Efficacy of Volatile, Low Molecular Weight Insecticides against Aedes

1
Efficacy of Volatile, Low Molecular Weight
Insecticides against Aedes Culex mosquitoes

• by Alexandra Chaskopoulou, Sam N. Nguyen, Philip
  G. Koehler, Michael E. Scharf
• Department of Entomology
• University of Florida

2
Introduction

• Volatile Insecticides- Fumigants
• Protection of stored agricultural commodities
• Management of structural pests
• For public health pests, dichlorvos was most
  studied (Miles et al. 1962,Maddock et al. 1963,
  Brooks Scoof 1964, Matthysse McClain 1972)
• Dichlorvos (DDVP)- Resin/Pest strips
• Registered for use in areas where flies,
  mosquitoes and other nuisance pests occur
• Initial registration 1948 (EPA Insecticide Fact
  Sheet)
• In 2006, use indoors was restricted
• Need for replacement chemistries

3
Introduction

• 30 novel low molecular weight insecticides from 6
  different families were tested on Drosophila
  melanogaster Meig. (Scharf et al. 2006)
• 1. Formate esters
• 2. Heterobicyclics
• 2. Acetate esters
• 4. Propionate esters
• 5. Butyrate esters
• 6. Valerate esters
• 7 highly effective insecticides with vapor
  toxicity
• 4 formate esters
• 3 heterobicyclics
• Drosophila was used as a model to assess
  potential efficacy of novel chemistries against
  mosquitoes flies

4
Introduction

• 6 families of novel chemical compounds and DDVP
  were tested directly on Aedes aegypti Culex
  quinquefasciatus
• Formates
• Heterobicyclics
• Acetates
• Propionates
• Butyrates
• Valerates

Aedes aegypti (L.)
Culex quinquefasciatus (Say)
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Formate Family

• Formate ester (composed of its corresponding
  alcohol formic acid)
• Physical properties
• Clear liquids with fruity/ethereal/floral/rum
  odors
• Natural occurrence apples, pineapples, pears,
  kumquats, plums
• Used as
• Flavoring/odor agents in
• Fruit products
• Wine
• Rum

Methyl formate
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Acetate Family

• Acetate ester (composed of its corresponding
  alcohol acetic acid)
• Physical properties
• Clear liquids with a fruity (pear, banana) odor
• Natural occurrence
• Fruits (apples)
• Used as
• Flavoring/odor agents
• Candy
• Ice cream
• Cheese
• Baked goods

Butyl acetate
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Propionate Family

• Propionate ester (composed of its corresponding
  alcohol and propionic acid)
• Physical properties
• Colorless liquids with a fruity, earthy sweet
  odor
• Natural occurrence apples, bananas, melons,
  peach, plums, mushrooms
• Used as
• Flavoring odor agents
• Fruit juice, caramel, coffee, dairy products

Ethyl propionate
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Butyrate Family

• Butyrate ester (composed of its corresponding
  alcohol butyric acid)
• Physical properties
• Colorless liquid with a fruity, sweet fragrance
• Natural occurrence apple, banana, strawberry
• Used as
• Flavoring/odor agents
• Fruit products

Methyl butyrate
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Valerate Family

• Valerate ester (composed of its corresponding
  alcohol and pentanoic acid)
• Physical properties
• Colorless to pale yellow liquid with a sweet,
  fruity odor
• Natural occurrence apple, pineapple, cheese,
  mint, strawberry, and other fruits
• Used as
• Flavoring/Odor agent
• Fruit and dairy products
• Alcoholic beverages (rum, wine)

Methyl valerate
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Heterobicyclic Family

• Composed of fused 5,6-membered rings
• Physical properties
• Colored (bluish, yellowish) liquids with strong
  phenolic/musty/nutty odor
• Benzothiophene and indole are in solid
  crystalline form with an odor similar to
  naphthalene
• Natural occurrence peppermint oil, cade oil,
  tobacco, petroleum deposits
• Used as
• Flavoring/odor agents
• Coffee, chocolate, tobacco
• Chemical structure of pharmaceutical drugs
• Osteoporosis treatment (raloxifen)
• Asthma treatment (zileuton)
• Insomnia treatment

Menthofuran
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Objectives

• Evaluate vapor toxicities of the 6 families of 30
  novel compounds to
• Aedes aegypti (L.)
• Culex quinquefasciatus (Say)
• Determine the compound families with best
  toxicities
• Compare the toxicities between mosquitoes
  Drosophila
• Determine structure activity relationships

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Bioassay Set-up
Drosophila Bioassay Set-up
Mosquito Bioassay Set-up
Metal Lid
0.5 L glass jar
Septum cap with mesh on top
7.0 ml dram vial
10 adult insects
Food source
Filter paper Tent
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Hetero- bicyclics
Formates
Acetates
Valerates
Propionates
Butyrates
Ae. aegypti
Cu. quinquefasciatus
Drosophila
DrosophilagtAe.aegyptigtCu.quinquefasciatus
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Comparing Toxicities Among Mosquitoes Drosophila
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1. Structure-Activity Relationships

