia Janulewicz, Jane Kvalsvig, Pumla Mkhiva, Dr. Saloshni Naidoo, Dr. Roberta White, Simphiwe Mnyzaiza, Mtheliseni Dladla, Dr. Lawrence Mubaiwa

Study team 1: South AfricaStudy team 1: South Africa

Leslie LondonLeslie London– Occupational medicineOccupational medicine– Environmental epidemiologyEnvironmental epidemiology

Saloshni NaidooSaloshni Naidoo– Occupational and environmental medicineOccupational and environmental medicine

Lawrence MubaiwaLawrence Mubaiwa– Pediatric neurologyPediatric neurology

Simphiwe MnyzaizaSimphiwe Mnyzaiza– Environmental exposure assessmentEnvironmental exposure assessment

Study team-2: USAStudy team-2: USA

Roberta WhiteRoberta White– NeuropsychologyNeuropsychology– Behavioral toxicologyBehavioral toxicology

Richard ClappRichard Clapp– Environmental epidemiologyEnvironmental epidemiology

Veronica VieiraVeronica Vieira– Exposure assessmentExposure assessment– GIS methodologyGIS methodology

Patricia JanulewiczPatricia Janulewicz– Developmental assessment/neuroscienceDevelopmental assessment/neuroscience– Environmental health sciencesEnvironmental health sciences

Background historyBackground history– Pesticides commonly used as mode of suicide Pesticides commonly used as mode of suicide

and poisoning and occupational exposures and poisoning and occupational exposures (Leslie London) (Leslie London)

– Years of soil contamination of pesticides from Years of soil contamination of pesticides from agricultural use and mosquito controlagricultural use and mosquito control

– People live close to and work on the fields and People live close to and work on the fields and have for yearshave for years

– Homogeneous group who have lived there for Homogeneous group who have lived there for generationsgenerations

Types of pesticides used in this areaTypes of pesticides used in this area

DDTDDT Organophosphates Organophosphates Carbamates Carbamates PyrethroidsPyrethroids

– Diuron Diuron – MetribuzinMetribuzin

Neurotoxicity of these compoundsNeurotoxicity of these compounds

Insect CNS target of compoundsInsect CNS target of compounds Cholinesterase effectsCholinesterase effects Endocrine disruptionEndocrine disruption

Overall study aimsOverall study aims

Determine relationship between prenatal Determine relationship between prenatal exposure to pesticides and CNS function in exposure to pesticides and CNS function in early childhood early childhood (Exposure-outcome relationships)(Exposure-outcome relationships)

Create dose-outcome curves relating Create dose-outcome curves relating measures of exposure to measures of CNS measures of exposure to measures of CNS function function (Dose-effect relationships)(Dose-effect relationships)

Routes of ExposureRoutes of Exposure OccupationalOccupational

– Dermal - lack of proper protective gear and use of soil as Dermal - lack of proper protective gear and use of soil as sunscreen and foot protection for those without shoessunscreen and foot protection for those without shoes

– Inhalation - lack of proper protective gearInhalation - lack of proper protective gear– Ingestion - lack of knowledge concerning hygieneIngestion - lack of knowledge concerning hygiene

Home environmentHome environment– Dermal - use of soil as sunscreenDermal - use of soil as sunscreen– Inhalation - use of pesticides in the home and being downwind of Inhalation - use of pesticides in the home and being downwind of

the farmsthe farms– Ingestion - use of old pesticide containers for waterIngestion - use of old pesticide containers for water

Routes of Exposure – Routes of Exposure – Occupational (dermal, Occupational (dermal, inhalation, ingestion)inhalation, ingestion)

Routes of Exposure - dRoutes of Exposure - dermalermal

Routes of Exposure – Routes of Exposure – home use of pesticideshome use of pesticides

Routes of Exposure - Routes of Exposure - ingestioningestion

Pesticides used on fields are kept inside the Pesticides used on fields are kept inside the workers homesworkers homes

Pilot study aimsPilot study aims Pilot feasibility of neurobehavioral tests on 2.5 and 4 Pilot feasibility of neurobehavioral tests on 2.5 and 4

year old children at the crêche in Makhathini.year old children at the crêche in Makhathini. Pilot neurological and physical exam on six week olds in Pilot neurological and physical exam on six week olds in

clinics in Jozini and Bethesda, and 2.5 and 4 year old clinics in Jozini and Bethesda, and 2.5 and 4 year old children at the crêche in Makhathini.children at the crêche in Makhathini.

