Transcript Types of chronic effects(1)

Pesticide Illness
Part 4
Chronic Health Effects
Laws 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
Pesticides
Chronic Health Effects
 Respiratory
(asthma)
 Neurological
 Reproductive and Developmental
 Carcinogenic
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Chronic Toxicity of Pesticides
 Types
of chronic effects
– Cumulative effects of low level
exposures
– Persistent effects of acute exposure
 Individual
evaluations
– Epidemiologic studies
– Specific associations
– Classification of reproductive, cancer
toxicity
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Chronic Effect Studies:
Design & Interpretation
 Pre-exposure
information absent
 Exposure
difficult to measure
 Selection
of control groups important
 Multiple,
variable compounds
 Confounders,
unknown exposures
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Pesticides and Asthma, Children
 Increase
in pediatric asthma
 Suspected factors
– Air pollution
– Genetics
– Hygiene hypothesis
– Chemicals, including pesticides
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Pesticides and Asthma, Adults
 Farmer
occupation
– Canada (Hoppin et al. 2002)
– US (Senthilselvan et al. 1992)
 Case
reports
– Pyrethrin, tetramethrin,
allethrin, chlorothalonil,
fluazinam
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Chronic Neurologic Effects of
Pesticides
Organophosphates Increased vibration
Methyl bromide,
sulfuryl fluoride
sense; Motor, sensor
neuropathy; Cognitive,
affective deficits
Olfactory, cognitive,
behavioral deficits
Paraquat, others
Parkinson’s Disease?
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Case
Subway Rider Exposed to Sarin


35 year-old man
exposed to sarin
with severe dyspnea,
convulsions
Comatose, slightly
cyanotic; miosis;
profuse muscarinic
symptoms
Source: EHP/NIEHS
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Subway Rider Exposed to Sarin
Neurobehavioral Status at 6 months
 Test
results
– No global intellectual impairment
– Performance impairments
– Retrograde amnesia
– Passivity and shallow affect
 Mild
neurobehavioral dysfunction
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Parkinson’s Disease
Association with Paraquat
MPTP
MPP+
Paraquat
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Parkinson’s Disease
Pesticide Theory
 Direct
toxins
– Neurotoxins
 Dieldrin,
rotenone
– Mitochondrial toxins
 Chlordane,
 Modulators
paraquat, permethrin
of metabolism
– DDT, organophosphates, pyrethrins
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Parkinson’s Disease
Postulated Causes
 20%
family history
 Environmental associations
– Farmer occupation
– Any occupational pesticide exposure
– Living on a farm
 Pesticides
– Initiator, promoter, or effect modifier?
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Reproductive & Developmental
Effects of Pesticide Exposure
 Endpoints
–Reproductive
–Developmental
 Exposure
–Maternal
–Paternal
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Reproductive & Developmental Effects
Maternal Exposure
 Agricultural
exposure
– Spontaneous abortions & fetal death
– Congenital malformations
 Greenhouse
workers
– Reduced fecundability
– Excess stillbirths
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Reproductive & Developmental Effects
Paternal Exposure
 Documented
–Azospermia, Oligospermia
 Dibromochloropropane
(DBCP)
 Suggested
–Reduced sex ratio (M/F)
–Spontaneous abortion, preterm
delivery
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Reproductive & Developmental Effects
Methodological Problems
 Occupation
 Poor
surrogate for exposure
exposure assessment
 Exposure
pesticides
 Timing
 Control
usually to multiple
of exposure uncertain
for other toxins may be poor
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Case
Woman with Spontaneous Abortion
•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.
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Woman with Spontaneous Abortion
Occupational History



