1. The Road Towards Reduced-Risk Insecticides Selective Targeting of Insect Physiology Understanding The Connections Between Environmental Exposures and Human Disease

2. Traditional Insecticides: Low Target Selectivity Affect Common Systems –Major target: Nervous system – Other targets: mitochondria Risk to Non-Target Organisms –Beneficial insects –Fish, mammals –Humans

3. Organochlorines –DTT, lindane, cyclodienes –alter ion permeabilities of nerve membranes Organophosphates and Carbamates –malathion, parathion, cabaryl –inhibit acetylcholinesterase and increase levels of acetylcholine Insecticides that Target the Nervous System

4. Insecticides that Target the Mitochondria Rotenone –Inhibits mitochondrial electron transport at complex I

5. Presidential Green Chemistry Challenge Award Development of Bisacylhydrazine Insecticides by Rohm and Haas Company

6. Bisacylhydrazine Insecticides: Targeting Insect Physiology Insect growth requires “molting” Molting is regulated by the levels of 20E Bisacylahydrazine insecticides are stable agonists of the 20E receptor Bisacylhydrazine insecticides cause a “lethal molt”

7. Is Targeting Insect Physiology Enough? 1. What are the connections between environmental exposures and human diseases? 2. Do insecticides affect long-term human health by mechanisms that are unrelated to acute toxicity?

8. Insecticides Affect Functions Important for Long-Term Health Mitochondrial Electron Transport –Insecticides inhibit electron transport; an effect that has been linked to Parkinson’s Disease-like symptoms –A primary target of rotenone but an additional target of organophosphates? Detoxification by CYP Monooxygenases –Insecticides including organophosphates may adversely affect detoxification systems Endocrine Disruption –Links to cancers and reproductive disorders?

9. Continuing on The Road Towards Reduced-Risk Insectides Targeting the unique physiology of insects Understanding the effects of insecticides on physiological functions important for long- term human health