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, 2005 Spokane, WA Steven G. Gilbert, PhD, DABT

A Small Dose of ToxicologyNeurotox – Pesticides – 9/8/05 Definition - Simple The function of a pesticide is to kill or harm some form of life.

A Small Dose of ToxicologyNeurotox – 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 ToxicologyNeurotox – 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 ToxicologyNeurotox – Pesticides – 9/8/05 Pesticide Application

A Small Dose of ToxicologyNeurotox – Pesticides – 9/8/05 Key Words Risk = Hazard X Exposure Dose / Response Individual Sensitivity

A Small Dose of ToxicologyNeurotox – Pesticides – 9/8/05 What Is This Pesticide? N N N N CH 3 O O 1 3 7

A Small Dose of ToxicologyNeurotox – Pesticides – 9/8/05 N CH 3 N What Is This Pesticide?

A Small Dose of ToxicologyNeurotox – Pesticides – 9/8/05 Effects of Amount on Response

A Small Dose of ToxicologyNeurotox – Pesticides – 9/8/05 Effects of Size on Response

A Small Dose of ToxicologyNeurotox – Pesticides – 9/8/05 Insecticides  Insecticides (kill insects) Organochlorines Organophosphates Carbamates Synthetic Pyrethroids

A Small Dose of ToxicologyNeurotox – Pesticides – 9/8/05 Dose / Response 10 mg/kg is lethal Adult70 kg (150 lbs)700 mg Child10 kg (22 lbs)100 mg Insect1 mg mg Example – killing fleas on pets

A Small Dose of ToxicologyNeurotox – Pesticides – 9/8/05 Organochlorines Examples DDT, methoxychlor, aldrin, dieldrin, endrin, heptachlor, kepone, lindane, chlordane, endosulfan Toxicity Acute toxicity variable, CNS – convulsions, coma Environmental characteristics Highly persistent in environment, fat soluble, bioaccumulation, biomagnification Mostly banned in US and Europe

A Small Dose of ToxicologyNeurotox – Pesticides – 9/8/05 Organophosphates-1 Examples Malathion, parathion, guthion, diazinon, Chlorpyrifos (Lorsban) TPN, TOCP, nerve gases – tabun, sarin, soman, VX Toxicity Acute toxicity highly variable – Parathion, TPN, sarin very toxic, malathion much less Environmental characteristics Rapidly degrade in outdoor environment (last longer in doors), do not bioaccumulate

A Small Dose of ToxicologyNeurotox – Pesticides – 9/8/05 Chlorpyrifos (Lorsban) Organophosphorus Insecticide

A Small Dose of ToxicologyNeurotox – Pesticides – 9/8/05 Organophosphates-2 Mechanism of toxicity Inhibition of acetylcholinesterase (AchE) in nerve tissue Symptoms Over-stimulation of parasympathetic nervous system --- salivation, constricted pupils, diarrhea, sweating, muscle twitching, CNS disturbances – coma and death Treatment Reverse AchE inhibition effects – use Atropine to block Ach receptors or AchE inhibiton with 2-PAM

A Small Dose of ToxicologyNeurotox – 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 ToxicologyNeurotox – Pesticides – 9/8/05 Mechanism of Action Oganochlorines & Pyrethroids - Enzymes, axonal membranes (Na +, K +, Ca ++, Cl - ) Organophosphates & Carbamates - excess acetylcholine

A Small Dose of ToxicologyNeurotox – Pesticides – 9/8/05  Neurotoxicological and Statistical Analyses of a Mixture of Five Organophosphorus Pesticides Using a Ray Design V. 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 ToxicologyNeurotox – Pesticides – 9/8/05  Epigenetic Transgenerational Actions of Endocrine Disruptors and Male Fertility Matthew 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 ToxicologyNeurotox – 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 ToxicologyNeurotox – 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 ToxicologyNeurotox – Pesticides – 9/8/05 A Small Dose of ™ Pesticide

A Small Dose of ToxicologyNeurotox – Pesticides – 9/8/05 Additional Information  WSU – Washington State Pest Management Resources Service (WSPMRS) -  UW – Welcome to the Pacific Northwest Agricultural Safety and Health Center (PNASH) -  Pesticide ActionNetwork North America -  Washington Toxics Coalition -  Pesticide Database site -  US EPA Office of Pesticides -  USGS - NAWQA Pesticide National Synthesis Project -  University of Illinois – Pesticide Impact Assessment -

A Small Dose of ToxicologyNeurotox – Pesticides – 9/8/05 Authorship Information For Additional Information Contact Steven G. Gilbert, PhD, DABT Web: This presentation is supplement to “A Small Dose of Toxicology”

A Small Dose of ToxicologyNeurotox – 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)