PESTICIDES Toxicology of Pesticides Curtis Harper 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 Miracles Pesticide 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 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 Medical 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 populations 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 pesticide 1 Vulnerability of Children Greater exposure Vulnerability of Children 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 respiration Safety 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 treatment Insecticides Herbicides Fungicides Fumigants Rodenticides Period of rapid development of Nerve Cells Loss of organ function can be permanently imprinted Absorption and elimination of pesticides Metabolizing enzymes not fully developed EPA Registration Data Acute Subchronic Chronic Reproductive INSECTICIDES Types of Pesticides Greater physiological susceptibility 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 life 2 Normal Neuron Insecticide toxicity Classes of Insecticides Organochlorine Insecticides Organophosphate Insecticides Carbamates Pyrethroid insecticides Botanical Insecticides Organochlorine Insecticides Dichlorodiphenylethanes Hexochlorocyclohexanes Cyclodienes 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 effects Insectisticide 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 endings Organochlorine Classification DDT Lindane or Benzene hexachloride Dieldrin Aldrin Chlordecone Kepone Mirex 3 HISTORY 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 degradation Disadvantages of DDT Persistence in the environment Bioconcentration Biomagnification in food chain Silent Spring Health 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 minor Health Effects of DDT Estrogenic Induces Enzymes Interferes with reproduction Insufficient Calcium to produce eggshells 4 Reflex arc Action Potential Sites of DDT poisoning DDT Treatment 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 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 Malaria Other organochlorine isecticides lindane Lindane Hexachlorocyclohexane HCH HCH is often Confused with Hexachlorobenzene HCB a fungicide Very similar to DDT Mechanism of action unknown 5 Effects of Chlorinated Hydrocarbons on Inuit People Inuit People 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 Other Organochlorine Insecticides Cyclodienes 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 people Pesticides in Artic Effects of Chlorinated Hydrocarbons on Inuit People Symptoms Cancer Birth Defects Reproductive harm Neurological toxicity Immunotoxicity Endocrine Toxicity Effects of Halogenated Hydrocarbons on Inuit People Chemicals Polychlorinated Biphenyls PCB Hexachlorobenzene HCB Hexchlorocyclohexane HCH Cyclodiene Sites Among the most toxic and environmentally persistent pesticides known Efficiently absorbed through the skin Sites of Action Inhibits GABA action on chloride transport 6 Cubane Cl KEPONE O C Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Mirex Cl Cl C Cl Cl Cl Cl Cl Cl Kepone and Mirex Cl Cl Cl Cl Treatment for Kepone Oral Cholestyramine The anionexchange resin causes up to 18 fold fecal excretion of kepone chlordecone Mechanism Resin binds chlordecone and prevents enterohepatic reabsorption and recirculation Factory workers in Hopewell VA Kepone Shakes tremors altered gait behavorial changes headache chest pains impotence weight loss hepatosplenomegaly etc Discovered by veterinarian Anticholinesterase Insecticides First synthesized in 1937