neurological and long-term effects of pesticides exposure

Neurotox – Pesticides – 9/8/05

Neurological and Long-Term Effects of

Pesticides Exposure

A Small Dose of Pesticide

“Out of Harm’s Way: Preventing Toxic Threats to our Children’s Health”

October 15, 2005Spokane, WA

Steven G. Gilbert, PhD, DABTwww.asmalldoseof.org

A Small Dose of Toxicology Neurotox – Pesticides – 9/8/05

Definition - Simple

The function of a pesticide is to kill or

harm some form of life.

A Small Dose of Toxicology Neurotox – Pesticides – 9/8/05

Definition - EPA

“…a pesticide is any substance or mixture of substances intended for preventing, destroying, repelling, or mitigating any pest.”

“…a pest is any harmful, destructive, or troublesome animal, plant or microorganism.”

US Environmental Protection Agency (EPA)

A Small Dose of Toxicology Neurotox – Pesticides – 9/8/05

Definition - FIFRA

“… any substance or mixture of substances intended for preventing, destroying, repelling or mitigating any insects, rodents, nematodes, fungi, or weeds or any other form of life declared to be pests. … and any substance or mixture of substances intended for use as a plant regulator, defoliant or desiccant.”

Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA – 1947)

A Small Dose of Toxicology Neurotox – Pesticides – 9/8/05

Pesticide Application

A Small Dose of Toxicology Neurotox – Pesticides – 9/8/05

Key Words

Risk =

Hazard X Exposure

Dose / Response

Individual Sensitivity

A Small Dose of Toxicology Neurotox – Pesticides – 9/8/05

What Is This Pesticide?

N

NN

N

CH3

CH3

CH3

O

O

1

3

7

A Small Dose of Toxicology Neurotox – Pesticides – 9/8/05

N

CH3N

What Is This Pesticide?

A Small Dose of Toxicology Neurotox – Pesticides – 9/8/05

Effects of Amount on Response

A Small Dose of Toxicology Neurotox – Pesticides – 9/8/05

Effects of Size on Response

A Small Dose of Toxicology Neurotox – Pesticides – 9/8/05

Insecticides

Insecticides (kill insects)• Organochlorines• Organophosphates• Carbamates• Synthetic Pyrethroids

A Small Dose of Toxicology Neurotox – Pesticides – 9/8/05

Dose / Response

10 mg/kg is lethal

Adult 70 kg (150 lbs) 700 mg

Child 10 kg (22 lbs) 100 mg

Insect 1 mg 0.00001 mg

Example – killing fleas on pets

A Small Dose of Toxicology Neurotox – Pesticides – 9/8/05

Organochlorines

ExamplesDDT, methoxychlor, aldrin, dieldrin, endrin,

heptachlor, kepone, lindane, chlordane, endosulfan

ToxicityAcute toxicity variable, CNS – convulsions,

coma

Environmental characteristicsHighly persistent in environment, fat

soluble, bioaccumulation, biomagnification

Mostly banned in US and Europe

A Small Dose of Toxicology Neurotox – Pesticides – 9/8/05

Organophosphates-1

ExamplesMalathion, parathion, guthion, diazinon,

Chlorpyrifos (Lorsban) TPN, TOCP, nerve gases – tabun, sarin, soman, VX

ToxicityAcute toxicity highly variable – Parathion, TPN,

sarin very toxic, malathion much less

Environmental characteristicsRapidly degrade in outdoor environment (last

longer in doors), do not bioaccumulate

A Small Dose of Toxicology Neurotox – Pesticides – 9/8/05

Chlorpyrifos (Lorsban)

Organophosphorus Insecticide

A Small Dose of Toxicology Neurotox – Pesticides – 9/8/05

Organophosphates-2

Mechanism of toxicityInhibition of acetylcholinesterase (AchE) in

nerve tissue

SymptomsOver-stimulation of parasympathetic nervous

system --- salivation, constricted pupils, diarrhea, sweating, muscle twitching, CNS disturbances – coma and death

