1. The Human Health Effects of Pesticide Exposure
Acute Effects
Skin Problems
Respiratory Problems
Reproduction
Risks to Children
Nervous System
Cancers

2. Agriculture in Asia
A Typical North Vietnamese Farming Village

3. Focus on OP’s Most commonly used insecticide in agriculture
Children at risk for neurodevelopmental problems
Most commonly used insecticide in agriculture
Common cause of poisoning

4. Normal Electrical Nerve Impulse Transmission
nerve cell
Electrical nerve impulse coming from nerve cell stimulates the body to produce acetylcholine.
Acetylcholine acts as a bridge transmitting the electrical charge to the muscle cell.
Muscles and glands contract.
After electrical nerve impulse transmission is completed, the body produces cholinesterase.
Cholinesterase breaks up acetylcholine into acetate and choline.
acetate
choline
Once acetylcholine is broken, it can no longer transmit electrical nerve impulses.
Electrical nerve impulses stop and the muscles and glands are quiet
muscle cell

5. Organophosphate-Carbamate Disruption of Electrical Nerve Impulse Transmission Therapeutic Effect of Atropine
nerve cell
If an organophosphate (Op) or carbamate is present, they bind with cholinesterase. [This is an irreversible effect with an Op but not with a carbamate]
The bound cholinesterase cannot penetrate acetylcholine to break it up.
The body continues to produce acetylcholine unimpeded.
This results in a build up of acetylcholine with continuous electrical nerve impulse transmission and over stimulation of muscle and glands.
Atropine relieves the over stimulation of the muscles and glands by reducing the amounts of acetylcholine.
The effect only lasts 15 minutes. Therefore the dose must be repeated until the organophosphate binding effect has worn off.
muscle cell
Electrical nerve impulse
acetate
choline
cholinesterase
organophosphate
atropine

7. Signs and Symptoms in Adults
Miosis
Blurring
Eye
CNS
Lungs GI
Glands
Muscle
Heart
Fatigue
Dizziness
Headache
Tremors
Ataxia
Seizures
LOC
Coma
Insomnia
Mental Δ
Tightness
Wheezing
Cough
Rhinorrhea
Weakness Cramps
Fasciculations
Abd. cramps
Nausea
Vomiting
Diarrhea
Drooling
Sweating
Tearing
Tachy
Brady
 BP
↓ BP
Exercise: Body Mapping

8. Parathion Story
On the day her house was sprayed, previously healthy girl 4 months of age became irritable and seemed congested in her upper airway, with a thick whitish nasal discharge. Over the next several days these symptoms persisted, and she began to refuse food, developed a fever, more frequent bowel movements, and decreased sleep. On day 6, she was brought to the emergency department (ED) and was given iv antibiotics, fluids, oxygen, and a series of tests to determine infection status. She was discharged with a diagnosis of upper respiratory infection and a prescription for an antibiotic. That night the child got worse paramedics were called and she was transported by air ambulance to a pediatric intensive care unit . She was sleepy, dehydrated, and had black, foul-smelling stools showing blood coming from the upper intestines. The diagnosis was dehydration and high salt in her blood (sodium). She remained in the hospital for more than 1 week, receiving fluids and antibiotics. She was discharged home without medications, but she continued to have abnormal head movement. Fourteen months later her home was evaluated for methyl parathion contamination, and her urinary metabolite of methyl parathion was 89 . The general population reference range is 0-63.

9. Signs of Pesticide Poisoning in a CHILD
Seizures
Lethargic sleepy
Coma
Can be confused with the flu

10. Respiratory Problems
Organophosphates and carbamates inhibit cholinesterase resulting in
Constriction of the bronchial tubes
Increased secretions
Difficulty in breathing
Many pesticides are ‘sensitizers’ causing allergic reactions along with OTHER triggers
dusts, pollens, animals, diesel, molds, grains, hay, disinfectants

11. Typical Pesticide Application
North Vietnam

12. Respiratory Problems Insecticide related wheezing with*:
parathion
chlorpyriphos
malathion
Herbicide related wheezing with*:
paraquat
atrazine
alachlor
chlorimuron ethyl (Classic)
EPTC
Children exposed to pesticides in 1st year of life 4.5x greater risk of developing asthma before age 5.
*Source: Agriculture Health Study:

13. Transplanting Rice
West Sumatra, Indonesia

14. Skin Disorders Dermatitis with any pesticide
Allergic
Contact
12%-68% prevalence of skin problems in agriculture
Paraquat irritant/burn = 53% applicators in one study*
Chloracne from dioxins: 2,4,5 –T (Agent Orange) and possibly 2,4 –D, diuron, linuron (Viktor Yushchenko
* Source: Castro-Gutierrez N, McConnell R, Andersson K, Pacheco-Anton F, Hogstedt,C. Respiratory symptoms, spirometry and chronic occupational paraquat exposure. Scand J Work Environ Health 1997;23:421–427.