Seasonal worker in
seed-retailing
Became pregnant
one month after
starting work.
Husband is a
postal worker
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Woman with Spontaneous Abortion
Maternal Exposure History
 Occupational
– Captan: animal teratogen
– Carboxin: growth suppression, high doses
– Chlorpyrifos: no evidence
– Methoxychlor: teratogen; estrogenic
– Thiram: reduced growth at high doses
 Home
– Permethrin: reduced fertility, high doses
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Pesticides and Cancer
 Animal
data
– High dose laboratory studies
 Human
data
– Epidemiological studies
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Postulated Mechanisms of
Pesticide Carcinogenicity
Mechanism
Pesticide Examples
Genotoxicity
Captan, DBCP
Tumor promotion
Organochlorines
Hormonal action
Atrazine, ziram
Immunotoxicity
Aldicarb, 2,4-D
Peroxisome
proliferation
2,4-D, 2,4,5-T
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Pesticide Animal Carcinogens
 Insecticides:
dichlorvos, organochlorines
 Herbicides:
amitrole, cyanazine
 Fumigants:
ethylene oxide, formaldehyde
 Fungicides:
captan, maneb, zineb
 Growth
regulators: daminozide
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Pesticides & Cancer in Farmers
 Low
mortality due to other causes
 Elevated
 Most
risks for cancer
studies on male farmers
 Limited
 Other
data on specific exposures
hazards
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Pesticides and Cancer Associations:
Human Epidemiologic Studies
 Lindane:
Lymphoma
 Dichlorvos,
methoxyclor: Leukemia
 2,4-D,
diazinon: Non-Hodgkin’s
lymphoma
 Atrazine:
Ovarian
 Arsenicals:
Lung, skin
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Pesticides Associated with Cancer:
Organophospates, Carbamates
 Non-Hodgkin’s
lymphoma
– Organophosphates
– Carbamates
 Lung
cancer
 Leukemia
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Pesticides Associated with Cancer:
Chlorophenoxy Herbicides
 Non-Hodgkin’s
lymphoma
– Farmers, gardeners
 Soft
tissue sarcoma
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Pesticides and Childhood Cancer
 Malignancies
linked to pesticides
– Leukemia
– Brain cancer
– Non-Hodgkin’s lymphoma
– Wilm’s tumor
– Ewing’s sarcoma
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Pesticides and Childhood Cancer
Childhood Pesticide Exposure
 Widespread
home pesticide use
 Pet
products, insecticidal
shampoos
 Vertical
concentration gradient
 Deposit
on toys, furniture
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Pesticides and Childhood Cancer
Risk Factors
home/garden pesticide use
 Parental
occupational exposure
 Prenatal
exposure
Source: USDA
 Parental
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Human Pesticide Cancer Studies:
Methodological Issues
 Case
definition may not be precise
 Recall bias
 Small samples
 Crude exposure assessment
 Timing of exposure cannot be
confirmed
 Genetic-environmental interactions
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Summary
Chronic Pesticide Illness
 Risks
depend on pesticide
– Neurological disease:
Organophosphates
– Cancer: Chlorophenoxy herbicides
– Reproductive toxicity: Methyl bromide
 Preventing
illness
– Targeted use reduction
– Worker protection
– Reduced home use
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Pesticide Laws and Regulations
 Federal
– Federal Insecticide, Fungicide, and
Rodenticide Act (1972)
– Federal Food, Drug, and Cosmetic Act
(1939)
– Worker Protection Standard (1992)
– Food Quality Protection Act (1996)
 State
laws vary
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Federal Insecticide, Fungicide, and
Rodenticide Act (FIFRA)
 Control
of distribution, sale, use
 Gives US EPA authority to
– Study pesticide consequences
– Require pesticide purchase registration
 Requires
– Pesticide applicator certification
– Registration, proper labeling
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Federal Food, Drug, and
Cosmetic Act (FFDCA)


Allows US EPA to
establish
tolerances for
pesticides in food
Small fraction of
marketed food
tested for pesticide
residue
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Worker Protection Standard
 Reduce
farmworker pesticide illness
 Hazard
training and communication,
decontamination facilities,
notification, emergency medical care
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Food Quality Protection Act (FQPA)
 Health-based
standard for
pesticides in foods
 Requires
US EPA to review
tolerances for pesticide
tolerances in food
 Focus
on children
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