Pesticide Illness

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Pesticide Illness

• Part 4
• Chronic Health Effects
• Laws and Regulations

Prepared by Rupali Das, MD, MPH, California
Department of Health Services, Michael OMalley,
MD, MPH, University of California, Davis,
Laura Styles, MPH, Public Health Institute
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PesticidesChronic 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 sense Motor, sensor neuropathy Cognitive, affective deficits
Methyl bromide, sulfuryl fluoride Olfactory, cognitive, behavioral deficits
Paraquat, others Parkinsons 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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Parkinsons Disease Association with Paraquat
MPTP
MPP
Paraquat
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Parkinsons Disease Pesticide Theory

• Direct toxins
• Neurotoxins
• Dieldrin, rotenone
• Mitochondrial toxins
• Chlordane, paraquat, permethrin
• Modulators of metabolism
• DDT, organophosphates, pyrethrins

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Parkinsons 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 surrogate for exposure
• Poor exposure assessment
• Exposure usually to multiple pesticides
• Timing of exposure uncertain
• Control for other toxins may be poor

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CaseWoman 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 risks for cancer
• Most studies on male farmers
• Limited data on specific exposures
• Other hazards

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Pesticides and Cancer Associations Human
Epidemiologic Studies

• Lindane Lymphoma
• Dichlorvos, methoxyclor Leukemia
• 2,4-D, diazinon Non-Hodgkins lymphoma
• Atrazine Ovarian
• Arsenicals Lung, skin

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Pesticides Associated with Cancer
Organophospates, Carbamates

• Non-Hodgkins lymphoma
• Organophosphates
• Carbamates
• Lung cancer
• Leukemia

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Pesticides Associated with Cancer Chlorophenoxy
Herbicides

• Non-Hodgkins lymphoma
• Farmers, gardeners
• Soft tissue sarcoma

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Pesticides and Childhood Cancer

• Malignancies linked to pesticides
• Leukemia
• Brain cancer
• Non-Hodgkins lymphoma
• Wilms tumor
• Ewings 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

• Parental home/garden pesticide use
• Parental occupational exposure
• Prenatal exposure

Source USDA
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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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SummaryChronic 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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