15. Paraquat Application by Burmese Migrant Workers in Thailand
Mae Sot, Thailand

16. Skin Disorders
Soil fumigants can cause irritant dermatitis and chemical burns
methyl bromide
dichloropropene (Telone)
Metam sodium
Herbicide induced contact or allergic dermatitis
miticide propargite
paraquat and diquat
Fungicide induced contact or allergic dermatitis
Maneb
Mancozed
Zineb
Sulfur
Ziram
Benomyl
Captan
Source: Solomon G, Ogunseitan OA, Kirsch A. Pesticides and Human Health: A Resource for Health Care Professionals. PSR

17. Methamidiphos Contact Dermatitis
North Vietnam

18. Severe Contact Dermatitis Cartap + [Fenobucarb, Dimethoate and Methyl Parathion x 20 yrs]
Prey Vang, Cambodia

19. Pesticides Associated to Allergic Contact Dermatitis*
Acephate
Benomyl
Captan
Carbaryl
Chlorothalonil
Chlorpyrifos
DCNA
Diazinon
Dienochlor
Dimethoate
Ethoxyquin
Fenbutatin-oxide
Fluvalinate
Folpet
Malathion
Mancozeb
Maneb
Norflurazon
Omethoate
PCNB
Permethrin
Pyrethrum
Sulfur
Thiram
Vinclozolin
Zineb
Ziram
*Source: M.A. O’Malley, Skin reactions to pesticides, Occup Med State Art Rev 12 ([1997]2): 327–45.

20. Mixing Pesticides
Siem Riep Province, Cambodia

21. Reproductive Effects
Birth defects: Difficult to study but consist findings w/
Limb reductions - Uro-genital defects
Central nervous system
Cleft palates/lips
Eye – heart defects
Glyphosate: 3.6 risk of neurobehavioral problems in offspring
Time to Pregnancy: occupational exposure increase time needed to get pregnant
20%  in women engaged in pesticide activities
Dicamba, glyphosate, 2,4-D, thiocarbamates, OP’s.
Reproductive n=62
Congenital defects +: add to the growing body of evidence but still problems in designs.  risk limb, urogenital, CNS, orofacial, heart, eye. Glyphosate and pyridil derivatives
Time to PG + : n=8 consistent ~ suggest occupational exposure causes  time to pregnancy
Fertility ?: inconclusive-design problems
LBW, prematurity, IUGR:? n=10 7/10 + pyrethroid and chlorpyrifos. One paper mixed and 2 negative. May be an association more study needed
Fetal death + 9/11 positive assoc c/ SB or NND only 1 neg. Strong assoc w/ SaB or B defect and conventional pesticide prenatally vs IPM…phenoxy herbicides and SAB and hexachlorobenzene contaminated seeds in childhood and SaB

22. Growth Monitoring Clinic
Lombok, Indonesia

23. Reproductive Effects Small for Age Births: 7/10 studies +
Fetal and maternal blood samples for Op by products and newborn lengths
Chlorpyrifos and diazon residentially ~ lower birth weight and length*
Fetal deaths (still births, neonatal death, or miscarriages)
9/11 studies +
Strong association to miscarriages farming households using conventional pesticides 3 months before conception compared to IPM farms
* Source: Whyatt RM et al. Biomarkers in assessing residential insecticide exposures during pregnancy and effects on fetal growth.Tox Applied Pharm 206 (2): AUG

24. New York Study Following 700 mother/baby pairs for 7 years.
mother’s air intake for pesticides
mother’s blood
umbilical cord blood of baby

25. New York City Study
Fetal exposure to chlorpyrifos is associated with lower birth-weight and birth length
Same effect as SMOKING- as if the mother was a heavy smoker
At age 3 those more exposed had delayed movement and mental skills and attention deficits – temporary?