Pilot environmental sampling techniques in the homes Pilot environmental sampling techniques in the homes in Makhathini and hand wipes at crêche.in Makhathini and hand wipes at crêche.

Pilot and collect data from focus groups with 10 Pilot and collect data from focus groups with 10 women/day residing in Makhathini. Total of 50.women/day residing in Makhathini. Total of 50.

Meet with local public health and governmental leaders.Meet with local public health and governmental leaders. Recruit a sample of 60 expectant mothersRecruit a sample of 60 expectant mothers Pilot questionnaire methodsPilot questionnaire methods Pilot biomarker sampling and analysisPilot biomarker sampling and analysis

Pilot study vs. Full studyPilot study vs. Full study

Full study –Full study – Make connections Make connections ProspectiveProspective LongitudinalLongitudinal Biological samples Biological samples (meconium, cord blood, hair, urine, blood)(meconium, cord blood, hair, urine, blood) Environmental samples Environmental samples (home, hand wipes, *work environment)(home, hand wipes, *work environment) Neurological and physical examsNeurological and physical exams Neurobehavioral testingNeurobehavioral testing (*behavioral and diagnostic questionnaires/methods)(*behavioral and diagnostic questionnaires/methods) Seen at birth, six weeks, 2.5 years, 4 years (other ages?)Seen at birth, six weeks, 2.5 years, 4 years (other ages?)

Pilot study –Pilot study – Assess feasibility Assess feasibility Pilot ability to… Pilot ability to… collect and run biological and environmental samplescollect and run biological and environmental samples Administer neuro and physical exams Administer neuro and physical exams (do they work? Do they give us (do they work? Do they give us

enough info?)enough info?) Administer neurobehavioral tests Administer neurobehavioral tests (do they work? Can the kids do them? How (do they work? Can the kids do them? How

much do they need to be adapted? )much do they need to be adapted? )

The kids at the CrècheThe kids at the Crèche (infants to 5 year olds)(infants to 5 year olds)

The classroomThe classroom

The playgroundThe playground

Aim 1Aim 1

Neurobehavioral TestingNeurobehavioral Testing

Neurobehavioral Testing – 2.5 year olds – Neurobehavioral Testing – 2.5 year olds – Bayley Scales of Infant DevelopmentBayley Scales of Infant Development

Cognitive Domains to assessCognitive Domains to assess

LanguageLanguage Memory (verbal and nonverbal)Memory (verbal and nonverbal) Visual spatial (drawing and constructional)Visual spatial (drawing and constructional) AttentionAttention MotorMotor

Neurobehavioral Testing – 4 year oldsNeurobehavioral Testing – 4 year olds

BatteryBatteryBoston Naming Test (with recall condition) Boston Naming Test (with recall condition) Stanford-Binet Copying Test (with recall condition) Stanford-Binet Copying Test (with recall condition) Block DesignBlock DesignFinger TappingFinger TappingDigit SpanDigit SpanSpatial SpanSpatial Span

Boston Naming TestBoston Naming Test

Block DesignBlock Design

Finger TappingFinger Tapping

Spatial SpanSpatial Span

Aim 2Aim 2

Physical and Neurological Exams: 2.5 and Physical and Neurological Exams: 2.5 and 4.0 year olds4.0 year olds

Clinic in JoziniClinic in Jozini (six week olds)(six week olds)

Physical Exam Physical Exam (2.5 year old)(2.5 year old)