TreatmentReverse AchE inhibition effects – use

Atropine to block Ach receptors or AchE inhibiton with 2-PAM

A Small Dose of Toxicology Neurotox – Pesticides – 9/8/05

Organophosphates-3

Other Toxic Effects• Delayed peripheral neuropathy (TOCP)• Generally not carcinogenic• Long term neurological consequences

from repeated exposures

A Small Dose of Toxicology Neurotox – Pesticides – 9/8/05

Mechanism of Action

Oganochlorines & Pyrethroids - Enzymes, axonal membranes (Na+, K+, Ca++, Cl-)

Organophosphates & Carbamates - excess acetylcholine

A Small Dose of Toxicology Neurotox – Pesticides – 9/8/05

Neurotoxicological and Statistical Analyses of a Mixture of Five Organophosphorus Pesticides Using a Ray DesignV. C. Moser, M. Casey, A. Hamm, W. H.

Carter, Jr., J. E. Simmons, and C. Gennings

TOXICOLOGICAL SCIENCES 86(1), 101–115 (2005)

Multiple Exposures

A Small Dose of Toxicology Neurotox – Pesticides – 9/8/05

Epigenetic Transgenerational Actions of Endocrine Disruptors and Male FertilityMatthew D. Anway, Andrea S. Cupp,*

Mehmet Uzumcu,.Michael K. Skinner

SCIENCE 3 JUNE 2005 VOL 308

“The ability of an environmental factor (for example, endocrine disruptor) to reprogram the germ line and to promote a transgenerational disease state has significant implications for evolutionary biology and disease etiology.”

Multiple Generational Effects

A Small Dose of Toxicology Neurotox – Pesticides – 9/8/05

Worker Exposure Issues

• Cholinesterase Levels – depressed by CPF and other

organophosphate/carbamate pesticides

• Monitoring indicates that works have depressed cholinesterase levels

A Small Dose of Toxicology Neurotox – Pesticides – 9/8/05

Acute effects are major concern for pesticides used widely in WA agriculture

Chronic effects of concern, too. Children of workers as well as workers are

exposed and are at greater risk. Multiple exposures are occurring,

potentially increasing risks. There may be multiple generation effects. Precaution is a prudent approach

Health & Pesticide - Summary

A Small Dose of Toxicology Neurotox – Pesticides – 9/8/05

A Small Dose of ™ Pesticide

A Small Dose of Toxicology Neurotox – Pesticides – 9/8/05

Additional Information WSU – Washington State Pest Management

Resources Service (WSPMRS) - http://wsprs.wsu.edu/

UW – Welcome to the Pacific Northwest Agricultural Safety and Health Center (PNASH) - http://depts.washington.edu/pnash/

Pesticide ActionNetwork North America- http://www.panna.org

Washington Toxics Coalition- http://www.watoxics.org

Pesticide Database site- http://www.pesticideinfo.org/

US EPA Office of Pesticides- http://www.epa.gov/pesticides/

USGS - NAWQA Pesticide National Synthesis Project - http://water.wr.usgs.gov/pnsp/

University of Illinois – Pesticide Impact Assessment - http://ext.agn.uiuc.edu/piap/

A Small Dose of Toxicology Neurotox – Pesticides – 9/8/05

Authorship Information

For Additional Information ContactSteven G. Gilbert, PhD, DABT

E-mail: smdose@asmalldoseof.orgWeb: www.asmalldoseof.org

This presentation is supplement to “A Small Dose of Toxicology”

A Small Dose of Toxicology Neurotox – Pesticides – 9/8/05

• Focus – long-term prevention of pest problems

• Reduce or eliminate chemical pest control methods

• Monitor for the presence of pests before treating

• Nonchemical strategies (make habitat less attractive, physical controls)

• Learn about your pests

Integrated Pest Management (IPM)