26. California Studies
600 pregnant Latina women farm working families living in Salinas, a heavy agriculture area.
OP by-products in urine during pregnancy and after delivery
Birth outcomes

27. California Study
OP pesticide by products in during DURING pregnancy associated to:
Shorter pregnancy – early deliveries
Abnormal reflexes at birth
Now watching these children’s nervous system as they grow

28. Summary Long Term Effects of OP’s
Length of gestation is shorter in women with higher organophosphate pesticide exposures
Newborns of mothers with higher organophosphate pesticide exposures have more abnormal reflexes
Pre-natal chlorpyrifos exposure is associated with reduced birth-weight and birth length
Children exposed to highest exposures had significantly higher risk of motor and cognitive delay compared to those with lowest exposures
Using child behavior checklist, highest exposed group had symptoms of inattentive disorder.

29. Some Important Facts
The younger you are the worse the consequences of OP exposure for development
Fetus
Soon after birth
Nerve system affected
Levels so low that they do not inhibit ChE but still effect neural development.

30. A Women’s Health Project
Andhra Pradesh, India

31. Risks to Children
Asthma
Brain and kidney tumors
Leukemia
Neuro-developmental problems
Small for age at birth
Congenital defects

32. Health History Interviewing
Batambang Province, Cambodia

33. Neurological and Mental Health
Depression, emotional disorders and suicides
Earlier poisonings ~ minor depression
Canada suicides ~ pesticide use
Subtle diminished function of nervous system
Occur after severe acute poisonings
Chronic low level exposure
Parkinson’s Disease [genetics + environmental exposures]
Consistent evidence w/ past occupational exposures
Mixed pesticides /herbicides investigated

34. Animal Studies (rodents)
Rodents exposed to low levels of OP’s over a long time during pregnancy and right after birth:
Problems with gait
Tremors
Balance problems
Run into cliffs
Cannot right themselves
Eskenazi B. Exposures of children to organophosphate pesticides and their potential adverse health effects.
EHP 1999;107 (Suppl 3):

35. Cancers
Brain tumors: 1.7 risk with a dose - response (more pesticide use the higher the risk) 323,292 offspring of Norwegian farmers
Breast (?): 1.8 x risk sprayed field, 2.0 x if not use PPE
Kidney: children of occupationally exposed men 1.59 x risk. Mortality rate 502 in pentachlorophenol chemical company workers
Brain: n=11 [5 cohort +, 5 c/c, 1 eco.] 1.7x risk in children associated to prenatal use of tick –flea products
Breast n= 6 [1 cohort, 2 c/c, 3 eco]
Cohort:  risk abnormal mammography but n/s for malignancy in greenhouse workers vs non
C/C :  risk in veg, fruit and crop farmers . OR 1.8 ( ) if in sprayed field 2.0 ( ) if did not use PPE but inverse risk with longer duration of farming (re: physical activity, sunlight or anti-estrogenic pesticides?)
Eco: # acres ~  risk of B cancer mortality [rice and catfish], Triazine medium exposure 1.14 and high exposure 1.2
Kidney n=6 [2 cohort, 4 c/c]
Cohort: 1657,703 kids of occupationally exposed men, PMR 1.59 ( ) + chemical company and death SMR 502 ( )
4 c/c + assoc most consistent for longer duration of exposure and kids of parents occupationally exposed
Pancreatic n=3 (2 c/c, 1 cohort)
All + especially with high exposure herbicides and fungicides
Cohort male aerial pesticides SMR 2.71 ( ) ? smoking
c/c arsenical OR = 3.4 ( ) other OR=3.17 ( ) job matrix fungicides 1.5 ( ) herb 1.6 ( )
Non Hodgkin’s Lymphoma n= 27 [cohort 11, c/c 14, Eco 2]
2,4-D implicated previously w/ these studies consistent
23/27 studies show statist sign association w/pesticides and NHL
cohort 9/11 + assoc, 3 ss 2 neg
c/c 12/14 + assoc, 8 ss, 2 neg
eco 2/2 +
Source: Sanborn M, Cole D, Kerr K, Vakil C, Sanin LH, Bassil K. Pesticides Literature Review. Ontario College of Family Physicians. Toronto 2004.

36. Cancers
Pancreatic: Aerial applicators (9,961) 2.71x risk than flight instructors (9969)
Prostate: 55,322 male applicators 3.75 risk > age 50 with methyl bromide or chlorinated pesticides (organochlorines like DDT or endosulfan)
Non Hodgkin’s Lymphoma [Immunologic + environmental factors]: 23/27 studies positive. 2-4 D a precipitant.
Leukemia 14/16 studies positive

37. IPM School
Chiang Mai Province, Thailand

38. Occupational Hazards of Pesticide Studies