PLANT-DERIVED INSECTICIDES Nicotine • Source: – Nicotiana tabacum, Nicotiana rusticum • Characteristics – – – – – Colorless liquid Oxidizes to brown Hygroscopic Water miscible below 60o Soluble in many organic solvents Nicotine • Source: – Nicotiana tabacum, Nicotiana rusticum • Characteristics – Colorless liquid – Oxidizes to brown – Hygroscopic – Water miscible below 60o – Soluble in many organic solvents Nicotine • Mechanism – Mimics acetylcholine at nerve synapse • Stomach and contact poison • Site of action: • Formulations – CNS – Sprays: 0.05-0.1% – Autonomic nerves • Easier form to manage – Some voluntary peripheral nerves – Dusts:1-2% • LD50 • Irritant – Rats, po: 50 mg/kg • More likely to cause applicator – Rabbits, dermal: 50 mg/kg exposure • Symptoms • Minor use insecticide since – Vomiting, tremors, convulsions, synthetics were developed altered blood pressure – Death from block at respiratory neuromuscular junctions • Uses: – Against sucking insects LD50 = 450 mg/kg Sabadilla • Sabadilla CAS # = 802-85-77 • Source: • Seeds of Schoenocaulum officinale – Member of lily family • Toxin not present in other plant parts • Active ingredients are alkaloids – Veratrine and cevadine thought to be primary toxicants – cevine, cevacine, and sabadine – Other alkaloids also present and contribute to toxicity • Characteristics – Poor selectivity – Generally used as ground up seeds – Toxic to honey bees Sabadilla Sabadilla • Internally – Anthelmintic (obsolete) • Externally • – Against lice? (Also obsolete?) Gardening – 5-20% dust or spray – Contact and stomach poison – Labeled for use on vegetables – Controls • caterpillars, leafhoppers, thrips, stink bugs, squash bugs. • Toxicology – Veratrine and cevadine may be critical toxicants – Mechanism • Affect voltage-dependent Na channels – Delays channel shutting – Increases probability of channel opening – Direct effect on muscle contraction – Heart stops in systole as contractions become fewer and longer – LD50 of sabadilla • Rats, po: 4,000-5,000 mg/kg • Blackbirds, po: 18 mg/kg Rotenone • Source – Various tropical legumes, including • Derris elliptica, D. malaccensis (Malaysia) • Lonchocarpus utilis, L. urucu (South America) • 5 active ingredients known – Rotenone most effective » 5-10x activity of other compound Uses • Labeled for – Vegetables, berries, tree fruits, nuts, forage crops, sugar cane – Dusts, wettable powders, sprays • Usually < 5% • Original use included fishing • Is used to control undesirable fish in managed waters • Active 1-2 days on plants Toxicology • Mechanisms – Inhibits NADH ---> NAD by cytochrome b – Same in insects and mammals – Efficiently metabolized by mammalian liver • LD50 – Rats • po: 60-130 mg/kg • ip: 1-2 mg/kg – Other effects • Contact dermatitis • Chronic effects – Fetotoxicity at maternally lethal doses – Carcinogenic? • Delays progression of cells through cell cycle – Mechanism uncertain Ryanodine • Source – Powdered stem of Ryania speciosa – Water-soluble extract contains several structurally related ryanoids • Uses – Apple and citrus – Voluntary cancellation by manufacturers in 1990s – Sales did not warrant carrying out required toxicity studies Toxicology • Mechanism – At µM levels, irreversibly activates Ca++ channel in sarcoplasmic reticulum of muscle • Floods muscle cell with Ca++ ions • Induces sustained contraction of skeletal muscles • Paralysis results – Ryanodine receptor • Calcium channels in muscle, other excitable aimal tissue • Several subtypes – – – – RyR1 in skeletal muscles RyR2 in heart muscle RyR3 - wide distribution; also in brain RyR4: only in fish • Major mediator of Ca-induced Ca-release • LD50 po, rats: 750-1250 mg/kg Strychnine • Source – Strychnos bux vomica tree • seeds • Mechanism – Antagonizes strychninesensitive glycine receptor • ligand-gated chloride channel in CNS • Uses – Against vertebrtates • LD50 1 mg/kg po • Current Regulatory Status – ????