Toxicology of PesticidesCurtis HarperPESTICIDES A chemical, physical, or biological agent that will kill an undesirable plant or animal pest All pesticides possess an inherent degree of toxicity to some living organism; otherwise they would be of no practical use.Pesticide Use Pesticides provide us with abundantly inexpensive, wholesome, and attractive fruits and vegetables Agricultural production has increased 82% in the past 30 years due to pesticides Medical MiraclesMedical Miracles Suppression of typhus epidemic in Italy, 1943-1944 Control of blindness in West Africa by killing the black fly that carried the disease Control of Malaria in Africa, Middle East, and Asia by eliminating the mosquito populationsPesticide Danger Of all the dangerous chemical substances to which we are exposed, only pesticides, antibiotic drugs, and anti cancer drugs are designed specifically to kill cells.Target Species of Pesticides Not very well developed Non-target species are affected because the have the same physiological systems as target organisms No such thing as a completely safe pesticideVulnerability of ChildrenGreater exposure On a body-weight: caloric consumption ratio Children are 2.5X adults. Diet less varied (fruit and milk) ↑ Hand to mouth activity Skin surface area per body weight is double that of an adult ↑ Rate of respirationVulnerability of Children Greater physiological susceptibility Period of rapid development of Nerve Cells Loss of organ function can be permanently imprinted ↑ Absorption and ↓ elimination of pesticides Metabolizing enzymes not fully developedSafety of Pesticides Depends on how they are used Must be used according to the instructions on the label As long as they are used, accidental and/or incidental poisoning of wildlife, domestic stock, and humans will require treatmentEPA Registration Data Acute Subchronic Chronic ReproductiveTypes of Pesticides Insecticides Herbicides Fungicides Fumigants RodenticidesINSECTICIDES Most chemical insecticides act by poisoning the nervous system of the target organisms CNS of insects are highly developed and similar to that of the mammal. Chemicals that act on the insect nervous system may have similar effects on higher forms of lifeNormal NeuronInsecticide toxicity A chemical that poisons the insect nervous system will will elicit similar effects on higher forms of life. Only the dosage will indicate the intensity of biological effectsClasses of Insecticides Organochlorine Insecticides Organophosphate Insecticides Carbamates Pyrethroid insecticides Botanical InsecticidesInsectisticide General Mode of Action Interference with transport of, Na+, K+, Ca2+, or Cl-ions Inhibition of specific enzyme activities Contribution to the release or persistence of chemical transmitters at nerve endingsOrganochlorine Insecticides Dichlorodiphenylethanes DDT Hexochlorocyclohexanes Lindane or Benzene hexachloride Cyclodienes Dieldrin Aldrin Chlordecone Kepone MirexOrganochlorine ClassificationHISTORY OF DDT WWII – DDT was used by the allies to suppress a typhus epidemic in Naples 1943-1944 DDT was applied directly to the head of humans to control lice Success with DDT hastened the development of aldrin, dieldrin, endrin, chlordane, benzene hexachloride etc.Insecticide advantages of DDT Low volatility Chemical stability Lipid solubility Slow rate of biotransformation and degradationDisadvantages of DDT Persistence in the environment Bioconcentration Biomagnification in food chain Silent SpringHealth Effects of DDT Paresthesia of tongue, lips, and face Apprehension Irritability, dizziness, vertigo, tremor, and convulsions Hypersusceptibility to external (light, touch, and sound)Health Effects of DDT Hypertrophy of hepatocytes Hepatic tumors No epidemiological evidence linking DDT to carcinogenicity in humans Low rate of absorption through the skin Human health effects minorHealth Effects of DDT Estrogenic Induces Enzymes Interferes with reproduction Insufficient Calcium to produce eggshellsReflex arcAction PotentialSites of DDT poisoningDDT Banned in North America and Europe because of its harmful effects on wildlife and fresh water fish. Not banned in other countries because it is highly effective, inexpensive to manufacture, and safe DDT is making a comeback in other countries because it is the only effective agent against the spread of MalariaTreatment of Poisoning Diazepam and phenobarbital are administered by slow injection to control convulsions Anion-exchange resin, cholestyramine, increases the fecal excretion of the insecticide and inhibits the enterohepatic circulation. It binds the insecticide, reducing the reabsorption of the bound agent, causing fecal excretion of the bound material.Other organochlorineisecticides: lindane Lindane = Hexachlorocyclohexane (HCH) HCH is often Confused with Hexachlorobenzene (HCB): a fungicide Very similar to DDT Mechanism of action unknownEffects of Chlorinated Hydrocarbons on Inuit People Inuit People 450 People on small island in Canadian Artic More polluted than any other place. Contain some of worlds most toxic chemicals.  Concentration of chemicals 70-100 fold greater than other peopleEffects of Chlorinated Hydrocarbons on Inuit People Symptoms Cancer Birth Defects Reproductive harm Neurological toxicity Immunotoxicity Endocrine ToxicityPesticides in Artic Volatile chemicals boil off into the air in tropical climate Carried by the winds until the hit cooler climates Condense and fall to the earth (different groups of chemicals condense at different temperatures – fractional distillation)Effects of Halogenated Hydrocarbons on Inuit People Chemicals Polychlorinated Biphenyls (PCB) Hexachlorobenzene (HCB) Hexchlorocyclohexane (HCH)Other OrganochlorineInsecticides:Cyclodienes Among the most toxic and environmentally persistent pesticides known Efficiently absorbed through the skin Sites of Action: Inhibits GABA action on chloride transportCyclodiene SitesCubaneClClClClClClClClKEPONEOCClClClClClClClClClClMirexCClClClClClClClClClClClClKepone and Mirex Factory workers in Hopewell, VA Kepone Shakes: tremors, altered gait, behavorial changes, headache, chest