Neurological Exam Neurological Exam (4 year old)(4 year old)

Aim 3Aim 3

Environmental SamplingEnvironmental Sampling

Environmental SamplingEnvironmental Sampling

At homes of the children who had neurobehavioral testing At homes of the children who had neurobehavioral testing (10 (10 randomly selected)randomly selected)

– Floor wipes Floor wipes (3 areas, two samples at each site)(3 areas, two samples at each site)

Sleeping areaSleeping area Play areaPlay area Work boot areaWork boot area

– Soil samples Soil samples (1 area, two samples at site)(1 area, two samples at site)

– ControlControl

At the Crèche, near the end of the day At the Crèche, near the end of the day (same kids that had home samples (same kids that had home samples taken)taken)

– Hand samples Hand samples (two wipes from each hand)(two wipes from each hand)

– One soil sample at the crèche, with a blankOne soil sample at the crèche, with a blank

Floor wipesFloor wipes

More floor wipesMore floor wipes

Soil SamplesSoil Samples

Sample collectionSample collection

Cohort recruitmentCohort recruitment

Recruit 60 women in second trimester of Recruit 60 women in second trimester of pregnancypregnancy

Questionnaires:Questionnaires:– Pregnancy, delivery, 6 weeks post, 6 months postPregnancy, delivery, 6 weeks post, 6 months post

Biological samplesBiological samples– Birth: cord blood, meconium, infant urine, maternal Birth: cord blood, meconium, infant urine, maternal

bloodblood– Four weeks post delivery: infant urine, breast milkFour weeks post delivery: infant urine, breast milk

Issues/IdeasIssues/IdeasNeurobehavioral TestingNeurobehavioral Testing ExaminersExaminers

– Need examiners fluent in English and Zulu.Need examiners fluent in English and Zulu.– Need to train examiners.Need to train examiners.– Need to create and organize testing materials, administration Need to create and organize testing materials, administration

manuals, and testing protocols.manuals, and testing protocols.

TestsTests– Need to add diagnostic tests.Need to add diagnostic tests.– Verbal vs. visuospatial tests.Verbal vs. visuospatial tests.– Cultural context of test stimuli.Cultural context of test stimuli.

KidsKids– Need to be knowledge enough about tests and kids in general to Need to be knowledge enough about tests and kids in general to

know if tests work, kids are giving full effort, distractions too know if tests work, kids are giving full effort, distractions too much etc…much etc…

Issues/Ideas cont…Issues/Ideas cont…

Physical and Neurological examsPhysical and Neurological exams Six week oldsSix week olds

– Lack of communication or presence of miscommunication between the Lack of communication or presence of miscommunication between the sisters (nurses) at the same clinic and between clinics.sisters (nurses) at the same clinic and between clinics.

2.5 and 4 year olds2.5 and 4 year olds– Need more in depth tools.Need more in depth tools.

GeneralGeneral– Need to hire a nurse or midwife or OT to recruit and be present and Need to hire a nurse or midwife or OT to recruit and be present and

able to administer infant exams able to administer infant exams

Issues/Ideas cont…Issues/Ideas cont…

Environmental SamplingEnvironmental Sampling People were very welcoming and willing to allow us into People were very welcoming and willing to allow us into

their homestheir homes Need help from one of the villagers (school teachers) to Need help from one of the villagers (school teachers) to

find the homes of the childrenfind the homes of the children Could possibly train some of the school teachers to help Could possibly train some of the school teachers to help

with collection of sampleswith collection of samples

Issues/Ideas cont…Issues/Ideas cont…

Focus GroupsFocus Groups HIV/AIDSHIV/AIDS Water and lack there ofWater and lack there of Work environment – bootsWork environment – boots Knowledge of clinical effects of pesticide poisoningKnowledge of clinical effects of pesticide poisoning

Issues/Ideas cont…Issues/Ideas cont…

Sample RecruitmentSample Recruitment HIV ratesHIV rates Follow-up successFollow-up success Follow-up problemsFollow-up problems

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