The Road Towards ReducedRisk Insecticides

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
Insecticides that Target the Nervous System

• Organochlorines
• DTT, lindane, cyclodienes
• alter ion permeabilities of nerve membranes
• Organophosphates and Carbamates
• malathion, parathion, cabaryl
• inhibit acetylcholinesterase and increase levels
  of acetylcholine

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 Parkinsons
  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