Toxic Effects of Pesticides Pesticides are substances used to prevent destroy repel or mitigate any pest ranging from insects animals and weeds to microorganisms such as fungi molds bacteria and viruses insect killers insecticides mold and fungi killers fungicides weed killers herbicides slug pellets molluscicides plant growth regulators bird and animal repellents rat and mouse killers rodenticides Pesticides help to manage and prevent pests that spread disease that damage crops buildings and other property and that are a public nuisance Pesticides help to manage and prevent pests that spread disease that damage crops buildings and other property and that are a public nuisance Agricultural production has increased 82 in the past 30 years due to pesticides Medical uses 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 Klaassen CD CASARETT AND DOULL s Toxicology The Basic Science of Poisons McGraw Hill 2001 World production 1995 2 6x109 kg US production 1997 0 54x109 kg World production of DDT 1943 74 2 8x109 kg Stenersen J Chemical pesticides Mode of Action and Toxicology CRC Press 2004 Regulations US Federal Insecticide Fungicide and Rodenticide Act FIFRA Established in 1947 under USDA Turned over to the EPA in 1972 FDA retains authority over monitoring residues in foods USDA is responsible for monitoring residues in meat and poultry Food Quality Protection Act 1996 Special 10 fold safety factor and other precautions added to consider possible effects in infants and children Klaassen CD CASARETT AND DOULL s Toxicology The Basic Science of Poisons McGraw Hill 2001 Vulnerability of Children Greater 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 respiration Vulnerability 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 developed Klaassen CD CASARETT AND DOULL s Toxicology The Basic Science of Poisons McGraw Hill 2001 Estimated cost to develop new pesticide product 80 mln 1999 Complexities of the Nomenclature Example Stenersen J Chemical pesticides Mode of Action and Toxicology CRC Press 2004 Modes of action of pesticides Disturbance in energy production Inhibition of photosynthesis Free radical generation SH group reactivity Interference with cell division Inhibition of nucleic acid synthesis Inhibition of enzymes Ergosterol synthesis Amino acid synthesis Chitin synthesis Cholinesterase Hormone like and behavior modifying agents Disturbance in energy production Naturally occurring compound Blocks electron transfer from NADH to ubiquinone in mitochondria Highly toxic to fish Stenersen J Chemical pesticides Mode of Action and Toxicology CRC Press 2004 Disturbance in energy production Stenersen J Chemical pesticides Mode of Action and Toxicology CRC Press 2004 Inhibition of photosynthesis Herbicide action may be via Disruption of H ion gradients weak organic acids Free radical generators e g paraquat Binding to D1 protein at plastoquinone binding site D1 blockers urea derivatives triazines Inhibition or destruction of protective carotenoids e g amitrole aclonifen Stenersen J Chemical pesticides Mode of Action and Toxicology CRC Press 2004 Free radical generation SH reactivity Mercury containing agents mercurials binding to DNA RNA proteins and formation of cross links SH group reactive agents Form protein compound and protein compound protein cross links Copper containing agents promote redox cycling and generation of free radicals Interference with cell division Common mode of action inhibition of tubulin blockage of microtubules that separate chromosomes during cell division Inhibition of nucleic acid synthesis Sporulation inhibiting fungicides Herbicides inhibiting incorporation of uridine into RNA chloroacetanilides and phenylamides Stenersen J Chemical pesticides Mode of Action and Toxicology CRC Press 2004 Inhibition of ergosterol synthesis Squalene epoxidase Stenersen J Chemical pesticides Mode of Action and Toxicology CRC Press 2004 Inhibition of ergosterol synthesis 14 demethylase CYP51 Demethylase DMI inhibiting fungicides Azoles and triazoles Pyridines and pyrimidines Pyperazines Amines Morpholines Stenersen J Chemical pesticides Mode of Action and Toxicology CRC Press 2004 Inhibition of amino acid synthesis Glyphosate Roundup Vision Inhibits 5 enolpyruvyl shikimate3 phosphate synthase EPSP Gluphosinate Basta Total Inhibits glutamine synthase Stenersen J Chemical pesticides Mode of Action and Toxicology CRC Press 2004 Inhibition of choline esterase or action potential Organochlorine Insecticides Organophosphate Insecticides Carbamates Pyrethroid insecticides Botanical Insecticides Klaassen CD CASARETT AND DOULL s Toxicology The Basic Science of Poisons McGraw Hill 2001 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 Stenersen J Chemical pesticides Mode of Action and Toxicology CRC Press 2004 General Modes of Action Pesticides acting on the axon impulse transmission Interference with transport of Na K Ca2 or Cl ions Pesticides acting on synaptic transmission Inhibition of specific enzyme activities GABA ergic inhibitory synapses Cholinergic synapses Contribution to the release or persistence of chemical transmitters at nerve endings Stenersen J Chemical pesticides Mode of Action and Toxicology CRC Press 2004 Organochlorine Insecticides Dichlorodiphenylethanes DDT Hexochlorocyclohexanes Lindane Benzene hexachloride Cyclodienes Dieldrin Aldrin Chlordecone Kepone Mirex HISTORY OF DDT 1 1 1 trichloro 2 2 bis p chlorophenyl ethane DDT was discovered to be an insecticide in 1939 by Paul Muller He was a scientist working for Geigy a Swiss firm that was focused on the chemical development of agricultural insecticides Products with DDT entered the Swiss market in 1941 Seven years later in 1948 Muller received the Nobel Prize for medicine and physiology in recognition for the lives DDT saved