• Formic acid in the structure of esters is
  associated with higher toxicity when tested on
  mosquitoes (Haritos VS Dojchinov G, 2003)

Other esters
Ae.aegypti
Cu.quinquefasciatus
Formate ester
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2. Structure-Activity Relationships

• Formates Acetates
• n-configurationgtt-configuration
• n-configurationgtt-configuration

t
t
t
n
n
n
H
n-configuration
t
t
t
n
n
n
t-configuration
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3. Structure-Activity Relationships
As the size of the aliphatic chain of the
formates increases toxicity decreases (observed
only at Ae.aegypti)
Ae. aegypti
Cu. quinquefasciatus
R2 0.594
R2 -0.345
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Conclusions/Future Recommendations

• Compounds were toxic to mosquitoes and Drosophila
• DrosophilaltAedesltCulex
• Differences on insect handling techniques
• Species difference on acquiring insecticides
• Different breathing patterns
• Species differences on metabolizing/detoxifying
  insecticide
• There was some structure activity trends
• 1. Formic acid was correlated with higher
  toxicity in mosquitoes
• 2. n-configurationgtt-configuration in both
  mosquitoes and Drosophila
• 3. There seems to be a positive correlation
  between aliphatic chain length and toxicity for
  the formate esters in Ae. aegypti
• The toxicity differences observed between Aedes
  Culex indicate potentially variable toxicity
  among mosquito genera/species
• Additional species should be considered in the
  future

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Conclusions/Future Recommendations

• New chemistries have potential to replace DDVP
• Effective toxicities
• Low mammalian toxicities
• Oral LD50s in a range of 1,500-5,000 mg/kg versus
  DDVP 68 mg/kg
• Pleasant odors
• n-butyl formate has consistently good toxicity to
  all tested dipterans
• Low mammalian oral LD50 of 2,656 mg/kg
• It should be further tested for other species and
  formulated
• Might have potential as repellents
• Metofluthrin- Pyrethroid Ester
• Newly registered EPA insecticide formulated in
  resin strips with repellency
• Might have potential as contact toxicants

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Acknowledgements

• Deployed Warfighter Protection (DWFP) Program
• Procter Gamble
• Dr. Daniel Kline Ms. Joyce Urban
• Dr. Sandra Allen Ms. Erin Vrzal
• Urban Laboratory of the University of Florida
• Toxicology Laboratory of the University of
  Florida

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Citations/Photo Credits

• Brooks, G.D., and H.F. Schoof. 1964.
  Effectiveness of various dosages of dichlorvos
  resin against Culex pipiens quinquefasciatus.
  Mosq. News. 24(2) 141-143.
• EPA Regulatory changes proposed on insecticide
  pest strip and other DDVP products
  www.epa.gov/pesticides/op/ddvp.htm
• EPA Dichlorvos Pesticide Fact Sheet (1987)
• Haritos VS and Dojchinov G, Cytrochrome c oxidase
  inhibition in the rice weevil Sitophilus oryzae
  L. by formate, the toxic metabolite of volatile
  alkyl formates. Comparative Biochemistry and
  Physiology Part C 136 135-143 (2003)
• Maddock, D.R., C.M. Elmore, and H.F. Schoof.
  1963. Preliminary tests with DDVP vapor for the
  control of Culex pipiens quinquefasciatus in
  catch basins. Mosq. News. 23(2) 69-74.
• Mathis, W., W. Richard, H.F. Schoof, and K.D.
  Quarterman. 1959. Residual fumigants. Their
  potential in malaria eradication. Pu. Hlth. Rep.
  74(5) 379-381.
• Miles, J.W., G.W. Pearce, and J.E. Woehst. 1962.
  Stable formulations for sustained release of
  DDVP. Agric. Food Chem. 10 240-244.
• Nguyen SN, Song C and Scharf ME,
  Toxicity,synergism and neurological effects of
  novel volatile insecticides in insecticide
  susceptible and resistant Drosophila strains.
  Journal of Economical Entomology (2007)
• Physical properties of compounds
  www.inchem.org/documents/jecfa/jeceval/jec_981.htm
  http//www.thegoodscentscompany
• Scharf ME, Nguyen SN and Song C, Evaluation of
  volatile low molecular weight insecticides using
  Drosophila malanogaster as a model. Pest
  Management Science 62 655-663 (2006)
• Aedes aegypti photo www.interet-general.info,
  www.fmel.edu
• Drosophila melanogaster photo www.biologie.de
• Culex quinquefasciatus photo www.sciencemag.org
  

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Thank you!