The Human Health Effects of Pesticide Exposure

• Acute Effects• Skin Problems• Respiratory Problems • Reproduction • Risks to Children • Nervous System • Cancers

Agriculture in Asia

A Typical North Vietnamese Farming Village

Focus on OP’s

Children at risk for neurodevelopmental problems

Most commonly used insecticide in agriculture

Common cause of poisoning

Normal Electrical Nerve Impulse Transmission

nerve cell

muscle cell

Once acetylcholine is broken, it can no longer transmit electrical nerve impulses.

Electrical nerve impulses stop and the muscles and glands are quiet

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

Organophosphate-Carbamate Disruption of Electrical Nerve Impulse Transmission Therapeutic Effect of Atropine

nerve cell

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.

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.

muscle cell

Electrical nerve impulse

acetate

choline

cholinesterase

organophosphate

atropine

Signs and Symptoms in Adults

• Miosis

• Blurring

Eye CNS Lungs GI Glands Muscle Heart

Exercise: Body Mapping

• Fatigue• Dizziness• Headache• Tremors• Ataxia • Seizures• LOC• Coma • Insomnia• Mental Δ

TightnessWheezingCoughRhinorrhea

Abd. crampsNauseaVomitingDiarrhea

Drooling

Sweating

Tearing

Weakness CrampsFasciculations

Tachy

Brady

BP

↓ BP

Parathion StoryOn 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.

Signs of Pesticide Poisoning in a CHILD

Lethargic sleepy

Seizures

Coma

Can be confused with the flu

Respiratory Problems

• Organophosphates and carbamates inhibit cholinesterase resulting in Constriction of the bronchial tubes Increased secretionsDifficulty in breathing

• Many pesticides are ‘sensitizers’ causing allergic reactions along with OTHER triggersdusts, pollens, animals, diesel, molds, grains, hay,

disinfectants

Typical Pesticide Application

North Vietnam

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: http://www.aghealth.org/

Transplanting Rice

West Sumatra, Indonesia

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.

Paraquat Application by Burmese Migrant Workers in Thailand

Mae Sot, Thailand

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. 2000.

Methamidiphos Contact Dermatitis

North Vietnam

Severe Contact DermatitisCartap + [Fenobucarb, Dimethoate and Methyl Parathion x 20 yrs]

Prey Vang, Cambodia

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.

Mixing Pesticides

Siem Riep Province, Cambodia

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.

Growth Monitoring Clinic

Lombok, Indonesia

• 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

Reproductive Effects

* Source: Whyatt RM et al. Biomarkers in assessing residential insecticide exposures during pregnancy and effects on fetal growth.Tox Applied Pharm 206 (2): 246-254 AUG 7 2005

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

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?

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

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

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.

Some Important Facts

The younger you are the worse the consequences of OP exposure for developmentFetusSoon after birth

Nerve system affected Levels so low that they do not inhibit ChE

but still effect neural development.

A Women’s Health Project

Andhra Pradesh, India

Risks to Children

• Asthma • Brain and kidney tumors • Leukemia• Neuro-developmental problems• Small for age at birth • Congenital defects

Health History Interviewing

Batambang Province, Cambodia

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

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):409-419

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

Source: Sanborn M, Cole D, Kerr K, Vakil C, Sanin LH, Bassil K. Pesticides Literature Review. Ontario College of Family Physicians. Toronto 2004.

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

IPM School

Chiang Mai Province, Thailand

Occupational Hazards of Pesticide Studies