Pesticides lecture from Toxicology 19. 10. 2021 M. Chalupová History • chemicals used to kill or control pests for centuries • the Chinese used arsenic to control insects • the early Romans used common salt to control weeds and sulfur to control insects • 1800 – pyrethrin was found as an insecticide • 1920s – petroleum oils to control scale insects and red spider mites • 1940s – DDT as an insecticide Definitions and Terms PESTICIDES • used to control pests attacking food or other essential goods (leather, clothing), transmitting or causing diseases themselves • algicides • fumigants • fungicides • herbicides • insecticides • nematocides • molluscicides • acaricides • rodenticides Benefits vs. Risks • ideal pesticides should be selective, destroying target organisms while leaving nontarget organisms unharmed • benefits must be weighted against the risk to human health and environment Benefits • control of vector-borne diseases • increased agricultural productivity Risks • environmental contamination (food chains, natural water systems) • persistence in the environment, bioaccumulation Organochlorine Insecticides • introduced in the 1940s and 1950s • DDT, methoxychlor, chlordane, aldrin, dieldrin, lindane DDT (dichlorodiphenyltrichloroethane) • synthesized in 1874, insecticidal properties discovered in 1939 by Dr. Mueller • during WWII large quantities of DDT used to control vector-borne diseases (typhus, malaria) • extensively used from 1940s through the 1960s in agriculture and mosquito control • 1962 – Rachel Carson published The Silent Spring focused on the environmental impacts of DDT DDT • opening Na+- channels in the neurons of insects causing their spontaneous firing, spasms and death • potential mechanisms of action on humans – neurotoxicity – genotoxicity – endocrine disruption (antiandrogen) – suspected to cause cancer (liver, pancreas, breast) • persistent, risk of bioaccumulation (plants, fatty tissue) • DDT production and usage restricted by Stockholm Convention on Persistent Organic Pollutants (2001) • still used under WHO guidelines against mosquitos (malaria) Organophosphates • phosphoric or thiophosphoric acid esters • insecticides, fungicides • parathion, diazinon, malathion, chlorpyrifos • inhibition of the acetylcholinesterase leads to accumulation of acetylcholine and overstimulation of nicotinic and muscarinic Ach receptors • acute toxicity – muscle weakness, dizziness, muscle cramps, paralysis, tremor – SLUDGEM (Salivation, Lacrimation, Urination, Defecation, GIT motility, Emesis, Miosis) • delayed neurotoxicity – organophosphorus-induced delayed neuropathy Organophosphates Carbamates • esters of N-methyl carbamic acid (H2NCOOH) • insecticides, fungicides, herbicides, nematocides • similar toxic mechanisms to OP, but the AchE inhibition is more rapidly reversed, so they are less toxic Carbaryl • a broad-spectrum insecticide used widely in agriculture or home gardens (applied as a dust) • not persistent, it is readily hydrolyzed • oral LD50 of 250 mg/kg (rat) Aldicarb • application to soils on crops such as cotton, citrus, and sweet potatoes • moves readily through soil profiles and contaminates groundwater supplies Plant Insecticides Nicotine • alkaloid first used in 1763 • oral and dermal toxicity • acute oral LD50 of nicotine sulfate for rats is 83 mg/kg, dermal LD50 is 285 mg/kg • respiratory failure due to paralysis of respiratory muscles in serious poisoning cases Neonicotinoids • synthetic analogues of the natural insecticide nicotine • nicotinic acetylcholine receptor agonists • sprays, drenches, seed and soil treatments • lead to leg tremor, rapid wing motion, paralysis and death • imidacloprid Plant Insecticides Pyrethrin • extract from several types of chrysanthemum • nonpersistent sodium channel modulators lead to prolonged excitation of nerves, paralysis and death • low mammalian toxicity because of rapid breakdown by liver microsomal enzymes Pyrethroids • cypermethrin, empenthrin, imiprothrin • synthetic mimics of pyrethrins being more persistent • greater insecticidal activity, photostability • agricultural and urban settings, repellents • acute toxicity: CNS (seizures, clouded consciousness) and GIT (nausea, vomiting) symptoms New Insecticides Fiproles • fipronil • used on corn, termiticide • long-term effectiveness Insect growth regulators • insect juvenile hormone analogues – diflubenzuron • the benzoylphenyl ureas inhibiting chitin synthesis – methoprene (mosquitoes, flies, fleas) • ecdysone agonists – tebufenozide (catterpillars) Herbicides • the most widely used class of pesticides • control and eliminate weed population • new families of herbicides are developed to be relatively nonphytotoxic to beneficial plants and environmentally friendly Imidazolinones • inhibit the action of acetohydroxyacid synthase producing branched-chain amino acids in plants • low toxicity to mammals, fish, insects and birds Chlorophenoxy Herbicides 2,4-D and 2,4,5-T • control of broadleaf plants by chemical similarity to the natural growth hormon auxin Agent Orange • used as a defoliant by US military during Vietnam war • TCDD dioxin as a major contaminant • toxic to developing embryos in pregnant rats • proven carcinogen in both mice and rats (liver) • altering the immune system Bipyridylium Herbicides Paraquat, Diquat • water-soluble non-selective herbicides • inhibits photosynthesis by the formation of reactive oxygen species/radicals (ROS) • active against a broad range of plants, defoliant • binds tightly to soil particles • preferential uptake by the lungs • toxicity: – vomiting, gastroenteritis – toxic nephritis with renal dysfunction and liver necrosis – pulmonary impairment (ARDS) and fibrosis by reactive oxygen species Fungicides • compounds used to kill or inhibit fungi or fungal spores • used on variety of crops including grapes, sugar beets and ornamental plants • natural fungicides – tea trea oil, jojoba oil, cinnamon oil, rosemary oil Chlorothalonil • used widely in urban environments • relatively nontoxic Fungicides Dicarboximides • captan, vinclozolin, iprodion • inhibit triglyceride synthesis in sclerotia-forming fungi • repeated use leads to resistance Dithiocarbamates • mancozeb, maneb, zineb • used widely in urban environments • relatively nontoxic • do hydrolyze producing known carcinogens such as ethylthiourea (ETU) Rodenticides • used to control rodents causing losses in grain and other food storage facilities • they harbor diseases in the form of fleas carrying bacteria and other infectious agents Coumarins and 4-hydroxycoumarins • warfarin • anticoagulant prevent blood from clotting • animals bleed to death in about a week • vitamin K as an antidote Rodenticides Fluorides • fluoroacetamide – bait pellets of grains Thioureas • α-naphthylthiourea (ANTU) Alkaloids • strychnine • human poisonings associated with accidental or suicidal ingestion Fumigants • extremely toxic gases used to protect stored products (grains) and to kill soil nematodes • applied to storage warehouses, freight car • hazard due to inhalation exposure and rapid diffusion to pulmonary blood • compounds requiring a license for the use Methyl bromide • sterilizes the soil, kill insects, nematodes, and weed seeds • overexposure causes respiratory distress, cardiac arrest, and CNS Chloropicrin • highly toxic by inhalation, causes heart impairment or severe eye damage